Magnetic Therapy and Epilepsy; a pulsed electromagnetic field - repetitive transcranial magnetic stimulation (rTMS/TMS) research bibliography.

Below, please find dozens of peer reviewed research studies which support a finding that magnetic therapy utilizing pulsed electromagnetic fields called repetitive transcranial magnetic stimulation  (rTMS/TMS) reduces seizure activity in epilepsy (and reduces symptoms of Parkinson's disease, depression, MS, migraine headache) without side effects or expected/unexpected reactions.

We've followed Professor Anninos' research since summer 2000 and recently, happened to meet 4 person's who had been to see Professor Anninos in Greece.  We've talked at length and seen video tape of the electromagnetic field therapy process used upon dozens of his patients. If you've got Parkinson's disease, MS, Epilepsy, migraine headache, cluster headache, ADD, ADHD, or suffer with depression and can afford the time and expense of travel, we HIGHLY recommend you see them for picoTesla electromagnetic field therapy.

We can assist your participation in the next electromagnetic field therapy 'excursion' to Greece; just email us; the IABC contact we've got will be glad to send you out information which will probably convince you that a trip to Greece for electromagnetic field therapy is worth the time and expense. See IABC press release on Professor Anninos.

EarthPulse™ has discovered that our patent pending magnetic field supplementation device and methods substantially enhance human (and animal) performance.

Frequency Specific Pulsed Electromagnetic Field (PEMF) Research Bibliographies:

Several hundred pulsed electromagnetic field therapy citations contained in our research bibliographies are linked directly to PubMed a service of the U.S. National Library of Medicine and the U.S. National Institutes of Health. These studies are offered for your education only and are not intended as promotional material.

See also; Sandyk R, Anninos PA , Jacobson JI; three pioneers of electromagnetic field therapy to treat Parkinson's, Alzheimer's and epilepsy.

PEMF Background:

introduction to electromedicine

brain wave entrainment

brain wave entrainment II

Dr. Oz on PEMF treatment for pain (video)

Electromagnetism & Life; by Andrew Marino & R.O. Becker (due to file size this pdf takes up to minutes to load)

PEMF Research By Effect:

Alzheimer's and frequency specific pulsed electromagnetic fields

anti-aging and frequency specific pulsed electromagnetic field therapy research

arthritis and frequency specific pulsed electromagnetic field therapy research

athletic performance enhancement (ergogenic effect) and frequency specific pulsed electromagnetic field therapy research

bone / connective tissue regeneration and frequency specific pulsed electromagnetic field therapy research

depression and frequency specific pulsed electromagnetic field therapy research

EMF protection - electropollution research (your brain and your wireless technologies)

epilepsy and frequency specific pulsed electromagnetic field therapy research

fibromyalgia and frequency specific pulsed electromagnetic field therapy research

insomnia and frequency specific pulsed electromagnetic field therapy research

migraine headache and frequency specific pulsed electromagnetic field therapy research

multiple sclerosis and frequency specific pulsed electromagnetic field therapy research

nerve regeneration and frequency specific pulsed electromagnetic field therapy research

neuropathy and frequency specific pulsed electromagnetic field therapy research

osteoporosis and frequency specific pulsed electromagnetic field therapy research

pain and frequency specific pulsed electromagnetic field therapy research

Parkinson's disease and frequency specific pulsed electromagnetic field therapy research

sleep and radio frequency microwave telecommunications fields

stroke and frequency specific pulsed electromagnetic field therapy research

thyroid and frequency specific pulsed electromagnetic field therapy research

tinnitus and frequency specific pulsed electromagnetic field therapy research

transcranial magnetic stimulation (rTMS / TMS) research

EarthPulse research:

video evidence

client feedback forms

chronic lower back pain/sleep study

magnetic fields in the news

Epilepsy Res. 2011 Oct;96(3):231-40. Epub 2011 Jun 29.
Antiepileptic effects of low frequency repetitive transcranial magnetic stimulation: A meta-analysis.
Hsu WY, Cheng CH, Lin MW, Shih YH, Liao KK, Lin YY.
Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan; Laboratory of Neurophysiology, Taipei Veterans General Hospital, Taipei, Taiwan; Integrated Brain Research Laboratory, Taipei Veterans General Hospital

Epilepsy Behav. 2011 Feb;20(2):355-9. Epub 2011 Jan 7.
An estimate of placebo effect of repetitive transcranial magnetic stimulation in epilepsy.
Bae EH, Theodore WH, Fregni F, Cantello R, Pascual-Leone A, Rotenberg A.
Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Clin EEG Neurosci. 2011 Jan;42(1):40-4.
Low-frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy.
Sun W, Fu W, Mao W, Wang D, Wang Y.
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China.

Eur Neurol. 2010;63(4):205-10. Epub 2010 Feb 11.
Transcranial magnetic stimulation for drug-resistant epilepsies: rationale and clinical experience.
Kimiskidis VK.
Department of Neurology III, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Epilepsy Behav. 2009 Oct;16(2):353-5. Epub 2009 Sep 10.
In-session seizures during low-frequency repetitive transcranial magnetic stimulation in patients with epilepsy.
Rotenberg A, Bae EH, Muller PA, Riviello JJ Jr, Bourgeois BF, Blum AS, Pascual-Leone A.
Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA

Epilepsy Behav. 2009 Jan;14(1):253-7. Epub 2008 Oct 30.
Repetitive transcranial magnetic stimulation in the treatment of epilepsia partialis continua.
Rotenberg A, Bae EH, Takeoka M, Tormos JM, Schachter SC, Pascual-Leone A.
Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Seizure. 2008 Dec;17(8):677-83. Epub 2008 May 20.
Repetitive transcranial magnetic stimulation decreases the number of seizures in patients with focal neocortical epilepsy.
Santiago-Rodríguez E, Cárdenas-Morales L, Harmony T, Fernández-Bouzas A, Porras-Kattz E, Hernández A.
Unidad de Investigación en Neurodesarrollo "Dr. Augusto Fernández Guardiola", Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico.

1: Epilepsy Behav. 2008 Jul;13(1):260-2. Epub 2008 Mar 4.

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Transient suppression of seizures by repetitive transcranial magnetic stimulation in a case of Rasmussen's encephalitis.

Rotenberg A, Depositario-Cabacar D, Bae EH, Harini C, Pascual-Leone A, Takeoka M.

Division of Epilepsy and Clinical Neurophysiology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. alexander.rotenberg@childrens.harvard.edu

Repetitive transcranial magnetic stimulation (rTMS) has been applied with variable success to terminate the seizures of epilepsia partialis continua. The rationale for using this technique to suppress ongoing seizures is the capacity of rTMS to interrupt ongoing neuronal activity, and to produce a lasting decrease in cortical excitability with low-frequency (1 Hz) stimulation. We report a case of epilepsia partialis continua in a child with Rasmussen's encephalitis, in whom seizures were transiently suppressed by 1-Hz rTMS delivered in nine daily 30-minute sessions. In this case, total ictal time was significantly reduced during stimulation, but the daily baseline seizure rate remained unchanged. Notably, the detection and quantification of this short-lived improvement were enabled by recording EEG continuously during the rTMS session. Thus, we present this case to illustrate a potential utility of combined continuous EEG recording and rTMS in seizure treatment.

Publication Types:

• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov't

PMID: 18304879 [PubMed - in process]

3: Seizure. 2008 May 19. [Epub ahead of print]Related Articles, Links

Repetitive transcranial magnetic stimulation decreases the number of seizures in patients with focal neocortical epilepsy.

Santiago-Rodríguez E, Cárdenas-Morales L, Harmony T, Fernández-Bouzas A, Porras-Kattz E, Hernández A.

Unidad de Investigación en Neurodesarrollo “Dr. Augusto Fernández Guardiola”, Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico.

PURPOSE: To evaluate the number of seizures and interictal epileptiform discharges (IEDs) in patients with focal neocortical epilepsy before, during and after rTMS. METHODS: Twelve patients (seven men and five women, mean age 29.3+/-15.8 years) were studied. An open-label study with baseline (4 weeks), intervention (2 weeks) and follow-up (8 weeks) periods was carried out. Repetitive transcranial magnetic stimulation (rTMS) with 900 pulses, intensity of 120% motor resting threshold and 0.5Hz frequency was used. A 120 channel EEG was recorded; an electrical source analysis of IEDs with Variable Resolution Electromagnetic Tomography (VARETA) was performed. The number of seizures per week and IEDs per minute were measured and compared in the three periods. RESULTS: During the basal period the mean seizure frequency was 2.25 per week; in the intervention period it decreased to 0.66 per week (F=2.825; p=0.0036) which corresponds to a 71% reduction. In the follow-up period the mean frequency was 1.14 seizures per week, that is, a 50% reduction in the number of seizures. In the visual EEG analysis, the baseline IED frequency was 11.9+/-8.3events/min; it decreased to 9.3+/-7.9 during 2 weeks of rTMS with a further reduction to 8.2+/-6.6 in the follow-up period. These differences however were not significant (p=0.190). CONCLUSION: We conclude that 2 weeks of rTMS at 0.5Hz with a figure-of-eight coil placed over the epileptic focus, determined with VARETA, decreases the number of seizures in patients with focal epilepsy, without reduction in IEDs.

PMID: 18495500 [PubMed - as supplied by publisher]

4: Cereb Cortex. 2008 Mar;18(3):664-9. Epub 2007 Jul 5.

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Intracortical hyperexcitability in humans with a GABAA receptor mutation.

Fedi M, Berkovic SF, Macdonell RA, Curatolo JM, Marini C, Reutens DC.

Department of Medicine, The University of Melbourne, Heidelberg, Victoria, Australia.

A missense mutation of the gamma2 subunit of the gamma-aminobutyric acid A (GABA(A)) receptor has been linked to an inherited human generalized epilepsy. As synaptic inhibition in the human brain is largely mediated by the GABA(A) receptor, we tested the hypothesis that the GABRG2(R43Q) mutation alters cortical excitability. Fourteen subjects affected by the GABRG2(R43Q) mutation (5 males, mean age: 44 +/- 15 years) and 24 controls (11 males, mean age: 38 +/- 11 years) were studied with transcranial magnetic stimulation (TMS). To assess the specificity of the effect of the mutation, 4 additional family members unaffected by the GABRG2(R43Q) mutation (2 males, mean age: 41 +/- 16 years) were included. Subjects affected by the GABRG2(R43Q) mutation demonstrated reduced net short-interval intracortical inhibition and increased intracortical facilitation assessed with paired-pulse stimulation. Subjects with the mutation had similar motor thresholds to controls both at rest and with weak voluntary activation. No significant differences were noted between groups in the cortical silent period. Our findings provide in vivo evidence for increased intracortical excitability in subjects affected by the GABRG2(R43Q) mutation. These findings are also likely to represent an important clue to the mechanisms linking this gene defect and the epilepsy phenotype.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't

PMID: 17615250 [PubMed - indexed for MEDLINE]

5: Clin Neurophysiol. 2008 Mar;119(3):504-32. Epub 2007 Dec 11.

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The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee.

Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, Mills K, Rösler KM, Triggs WJ, Ugawa Y, Ziemann U.

Division of Neurology, Toronto Western Research Institute, University of Toronto, 7MC411, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ont., Canada M5T 2S8. robert.chen@uhn.on.ca

The review focuses on the clinical diagnostic utility of transcranial magnetic stimulation (TMS). The central motor conduction time (CMCT) is a sensitive method to detect myelopathy and abnormalities may be detected in the absence of radiological changes. CMCT may also detect upper motor neuron involvement in amyotrophic lateral sclerosis. The diagnostic sensitivity may be increased by using the triple stimulation technique (TST), by combining several parameters such as CMCT, motor threshold and silent period, or by studying multiple muscles. In peripheral facial nerve palsies, TMS may be used to localize the site of nerve dysfunction and clarify the etiology. TMS measures also have high sensitivity in detecting lesions in multiple sclerosis and abnormalities in CMCT or TST may correlate with motor impairment and disability. Cerebellar stimulation may detect lesions in the cerebellum or the cerebellar output pathway. TMS may detect upper motor neuron involvement in patients with atypical parkinsonism and equivocal signs. The ipsilateral silent period that measures transcallosal inhibition is a potential method to distinguish between different parkinsonian syndromes. Short latency afferent inhibition (SAI), which is related to central cholinergic transmission, is reduced in Alzheimer's disease. Changes in SAI following administration of cholinesterase inhibitor may be related to the long-term efficacy of this treatment. The results of MEP measurement in the first week after stroke correlate with functional outcome. We conclude that TMS measures have demonstrated diagnostic utility in myelopathy, amyotrophic lateral sclerosis and multiple sclerosis. TMS measures have potential clinical utility in cerebellar disease, dementia, facial nerve disorders, movement disorders, stroke, epilepsy, migraine and chronic pain.

Publication Types:

• Review

PMID: 18063409 [PubMed - indexed for MEDLINE]

6: Epilepsia. 2008 Mar;49(3):470-80. Epub 2007 Nov 19.

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Late EEG responses triggered by transcranial magnetic stimulation (TMS) in the evaluation of focal epilepsy.

Valentin A, Arunachalam R, Mesquita-Rodrigues A, Garcia Seoane JJ, Richardson MP, Mills KR, Alarcon G.

Department of Clinical Neuroscience, Institute of Psychiatry, King's College London, United Kingdom.

PURPOSE: To evaluate the use of EEG responses to transcranial magnetic stimulation (TMS-EEG responses) as a noninvasive tool for the diagnosis of focal epilepsy. METHODS: Fifteen patients and 15 healthy subjects were studied. TMS at an intensity set at resting corticomotor threshold were delivered at the standard EEG electrode positions. For each position, EEG responses to TMS were evaluated before and after averaging EEG recordings synchronized with the TMS pulse. RESULTS: Two types of TMS-EEG responses were seen: (A) early responses: consisting of a single slow wave seen after the TMS pulse; and (B) late TMS-EEG responses, which were subclassified into (b.1) delayed responses: waveforms resembling interictal epileptiform discharges induced by TMS; or (b.2) repetitive responses: onset of a new rhythym induced by TMS. Early responses were observed in patients and healthy subjects when stimulating at various sites and were considered normal responses to TMS. Late TMS-EEG responses were not seen in healthy subjects, whereas they were seen in 11 of the 15 epileptic patients. Late TMS-EEG responses occurred when stimulating the epileptogenic side in eight out of the nine patients who had lateralized late TMS-EEG responses. The combined use of late TMS-EEG responses and interictal scalp EEG would have suggested the diagnosis of focal epilepsy in all patients, despite the absence of late TMS-EEG responses in four patients and the presence of normal interictal scalp EEG in three. CONCLUSIONS: TMS-EEG responses can identify epileptogenic cortex and may substantially improve the diagnosis of focal epilepsy, particularly, if combined with standard EEG studies.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't

PMID: 18028404 [PubMed - indexed for MEDLINE]

7: Neurorehabil Neural Repair. 2008 Mar-Apr;22(2):185-92. Epub 2007 Sep 17.

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Safety of 6-Hz primed low-frequency rTMS in stroke.

Carey JR, Evans CD, Anderson DC, Bhatt E, Nagpal A, Kimberley TJ, Pascual-Leone A.

Program in Physical Therapy, University of Minnesota, Minneapolis 55455, USA. carey007@umn.edu

BACKGROUND: Suppression of activity in the contralesional motor cortex may promote recovery of function after stroke. Furthermore, the known depressant effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) can be increased and prolonged by preceding it with 6-Hz priming stimulation. OBJECTIVE: The authors explored the safety of 6-Hz primed low-frequency rTMS in 10 patients with ischemic stroke. METHODS: Priming consisted of 10 minutes of 6-Hz rTMS applied to the contralesional hemisphere at 90% of resting motor threshold delivered in 2 trains/min with 5 s/train and 25-second intervals between trains. Low-frequency rTMS consisted of an additional 10 minutes of 1-Hz rTMS at 90% of resting motor threshold without interruption. Possible adverse effects were assessed with the National Institutes of Health Stroke Scale (NIHSS), the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Hopkins Verbal Learning Test-Revised (HVLT-R), the Beck Depression Inventory-Second Edition (BDI-II), a finger movement tracking test, and individual self-assessments. Pretest, treatment, and posttest occurred on the first day with follow-up tests on the next 5 weekdays. RESULTS: There were no seizures and no impairment of NIHSS, WAIS-III, or BDI-II scores. Transient impairment occurred on the HVLT-R. Transient tiredness was common. Occasional reports of headache, neck pain, increased sleep, reduced sleep, nausea, and anxiety occurred. CONCLUSION: Because there were no major adverse effects, the authors concluded that the treatment was safe for the individuals in this study and that further investigation is now warranted to examine efficacy and safety of serial treatments of 6-Hz primed low-frequency rTMS.

Publication Types:

• Clinical Trial
• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov't

PMID: 17876070 [PubMed - indexed for MEDLINE]

8: Int J Neuropsychopharmacol. 2008 Feb;11(1):131-47. Epub 2007 Sep 20.

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A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression.

Loo CK, McFarquhar TF, Mitchell PB.

School of Psychiatry, University of New South Wales, Sydney, Australia. colleen.loo@unsw.edu.au

There is growing interest worldwide in rTMS as a clinical treatment for depression. Apart from efficacy, its safety as a clinical treatment must be considered before its widespread use can be advocated. All published, sham-controlled rTMS depression trials were reviewed for reported side-effects and outcomes of formal neuropsychological testing. In addition, all reports of seizures occurring with rTMS were reviewed. Other safety concerns (effects on hearing; headache, pain, induced currents in electrical circuits, histotoxicity, electromagnetic field exposure, psychiatric complications, safety in pregnancy) are discussed. Common side-effects were of a minor nature, e.g. headache. There was a low incidence of accidental seizures and induced hypomania, both of which were associated with identified risk factors for which subjects should be screened. Long-term effects of repeated rTMS sessions are as yet unknown. When given within recommended guidelines, the overall safety profile of rTMS is good, and supports its further development as a clinical treatment.

Publication Types:

• Research Support, Non-U.S. Gov't
• Review

PMID: 17880752 [PubMed - indexed for MEDLINE]

9: Exp Brain Res. 2008 Jan;184(3):439-43. Epub 2007 Nov 24.

Related Articles, Links

Cortical silent period following TMS in a patient with supplementary sensorimotor area seizures.

Nardone R, Venturi A, Ausserer H, Ladurner G, Tezzon F.

Department of Neurology, Franz.Tappeiner Hospital, Via Rossini, 5, 39012, Merano, Italy. raffaele.nardone@asbmeran-o.it

The cortical silent period (CSP) following transcranial magnetic stimulation (TMS) was evaluated in a patient with a dysembrioplastic neuroepithelial tumor (DNET) in the lateral portion of the right superior frontal gyrus (SFG) who suffered from supplementary sensorimotor area (SSMA) seizures. CSP duration was shortened on the affected side. Ipsilateral alterations of motor cortex excitability with TMS in epileptogenic DNET located outside the PMA argue in favour of cortico-cortical connections to primary motor cortex from SSMA. This functional connectivity should be taken into consideration to better understand the pathophysiology of ictal motor manifestations.

Publication Types:

• Case Reports

PMID: 18038265 [PubMed - indexed for MEDLINE]

10: Med Hypotheses. 2008;71(2):279-82. Epub 2008 Apr 22.

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Can the 'yin and yang' BDNF hypothesis be used to predict the effects of rTMS treatment in neuropsychiatry?

Brunoni AR, Boggio PS, Fregni F.

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, KS 430, Boston, MA 02215, USA; Institute of Psychiatry, University of São Paulo, Brazil.

Repetitive transcranial magnetic stimulation (rTMS) is a novel technique of non-invasive brain stimulation which has been used to treat several neuropsychiatric disorders such as major depressive disorder, chronic pain and epilepsy. Recent studies have shown that the therapeutic effects of rTMS are associated with plastic changes in local and distant neural networks. In fact, it has been suggested that rTMS induces long-term potentiation (LTP) and long-term depression (LTD) - like effects. Besides the initial positive clinical results; the effects of rTMS are still mixed. Therefore new tools to assess the effects of plasticity non-invasively might be useful to predict its therapeutic effects and design novel therapeutic approaches using rTMS. In this paper we propose that brain-derived neurotrophic factor (BDNF) might be such a tool. Brain-derived neurotrophic factor is a neurotrophin that plays a key role in neuronal survival and synaptic strength, which has also been studied in several neuropsychiatric disorders. There is robust evidence associating BDNF with the LTP/LTD processes, and indeed it has been proposed that BNDF might index an increase or decrease of brain activity - the 'yin and yang' BDNF hypothesis. In this article, we review the initial studies combining measurements of BDNF in rTMS clinical trials and discuss the results and potential usefulness of this instrument in the field of rTMS.

PMID: 18434040 [PubMed - in process]

11: Zhonghua Wai Ke Za Zhi. 2007 Dec 15;45(24):1685-7.

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[The effect of low frequency transcranial magnetic stimulation on neuropeptide-Y expression and apoptosis of hippocampus neurons in epilepsy rats induced by pilocarpine]

[Article in Chinese]

Wang YL, Zhai Y, Huo XL, Zhang JN.

Department of Neurosurgery, General Hospital of Tianjin Medical University, Tianjin 300052, China. wang19690924@sina.com

OBJECTIVE: To analyze the effect of low frequency transcranial magnetic stimulation (LF-TMS) on changing neuropeptide-Y (NPY) expression and apoptosis of hippocampus neurons in epilepsy rats induced by pilocarpine (PLO). METHODS: Thirty male Sprague Dawley rats (240 g +/- 20 g) were randomly divided into 2 groups. I group simply celiac injected pilocarpine. II group celiac injected PLO after LF-TMS. Pathological item included HE staining, NPY immunohistochemical staining and apoptosis staining. RESULTS: HE staining revealed neurons of hippocampus were obviously death and cell's structure was destroyed in PLO group. The PLO + LF-TMS group was less injured and destroyed. Using One-Way ANOVA, NPY immunohistochemical staining shown the positive cell number was increased at all areas of hippocampus in PLO group contrasting with the low positive cell number in the PLO + LF-TMS group. In PLO group the number of apoptosis cell at hippocampus areas was significant higher than the PLO + LF-TMS group. CONCLUSIONS: Using the PLO evoked epilepsy model, LF-TMS alleviated neurons injury at hippocampus area, so LF-TMS might playing an important role in resisting the progressing of epilepsy. The positive cell number of NPY increased at all areas of hippocampus, which indicated the close relation between NPY and epilepsy. NPY might have some function on resisting epilepsy.

Publication Types:

• English Abstract

PMID: 18476527 [PubMed - in process]

12: Brain Res Rev. 2007 Dec;56(2):346-61. Epub 2007 Aug 28.

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The use of tDCS and CVS as methods of non-invasive brain stimulation.

Been G, Ngo TT, Miller SM, Fitzgerald PB.

Alfred Psychiatry Research Centre, The Alfred Hospital and Monash University School of Psychology, Psychiatry and Psychological Medicine, Commercial Rd, Melbourne, VIC 3004, Australia.

Transcranial direct current stimulation (tDCS) and caloric vestibular stimulation (CVS) are safe methods for selectively modulating cortical excitability and activation, respectively, which have recently received increased interest regarding possible clinical applications. tDCS involves the application of low currents to the scalp via cathodal and anodal electrodes and has been shown to affect a range of motor, somatosensory, visual, affective and cognitive functions. Therapeutic effects have been demonstrated in clinical trials of tDCS for a variety of conditions including tinnitus, post-stroke motor deficits, fibromyalgia, depression, epilepsy and Parkinson's disease. Its effects can be modulated by combination with pharmacological treatment and it may influence the efficacy of other neurostimulatory techniques such as transcranial magnetic stimulation. CVS involves irrigating the auditory canal with cold water which induces a temperature gradient across the semicircular canals of the vestibular apparatus. This has been shown in functional brain-imaging studies to result in activation in several contralateral cortical and subcortical brain regions. CVS has also been shown to have effects on a wide range of visual and cognitive phenomena, as well as on post-stroke conditions, mania and chronic pain states. Both these techniques have been shown to modulate a range of brain functions, and display potential as clinical treatments. Importantly, they are both inexpensive relative to other brain stimulation techniques such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS).

Publication Types:

• Research Support, Non-U.S. Gov't
• Review

PMID: 17900703 [PubMed - indexed for MEDLINE]

13: Neurosci Behav Physiol. 2007 Nov;37(9):849-52.

Related Articles, Links

Evoked motor response thresholds during transcranial magnetic stimulation in patients with symptomatic partial epilepsy.

Kotova OV, Vorob'eva OV.

Department of Nervous Diseases, Postgraduate Professional Educational Faculty, I. M. Sechenov Moscow Medical Academy.

Transcranial magnetic stimulation (TMS) occupies a leading position among noninvasive neurophysiological methods used for evaluating the balance of processes of cortical inhibition and excitation. The aim of the present work was to assess motor cortical excitability in symptomatic partial epilepsy using TMS in relation to the effects of antiepileptic treatment. A total of 31 patients were studied. A decrease in the motor response threshold was seen in a group consisting of untreated patients, with changes in cortical excitability during seizures. Treated patients showed no difference as compared with healthy subjects. The shorter the interval between a seizure and TMS, the smaller the evoked motor response threshold. The low threshold seen in patients with symptomatic partial epilepsy showed a significant correlation with clinical signs of neuromuscular excitability. The data obtained here provide evidence of changes in the functional state of the cortex and, thus, the motor response threshold, in patients with epilepsy.

PMID: 17955376 [PubMed - indexed for MEDLINE]

14: Clin Neurophysiol. 2007 Sep;118(9):2072-5. Epub 2007 Jul 24.

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Safety study of high-frequency transcranial magnetic stimulation in patients with chronic stroke.

Lomarev MP, Kim DY, Richardson SP, Voller B, Hallett M.

Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, NIH Building 10, Room 5N240, 10 Center Dr MSC 1428, Bethesda, MD 20892-1428, USA. lomarevm@ninds.nih.gov

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a potential therapeutic tool to rehabilitate chronic stroke patients. In this study, the safety of high-frequency rTMS in stroke was investigated (Phase I). METHODS: The safety of 20 and 25 Hz rTMS over the motor cortex (MC) of the affected hemisphere, with intensities of 110-130% of the motor threshold (MT), was evaluated using surface electromyography (EMG) of hand and arm muscles. RESULTS: Brief EMG bursts, possibly representing peripheral manifestations of after discharges, and spread of excitation to proximal muscles are considered to be associated with a high risk of seizure occurrence. These events were recorded after the rTMS trains. Neither increased MC excitability nor improved pinch force dynamometry was found after rTMS. CONCLUSIONS: Stimulation parameters for rTMS, which are safe for healthy volunteers, may lead to a higher risk for seizure occurrence in chronic stroke patients. SIGNIFICANCE: rTMS at rates of 20 and 25 Hz using above threshold stimulation potentially increases the risk of seizures in patients with chronic stroke.

PMID: 17652018 [PubMed - indexed for MEDLINE]

15: Epilepsia. 2007 Sep;48(9):1756-63. Epub 2007 Jun 11.

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Ketogenic diet: electrophysiological effects on the normal human cortex.

Cantello R, Varrasi C, Tarletti R, Cecchin M, D'Andrea F, Veggiotti P, Bellomo G, Monaco F.

Department of Clinical and Experimental Medicine, Section of Neurology, A. Avagadro University, Novara, Italy. cantello@med.unipmn.it

PURPOSE: To explore the cortical electrophysiology of the ketogenic diet (KD) in the normal human. KD is effective against refractory epilepsy, but its precise mechanism is obscure. At the transmitter level, an enhancement of GABA inhibition has often been proposed. METHODS: We studied eight healthy volunteers undergoing a "classic" KD for 2 weeks. We measured several biochemical variables at baseline (T0), after 1 week (T1) and 2 weeks (T2) of KD, then 3 months after the KD conclusion (T3). Ketosis was quantified as 24-h ketonuria. At the same time, we studied the motor cortical excitability by means of transcranial magnetic stimulation (TMS). We also quantitatively evaluated the EEG signal in search of frequency shifts over the rolandic areas. RESULTS: Significant (p < 0.05) neurophysiological changes appeared at T2. These consisted of a strengthening of short-latency cortical inhibition (SICI), a TMS index which is thought to reflect GABA-A inhibition in the cortex. Then, there was an enhancement of the beta EEG band over the perirolandic region, similar to that following administration of GABA-A agonists. All changes disappeared at T3. CONCLUSIONS: A standard, short-term KD affected the cortical physiology of the normal human. The main changes were an augmented SICI and an increased perirolandic beta EEG activity, which are compatible with a lower level of neural excitation within the cortex.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't

PMID: 17561954 [PubMed - indexed for MEDLINE]

16: Epilepsia. 2007 Aug;48(8):1538-42. Epub 2007 Apr 13.

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A hypothesis for how non-REM sleep might promote seizures in partial epilepsies: a transcranial magnetic stimulation study.

Salih F, Khatami R, Steinheimer S, Kretz R, Schmitz B, Grosse P.

Neurologische Klinik und Poliklinik, and Interdisziplinäres Schlafmedizinisches Zentrum, Charité-Universitätsmedizin Berlin, Augustenburgerplatz 1, 13353 Berlin, Germany. Farid.Salih@charite.de

PURPOSE: To investigate alterations of inhibitory and excitatory cortical circuits during non-rapid eye movement (NREM) sleep in drug-naive patients with partial epilepsies and sleep-bound seizures only. METHODS: A paired-pulse TMS paradigm was used to test intracortical inhibition (ICI) and facilitation (ICF) in the hemisphere of the epileptic focus in three untreated patients with nonlesional, nongenetic frontal lobe epilepsy in NREM2 (three patients), NREM3/4 (one patient), and wakefulness (three patients). RESULTS: All three patients exhibited a major decrease of ICI in NREM sleep as opposed to the physiological enhancement of ICI with the progression of NREM sleep. CONCLUSIONS: Decreased ICI might reflect a substrate for the association of epileptic processes with thalamocortical networks that propagate sleep. Thus our findings contribute to a hypothesis of how NREM sleep could promote seizures.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't

PMID: 17433053 [PubMed - indexed for MEDLINE]

17: J Neurol Sci. 2007 Jul 15;258(1-2):144-7. Epub 2007 Mar 29.

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Heightened seizure susceptibility associated with brain dermoid cyst and the administration of human chorionic gonadotropin (hCG).

Milani P, Rocchi R, Cerase A, Rossi A, Mazzocchio R.

Section of Clinical Neurophysiology, Department of Neurological and Behavioral Sciences, University of Siena, Italy.

It is known that the intramuscular injection of human chorionic gonadotropin (hCG) lowers the threshold for motor evoked responses (MEPs) in the first dorsal interosseous (FDI) muscle to transcranial magnetic stimulation (TMS) in humans. We describe the case of a patient with a clinically silent left-sided nasofrontal dermoid cyst who, while being treated with hCG/LH for hypogonadotropic hypogonadism, presented with simple partial seizures, ipsilateral to the cyst, with secondary generalization. Motor cortex excitability was studied by single and paired TMS and MEPs were recorded from FDI. Resting motor threshold (RMT), active motor threshold (AMT), MEP size, intracortical inhibition (ICI) and intracortical facilitation (ICF) were tested during and after suspension of hormonal therapy. RMT and AMT were lower, MEP size was larger, ICI was decreased while ICF was slightly diminished during treatment. Overall, this indicated a reduced intracortical inhibition during hormonal therapy. It is concluded that treatment with hCG/LH may favour seizure onset in the presence of potentially epileptogenic lesions such as an intracranial dermoid cyst.

Publication Types:

• Case Reports

PMID: 17395206 [PubMed - indexed for MEDLINE]

18: Epilepsy Res. 2007 Jul;75(2-3):197-205.

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Motor representation areas in epileptic patients with focal motor seizures: a TMS study.

Labyt E, Houdayer E, Cassim F, Bourriez JL, Derambure P, Devanne H.

Department of Clinical Neurophysiology, EA 2683, R. Salengro Hospital, Lille University Medical Centre, F-59037 Lille, France. etienne.labyt@wanadoo.fr

PURPOSE: This study used TMS mapping to investigate the motor representation of the abductor pollicis brevis (APB) muscles in a group of patients with focal epilepsy originating in central or pre-central region. METHODS: Eight epileptic patients and eight control subjects participated in the study. The coil was moved in 1.5-cm steps along a grid drawn on the subject's skull over the motor cortex of both hemispheres. At each site, six APB motor responses (evoked by TMS at 1.2 times the resting motor threshold) were recorded and averaged. The peak-to-peak amplitude was measured and plotted against the mediolateral and anteroposterior coil positions. The area of each APB muscle representation was measured and the position of the optimal point was calculated. RESULTS: The resting motor threshold was increased bilaterally in epileptic patients. The maps were distorted in most patients (but not in control subjects), as evidenced by an off-centre optimal point. Interhemispheric differences in APB map areas were greater in patients than in control subjects. However, whether these increases in map area were on the epileptic side or on healthy side depended on the given subject. CONCLUSIONS: The changes in APB representation observed in epileptic patients demonstrate that reorganization occurs within the motor cortex. The heterogeneity of the present results is probably related to different locations of the epileptogenic and/or lesional areas and to a variety of compensatory phenomena that may occur, notably with respect to the disease duration.

PMID: 17628428 [PubMed - indexed for MEDLINE]

19: Nat Clin Pract Neurol. 2007 Jul;3(7):383-93.

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Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS.

Fregni F, Pascual-Leone A.

Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

In neurology, as in all branches of medicine, symptoms of disease and the resulting burden of illness and disability are not simply the consequence of the injury, inflammation or dysfunction of a given organ; they also reflect the consequences of the nervous system's attempt to adapt to the insult. This plastic response includes compensatory changes that prove adaptive for the individual, as well as changes that contribute to functional disability and are, therefore, maladaptive. In this context, brain stimulation techniques tailored to modulate individual plastic changes associated with neurological diseases might enhance clinical benefits and minimize adverse effects. In this Review, we discuss the use of two noninvasive brain stimulation techniques--repetitive transcranial magnetic stimulation and transcranial direct current stimulation--to modulate activity in the targeted cortex or in a dysfunctional network, to restore an adaptive equilibrium in a disrupted network for best behavioral outcome, and to suppress plastic changes for functional advantage. We review randomized controlled studies, in focal epilepsy, Parkinson's disease, recovery from stroke, and chronic pain, to illustrate these principles, and we present evidence for the clinical effects of these two techniques.

Publication Types:

• Research Support, N.I.H., Extramural
• Review

PMID: 17611487 [PubMed - indexed for MEDLINE]

20: Epilepsy Behav. 2007 Jun;10(4):521-8. Epub 2007 May 9.

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Safety and tolerability of repetitive transcranial magnetic stimulation in patients with epilepsy: a review of the literature.

Bae EH, Schrader LM, Machii K, Alonso-Alonso M, Riviello JJ Jr, Pascual-Leone A, Rotenberg A.

Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a new therapeutic tool in epilepsy, where it can be used to suppress seizures or treat comorbid conditions such as mood disorder. However, as rTMS carries a risk of inducing seizures among other adverse events, its safety and tolerability in the population with epilepsy warrant distinct consideration, as this group is especially seizure-prone. Accordingly, we performed a review of the literature to estimate the risk of seizures and other adverse events associated with rTMS in patients with epilepsy. We performed an English-language literature search, and reviewed all studies published from January 1990 to February 2007 in which patients with epilepsy were treated with rTMS, and complemented the literature search with personal correspondence with authors when necessary. We identified 30 publications that described patients with epilepsy who underwent rTMS, and noted total number of relevant subjects, medication usage, incidence of adverse events, and rTMS parameters including stimulus frequency, number of stimuli, train duration, intertrain interval, coil type, and stimulation sites. The data were analyzed for adverse events related to rTMS. Crude per-subject risk, as well as per-subject mean risk weighted by sample size and risk per 1000 stimuli weighted by number of stimuli in each study, were computed for seizures and for other adverse events. Adverse events or lack thereof was reported in 26 studies (n=280 subjects). Adverse events attributed to rTMS were generally mild and occurred in 17.1% of subjects. Headache was most common, occurring in 9.6%. The most serious adverse event was seizure during treatment, which occurred in four patients (1.4% crude per-subject risk). All but one case were the patients' typical seizures with respect to duration and semiology, and were associated with low-frequency rTMS. A single case of an atypical seizure appearing to arise from the region of stimulation during high-frequency rTMS is reported. No rTMS-related episodes of status epilepticus were reported. We cautiously conclude that the risk of seizure in patients with epilepsy undergoing rTMS is small, and the risk of other mild adverse events is comparable to that seen when rTMS is used to treat other diseases. Status epilepticus or life-threatening seizures have not been reported in patients undergoing rTMS treatment. rTMS thus appears to be nearly as safe in patients with epilepsy as in nonepileptic individuals, and warrants further investigation as a therapy in this population.

Publication Types:

• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov't
• Review

PMID: 17493877 [PubMed - indexed for MEDLINE]

21: AJNR Am J Neuroradiol. 2007 May;28(5):958-64.

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Diffusion tensor microscopy indicates the cytoarchitectural basis for diffusion anisotropy in the human hippocampus.

Shepherd TM, Ozarslan E, Yachnis AT, King MA, Blackband SJ.

Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32209, USA. tms@mbi.ufl.edu

BACKGROUND AND PURPOSE: Observing changes to water diffusivity and fractional anisotropy (FA) for particular hippocampal regions may improve the sensitivity and specificity of diffusion tensor MR imaging for hippocampal pathologies like Alzheimer disease and mesial temporal sclerosis. As a first step toward this goal, this study characterized the cytoarchitectural features underlying diffusion anisotropy in human hippocampus autopsy specimens at 60-microm in-plane resolution. MATERIALS AND METHODS: Eight-millimeter coronal segments of the hippocampal body were dissected from 5 autopsy specimens (mean = 55.6 +/- 6.2 years of age) with short postmortem intervals to fixation (21.2 +/- 5.7 hours) and no histologic evidence of neuropathology. Diffusion tensor microscopy data were collected from hippocampal specimens by using a 14.1T magnet with a protocol that included 21 unique diffusion gradient orientations (diffusion time = 17 ms, b = 1250 s/mm(2)). The resulting images were used to determine the mean diffusivity, FA, and principal fiber orientation for manually segmented hippocampal regions that included the stratum oriens, stratum radiatum, stratum pyramidale (CA1 and CA3), stratum lacunosum-molecular, hilus, molecular layer, granule cell layer, fimbria, and subiculum. RESULTS: Diffusion-weighted images had high signal-to-noise ratios (31.1 +/- 13.0) and delineated hippocampal anatomy well. Water diffusivity ranged from 1.21 +/- 0.22 x 10(-4) mm(2)/s in the fimbria to 3.48 +/- 0.72 x 10(-4) mm(2)/s in granule cells (analysis of variance, P<.001). Color fiber-orientation maps indicated the underlying microstructures responsible for diffusion anisotropy in the hippocampal lamina. CONCLUSION: Diffusion tensor microscopy provided novel microstructural information about the different lamina of the human hippocampus. These ex vivo data obtained at high-magnetic-field strengths can be used to study injury-specific diffusion changes to susceptible hippocampal regions and may lead to more specific MR imaging surrogate markers for Alzheimer disease or epilepsy.

Publication Types:

• Research Support, N.I.H., Extramural

PMID: 17494678 [PubMed - indexed for MEDLINE]

22: Epilepsy Res. 2007 May;74(2-3):239-42. Epub 2007 Apr 19.

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Comment in:

• Epilepsy Res. 2008 Feb;78(2-3):244-5.

Lack of differences of motorcortical excitability in the morning as compared to the evening in juvenile myoclonic epilepsy--a study using transcranial magnetic stimulation.

Pfütze M, Reis J, Haag A, John D, Hattemer K, Oertel WH, Rosenow F, Hamer HM.

Interdisciplinary Epilepsy Center, Department of Neurology, Philipps-University Marburg, Marburg, Germany. pfuetze@med.uni-marburg.de

We used transcranial magnetic stimulation (TMS) in patients with juvenile myoclonic epilepsy (JME) and healthy controls to characterise motorcortical excitability in the morning as compared to the evening. Intra- and interindividual comparisons in JME-patients and controls showed no significant differences of any TMS parameter. The expected rise of the resting motor thresholds (RMT) in JME-patients taking anticonvulsants could not be detected which may indicate a decreased RMT in JME-patients.

Publication Types:

• Comparative Study

PMID: 17448635 [PubMed - indexed for MEDLINE]

23: Brain. 2007 Mar;130(Pt 3):610-22. Epub 2006 Nov 29.

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Stimulating language: insights from TMS.

Devlin JT, Watkins KE.

FMRIB Centre, Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK. devlin@fmrib.ox.ac.uk

Fifteen years ago, Pascual-Leone and colleagues used transcranial magnetic stimulation (TMS) to investigate speech production in pre-surgical epilepsy patients and in doing so, introduced a novel tool into language research. TMS can be used to non-invasively stimulate a specific cortical region and transiently disrupt information processing. These 'virtual lesion' studies offer not only the ability to explore causal relations between brain regions and language functions absent in functional neuroimaging, but also spatial and temporal precision not typically available in patient studies. For instance, TMS has been used to demonstrate functionally distinct sub-regions of the left inferior frontal gyrus; to clarify the relationship between pre-morbid language organization and susceptibility to unilateral lesions and to investigate the contribution of both left and right hemisphere language areas in recovery from aphasia. When TMS is used as a measure of functional connectivity, it demonstrates a close link between action words and motor programmes; it suggests a potential evolutionary link between hand gestures and language and it suggests a role in speech perception for the motor system underlying speech production. In combination with functional neuroimaging, it can elucidate the circuits responsible for this involvement. Finally, TMS may even be useful for enhancing recovery in aphasic patients. In other words, TMS has already become an important tool for studying language at both the cognitive and neural levels, and it is clear that further developments in TMS methodology are likely to result in even greater opportunities for language research.

Publication Types:

• Research Support, Non-U.S. Gov't
• Review

PMID: 17138570 [PubMed - indexed for MEDLINE]

PMCID: PMC1820607

24: Clin Endocrinol (Oxf). 2007 Mar;66(3):387-93.

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Excitability of the motor cortex during ovulatory and anovulatory cycles: a transcranial magnetic stimulation study.

Hattemer K, Knake S, Reis J, Rochon J, Oertel WH, Rosenow F, Hamer HM.

Department of Neurology, University of Marburg, Germany. hattemer@med.uni-marburg.de

OBJECTIVE: The pathophysiology of catamenial diseases such as epilepsy is unclear. Therefore, we investigated changes in cortical excitability during anovulatory and ovulatory cycles. PATIENTS AND METHODS: Using transcranial magnetic stimulation (TMS), eight healthy women were investigated during anovulatory and 12 during ovulatory cycles. On days 8, -14, -7 and 2 of the cycle, resting motor threshold (RMT), cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated. Repeated-measures analysis of variance (anova) and nonparametric methods were used for statistical analysis. RESULTS: A trend was seen for group by phase interaction regarding ICI (F = 2.5, P = 0.10). ICI varied during anovulatory cycles (median: 51.0% on day 8; 45.3% on day -14, 51.0% on day -7, and 28.6% on day 2; P = 0.040), mainly because of an increased inhibition on day 2. ICI was more pronounced in anovulatory cycles on day -14 (P = 0.021), -7 (P = 0.048) and 2 (P = 0.018) compared to ovulatory women who did not show intraindividual changes (P = 0.56). RMT, CSP and ICF showed no significant changes during anovulatory or ovulatory cycles. CONCLUSIONS: The results suggest fluctuations in cortical excitability during anovulatory cycles, possibly due to the withdrawal of 'excitatory' oestrogens that initiate menses in anovulatory cycles.

Publication Types:

• Randomized Controlled Trial

PMID: 17302873 [PubMed - indexed for MEDLINE]

25: Clin Neurophysiol. 2007 Mar;118(3):702-8. Epub 2007 Jan 16.

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Antiepileptic effects of low-frequency repetitive transcranial magnetic stimulation by different stimulation durations and locations.

Joo EY, Han SJ, Chung SH, Cho JW, Seo DW, Hong SB.

Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, 135-710 Seoul, South Korea.

OBJECTIVE: To evaluate the antiepileptic effect of low-frequency rTMS (repetitive transcranial magnetic stimulation) in the patients with intractable epilepsy. METHODS: We enrolled 35 patients with localization-related epilepsy who had experienced at least one complex partial seizure or a secondarily generalized seizure per week on a constant antiepileptic drug regimen over an 8-week period. rTMS was administered using a Rapid(2) magnetic stimulator with an air-cooled coil at 0.5Hz for 5 consecutive days at 100% of rMT (resting motor threshold). Patients were divided into a focal stimulation group with a localized epileptic focus, or a non-focal stimulation group with a non-localized or multifocal epileptic focus. These two groups were then randomly subdivided into four subgroups depending on the total number of stimulations administered, i.e., 3000 pulse and 1500 pulse subgroups. Weekly seizure frequencies were determined for 8 weeks before and after rTMS. To compare the number of interictal spikes before and after rTMS, EEG was recorded twice before (1st day) and after rTMS (5th day). RESULTS: Mean weekly seizure frequency was non-significantly decreased after rTMS (8.4-->6.8/week, -13.9%). Longer stimulation subgroups (3000 pulses, -23.0%) tended to have fewer seizures than shorter stimulation subgroups (1500 pulses, -3.0%), without statistical significance. TMS stimulation site and structural brain lesions did not influence seizure outcome. However, interictal spikes significantly decreased (-54.9%, P=0.012) after rTMS and they totally disappeared in 6 patients (17.1%, 6/35). CONCLUSIONS: Low-frequency rTMS reduced interictal spikes, but its effect on seizure outcome was not significant. Focal stimulation for a longer duration tended to further reduce seizure frequency. SIGNIFICANCE: These findings may help clinicians to further investigate the therapeutic potential of the rTMS for patients with intractable epilepsy.

Publication Types:

• Randomized Controlled Trial
• Research Support, Non-U.S. Gov't

PMID: 17223384 [PubMed - indexed for MEDLINE]

26: Seizure. 2007 Mar;16(2):113-9. Epub 2006 Dec 20.

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The relationship between paired pulse magnetic MEP and surgical prognosis in patients with intractable epilepsy.

Kamida T, Fujiki M, Baba H, Ono T, Abe T, Kobayashi H.

Department of Neurosurgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan. kamida@med.oita-u.ac.jp

PURPOSE: To assess whether paired pulse magnetic motor evoked potential (MEP) can predict surgical prognosis in patients with intractable epilepsy. METHODS: MEP of the unilateral hand muscles were recorded following paired pulse transcranial magnetic stimulation (TMS) of the motor cortex. The interstimulus intervals of paired stimulation were 1-16 ms with a conditioning stimulus that was 90% active motor threshold. Subjects were six patients with temporal lobe epilepsy (TLE) scheduled for anterior temporal lobectomy and three patients with myoclonic or head-drop seizures scheduled for anterior corpus callosotomy, resulting in the unilateralization of epileptic discharges. The hemisphere showing unilateral discharges was defined as the affected hemisphere. The intracortical inhibition and facilitation curve was drawn based on MEP before and after surgery and the relationship between MEP and surgical prognosis was investigated. RESULTS: In five patients with TLE showing class I surgical results (Engel's classification), the affected hemisphere showing cortical hyperexcitability preoperatively was almost normalized after surgery. However, in a patient with class III, the unaffected hemisphere showed cortical hyperexcitability before and after surgery. In the callosotomy group, two patients with excellent outcomes showed the same results as TLE group with class I. CONCLUSIONS: Paired pulse magnetic MEP may provide predictive value in terms of surgical outcome in those patients with intractable epilepsy.

PMID: 17188003 [PubMed - indexed for MEDLINE]

27: PLoS ONE. 2007 Feb 28;2(2):e259.

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A rapid sound-action association effect in human insular cortex.

Mutschler I, Schulze-Bonhage A, Glauche V, Demandt E, Speck O, Ball T.

Epilepsy Center, University Hospital Freiburg, Freiburg, Germany.

BACKGROUND: Learning to play a musical piece is a prime example of complex sensorimotor learning in humans. Recent studies using electroencephalography (EEG) and transcranial magnetic stimulation (TMS) indicate that passive listening to melodies previously rehearsed by subjects on a musical instrument evokes differential brain activation as compared with unrehearsed melodies. These changes were already evident after 20-30 minutes of training. The exact brain regions involved in these differential brain responses have not yet been delineated. METHODOLOGY/PRINCIPAL FINDING: Using functional mri (fmri), we investigated subjects who passively listened to simple piano melodies from two conditions: in the 'actively learned melodies' condition subjects learned to play a piece on the piano during a short training session of a maximum of 30 minutes before the fMRI experiment, and in the 'passively learned melodies' condition subjects listened passively to and were thus familiarized with the piece. We found increased fMRI responses to actively compared with passively learned melodies in the left anterior insula, extending to the left fronto-opercular cortex. The area of significant activation overlapped the insular sensorimotor hand area as determined by our meta-analysis of previous functional imaging studies. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence for differential brain responses to action-related sounds after short periods of learning in the human insular cortex. As the hand sensorimotor area of the insular cortex appears to be involved in these responses, re-activation of movement representations stored in the insular sensorimotor cortex may have contributed to the observed effect. The insular cortex may therefore play a role in the initial learning phase of action-perception associations.

PMID: 17327919 [PubMed]

PMCID: PMC1800344

28: Epilepsia. 2007 Feb;48(2):366-74.

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Slow repetitive TMS for drug-resistant epilepsy: clinical and EEG findings of a placebo-controlled trial.

Cantello R, Rossi S, Varrasi C, Ulivelli M, Civardi C, Bartalini S, Vatti G, Cincotta M, Borgheresi A, Zaccara G, Quartarone A, Crupi D, Laganà A, Inghilleri M, Giallonardo AT, Berardelli A, Pacifici L, Ferreri F, Tombini M, Gilio F, Quarato P, Conte A, Manganotti P, Bongiovanni LG, Monaco F, Ferrante D, Rossini PM.

Department of Clinical and Experimental Medicine, Section of Neurology, Amedeo Avogadro University, Novara, Italy. cantello@med.unipmn.it

PURPOSE: To assess the effectiveness of slow repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for drug-resistant epilepsy. METHODS: Forty-three patients with drug-resistant epilepsy from eight Italian Centers underwent a randomized, double-blind, sham-controlled, crossover study on the clinical and EEG effects of slow rTMS. The stimulus frequency was 0.3 Hz. One thousand stimuli per day were given at the resting motor threshold intensity for 5 consecutive days, with a round coil at the vertex. RESULTS: "Active" rTMS was no better than placebo for seizure reduction. However, it decreased interictal EEG epileptiform abnormalities significantly (p < 0.05) in one-third of the patients, which supports a detectable biologic effect. No correlation linked the rTMS effects on seizure frequency to syndrome or anatomic classification, seizure type, EEG changes, or resting motor threshold (an index of motor cortex excitability). CONCLUSIONS: Although the antiepileptic action was not significant (p > 0.05), the individual EEG reactivity to "active" rTMS may be encouraging for the development of more-powerful, noninvasive neuromodulatory strategies.

Publication Types:

• Comparative Study
• Multicenter Study
• Randomized Controlled Trial
• Research Support, Non-U.S. Gov't

PMID: 17295632 [PubMed - indexed for MEDLINE]

29: Epilepsia. 2007 Feb;48(2):359-65.

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rTMS reveals premotor cortex dysfunction in frontal lobe epilepsy.

Löscher WN, Dobesberger J, Szubski C, Trinka E.

Department of Neurology, University Innsbruck, Innsbruck, Austria. wolfgang.loescher@i-med.ac.at

PURPOSE: Studies of motor cortex excitability provided evidence that focal epilepsies may alter the excitability of cortical areas distant from the epileptogenic zone. In order to explore this hypothesis we studied the functional connectivity between premotor and motor cortex in seven patients with frontal lobe epilepsy and seizure onset zone outside the premotor or motor cortex. METHODS: Low-frequency subthreshold repetitive transcranial magnetic stimulation was applied to the premotor cortex and its impact on motor cortex excitability was measured by the amplitude of motor-evoked potentials in response to direct suprathreshold stimulation of the motor cortex. RESULTS: Stimulation of the premotor cortex of the non-epileptogenic hemisphere resulted in a progressive and significant inhibition of the motor cortex as evidenced by a reduction of motor evoked potential amplitude. On the other hand, stimulation of the premotor cortex of the epileptogenic hemisphere failed to inhibit the motor cortex. The reduced inhibition of the motor cortex by remote areas was additionally supported by the significantly shorter cortical silent periods obtained after stimulation of the motor cortex of the epileptogenic hemisphere. CONCLUSION: These results show that the functional connectivity between premotor and motor cortex or motor cortex interneuronal excitability is impaired in the epileptogenic hemisphere in frontal lobe epilepsy while it is normal in the nonepileptogenic hemisphere.

Publication Types:

• Comparative Study

PMID: 17295631 [PubMed - indexed for MEDLINE]

30: Acta Neurochir Suppl. 2007;97(Pt 2):261-72.

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Brain stimulation for epilepsy.

Theodore WH, Fisher R.

Clinical Epilepsy Section, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. theodorw@ninds.nih.gov

Brain stimulation has been receiving increasing attention as an alternative therapy for epilepsy that cannot be treated by either antiepileptic medication or surgical resection of the epileptogenic focus. The stimulation methods include transcranial magnetic stimulation (TMS) or electrical stimulation by implanted devices of the vagus nerve (VNS), deep brain structures (DBS) (thalamic or hippocampal), cerebellar or cortical areas. TMS is the simplest and least invasive approach. However, the most common epileptogenic areas (mesial temporal structures) probably lie too deep beneath the surface of the skull for effective TMS. The efficacy of VNS in reducing the frequency or severity of seizures is quite variable and depends on many factors which are currently investigated. VNS is well-tolerated and approved in many countries. DBS is much more invasive than either TMS or VNS. Currently, a number of targets for DBS are investigated including caudate, centromedian or anterior thalamic nuclei, and subthalamic nucleus. Direct stimulation of the epileptic cortical focus is another approach to the neuromodulation in epilepsy. Finally, another line of research investigates the usefulness of implantable seizure detection devices. The current chapter presents the most important evidence on the above methods. Furthermore, other important issues are reviewed such as the selection criteria of patients for brain stimulation and the potential role of brain stimulation in the treatment of depression in epileptic patients.

Publication Types:

• Review

PMID: 17691312 [PubMed - indexed for MEDLINE]

31: Neurosci Res. 2007 Jan;57(1):140-2. Epub 2006 Nov 7.

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Effects of repetitive transcranial magnetic stimulation on spike-and-wave discharges.

Conte A, Gilio F, Iacovelli E, Bettolo CM, Di Bonaventura C, Frasca V, Carbone A, Prencipe M, Berardelli A, Inghilleri M.

Department of Neurological Sciences, University of Rome La Sapienza, Rome, Italy.

Aim of this study was to evaluate the effect of 5Hz-suprathreshold repetitive transcranial magnetic stimulation (rTMS) on the duration of the spike-and-wave discharges (SWDs) in a patient presenting idiopathic absence seizures. At the moment of the study the patient presented a mild blunting of consciousness due to the high frequency of absences and EEG recordings showed sub-continuous, generalized, symmetrical and synchronous 3c/s SWDs, petit mal status. Trains of 10 stimuli (120% resting motor threshold) were delivered at 5Hz frequency at the beginning of the SWDs. 5Hz-rTMS trains significantly changed the EEG activity by reducing the duration of SWDs without changing the intervals between two consecutive discharges. rTMS had not significant after-effects on the epileptic activity and patient's clinical status. Despite the limitations of a single case report, our neurophysiological findings suggest that 5Hz-suprathreshold rTMS delivered in short trains induces a transitory interference of the ongoing epileptic activity.

Publication Types:

• Case Reports
• Evaluation Studies

PMID: 17088005 [PubMed - indexed for MEDLINE]

32: Indian J Exp Biol. 2006 Dec;44(12):949-54.

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Influence of transcranial magnetic stimulation on spike-wave discharges in a genetic model of absence epilepsy.

Godlevsky LS, Kobolev EV, van Luijtelaar EL, Coenen AM, Stepanenko KI, Smirnov IV.

Department of Biophysics, Informatics and Medical Devices, Medical University, Odessa, Valehovsky Lane 2, Ukraine. godlevsky@odmu.od.ua

Transcranial magnetic stimulation (TMS) impulses, (0.5 Hz, 3 impulses) were presented at threshold intensity to male WAG/Rij rats. One group received stimuli, which involved motor responses of hindlimbs, rats of the second group received sham stimulation. Electrocorticograms (ECoG) were recorded before and up to 2 hr from the moment of transcranial magnetic stimulation. It was established that such stimulation engendered a reduction of spike-wave discharge (SWD) bursts duration. This effect was most pronounced in 30 min from the moment of cessation of stimulation, when a decrease of 31.4% was noted in comparison with sham-stimulated control group. The number of bursts of spike-wave discharges was reduced, but did not reach significant difference when compared both with pre-stimulative base-line level and with sham-stimulated control rats. Bursts of spike-wave discharges restored up to pre-stimulative level in 90-150 minutes from the moment of cessation of transcranial stimulation. It can be concluded that transcranical magnetic stimulation possessed an ability to engender short-time suppression of bursts of spike-wave discharges in WAG/Rij rats.

PMID: 17176666 [PubMed - indexed for MEDLINE]

33: J ECT. 2006 Dec;22(4):265-6.

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Accidental seizure with repetitive transcranial magnetic stimulation.

Rosa MA, Picarelli H, Teixeira MJ, Rosa MO, Marcolin MA.

Institute of Psychiatry, University of Sao Paulo, Faculty of Medicine, Sao Paulo SP, Brazil. moarosa@hcnet.usp.br

Accidental induction of convulsions by using repetitive transcranial magnetic stimulation (rTMS) has been reported to have occurred in 6 normal voluntary subjects, in 1 patient with depression and in 1 patient who had temporal lobe epilepsy, with secondary generalization. In addition, 3 other cases have been published relating its use with seizure induction and in 1 case, using 1-Hz stimulation. In this paper, we report a patient who was participating in a protocol for the use of rTMS in chronic pain, with stimulation in the motor cortex, who developed a generalized seizure in the fifth application. Intertrain interval was within safety guidelines, but the combination of 10 Hz for 10 seconds was excessive and must be considered the main cause for the episode. No further complication has been noted after she was withdrawn from the study protocol.

Publication Types:

• Case Reports

PMID: 17143158 [PubMed - indexed for MEDLINE]

34: Neuropsychopharmacology. 2006 Dec;31(12):2758-66. Epub 2006 Jun 14.

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Modulation of human motor cortex excitability by single doses of amantadine.

Reis J, John D, Heimeroth A, Mueller HH, Oertel WH, Arndt T, Rosenow F.

Department of Neurology, Interdisciplinary Epilepsy Center, Philipps-University, Marburg, Germany.

Amantadine-sulfate has been used for several decades to treat acute influenza A, Parkinson's disease (PD), and acute or chronic drug-induced dyskinesia. Several mechanisms of actions detected in vivo/in vitro including N-methyl-D-aspartate (NMDA)-receptor antagonism, blockage of potassium channels, dopamine receptor agonism, enhancement of noradrenergic release, and anticholinergic effects have been described. We used transcranial magnetic stimulation (TMS) to evaluate the effect of single doses of amantadine on human motor cortex excitability in normal subjects. Using a double-blind, placebo-controlled, crossover study design, motor thresholds, recruitment curves, cortical stimulation-induced silent period (CSP), short intracortical inhibition (ICI), intracortical facilitation (ICF), and late inhibition (L-ICI) in 14 healthy subjects were investigated after oral doses of 50 and 100 mg amantadine with single and paired pulse TMS paradigms. Spinal cord excitability was investigated by distal latencies and M-amplitudes of the abductor digiti minimi muscle. After intake of amantadine, a significant dose-dependent decrease of ICF was noticed as well as a significant increase of L-ICI as compared to placebo. The effect on ICF and L-ICI significantly correlated with amantadine serum levels. ICI was slightly increased after amantadine intake, but the effect failed to be significant. Furthermore, amantadine had no significant effects on motor thresholds, MEP recruitment curves, CSP, or peripheral excitability. In conclusion, a low dose of amantadine is sufficient in modulating human motor cortex excitability. The decrease of ICF and increase of L-ICI may reflect glutamatergic modulation or a polysynaptic interaction of glutamatergic and GABA-ergic circuits. Although amantadine has several mechanisms of action, the NMDA-receptor antagonism seems to be the most relevant effect on cortical excitability. As L-ICI can be influenced by this type of drug, it may be an interesting parameter for studies of motor learning and use-dependent plasticity.

Publication Types:

• Randomized Controlled Trial
• Research Support, Non-U.S. Gov't

PMID: 16794570 [PubMed - indexed for MEDLINE]

35: Seizure. 2006 Dec;15(8):653-7. Epub 2006 Aug 21.

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Erratum in:

• Seizure. 2007 Mar;16(2):194.

Cyclical excitability of the motor cortex in patients with catamenial epilepsy: a transcranial magnetic stimulation study.

Hattemer K, Knake S, Reis J, Oertel WH, Rosenow F, Hamer HM.

Interdisciplinary Epilepsy Center, Department of Neurology, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35033 Marburg, Germany. hattemer@med.uni-marburg.de

PURPOSE: The pathophysiology of catamenial epilepsy is still unclear. Therefore, we investigated the cortical excitability of women with catamenial epilepsy during different phases of the menstrual cycle. METHODS: Using transcranial magnetic stimulation, six patients suffering from catamenial epilepsy were investigated during ovulatory cycles. On days 8, -14, -7 and 2 of the cycle (day 1 being the first day of menstrual bleeding), resting motor threshold (RMT), cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated. The non-parametric Friedman-test for multiple comparisons and Wilcoxon signed rank test were used for statistical analysis. RESULTS: Five patients suffered from focal epilepsy (three right hemispheric, one bitemporal, one unknown origin) and one patient had idiopathic generalized epilepsy. All patients experienced perimenstrual seizure clustering and two also showed an increased seizure frequency during the luteal phase. In the right hemispheres there was a significant change of CSP duration in the course of the menstrual cycle (chi(2)=8.3, P=0.041), due to a shorter CSP during the luteal phase (Z=-2.0, P=0.043) and menstruation (Z=-2.2, P=0.028) as compared to the follicular phase. There was no significant variation of CSP in the left hemispheres. RMT, ICI and ICF showed no significant changes in the course of the menstrual cycle. CONCLUSIONS: The CSP changes suggest a decreased inhibition involving GABA-ergic neurotransmission during the luteal phase and menstruation. These TMS alterations correlated with the clinical course of the epilepsies and were found in the hemispheres containing the majority of the epileptogenic zones.

Publication Types:

• Case Reports

PMID: 16919975 [PubMed - indexed for MEDLINE]

36: Sleep. 2006 Dec 1;29(12):1595-8.

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Increasing cortical excitability: a possible explanation for the proconvulsant role of sleep deprivation.

Scalise A, Desiato MT, Gigli GL, Romigi A, Tombini M, Marciani MG, Izzi F, Placidi F.

Department of Neurosciences, S. Maria della Misericordia Hospital, Udine, Italy. annascalise@libero.it

STUDY OBJECTIVE: Sleep deprivation (SD) is known to facilitate both seizures and interictal epileptiform abnormalities. For this reason, it is often used in the routine diagnostic workup of epileptic patients as an activating procedure for eliciting epileptiform and/or seizure patterns in their EEGs. In order to evaluate the effects of SD on cortical excitability, we studied the effects of sleep loss on healthy subjects by transcranial magnetic stimulation (TMS). DESIGN AND PARTICIPANTS: Seven normal subjects underwent TMS examination in baseline condition and after total sleep deprivation. The TMS investigation included two protocols: a) the evaluation of motor evoked potential and silent period parameters recorded in response to single-pulse magnetic stimulation; and b) the evaluation of the time course of intracortical motor activity tested with paired-pulse TMS applied at inter-stimulus intervals of 1-6 ms. SETTING: Clinical neurophysiology laboratory in a general hospital. INTERVENTIONS: None. RESULTS: After SD, the principal finding observed using single-pulse TMS was a decrease of the silent period duration, whereas a reduction of the intracortical inhibition, in particular at inter-stimulus intervals 1 and 2 ms, was found, using the paired-pulse TMS. CONCLUSION: Our findings suggest that SD may modify cortical excitability, seen as the balance between inhibitory and excitatory cortical phenomena, which could reduce the epileptic threshold.

PMID: 17252890 [PubMed - indexed for MEDLINE]

37: Neurology. 2006 Nov 14;67(9):1646-51.

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Cortical excitability predicts seizures in acutely drug-reduced temporal lobe epilepsy patients.

Wright MA, Orth M, Patsalos PN, Smith SJ, Richardson MP.

Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, UK.

OBJECTIVE: To test the hypothesis that cortical excitability changes prior to seizures, using transcranial magnetic brain stimulation (TMS). METHODS: We studied 18 patients with unilateral temporal lobe epilepsy (TLE) twice using TMS: prior to (day 1) and following (day 3) reduction of antiepileptic drugs in a monitored inpatient setting. Short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) were measured. Time since most recent seizure prior to day 1, and time until next seizure after day 3, were recorded. RESULTS: On day 1, prior to antiepileptic drug withdrawal, there were no correlations with recent or next seizures. On day 3, patients who had seizures in the subsequent 48 hours had weaker SICI and ICF in the hemisphere ipsilateral to seizure onset, vs patients who did not have seizures in the next 48 hours (p = 0.033). Additionally on day 3, there was a strong correlation between the difference between ICF and SICI in the ipsilateral hemisphere and time to next seizure (p < 0.001). CONCLUSIONS: Change in cortical excitability, measured with transcranial magnetic brain stimulation, may reflect a long-lasting and widespread pre-ictal state.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 17101898 [PubMed - indexed for MEDLINE]

38: Clin Neurophysiol. 2006 Nov;117(11):2566-7; author reply 2567-8. Epub 2006 Sep 22.

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Comment on:

• Clin Neurophysiol. 2006 Jul;117(7):1631-3.

Seizure or convulsive syncope during 1-Hz rTMS?

Epstein CM.

Publication Types:

• Comment
• Letter

PMID: 16996304 [PubMed - indexed for MEDLINE]

39: Ann Neurol. 2006 Oct;60(4):447-55.

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A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy.

Fregni F, Otachi PT, Do Valle A, Boggio PS, Thut G, Rigonatti SP, Pascual-Leone A, Valente KD.

Center for Non-invasive Brain Stimulation, Beth Israel Medical Center, Harvard Medical School, Boston, MA 02215, USA. ffregni@bidmc.harvard.edu

OBJECTIVE: To study the antiepileptic effects of rTMS in patients with refractory epilepsy and malformations of cortical development in a randomized, double-blind, sham-controlled trial. METHODS: Twenty-one patients with malformations of cortical development and refractory epilepsy underwent five consecutive sessions of low-frequency rTMS, either sham or active (1Hz, 1,200 pulses), focally targeting the malformations of cortical development. The number of epileptiform discharges in the electroencephalogram and the number of clinical seizures were measured before (baseline), immediately after, as well as 30 and 60 days after rTMS treatment. RESULTS: rTMS significantly decreased the number of seizures in the active compared with sham rTMS group (p < 0.0001), and this effect lasted for at least 2 months. Furthermore, there was a significant decrease in the number of epileptiform discharges immediately after (p = 0.01) and at week 4 (p = 0.03) in the active rTMS group only. There were few mild adverse effects equally distributed in both groups. The preliminary cognitive evaluation suggests improvement in some aspects of cognition in the active rTMS group only. INTERPRETATION: Noninvasive brain stimulation for epilepsy may be an alternative treatment for pharmaco-resistant patients with clearly identifiable seizure foci in the cortical convexity and who are not eligible for surgical treatment.

Publication Types:

• Randomized Controlled Trial
• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov't

PMID: 17068786 [PubMed - indexed for MEDLINE]

40: Neuroimage. 2006 Oct 1;32(4):1499-509. Epub 2006 Jun 27.

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Structural insights from high-resolution diffusion tensor imaging and tractography of the isolated rat hippocampus.

Shepherd TM, Ozarslan E, King MA, Mareci TH, Blackband SJ.

Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. tms@mbi.ufl.edu

The hippocampus is a critical structure for learning and memory formation injured by diverse neuropathologies such as epilepsy or Alzheimer's disease. Recently, clinical investigations have attempted to use diffusion tensor MRI as a more specific surrogate marker for hippocampal damage. To first better understand the tissue architecture of healthy hippocampal regions, this study characterized 10 rat hippocampi with diffusion tensor imaging (DTI) at 50-microm in-plane image resolution using a 14.1-T magnet. Chemical fixation of the dissected and straightened rat hippocampus provided a simple, effective way to reduce partial volume effects when segmenting hippocampal regions and improved mean signal-to-noise per unit time (e.g. 50.6+/-4.4 at b=1250 s/mm2 in 27 min). Contrary to previous reports that water diffusion is homogeneous throughout the nervous system, statistically different mean diffusivities were observed (e.g. 0.238+/-0.054 and 0.318+/-0.084 microm2/ms for the molecular and granule cell layers respectively) (ANOVA, P<0.05). Different hippocampal subregions had lower fractional anisotropy than uniformly fibrous structures like corpus callosum because of their complex architecture. DTI-derived color fiber orientation maps and tractography demonstrated most components of the trisynaptic intrahippocampal pathway (e.g. orientations in stratum lacunosum-moleculare were dominated by perforant and Schaffer fibers) and also permitted some assessment of connectivity in the rat hippocampus.

PMID: 16806988 [PubMed - indexed for MEDLINE]

41: Neurology. 2006 Sep 26;67(6):1018-22.

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Comment in:

• Neurology. 2007 Jul 17;69(3):318; author reply 318-9.

Sleep deprivation increases cortical excitability in epilepsy: syndrome-specific effects.

Badawy RA, Curatolo JM, Newton M, Berkovic SF, Macdonell RA.

Department of Neurology, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia.

OBJECTIVE: To use transcranial magnetic stimulation (TMS) to investigate the hypothesis that sleep deprivation increases cortical excitability in people with epilepsy. METHODS: We performed paired pulse TMS stimulation, using a number of interstimulus intervals (ISIs) on each hemisphere of 30 patients with untreated newly diagnosed epilepsy (15 idiopathic generalized epilepsy [IGE] and 15 focal epilepsy) and on the dominant hemisphere of 13 healthy control subjects, before and after sleep deprivation. RESULTS: Both hemispheres in patients with IGE and the hemisphere ipsilateral to the EEG seizure focus in those with focal epilepsy showed an increase in cortical excitability following sleep deprivation at a number of ISIs. This change in excitability was most prominent in the patients with IGE. Although there were minor changes after sleep deprivation in control subjects and the contralateral hemisphere in the focal epilepsy group seen at the 250-millisecond ISI, it was less than in the other groups. CONCLUSIONS: Sleep deprivation increases cortical excitability in epilepsy; the pattern of change is syndrome dependent.

Publication Types:

• Clinical Trial
• Comparative Study

PMID: 17000971 [PubMed - indexed for MEDLINE]

42: J Physiol. 2006 Sep 15;575(Pt 3):721-6. Epub 2006 Jun 29.

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GABAA receptor subtype specific enhancement of inhibition in human motor cortex.

Di Lazzaro V, Pilato F, Dileone M, Ranieri F, Ricci V, Profice P, Bria P, Tonali PA, Ziemann U.

Istituto di Neurologia, Università Cattolica, L.go A. Gemelli 8, 00168 Rome, Italy. vdilazzaro@rm.unicatt.it

Inhibition is of fundamental importance to regulate activity in cortical circuits. Inhibition is mediated through a diversity of different interneurones and gamma-aminobutyric acid A receptor (GABA(A)R) subtypes. Here we employed paired-pulse transcranial magnetic stimulation (TMS) to measure short interval intracortical inhibition (SICI), a GABA(A)R-mediated inhibition in human motor cortex, to address the question of which GABA(A)R subtype is responsible for this form of inhibition. It has been shown that classical benzodiazepines (diazepam and lorazepam) have a non-selective affinity profile at different alpha-subunit-bearing subtypes of the GABA(A)R while zolpidem has a 10-fold greater affinity to the alpha1-subunit-bearing GABA(A)R compared with those bearing the alpha2- or alpha3-subunit. We found that, in seven healthy subjects, a single oral dose of 20 mg of diazepam or 2.5 mg of lorazepam significantly increased SICI, whereas 10 mg of zolpidem did not change SICI. This dissociation occurred despite equal sedation by all three drugs, an alpha1-subunit GABA(A)R-mediated effect. The findings strongly suggest that SICI is not mediated by the alpha1-subunit-bearing subtype of the GABA(A)R but by those bearing either the alpha2- or alpha3-subunit. This study represents an attempt by means of TMS to identify GABA(A)R subtype-specific action at the systems level of human cortex, a highly relevant issue because the different alpha-subunit-bearing subtypes of the GABA(A)R are differently involved in benzodiazepine-mediated effects such as sedation, amnesia or anxiolysis, in developmental cortical plasticity, and in neurological disorders such as epilepsy.

PMID: 16809358 [PubMed - indexed for MEDLINE]

PMCID: PMC1995685

43: Arq Neuropsiquiatr. 2006 Sep;64(3A):639-44.

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[Morphological characteristics from the insula's lobe in patients with medial temporal lobe epilepsy]

[Article in Portuguese]

Chaddad Neto F, de Oliveira E, Paschoal E, Cendes F, Santana Filho M.

Instituto de Ciências Neurológicas, São Paulo, Brazil.

The temporal medial sclerosis (TMS) is characterized by hippocampal sclerosis in temporal and by distinguished grades of injury near to other neurological structures such as: amygdaloid nucleus, parahippocampal girus and entorhinal region. The study analyzed 40 patients with TMS and 40 people from the control cluster. All the cases were appreciated by one method for measurement of insula's cortex (E-Film) and another method to calculate the insula's volume (Neuroline). There is no variation statistical between the insula's volume and insula's measurement for the two clusters. This paper didn't show the insula's morphological variation when these two groups were compared.

Publication Types:

• English Abstract

PMID: 17119810 [PubMed - indexed for MEDLINE]

44: Neurophysiol Clin. 2006 Sep-Dec;36(5-6):293-7. Epub 2007 Jan 17.

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Myoclonus and transcranial magnetic stimulation.

Lefaucheur JP.

Service de physiologie, explorations fonctionnelles, hôpital Henri-Mondor, Assistance publique-Hôpitaux de Paris, 51, avenue du Marechal-Lattre-de-Tassigny, 94010 Créteil, France. jean-pascal.lefaucheur@hmn.aphp.fr

The neural dysfunction at the origin of myoclonus may locate at various anatomical levels within the central nervous system, including the motor cortices. Transcranial magnetic stimulation (TMS) can be used to assess the balance between inhibitory and excitatory processes involved in the regulation of motor cortex activity and thereby, may be of value to determine the pathophysiological mechanisms of myoclonus. Using paired-pulse paradigms with various interstimulus intervals, TMS studies showed that intracortical inhibition (ICI) was reduced in progressive myoclonic epilepsy (PME). In contrast, ICI was decreased only for short interstimulus intervals in patients with juvenile myoclonic epilepsy (JME). Transcallosal inhibition and sensorimotor integration were also both altered in PME but not in JME. Actually, the loss of inhibitory regulation within the central nervous system might represent an intrinsic mechanism of myoclonus, whether of epileptic origin or not. Finally, the other TMS parameters of excitability (motor threshold, silent period, intracortical facilitation) were found normal in most cases of myoclonus. According to these observations, it was quite conceivable that the application of repetitive trains of TMS (rTMS) at inhibitory low-frequency (around 1 Hz) might be able to relieve myoclonus by restoring ICI. A few reported cases illustrate the efficacy of low-frequency rTMS to alleviate myoclonic symptoms. Therapeutic-like perspectives are opened for rTMS in these forms of myoclonus that are related to motor cortical hyperexcitability secondary to the loss of ICI.

Publication Types:

• Review

PMID: 17336773 [PubMed - indexed for MEDLINE]

45: Exp Brain Res. 2006 Aug;173(1):180-4. Epub 2006 Jun 17.

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Effects of repetitive transcranial magnetic stimulation in a patient with fixation-off sensitivity.

Mecarelli O, Gregori B, Gilio F, Conte A, Frasca V, Accornero N, Inghilleri M.

Department of Neurological Sciences, University of Rome La Sapienza, Viale dell'Università 30, 00185 Rome, Italy.

Aim of the present study was to evaluate the acute and long-term effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on focal epileptiform interictal EEG activity in a patient with fixation-off sensitivity and partial epilepsy. Real and sham rTMS were delivered over the vertex. Two trains of 500 stimuli per day were delivered at 0.33 Hz frequency and threshold intensity for five consecutive days. The number of posterior EEG spikes and spike-and-wave complexes/min before and after the application of rTMS were compared in a blinded manner. In our patient, real-rTMS induced a long-lasting decrease in the number of posterior EEG spikes and spike-and-wave complexes/min. Despite the limitations of a single case report, our study confirms that low-frequency rTMS significantly reduces interictal focal epileptic activity over time.

Publication Types:

• Case Reports
• Comparative Study

PMID: 16783556 [PubMed - indexed for MEDLINE]

46: Brain Res. 2006 Jul 12;1099(1):160-6. Epub 2006 Jun 13.

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Excitability of the human epileptic cortex after chronic valproate: a reappraisal.

Cantello R, Civardi C, Varrasi C, Vicentini R, Cecchin M, Boccagni C, Monaco F.

Department of Clinical and Experimental Medicine, Section of Neurology, Università del Piemonte Orientale A. Avogadro, Novara, Italy. cantello@med.unipmn.it

We explored the action of chronic valproic acid (VPA) on the human epileptic cortex by means of transcranial magnetic stimulation (TMS). TMS is an emerging biomarker for neurotropic drugs. We had 15 drug-naive patients with different epileptic syndromes. Interictally, we measured several TMS indexes of cortical excitability before commencing VPA and 3 months later. At that time, all patients were clinical responders to the drug, whose plasma levels were in the "therapeutic range". We then compared the two conditions, while 18 healthy subjects, of whom 12 were retested at a similar delay, acted as controls. In the pooled patients, the baseline resting motor threshold to TMS was similar to that of controls, but it increased significantly (P < 0.05) after VPA. Intracortical facilitation, another index of cortical excitability, was abnormally enhanced at baseline but decreased significantly after VPA (P < 0.05). On splitting patients according to their diagnosis, the threshold increase was significant (P < 0.05) among partial, but not generalized epilepsies. The reverse was true for changes in intracortical facilitation. TMS phenomena had no linear relation to VPA serum levels. Based on the known pharmacology of TMS effects, VPA reduced the intrinsic membrane excitability of motor cortical neurons, possibly through changes in Na+ channel activity. Then, VPA corrected a transmitter-mediated interneuronal hyper-excitability of the primary motor cortex. The former effect was best seen in partial, and the latter in generalized epilepsy patients.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't
• Validation Studies

PMID: 16774745 [PubMed - indexed for MEDLINE]

47: Clin Neurophysiol. 2006 Jun;117(6):1217-27. Epub 2006 Apr 27.

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Homeostatic effects of plasma valproate levels on corticospinal excitability changes induced by 1Hz rTMS in patients with juvenile myoclonic epilepsy.

Fregni F, Boggio PS, Valle AC, Otachi P, Thut G, Rigonatti SP, Marcolin MA, Fecteau S, Pascual-Leone A, Fiore L, Valente K.

Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., KS 452, Boston, MA 02215, USA. ffregni@bidmc.harvard.edu

OBJECTIVE: The preliminary results of noninvasive brain stimulation for epilepsy treatment have been encouraging, but mixed. Two important factors may contribute to this heterogeneity: the altered brain physiology of patients with epilepsy and the variable presence of antiepileptic drugs. Therefore, we aimed to study the effects of 1 Hz rTMS on corticospinal excitability in patients with juvenile myoclonic epilepsy (JME) in two different conditions: low- or high-plasma valproate levels. METHODS: Fifteen patients with JME and 12 age-matched healthy subjects participated in this study. Corticospinal excitability before and after 1 Hz rTMS was assessed in JME patients with low- and high-plasma valproate levels; and these results were compared with those in healthy subjects. RESULTS: In patients with chronic use of valproate and low-plasma concentrations, 1 Hz rTMS had a similar significant inhibitory effect on corticospinal excitability as in healthy subjects. However, in the same patients when the serum valproate concentration was high, 1 Hz rTMS increased the corticospinal excitability significantly. In addition, there was a significant positive correlation between plasma valproate levels and the motor threshold changes after 1 Hz rTMS. CONCLUSIONS: Our findings can be accounted for by mechanisms of homeostatic plasticity and illustrate the dependency of the modulatory effects of rTMS on the physiologic state of the targeted brain cortex. SIGNIFICANCE: The therapeutic use of rTMS in epilepsy should take into consideration the interaction between rTMS and drugs that change cortical excitability.

Publication Types:

• Controlled Clinical Trial
• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov't

PMID: 16644277 [PubMed - indexed for MEDLINE]

48: Neurosci Lett. 2006 Apr 24;397(3):229-33. Epub 2006 Jan 19.

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Hemispheric cerebellar rTMS to treat drug-resistant epilepsy: case reports.

Brighina F, Daniele O, Piazza A, Giglia G, Fierro B.

Neurophysiological Unit, University of Palermo, Institute of Neuropsychiatry, Via G. La Loggia, 1, 90129 Palermo, Italy.

Electrical stimulation of the cerebellar cortex by implanted electrodes has been shown to ameliorate refractory epilepsy. We investigated the potential therapeutic role of high-frequency cerebellar rTMS in patients affected by refractory epilepsy due to single or multiple foci. Six patients, three with single and three with multiple epileptic foci, underwent 20 rTMS sessions. Each session was given daily, excluding weekends, and consisted of two trains of 50 stimuli (5 Hz frequency and 90% motor threshold intensity), separated by 50s interval. rTMS was delivered through a focal coil (2 cm below and lateral to the inion) bilaterally in patients with multiple foci (two trains for hemisphere: 100 stimuli each side) and contralaterally to the epileptic focus in the others. Seizure frequency was monitored four weeks before stimulation (pre-rTMS), during the four-week treatment (rTMS) and four weeks after the treatment (post-rTMS). The rTMS over the cerebellar cortex was associated with a significant decrease of rTMS versus pre-rTMS seizure frequency both in patients with single and multiple epileptic foci. However, during the post-rTMS period seizure frequency was back to the pre-rTMS frequency. Although the results are still preliminary, they encourage further studies on larger series of patients. In particular, this rTMS approach, as compared with others, might be more useful in patients with multiple epileptic foci.

Publication Types:

• Case Reports

PMID: 16426754 [PubMed - indexed for MEDLINE]

49: Neurology. 2006 Feb 28;66(4):566-71.

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Changes in motor cortex excitability with stimulation of anterior thalamus in epilepsy.

Molnar GF, Sailer A, Gunraj CA, Cunic DI, Wennberg RA, Lozano AM, Chen R.

Division of Neurology, Krembil Neuroscience Centre, Toronto Western Research Institute, University Health Network, University of Toronto, Ontario, Canada.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for movement disorders and pain. Recently, bilateral DBS of the anterior nucleus of thalamus (AN) was performed for the treatment of intractable epilepsy. This surgery reduced seizure frequency in an initial group of patients. However, its physiologic effects on the cortex and mechanisms of action remain poorly understood. Different classes of antiepileptic drugs (AEDs) have distinct effects on the excitatory and inhibitory circuits in the motor cortex, which can be studied noninvasively by transcranial magnetic stimulation (TMS). OBJECTIVE: To examine the effects of bilateral AN DBS on motor cortex excitability in epilepsy and compare these to the known effects of AEDs. METHODS: Cortical excitability was assessed in five medicated epilepsy patients with bilateral stimulators implanted in the anterior thalamus and nine healthy controls. Single and paired TMS were used to examine cortical inhibitory and facilitatory circuits. Electromyography was recorded from the dominant hand, and TMS was applied over the contralateral motor cortex. Patients were studied during DBS turned off (OFF condition), DBS with cycling stimulation mode (1 minute on, 5 minutes off; CYCLE), and DBS with continuous stimulation (CONTINUOUS) in random order on 3 consecutive days. RESULTS: Motor thresholds were increased in the patients regardless of DBS condition. Active short-interval intracortical inhibition (SICI) was significantly reduced in the OFF and CYCLE conditions but returned toward normal levels in the CONTINUOUS condition. Rest SICI, long interval intracortical inhibition, and silent period duration were unchanged. CONCLUSIONS: Increased short-interval intracortical inhibition with continuous deep brain stimulation (DBS) suggests that thalamic DBS might drive cortical inhibitory circuits, similar to antiepileptic drugs that enhance gamma-aminobutyric acid inhibition.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 16505313 [PubMed - indexed for MEDLINE]

50: J Neurol Neurosurg Psychiatry. 2006 Jan;77(1):56-60.

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Effects of sleep deprivation on cortical excitability in patients affected by juvenile myoclonic epilepsy: a combined transcranial magnetic stimulation and EEG study.

Manganotti P, Bongiovanni LG, Fuggetta G, Zanette G, Fiaschi A.

Dipartimento di Scienze Neurologiche e della Visione, Sezione di Neurologia Riabilitativa, Policlinico Borgo Roma, Via delle Menegone, 37134 Verona, Italy. paolo.manganotti@univr.it

OBJECTIVE: To investigate the effect of sleep deprivation on corticospinal excitability in patients affected by juvenile myoclonic epilepsy (JME) using different transcranial magnetic stimulation (TMS) parameters. METHODS: Ten patients with JME and 10 normal subjects underwent partial sleep deprivation. Motor threshold (MT), motor evoked potential amplitude (MEP), and silent period (SP) were recorded from the thenar eminence (TE) muscles. Short latency intracortical inhibition (SICI) and short latency intracortical facilitation (SICF) were studied using paired magnetic stimulation. TMS was performed before and after sleep deprivation; EEG and TMS were performed simultaneously. RESULTS: In patients with JME, sleep deprivation induced a significant decrease in SICI and an increase in SICF, which was associated with increased paroxysmal activity. A significant decrease in the MT was observed. No significant changes in any TMS parameters were noted in normal subjects after sleep deprivation. The F wave was unchanged by sleep deprivation in both control subjects and in patients with JME. CONCLUSIONS: In patients with JME, sleep deprivation produces increases in corticospinal excitability in motor areas as measured by different TMS parameters.

PMID: 16361593 [PubMed - indexed for MEDLINE]

51: J Clin Neurophysiol. 2005 Dec;22(6):418-21.

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Crossed inhibition of sensory cortex by 0.3 Hz transcranial magnetic stimulation of motor cortex.

Seyal M, Shatzel AJ, Richardson SP.

Department of Neurology, University of California-Davis Medical Center, 2315 Stockton Boulevard, Rm. 5308, Sacramento, CA 95817, U.S.A. mseyal@ucdavis.edu

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of motor cortex causes persistent inhibitory effects in the targeted area. rTMS of motor cortex impairs sensory perception and results in a persistent change in cortical function at remote sites. The ability of rTMS to induce sustained changes in cortical function has led to studies testing its therapeutic efficacy in neurologic disorders, including epilepsy. Studies on the effect of low-frequency rTMS of motor cortex on the contralateral motor cortex have provided evidence for both inhibitory and excitatory changes. This study was designed to determine the effect of low-frequency rTMS of the right motor cortex on the contralateral sensory cortex. Before and after 0.3-Hz rTMS of right motor cortex, perception of ipsilateral threshold of cutaneous stimuli was assessed and somatosensory evoked potentials (SEPs) recorded after stimulation of the right thumb in eight normal subjects. In a control group of six subjects, sensory responses were assessed after rTMS anterior to the right motor cortex. After rTMS of motor cortex, detection of threshold sensory stimuli decreased by more than 50% compared with pre-rTMS (P < 0.05). The change in sensory perception lasted at least 30 minutes. No change was detected in the control group. Amplitude of the N20-P25 waveform of the SEP decreased from a mean of 0.84 muV before rTMS to 0.54 muV immediately after rTMS of motor cortex (P < 0.05). 0.3 Hz rTMS of motor cortex inhibits the contralateral sensory cortex.

PMID: 16462199 [PubMed - indexed for MEDLINE]

52: Rev Neurol (Paris). 2005 Nov;161(11):1121-30.

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[Transcranial magnetic stimulation: applications in neurology]

[Article in French]

Lefaucheur JP.

Service de Physiologie - Explorations Fonctionnelles, Hôpital Henri Mondor, Créteil. jean-pascal.lefaucheur@hmn.ap-hop-paris.fr

INTRODUCTION: Transcranial magnetic stimulation (TMS) was first applied to assess conduction time along the corticospinal tract, namely by recording motor evoked potentials. STATE OF ART: At present, TMS techniques include cortical excitability and mapping studies using single or paired-pulse paradigms on the one hand, and repetitive TMS to induce cortical plasticity and to modify brain function on the other hand. TMS is a valuable, non-invasive tool in the diagnosis and the pathophysiological assessment of cortical dysfunction involved in various neurological diseases (multiple sclerosis, myelopathy, amyotrophic lateral sclerosis, movement disorders, epilepsy, stroke). PERSPECTIVES AND CONCLUSION: In the near future, repetitive TMS could have therapeutic applications in neurology (epilepsy, stroke rehabilitation program) as is already the case in some psychiatric diseases. However, most of the new indications for treatment with cortical stimulation will be based on surgically-implanted neuromodulation procedures.

Publication Types:

• English Abstract

PMID: 16288180 [PubMed - indexed for MEDLINE]

53: Rinsho Shinkeigaku. 2005 Nov;45(11):831-3.

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[Clinical applications of transcranial magnetic stimulation for the treatment of various neurological diseases]

[Article in Japanese]

Tsuji S.

Department of Neurology, University of Occupational and Environmental Health, School of Medicine.

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in various neurological and psychiatric diseases including depression, Parkinson disease, spinocerebellar degeneration, epilepsy, urinary incontinence, movement disorders, chronic pain, migraine and chronic tinnitus, etc. Several reports showed the therapeutic effects of rTMS as a treatment of depression and Parkinson disease (PD), whereas others found no significant effects. It is by now not yet fully understood whether rTMS has a therapeutic effect on those diseases. The controversy arises from the differences of the stimulation parameters and evaluation methods of the effects in those studies. The Japanese multi-center, double blinded, sham stimulation controlled trial in 85 patients with PD showed an efficacy in both the rTMS-treated and sham stimulated patients. This result does not prove the efficacy of the rTMS in PD; on the other hand, it does not rule out the efficacy. Possible mechanism of favorable effects of rTMS is related to increasing the release of dopamine in the mesolimbic and mesostriatal system. The other Japanese multi-center, double blinded, sham stimulation controlled trial in 99 patients with spinocerebellar degeneration revealed significant therapeutic effects of rTMS in 51 patients with SCA6. We studied the effects of rTMS on seizure susceptibility in rats which prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. This finding suggests the possibility of therapeutic use of rTMS in epilepsy. Further studies should be performed aiming to reveal the optimal stimulation parameters, and are necessary to reveal the therapeutic role of the rTMS in neurological and psychiatric diseases.

Publication Types:

• English Abstract

PMID: 16447738 [PubMed - indexed for MEDLINE]

54: Clin Neurophysiol. 2005 Oct;116(10):2501-4.

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A lack of effect from transcranial magnetic stimulation (TMS) on the vagus nerve stimulator (VNS).

Schrader LM, Stern JM, Fields TA, Nuwer MR, Wilson CL.

Department of Neurology, Geffen School of Medicine at UCLA, Reed Neurological Research Building, 710 Westwood Plaza, Room 1-194, Los Angeles, CA 90095, USA. lschrader@mednet.ucla.edu

OBJECTIVE: The effects of transcranial magnetic stimulation (TMS) on vagus nerve stimulation (VNS) are unknown. Understanding these effects is important before exposing individuals with an implanted VNS to TMS, as could occur in epilepsy or depression TMS research. To explore this issue, the TMS-induced current in VNS leads and whether TMS has an effect on the VNS pulse generator was assessed. METHODS: Ex vivo measurement of current in VNS leads during single-pulse TMS and pulse generator function before, during, and after single-pulse TMS was assessed. RESULTS: At the highest intensity and with the TMS coil held approximately 5 mm from the VNS wires, a 200 nA, 1.0 ms current was induced by TMS. This translates to an induced charge density of 3.3 nC/cm2/phase. The function of the pulse generator was unaffected by single-pulse TMS, even when its case was directly stimulated by the coil. CONCLUSIONS: TMS-induced current in VNS electrodes was not only well outside of the range known to be injurious to peripheral nerve, but also below the activation threshold of nerve fibers. SIGNIFICANCE: Using single-pulse TMS in individuals with VNS should not result in nerve stimulation or damage. Furthermore, single-pulse TMS does not affect the VNS pulse generator's function.

Publication Types:

• Clinical Trial
• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, P.H.S.

PMID: 16122980 [PubMed - indexed for MEDLINE]

55: Curr Psychiatry Rep. 2005 Oct;7(5):381-90.

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Transcranial magnetic stimulation for the treatment of depression in neurologic disorders.

Fregni F, Pascual-Leone A.

Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, KS 452, Boston, MA 02215, USA. ffregni@bidmc.harvard.edu

Depression is commonly associated with neurologic disorders. Although depression in neurologic conditions often is associated with a negative impact on quality of life, it frequently is poorly managed. Some factors, such as a multidrug regimen, lack of efficacy, and side effects of antidepressants may explain why depression is not adequately treated in patients with neurologic disorders. Therefore, this population needs new approaches for depression treatment, and repetitive transcranial magnetic stimulation (rTMS) may be one of them because it has been shown to be effective for the treatment of depression alone and depression in certain neurologic diseases such as Parkinson's disease and stroke. rTMS is a noninvasive, focal, and painless treatment associated with few, mild side effects. It may be effective in the treatment of neurologic diseases such as Parkinson's disease, stroke, and epilepsy. In this paper, we discuss the potential risks and benefits of rTMS treatment for depression in Parkinson's disease, epilepsy, stroke, multiple sclerosis, and Alzheimer's disease. Lastly, a framework that includes the parameters of stimulation (intensity, frequency, number of pulses, and site of stimulation) for the treatment of depression in neurologic diseases is proposed.

Publication Types:

• Review

PMID: 16216159 [PubMed - indexed for MEDLINE]

56: Rev Med Suisse. 2005 Sep 21;1(33):2162-4, 2166.

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[Novel brain stimulation techniques: therapeutic perspectives in psychiatry]

[Article in French]

Berney A, Vingerhoets F.

Service de psychiatrie de liaison, CHUV, 1011 Lausanne. Alexandre.Berney@chuv.ch

Recent advances have allowed the development of new physical techniques in neurology and psychiatry, such as Transcranial Magnetic Stimulation (TMS), Vagus Nerve Stimulation (VNS), and Deep Brain Stimulation (DBS). These techniques are already recognized as therapeutic approaches in several late stage refractory neurological disorders (Parkinson's disease, tremor, epilepsy), and currently investigated in psychiatric conditions, refractory to medical treatment (obsessive-compulsive disorder, resistant major depression). In Paralell, these new techniques offer a new window to understand the neurobiology of human behavior.

Publication Types:

• English Abstract
• Review

PMID: 16223219 [PubMed - indexed for MEDLINE]

57: Epilepsy Behav. 2005 Sep;7(2):182-9.

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Transcranial magnetic stimulation treatment for epilepsy: can it also improve depression and vice versa?

Fregni F, Schachter SC, Pascual-Leone A.

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. ffregni@bidmc.harvard.edu

Comorbidity with depression is an important determinant of the quality of life for patients with epilepsy. Antidepressant medications can effectively treat depression in epileptic patients, but drug-drug interactions and epileptogenic effects of these drugs pose therapeutic challenges. The mood-stabilizing effects of antiepileptic medications may not be sufficient to treat depression. Therefore, treatments that alleviate the burden of depression without increasing seizure risk or, better yet, with the possibility of improving seizure control are worth exploring. Neuroimaging techniques, such as functional magnetic resonance imaging, are providing novel insights into the pathophysiology of depression in epilepsy. For example, there appears to be prominent brain prefrontal hypoactivity, which may be sustained by the hyperactivity of the seizure focus. If so, neuromodulatory approaches that suppress epileptic focus hyperactivity and concurrently enhance prefrontal activity may be ideally suited. Indeed, vagus nerve stimulation has been shown to yield simultaneous antiseizure and mood effects. Another neuromodulatory technique, transcranial magnetic stimulation (TMS), can also modulate brain activity, but in a noninvasive, painless, and focal manner. Depending on the stimulation parameters, it is possible to enhance or reduce activity in the targeted brain region. Furthermore, TMS has been shown to be effective in treating depression, and preliminary data suggest that this treatment may also be effective for epilepsy treatment. This article reviews these data and explores further the question of whether depression and epilepsy can be simultaneously treated with TMS for optimal therapeutic impact.

Publication Types:

• Research Support, N.I.H., Extramural
• Research Support, U.S. Gov't, P.H.S.
• Review

PMID: 16054872 [PubMed - indexed for MEDLINE]

58: Seizure. 2005 Sep;14(6):387-92.

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Low-frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy-a pilot study.

Kinoshita M, Ikeda A, Begum T, Yamamoto J, Hitomi T, Shibasaki H.

Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan.

We evaluated the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure frequency in adult patients with medically intractable extratemporal lobe epilepsy (ETLE). Seven patients with medically intractable ETLE received low-frequency rTMS at 0.9 Hz, basically two sets of 15 min stimulation per day for five days in a week, with the stimulus intensity of 90% of resting motor threshold (RMT). The number of seizures during two weeks before and after the stimulation of one week was compared. Furthermore, RMT and active motor threshold (AMT) were measured before and after rTMS for each daily session. After low-frequency rTMS of one week, the frequency of all seizure types, complex partial seizures (CPSs) and simple partial seizures was reduced by 19.1, 35.9 and 7.4%, respectively. The patients with smaller difference between RMT and AMT before rTMS had higher reduction rate of CPSs. A favorable tendency of seizure reduction, though not statistically significant, during two weeks after low-frequency rTMS was demonstrated in medically intractable ETLE patients. As far as CPSs are concerned, smaller decrease of motor threshold by voluntary muscle contraction was associated with better response to rTMS.

Publication Types:

• Clinical Trial
• Research Support, Non-U.S. Gov't

PMID: 16046153 [PubMed - indexed for MEDLINE]

59: J Neurol Sci. 2005 Jul 15;234(1-2):37-9.

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Low-frequency transcranial magnetic stimulation for epilepsia partialis continua due to cortical dysplasia.

Misawa S, Kuwabara S, Shibuya K, Mamada K, Hattori T.

Department of Neurology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. sonoko.m@mb.infoweb.ne.jp

The potential therapeutic role of repetitive transcranial magnetic stimulation (rTMS) in epilepsy has been increasingly recognized. We investigated the effects of low-frequency rTMS in a patient with epilepsia partialis continua (EPC) due to cortical dysplasia. A 31-year-old female patient experienced EPC in the right upper and lower extremities, which had lasted for 15 years without generalized seizures. MRI showed focal megaencephaly around the motor cortex suggestive of cortical dysplasia. A figure of eight magnetic coil was placed over the hand motor area, and 100 stimuli with an intensity at 90% of motor threshold were given at 0.5 Hz. Immediately after rTMS, EPC was nearly abolished. The effects had continued approximately for 2 months, and the second trial resulted in the similar effects and time-course. Low-frequency rTMS was safe and well tolerated in this patient. These findings support the concept that rTMS decreases cortical excitability, and may be an effective treatment for focal partial seizures.

Publication Types:

• Case Reports

PMID: 15946689 [PubMed - indexed for MEDLINE]

60: J ECT. 2005 Jun;21(2):88-95.

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Transcranial magnetic stimulation in persons younger than the age of 18.

Quintana H.

Department of Psychiatry, Division of Child and Adolescent Psychiatry, Louisiana State University Health Science Center, School of Medicine, New Orleans, Louisiana 70112-2822, USA. Hquint@lsuhsc.edu

OBJECTIVES: To review the use of transcranial magnetic stimulation (single-pulse TMS, paired TMS, and repetitive TMS [rTMS]) in persons younger than the age of 18 years. I discuss the technical differences, as well as the diagnostic, therapeutic, and psychiatric uses of TMS/rTMS in this age group. METHODS: I evaluated English-language studies from 1993 to August 2004 on nonconvulsive single-pulse, paired, and rTMS that supported a possible role for the use of TMS in persons younger than 18. Articles reviewed were retrieved from the MEDLINE database and Clinical Scientific index. RESULTS: The 48 studies reviewed involved a total of 1034 children ages 2 weeks to 18 years; 35 of the studies used single-pulse TMS (980 children), 3 studies used paired TMS (20 children), and 7 studies used rTMS (34 children). Three studies used both single and rTMS. However, the number of subjects involved was not reported. CONCLUSIONS: Single-pulse TMS, paired TMS, and rTMS in persons younger than 18 has been used to examine the maturation/activity of the neurons of various central nervous system tracts, plasticity of neurons in epilepsy, other aspects of epilepsy, multiple sclerosis, myoclonus, transcallosal inhibition, and motor cortex functioning with no reported seizure risk. rTMS has been applied to psychiatric disorders such as ADHD, ADHD with Tourette's, and depression. Adult studies support an antidepressant effect from repetitive TMS, but there is only one study that has been reported on 7 patients that used rTMS to the left dorsal prefrontal cortex on children/adolescents with depression (5 of the 7 subjects treated responded). Although there are limited studies using rTMS (in 34 children), these studies did not report significant adverse effects or seizures. Repetitive TMS safety, ethical, and neurotoxicity concerns also are discussed.

Publication Types:

• Review

PMID: 15905749 [PubMed - indexed for MEDLINE]

61: Neurosci Lett. 2005 May 13;379(3):174-9. Epub 2005 Jan 26.

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Recordings from the rat locus coeruleus during acute vagal nerve stimulation in the anaesthetised rat.

Groves DA, Bowman EM, Brown VJ.

School of Psychology, University of St. Andrews, St. Mary's Quad, South Street, St. Andrews, FIFE KY169JP, Scotland, UK.

Vagal nerve stimulation (VNS) is used as a treatment for Epilepsy and is currently under investigation as a treatment for depression (see [M.S. George, Z. Nahas, X. Li, F.A. Kozel, B. Anderson, K. Yamanaka, J.H. Chae, M.J. Foust, Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS), Semin. Clin. Neuropsychiatry 7 (2002) 293-304; M.S. George, A.J. Rush, H.A. Sackeim, L.B. Marangell, Vagus nerve stimulation (VNS): utility in neuropsychiatric disorders, Int. J. Neuropsychopharmacol. 6 (2003) 73-83] for reviews). The mechanism of action of VNS is not fully understood [E. Ben-Menachem, Vagus-nerve stimulation for the treatment of epilepsy, Lancet Neurol. 1 (2002) 477-482] despite numerous imaging investigations (see [E. Ben-Menachem, Vagus-nerve stimulation for the treatment of epilepsy, Lancet Neurol. 1 (2002) 477-482; M.S. George, Z. Nahas, X. Li, F.A. Kozel, B. Anderson, K. Yamanaka, J.H. Chae, M.J. Foust, Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS), Semin. Clin. Neuropsychiatry 7 (2002) 293-304; M.S. George, A.J. Rush, H.A. Sackeim, L.B. Marangell, Vagus nerve stimulation (VNS): utility in neuropsychiatric disorders, Int J Neuropsychopharmacol 6 (2003) 73-83; M.S. George, H.A. Sackeim, L.B. Marangell, M.M. Husain, Z. Nahas, S.H. Lisanby, J.C. Ballenger, A.J. Rush, Vagus nerve stimulation. A potential therapy for resistant depression? Psychiatr. Clin. North Am. 23 (2000) 757-783] for reviews). However, there is some evidence to suggest that the locus coeruleus may play a role modulating the effects of VNS. This study investigated the effects of VNS (0.3mA), of sufficient intensity to recruit the A and B fibre components of the vagus [D.M. Woodbury, J.W. Woodbury, Effects of vagal stimulation on experimentally induced seizures in rats, Epilepsia 31 (Suppl. 2) (1990) S7-S19], on the discharge rate of single neurons from the locus coeruleus. This study is the first to demonstrate a direct neuronal response from the locus coeruleus following acute challenge of VNS in the anaesthetised rat. The results of this study indicate that neuronal activity of the locus coeruleus is modulated by VNS. This pathway through the locus coeruleus may be significant for mediating the clinical effects of VNS.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't

PMID: 15843058 [PubMed - indexed for MEDLINE]

62: Clin Neurophysiol. 2005 May;116(5):1105-12.

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Cortical excitability during prolonged antiepileptic drug treatment and drug withdrawal.

Lee HW, Seo HJ, Cohen LG, Bagic A, Theodore WH.

Clinical Epilepsy Section, National Institutes of Neurological Disorders and Stroke, Bethesda, MD, USA.

OBJECTIVE: Previous reports characterized the effects of administration of single oral doses of antiepileptic drugs (AED) on cortical excitability. However, AED effects on cortical excitability, and their relationship to plasma blood levels, during chronic drug administration at therapeutic doses are not known. The objective of the study was to determine whether plasma blood levels during chronic administration at therapeutic doses would accurately predict changes in corticomotor excitability. METHODS: We used transcranial magnetic stimulation (TMS) to measure cortical excitability during 5 weeks administration of carbamazepine (CBZ) and lamotrigine (LTG), and subsequent AED withdrawal in 20 healthy volunteers. Data were analyzed using ANOVA(RM) and regression analysis. RESULTS: Resting motor thresholds (r-MT) increased with increasing total and free CBZ and LTG levels during drug administration, but not drug withdrawal. After acute AED withdrawal, r-MT elevation persisted in most individuals with CBZ despite undetectable plasma levels, compared to a rapid normalization with LTG. In contrast, acute drug withdrawal resulted in a transient decrease in r-MT in 3/10 individuals with CBZ and 2/10 with LTG. CONCLUSIONS: Plasma levels provide information on motor cortical function during active treatment phases but not during AED withdrawal. SIGNIFICANCE: The transient decrease in r-MT associated with acute AED withdrawal could represent a physiological substrate contributing to AED withdrawal seizures.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 15826851 [PubMed - indexed for MEDLINE]

63: Brain. 2005 Apr;128(Pt 4):811-8. Epub 2005 Feb 23.

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Motor cortex excitability in focal epilepsies not including the primary motor area--a TMS study.

Hamer HM, Reis J, Mueller HH, Knake S, Overhof M, Oertel WH, Rosenow F.

Department of Neurology, University of Marburg, Rudolf-Bultmann-Str. 8, 35033 Marburg, Germany. hamer@staff.uni-marburg.de

It is unclear whether focal epilepsies chronically influence the processing of cortex distant to the epileptogenic zone. Therefore, motor cortex excitability was analysed in patients with temporal and extratemporal epilepsies whose epileptogenic zones did not include the primary motor area. Single and paired-pulse transcranial magnetic stimulation (TMS) was applied to the primary motor cortex in 20 healthy controls and 23 patients with focal epilepsy (39.4 +/- 13.2 years; 12 left, 11 right; 14 temporal, nine extratemporal: six frontal, three parieto-occipital) ipsi- and contralateral to the epileptogenic zone. In all patients, the epileptogenic zone did not include the primary motor cortex. The resting motor threshold (RMT), the cortical silent period (CSP), the intracortical inhibition [ICI; combined interstimulus intervals (ISI) 2 and 3 ms] and the intracortical facilitation (ICF; combined ISI 10 and 15 ms) were determined. The measures obtained ipsilateral to the epileptogenic zone were compared with those elicited in contralateral hemispheres and, in exploratory analyses, with controls using non-parametric tests, including Hodges-Lehmann estimates of median differences (HLE) with 95% confidence intervals (CI). In the patient group, the CSP elicited in the ipsilateral motor cortex (median 162.3 ms) was shortened compared with the contralateral CSP (median 174.6 ms; HLE 15.9 ms; CI 6.2, 27.0 ms; P = 0.002). This interhemispheric difference was more pronounced in extratemporal epilepsies (HLE 23.4 ms; CI -3.2, 67.6 ms) compared with temporal epilepsies (HLE 14.3 ms; CI 4.7, 26.2 ms). Patients with parieto-occipital epilepsies showed the greatest interhemispheric differences in CSP (HLE 33.5 ms) and patients with mesial temporal epilepsies the smallest (HLE 9.9 ms). No significant differences were found between ipsi- and contralateral RMT, ICI or ICF. In analyses of subgroups, the CSP was shorter in epileptic hemispheres of patients with extratemporal epilepsies (141.4 ms) than in controls (173.4 ms; HLE 40.0 ms; CI 3.2, 83.4 ms; P = 0.029). ICF was increased in epileptic hemispheres of extratemporal epilepsies (147.6%) compared with temporal epilepsies (114.6%; HLE 33.0%; CI 4.1, 68.3%; P = 0.038). The results suggest that focal epilepsies influence chronically distant cortex, leading to decreased inhibition and increased facilitation in the ipsilateral motor cortex even when the epileptogenic zone is apart from it. This alteration may be due to synaptic reorganization and appears to be more pronounced in extratemporal and neocortical temporal than in mesial temporal epilepsies. This may have diagnostic implications.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 15728658 [PubMed - indexed for MEDLINE]

64: J Neurol Neurosurg Psychiatry. 2005 Apr;76(4):527-33.

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Mirtazapine increases cortical excitability in healthy controls and epilepsy patients with major depression.

Münchau A, Langosch JM, Gerschlager W, Rothwell JC, Orth M, Trimble MR.

Sobell Department of Motor Neuroscience and Movement Disorders, Dept. of Clinical and Experimental Epilepsy, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. Muenchau@uke.uni-hamburg.de

BACKGROUND: Epilepsy is often complicated by depression requiring antidepressant treatment. Such treatment might be proconvulsive. OBJECTIVE: To examine the effects of the noradrenergic and specific serotonergic antidepressant mirtazapine on motor cortex excitability in epilepsy patients with depression and in healthy controls, using transcranial magnetic stimulation (TMS). METHODS: Seven clinically depressed epilepsy patients treated with anticonvulsant drugs and six healthy volunteers were studied. Before intake of mirtazapine and 24 hours afterwards (and also three weeks afterwards in the patients), the active and resting motor threshold (AMT, RMT), the size of the motor evoked potential (MEP), the cortical silent period (SP), and intracortical inhibition/facilitation and intracortical facilitatory I wave interactions were determined using single and paired pulse TMS. RESULTS: At baseline, AMT and RMT were higher (p = 0.049 and p = 0.04, respectively) and the ratio SP duration/MEP area greater in patients (p = 0.041). In patients but not in healthy subjects AMT was lower 24 hours after intake of mirtazapine (p = 0.028). Mirtazapine had no significant effect on the MEP size, duration of the SP, or the ratio of SP duration to MEP size in patients. The duration of the SP was longer (p = 0.037) but the ratio of SP duration to MEP size remained similar in healthy subjects after mirtazapine. There were no significant differences in paired pulse measures between the two groups either at baseline or after mirtazapine. CONCLUSIONS: Mirtazapine increased neuronal excitability of pyramidal tract axons in an activated state in both healthy controls and epilepsy patients with major depression.

PMID: 15774440 [PubMed - indexed for MEDLINE]

PMCID: PMC1739580

65: Neuron. 2005 Jan 20;45(2):181-3.

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Comment on:

• Neuron. 2005 Jan 20;45(2):201-6.

Toward establishing a therapeutic window for rTMS by theta burst stimulation.

Paulus W.

Department of Clinical Neurophysiology, University of Goettingen, D-37075 Goettingen, Germany.

In this issue of Neuron, Huang et al. show that a version of the classic theta burst stimulation protocol used to induce LTP/LTD in brain slices can be adapted to a transcranial magnetic stimulation (TMS) protocol to rapidly produce long lasting (up to an hour), reversible effects on motor cortex physiology and behavior. These results may have important implications for the development of clinical applications of rTMS in the treatment of depression, epilepsy, Parkinson's, and other diseases.

Publication Types:

• Comment
• Review

PMID: 15664167 [PubMed - indexed for MEDLINE]

66: J Neurosci. 2005 Jan 19;25(3):550-7.

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Linking out-of-body experience and self processing to mental own-body imagery at the temporoparietal junction.

Blanke O, Mohr C, Michel CM, Pascual-Leone A, Brugger P, Seeck M, Landis T, Thut G.

Functional Brain Mapping Laboratory, Department of Neurology, University Hospital, 1211 Geneva, Switzerland. olaf.blanke@epfl.ch

The spatial unity of self and body is challenged by various philosophical considerations and several phenomena, perhaps most notoriously the "out-of-body experience" (OBE) during which one's visual perspective and one's self are experienced to have departed from their habitual position within one's body. Although researchers started examining isolated aspects of the self, the neurocognitive processes of OBEs have not been investigated experimentally to further our understanding of the self. With the use of evoked potential mapping, we show the selective activation of the temporoparietal junction (TPJ) at 330-400 ms after stimulus onset when healthy volunteers imagined themselves in the position and visual perspective that generally are reported by people experiencing spontaneous OBEs. Interference with the TPJ by transcranial magnetic stimulation (TMS) at this time impaired mental transformation of one's own body in healthy volunteers relative to TMS over a control site. No such TMS effect was observed for imagined spatial transformations of external objects, suggesting the selective implication of the TPJ in mental imagery of one's own body. Finally, in an epileptic patient with OBEs originating from the TPJ, we show partial activation of the seizure focus during mental transformations of her body and visual perspective mimicking her OBE perceptions. These results suggest that the TPJ is a crucial structure for the conscious experience of the normal self, mediating spatial unity of self and body, and also suggest that impaired processing at the TPJ may lead to pathological selves such as OBEs.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 15659590 [PubMed - indexed for MEDLINE]

67: Child Adolesc Psychiatr Clin N Am. 2005 Jan;14(1):1-19, v.

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Emerging brain-based interventions for children and adolescents: overview and clinical perspective.

Hirshberg LM, Chiu S, Frazier JA.

The NeuroDevelopment Center, 260 West Exchange Street, Suite 302, Providence, RI 02903, USA. lhirshberg@neruodevelopmentcenter.com

Electroencephalogram biofeedback (EBF), repetitive transcranial magnetic stimulation (rTMS), and vagal nerve stimulation (VNS) are emerging interventions that attempt to directly impact brain function through neurostimulation and neurofeedback mechanisms. This article provides a brief overview of each of these techniques, summarizes the relevant research findings, and examines the implications of this research for practice standards based on the guidelines for recommending evidence based treatments as developed by the American Academy of Child and Adolescent Psychiatry for attention deficit hyperactivity disorder (ADHD). EBF meets the "Clinical Guidelines" standard for ADHD, seizure disorders, anxiety, depression, and traumatic brain injury. VNS meets this same standard for treatment of refractory epilepsy and meets the lower "Options" standard for several other disorders. rTMS meets the standard for "Clinical Guidelines" for bipolar disorder, unipolar disorder, and schizophrenia. Several conditions are discussed regarding the use of evidence based thinking related to these emerging interventions and future directions.

Publication Types:

• Review

PMID: 15564050 [PubMed - indexed for MEDLINE]

68: Stereotact Funct Neurosurg. 2005;83(2-3):57-62. Epub 2005 Jun 30.

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Antiepileptic effects of repetitive transcranial magnetic stimulation in patients with cortical malformations: an EEG and clinical study.

Fregni F, Thome-Souza S, Bermpohl F, Marcolin MA, Herzog A, Pascual-Leone A, Valente KD.

Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. ffregni@bidmc.harvard.edu

OBJECTIVE: To study the effects of repetitive transcranial magnetic stimulation (rTMS) on epileptic EEG discharges in patients with refractory epilepsy and malformations of cortical development (MCDs). METHODS: Eight patients with MCD and refractory epilepsy underwent 1 session of low-frequency rTMS (0.5 Hz, 600 pulses) focally targeting the MCD. The number of epileptiform discharges (EDs) in the EEG and seizures were measured before (baseline), immediately after as well as 15 and 30 days after rTMS treatment. RESULTS: Stimulation significantly decreased the number of EDs 15 and 30 days after rTMS treatment (mean reduction of 46.4%, 95% CI 12.7-80.2%, and mean reduction of 42.1%, 95% CI 8.2-75.7%, respectively). This was associated with a significant reduction in the number of seizures reported as compared with the 4-week period preceding rTMS (mean reduction of 57.3%, 95% CI 33.1-80.3%, and mean reduction of 51.2%, 95% CI 27.9-74.9%, respectively). CONCLUSION: This open study shows a significant antiepileptic effect of rTMS based on clinical and electrophysiological criteria and supports the therapeutic utility of rTMS for patients with well-localized epileptogenic cortical malformations. Copyright 2005 S. Karger AG, Basel.

Publication Types:

• Research Support, N.I.H., Extramural
• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, P.H.S.

PMID: 15990468 [PubMed - indexed for MEDLINE]

69: Neurology. 2004 Dec 14;63(11):2051-5.

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Cortical excitability in drug-naive patients with partial epilepsy: a cross-sectional study.

Varrasi C, Civardi C, Boccagni C, Cecchin M, Vicentini R, Monaco F, Cantello R.

Department of Medical Sciences, Section of Neurology, Università del Piemonte Orientale A. Avogadro, Novara, Italy.

OBJECTIVE: To use paired-pulse transcranial magnetic stimulation (TMS) to investigate cortical excitability in drug-naive patients with partial epilepsy. METHODS: Twenty-one drug-naive patients with partial epilepsy and 15 control subjects were studied. The relaxed threshold to TMS, the central silent period, and the intracortical inhibition/facilitation were measured. Statistics implied cluster analysis methods. Also assessed were the patient interictal EEG epileptiform abnormalities (EAs) on a semiquantitative basis. Then the TMS was contrasted to the clinical and EEG findings, using chi2 or Fisher exact tests. RESULTS: One-third of the patients made up a "pathologic" cluster with a disrupted intracortical inhibition (p < 0.01). Two-thirds had a normal inhibition. Interictal EAs predominated in the pathologic cluster, for frequency (p < 0.04), duration (p < 0.04), and focality (p < 0.02). CONCLUSIONS: Intracortical inhibition, which was impaired in one-third of the patients, reflects gamma-aminobutyric acid (GABA) activity within cortical area 4. Defective GABA inhibition is a typical pathogenic factor in partial epilepsy. Transcranial magnetic stimulation proved able to detect it. The weaker cortical inhibition had a direct relation to the severity of interictal epileptiform abnormalities.

PMID: 15596749 [PubMed - indexed for MEDLINE]

70: Clin Neurophysiol. 2004 Dec;115(12):2728-37.

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Seizure incidence during single- and paired-pulse transcranial magnetic stimulation (TMS) in individuals with epilepsy.

Schrader LM, Stern JM, Koski L, Nuwer MR, Engel J Jr.

Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Room 1-194 RNRC, Los Angeles, CA 90095, USA. ischrader@mednet.ucla.edu

OBJECTIVE: We reviewed published data and our own data to determine a quantitative incidence of seizure in subjects with epilepsy undergoing single- and paired-pulse transcranial magnetic stimulation (spTMS and ppTMS) and to explore conditions that may increase this risk. METHODS: A PubMed literature search was performed, and articles from this search were reviewed. Subjects from our institution also were included. RESULTS: The crude risk of a TMS-associated seizure ranges from 0.0 to 2.8% for spTMS and 0.0-3.6% for ppTMS. Medically intractable epilepsy and lowering antiepileptic drugs were associated with increased incidence. There was significant center-to-center variability that could not be explained by differences in patient population or by differences in reported stimulation parameters. In all cases, seizures were similar to each subject's typical seizure and without long-term adverse outcome. In most cases, doubt was expressed in the original reports as to whether the seizures were induced by TMS or merely coincidental. CONCLUSIONS: The incidence of seizure in a subject with epilepsy during spTMS and ppTMS appears to be small and not associated with long-term adverse outcome. The incidence is higher under the specific conditions mentioned above. SIGNIFICANCE: These findings may enable researchers to more accurately inform subjects of seizure risk during TMS.

Publication Types:

• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, P.H.S.
• Review

PMID: 15546781 [PubMed - indexed for MEDLINE]

71: Epilepsy Res. 2004 Nov;62(1):41-51.

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Levetiracetam influences human motor cortex excitability mainly by modulation of ion channel function--a TMS study.

Reis J, Wentrup A, Hamer HM, Mueller HH, Knake S, Tergau F, Oertel WH, Rosenow F.

Interdisciplinary Epilepsy-Center, Department of Neurology, Philipps-University, 35033 Marburg, Germany.

PURPOSE: Levetiracetam (LEV) is a new compound with anticonvulsive efficacy in focal and generalized epilepsies. Recent in vitro studies suggest LEV to act as a selective N-type-calcium-channel blocker. METHODS: We used transcranial magnetic stimulation (TMS) in order to investigate if ion-channel blockade is relevant to the inhibitory CNS effects of LEV in vivo and if motor thresholds (MTs) are a valid TMS parameter to detect this mode of action. In a double blind, placebo-controlled, crossover study, the effects of single oral doses of 500 and 2000 mg LEV on motor thresholds, recruitment curves (REC), cortical induced silent period (CSP) and on intracortical inhibition (ICI) and facilitation (ICF) were studied in 10 healthy subjects. RESULTS: A significant increase of motor thresholds was noticed after 2000 mg LEV as compared to placebo. The recruitment curve showed a trend towards motor evoked potential (MEP) amplitude reduction after LEV. LEV had no significant effect on CSP or on intracortical excitability as measured by inhibition and facilitation. CONCLUSIONS: We conclude that the modulation of ion-channel function, reflected by motor threshold elevation and a trend towards recruitment curve suppression, is relevant to the inhibitory CNS effects of LEV in vivo, and therefore, may contribute to the anticonvulsive efficacy of LEV. GABAergic or glutamatergic mechanisms seem to be less important in vivo as measured by TMS.

Publication Types:

• Clinical Trial
• Randomized Controlled Trial
• Research Support, Non-U.S. Gov't

PMID: 15519131 [PubMed - indexed for MEDLINE]

72: Laeknabladid. 2004 Nov;90(11):755-758.

Related Articles, Links

[Transcranial magnetic stimulation.]

[Article in Icelandic]

Mœller AL, Stefánsson SB.

Department of Neurology, Landspitali University Hospital, Fossvogi, 108 Reykjavík, Iceland. annaltho@landspitali.is.

Transcranial Magnetic Stimulation (TMS) is a new non-invasive method to investigate the central nervous system. Initially it was used to assess the functional integrity of the pyramidal pathways but more recently various other aspects of brain function have been studied including cortical excitability. By localised interference with brain function, it is possible to use TMS to assess the relationship between various brain regions and cognitive functions. The therapeutic effect of TMS has been explored in the treatment of neurological diseases and psychiatric disorders such as epilepsy, cerebellar ataxia and depressive illness.

PMID: 16819061 [PubMed - as supplied by publisher]

73: Seizure. 2004 Oct;13(7):481-5.

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Motor cortical thresholds and cortical silent periods in epilepsy.

Tataroglu C, Ozkiziltan S, Baklan B.

Department of Neurology, Medical Faculty, Mersin University, Zeytinlibahce Cadd., Mersin 33079, Turkey. cengizta@hotmail.com

We studied motor cortical thresholds (TIs) and cortical silent periods (SPs) evoked by transcranial magnetic stimulation (TMS) in 110 epileptic patients. Sixty-two had primary generalised, 48 had partial type seizures. Fifteen out 110 patients were analysed both before and after anticonvulsant medication. Our aims were to evaluate the TI levels and the duration of SPs in patients with epilepsy and to determine the reliability of TMS in patients with epilepsy. There was no negative effect of TMS on the clinical status and EEG findings in patients with epilepsy. TIs obtained from patients with partial epilepsy were higher than those obtained from both controls and primary epileptics. The duration of SP in patients with primary epileptics was more prolonged than those obtained from controls. There was no correlation between EEG lateralisation and both SP duration and TI values. In de novo patient group, SP duration was significantly prolonged after anticonvulsant medication. We concluded that TMS is a reliable electrophysiological investigation in patients with epilepsy. The analysis of SP duration may be an appropriate investigation in monitoring the effect of anticonvulsant medication on the cortical inhibitory activity.

Publication Types:

• Comparative Study

PMID: 15324826 [PubMed - indexed for MEDLINE]

74: Mult Scler. 2004 Aug;10(4):475-6.

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Transcranial magnetic stimulation as a provocation for epileptic seizures in multiple sclerosis.

Haupts MR, Daum S, Ahle G, Holinka B, Gehlen W.

Department of Neurology, Ruhr University/Knappschaftskrankenhaus, In der Schornau 23-25, D-44892 Bochum, Germany. Michael.Haupts@ruhr-uni-bochum.de

Epileptic seizures may be of a provoked origin in acute phases of multiple sclerosis (MS), while chronic epilepsy typically occurs in advanced stages of the disease. A case of seizure provocation during diagnostic transcranial magnetic stimulation (TMS) is described here with a corresponding central nervous system (CNS) lesion in cranial magnetic resonance imaging. A subsequent chronic epileptogenesis originating from the opposite cerebral hemisphere was observed without further TMS influence after several years. The case in its clinical rarity demonstrates that standard single pulse TMS may trigger epileptic seizures only under limited conditions. Single pulse TMS is still regarded a safe procedure in MS.

Publication Types:

• Case Reports

PMID: 15327050 [PubMed - indexed for MEDLINE]

75: Neurology. 2004 Jun 22;62(12):2310-2.

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Effects of vagus nerve stimulation on cortical excitability in epileptic patients.

Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Meglio M, Colicchio G, Barba C, Papacci F, Tonali PA.

Institutes of Neurology, Università Cattolica, Rome, Italy. vdilazzaro@rm.unicatt.it

Vagus nerve stimulation (VNS) is used as adjunctive treatment for medically refractory epilepsy, but little is known about its mechanisms of action. The effects of VNS on the excitatory and inhibitory circuits of the motor cortex were evaluated in five patients with epilepsy using single- and paired-pulse transcranial magnetic stimulation (TMS). Patients were examined with the stimulator on and off. VNS determined a selective and pronounced increase in the inhibition produced by paired-pulse TMS with no effects on the excitability by single-pulse TMS.

PMID: 15210904 [PubMed - indexed for MEDLINE]

76: Neurol India. 2004 Jun;52(2):224-7.

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Increased depressant effect of phenytoin sodium as compared to carbamazepine on cortical excitability: a transcranial magnetic evaluation.

Goyal V, Bhatia M, Behari M.

Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.

To evaluate the effect of monotherapy (phenytoin sodium (DPH) and carbamazepine (CBZ) on the threshold intensity (TI), cortical latency (CL), central conduction time (CCT), using transcranial magnetic stimulation (TMS). A single pulse transcranial magnetic stimulation was used for recording the motor-evoked potentials (MEP) from the thenar muscles of both hands, in 36 patients with well-controlled epilepsy on monotherapy, with normal EEG and imaging studies. The TI, CL, CCT and the MEP amplitude were recorded and compared with 20 healthy controls. The threshold intensity was significantly higher in patients on DPH, (P< 0.05) with a significant decrease in the MEP amplitude when compared with controls (P< 0.05). Anticonvulsants alter the excitability of human motor pathways in epileptic subjects. This effect differs among the drugs used; DPH had a greater depressant effect on the excitability than CBZ in the present study.

Publication Types:

• Clinical Trial
• Controlled Clinical Trial

PMID: 15269477 [PubMed - indexed for MEDLINE]

77: Neurol Sci. 2004 Jun;25(2):83-90.

Related Articles, Links

Serum levels of carbamazepine and cortical excitability by magnetic brain stimulation.

Turazzini M, Manganotti P, Del Colle R, Silvestri M, Fiaschi A.

Department of Neurology, Mater Salutis Hospital of Legnago, Via Gianella 1, I-37045, Legnago (VR), Italy. mturazzini@katamail.com

We investigated the correlation between serum levels of carbamazepine (CBZ) and motor excitability studied by different parameters of transcranial magnetic stimulation (TMS) in patients at the beginning of antiepileptic treatment. A total of 10 patients with complex partial seizures following stroke were treated with loading doses of CBZ. Motor evoked potential (MEP) was recorded from the thenar eminence (TE) muscles of the unaffected arm. In all patients, we studied rest and active motor threshold (rMT, aMT), MEP amplitude and cortical silent period (CSP). In three patients, intracortical inhibition (ICI) and intracortical facilitation (ICF) were measured using paired TMS at short interstimulus intervals (1-25 ms). The recording sessions were performed before treatment and after 7, 15 and 60 days (SD=16 days). Serum level of CBZ were monitored at each recording session. We observed a progressive increase in rMT and aMT until the serum levels of CBZ reached a steady state condition. No significant changes were observed in MEP amplitude, CSP, ICI and ICF. This study documents the increase of both motor threshold and drug serum levels in patients treated with loading doses of CBZ, suggesting a relationship between drug metabolism and the effect on motor cortical excitability.

Publication Types:

• Clinical Trial

PMID: 15221626 [PubMed - indexed for MEDLINE]

78: Rev Bras Psiquiatr. 2004 Jun;26(2):131-4. Epub 2004 Oct 27.

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[Transcranial magnetic stimulation: review of accidental seizures]

[Article in Portuguese]

Rosa MA, Odebrecht M, Rigonatti SP, Marcolin MA.

Instituto e Departamento de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil. moarosa@yahoo.com

Transcranial magnetic stimulation (TMS) is a new technique that has been used for the treatment of neuropsychiatric disorders, specially depression. It uses a magnetic stimulator that generates a magnetic field that is applied over the patient's skull with a coil. Possible seizures may be induced accidentally by TMS. TMS is usually used with sub threshold stimuli and seizures may occur by chance, especially when over the safety parameters. This article reviews the eight cases of undesirable seizures occurred with rTMS The possible mechanisms of seizure induction and the patients profile with a higher risk of convulsion are also described.

Publication Types:

• English Abstract
• Review

PMID: 15517065 [PubMed - indexed for MEDLINE]

79: Acta Neurol Scand. 2004 Apr;109(4):290-6.

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rTMS reduces focal brain hyperperfusion in two patients with EPC.

Graff-Guerrero A, Gonzáles-Olvera J, Ruiz-García M, Avila-Ordoñez U, Vaugier V, García-Reyna JC.

Instituto Nacional de Psiquiatría Ramón de la Fuente, División de Neurociencias, Laboratorio de Neurofisiología, México DF. agraff@imp.edu.mx

OBJECTIVE: This study was performed to evaluate the acute effect of a single repetitive transcranial magnetic stimulation (rTMS) session in a focal hyperperfusion epileptogenic region to induce a transitory decrease of epileptiform activity. CASE REPORT: Two epilepsia partialis continua (EPC)-diagnosed patients, received one session with 15 trains of rTMS (20 Hz; 2 s train, inter-train of 58 s). Before rTMS session, a brain ictal single photon emission computed tomography (SPECT) was performed to localize the focal frontal hyperperfusion region to establish the stimulation site. Immediately after the rTMS session another ictal SPECT was performed. Both patients showed a decrease of perfusion in the stimulated regions. For patient 1 epileptic seizures became intermittent until they stopped in the following 24 h. Patient 2 showed only a minimal improvement with a frequency decrease of epileptic spikes. CONCLUSIONS: Our findings suggest that a single rTMS session reduces focal epileptogenic activity and could be an alternative approach for epileptic-resistant patients, but efficacy should be confirmed in a larger series.

Publication Types:

• Case Reports
• Research Support, Non-U.S. Gov't

PMID: 15016013 [PubMed - indexed for MEDLINE]

80: J Pharmacol Exp Ther. 2004 Apr;309(1):1-7. Epub 2004 Jan 16.

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Brain stimulation for neurological and psychiatric disorders, current status and future direction.

Chang JY.

Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA. jchang@wfubmc.edu

Interest in brain stimulation therapies has been rejuvenated over the last decade and brain stimulation therapy has become an alternative treatment for many neurological and psychiatric disorders, including Parkinson's disease (PD), dystonia, pain, epilepsy, depression, and schizophrenia. The effects of brain stimulation on PD are well described, and this treatment has been widely used for such conditions worldwide. Treatments for other conditions are still in experimental stages and large-scale, well controlled studies are needed to refine the treatment procedures. In the treatment of intractable brain disorders, brain stimulation, especially transcranial magnetic stimulation (TMS), is an attractive alternative to surgical lesioning as it is relatively safe, reversible, and flexible. Brain stimulation, delivered either via deeply implanted electrodes or from a surface-mounted transcranial magnetic device, can alter abnormal neural circuits underlying brain disorders. The neural mechanisms mediating the beneficial effects of brain stimulation, however, are poorly understood. Conflicting theories and experimental data have been presented. It seems that the action of stimulation on brain circuitry is not limited to simple excitation or inhibition. Alterations of neural firing patterns and long-term effects on neurotransmitter and receptor systems may also play important roles in the therapeutic effects of brain stimulation. Future research on both the basic and clinical fronts will deepen our understanding of how brain stimulation works. Real-time computation of neural activity allows for integration of brain stimulation signals into ongoing neural processing. In this way abnormal circuit activity can be adjusted by optimal therapeutic brain stimulation paradigms.

Publication Types:

• Research Support, U.S. Gov't, P.H.S.

PMID: 14730004 [PubMed - indexed for MEDLINE]

81: Arq Neuropsiquiatr. 2004 Mar;62(1):21-5. Epub 2004 Apr 28.

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Experimental therapy of epilepsy with transcranial magnetic stimulation: lack of additional benefit with prolonged treatment.

Brasil-Neto JP, de Araújo DP, Teixeira WA, Araújo VP, Boechat-Barros R.

Laboratório de Neurociências e Comportamento, Departamento de Ciências Fisiológicas, Instituto de Biologia, Universidade de Brasília, Brasilia, DF, Brasil. jbrasil@unb.br

OBJECTIVE: To investigate the effect of three months of low-frequency repetitive transcranial magnetic stimulation (rTMS) treatment in intractable epilepsy. METHODS: Five patients (four males, one female; ages 6 to 50 years), were enrolled in the study; their epilepsy could not be controlled by medical treatment and surgery was not indicated. rTMS was performed twice a week for three months; patients kept records of seizure frequency for an equal period of time before, during, and after rTMS sessions. rTMS was delivered to the vertex with a round coil, at an intensity 5% below motor threshold. During rTMS sessions, 100 stimuli (five series of 20 stimuli, with one-minute intervals between series) were delivered at a frequency of 0.3 Hz. RESULTS: Mean daily number of seizures (MDNS) decreased in three patients and increased in two during rTMS--one of these was treated for only one month; the best result was achieved in a patient with focal cortical dysplasia (reduction of 43.09% in MDNS). In the whole patient group, there was a significant (p<0.01) decrease in MDNS of 22.8%. CONCLUSION: Although prolonged rTMS treatment is safe and moderately decreases MDNS in a group of patients with intractable epilepsy, individual patient responses were mostly subtle and clinical relevance of this method is probably low. Our data suggest, however, that patients with focal cortical lesions may indeed benefit from this novel treatment. Further studies should concentrate on that patient subgroup.

PMID: 15122428 [PubMed - indexed for MEDLINE]

82: Rev Neurol. 2004 Feb 16-29;38(4):374-80.

Related Articles, Links

[Transcranial magnetic stimulation. Applications in cognitive neuroscience]

[Article in Spanish]

Calvo-Merino B, Haggard P.

Institute of Movement Neuroscience, University College, Londres, UK. b.calvo@ion.ucl.ac.uk

OBJECTIVE: In this review we trace some of the mayor developments in the use of transcranial magnetic stimulation (TMS) as a technique for the investigation of cognitive neuroscience. Technical aspects of the magnetic stimulation are also reviewed. DEVELOPMENT: Among the many methods now available for studying activity of the human brain, magnetic stimulation is the only technique that allows us to interfere actively with human brain function. At the same time it provides a high degree of spatial and temporal resolution. Standard TMS applications (central motor conduction time, threshold and amplitude of motor evoked potentials) allow the evaluation of the motor conduction in the central nervous system and more complex TMS applications (paired pulse stimulation, silent period) permit study the mechanisms of diseases causing changes in the excitability of cortical areas. These techniques also allow investigation into motor disorder, epilepsy, cognitive function and psychiatric disorders. CONCLUSIONS: Transcranial magnetic stimulation applications have an important place among the investigative tools to study cognitive functions and neurological and psychiatric disorders. Even so, despite the many published research and clinical studies, a systematic study about the possible diagnostic value and role in neurocognitive rehabilitation of TMS testing need to be realized to offer new possibilities of future applications.

Publication Types:

• English Abstract
• Research Support, Non-U.S. Gov't
• Review

PMID: 14997463 [PubMed - indexed for MEDLINE]

83: Neuroreport. 2004 Feb 9;15(2):293-6.

Related Articles, Links

Reduction of cortical myoclonus-related epileptic activity following slow-frequency rTMS.

Rossi S, Ulivelli M, Bartalini S, Galli R, Passero S, Battistini N, Vatti G.

Dipartimento di Neuroscienze, Sezione Neurologia, Università di Siena, Policlinico Le Scotte, Viale Bracci I-53100, Italy. Rossimo@unisi.it

In a drug-resistant epilepsy patient with continuous forearm/hand positive myoclonia due to a focal cortical dysplasia of the right motor cortex, cortical jerk-related and electromyographic activity were recorded for 15 min before and after 1 Hz rTMS (15 min, 10% below the resting excitability threshold) of the right motor cortex. A stable negative cortical spike, time-locked with contralateral muscle jerks (60 > 100 microV), was detected only at perirolandic electrodes (maximal amplitudes: block 1 = 21.3 microV, block 2 = 22 microV, block 3 = 25.9 microV). After rTMS, only 20 muscle jerks accomplished the criterion of > 100 microV; blind back-averaging of these disclosed a topographically similar cortical spike, but with amplitude reduced by at least 50% (11.2 microV). This represents in vivo evidence of the possibility to selectively modulate the activity of an epileptic focus by intervening with local low-frequency rTMS.

Publication Types:

• Case Reports
• Clinical Trial

PMID: 15076755 [PubMed - indexed for MEDLINE]

84: Neurosci Lett. 2004 Jan 9;354(2):91-4.

Related Articles, Links

Intracranial measurement of current densities induced by transcranial magnetic stimulation in the human brain.

Wagner T, Gangitano M, Romero R, Théoret H, Kobayashi M, Anschel D, Ives J, Cuffin N, Schomer D, Pascual-Leone A.

Laboratory for Magnetic Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave KS-454, Boston, MA 02215, USA.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that uses the principle of electromagnetic induction to generate currents in the brain via pulsed magnetic fields. The magnitude of such induced currents is unknown. In this study we measured the TMS induced current densities in a patient with implanted depth electrodes for epilepsy monitoring. A maximum current density of 12 microA/cm2 was recorded at a depth of 1 cm from scalp surface with the optimum stimulation orientation used in the experiment and an intensity of 7% of the maximal stimulator output. During TMS we recorded relative current variations under different stimulating coil orientations and at different points in the subject's brain. The results were in accordance with current theoretical models. The induced currents decayed with distance form the coil and varied with alterations in coil orientations. These results provide novel insight into the physical and neurophysiological processes of TMS.

PMID: 14698446 [PubMed - indexed for MEDLINE]

85: Clin EEG Neurosci. 2004 Jan;35(1):4-13.

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Current status of the utilization of antiepileptic treatments in mood, anxiety and aggression: drugs and devices.

Barry JJ, Lembke A, Bullock KD.

Department of Psychiatry, Stanford University Medical Center, 401 Quarry Road MC 5723, Stanford, CA 94305, USA. jbarry@leland.stanford.edu

Interventions that have been utilized to control seizures in people with epilepsy have been employed by the psychiatric community to treat a variety of disorders. The purpose of this review will be to give an overview of the most prominent uses of antiepileptic drugs (AEDs) and devices like the Vagus Nerve Stimulator (VNS) and Transcranial Magnetic Stimulation (TMS) in the treatment of psychiatric disease states. By far, the most prevalent use of these interventions is in the treatment of mood disorders. AEDs have become a mainstay in the effective treatment of Bipolar Affective Disorder (BAD). The U.S. Food and Drug Administration has approved the use of valproic acid for acute mania, and lamotrigine for BAD maintenance therapy. AEDs are also effectively employed in the treatment of anxiety and aggressive disorders. Finally, VNS and TMS are emerging as possibly useful tools in the treatment of more refractory depressive illness.

Publication Types:

• Comparative Study
• Review

PMID: 15112459 [PubMed - indexed for MEDLINE]

86: Epilepsia. 2004 Jan;45(1):77-80.

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Motor responses to afferent stimulation in juvenile myoclonic epilepsy.

Manganotti P, Tamburin S, Bongiovanni LG, Zanette G, Fiaschi A.

Department of Neurological Sciences and Vision, Section of Neurological Rehabilitation Clinical Neurology, University of Verona, Verona, Italy.

PURPOSE: To document whether the mechanisms responsible for myoclonic jerks in juvenile myoclonic epilepsy (JME) are similar to those causing other forms of myoclonus. METHODS: We studied somatosensory evoked potentials, the conditioning effect of cutaneous afferents on motor potentials evoked by transcranial magnetic stimulation (TMS), and intracortical inhibition and facilitation in response to paired TMS in a group of nine patients with JME and 20 normal controls. RESULTS: Intracortical inhibition was abnormal, whereas cortical somatosensory evoked potentials and TMS conditioned by cutaneous afferents were unaltered in JME patients. CONCLUSIONS: Abnormal processing of cutaneous afferents would not appear to contribute to myoclonus in JME.

Publication Types:

• Comparative Study

PMID: 14692911 [PubMed - indexed for MEDLINE]

87: Zh Nevrol Psikhiatr Im S S Korsakova. 2004;104(3):25-31.

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[Clinical and neurophysiological aspects of epilepsy with photosensitivity]

[Article in Russian]

Karlov VA, Dondov B, Gnezditskiĭ VV, Savitskaia NV, Andreeva OV.

Using mapping EEG with dipole source location, transcranial magnetic stimulation (TMS), and visual evoked potential (VEP), clinico-neurophysiological analysis of photosensitivity was carried out in 7 patients with different types of epilepsy. In all the patients, an increase of visual response amplitude in VEP assessment and location of photogenic and eye-closing spike activity was observed in parietal and occipital areas that suggested a significant role of the striate and para striate cortex, along with primary projection cortex, in photosensitivity. Although motor cortex excitability by TMS causes hypersynchronization of the background activity and increase of slow wave discharge on the EEG after TMS. TMS is supposed to cause an activation of antiepileptic system.

Publication Types:

• English Abstract

PMID: 15071841 [PubMed - indexed for MEDLINE]

88: J Neurosci. 2003 Nov 26;23(34):10867-72.

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Priming stimulation enhances the depressant effect of low-frequency repetitive transcranial magnetic stimulation.

Iyer MB, Schleper N, Wassermann EM.

Brain Stimulation Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1430, USA.

Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) can depress the excitability of the cortex locally and has been proposed for the treatment of disorders such as schizophrenia and epilepsy. Some have speculated that the depressant effect is related to long-term depression (LTD) of cortical synapses. Because in vitro LTD can be enhanced by pretreatment of synapses with higher-frequency stimulation, we hypothesized that if rTMS depression had mechanisms in common with LTD, higher-frequency priming would increase it also. In 25 healthy volunteers in two experiments, we measured motor-evoked potentials (MEPs) from TMS of the motor cortex to define the baseline response. Subthreshold rTMS (6 Hz, fixed rate or frequency modulated) was used to prime the motor cortex, followed by suprathreshold 1 Hz stimulation for 10 min at just above the MEP threshold. Over the next 60 min, we recorded MEPs every 10 sec and found significant increases in the amount of cortical depression with both types of 6 Hz priming rTMS relative to sham. The MEP depression from 6 Hz-primed 1 Hz rTMS showed no evidence of decay after 60 min. Pretreatment with 6 Hz primes both 1 Hz rTMS depression and LTD. Although not conclusive evidence, this strengthens the case for overlapping mechanisms and suggests a potent new technique for enhancing low-frequency rTMS depression that may have experimental and clinical applications.

Publication Types:

• Clinical Trial
• Research Support, Non-U.S. Gov't

PMID: 14645480 [PubMed - indexed for MEDLINE]

89: Neurosci Lett. 2003 Nov 6;351(1):9-12.

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Anti-kindling effect of slow repetitive transcranial magnetic stimulation in rats.

Anschel DJ, Pascual-Leone A, Holmes GL.

Laboratory for Magnetic Brain Stimulation, Beth Israel Deaconess Medical Center, and Department of Neurology, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. danschel@stanford.edu

The cerebrospinal fluid (CSF) of animals exposed to electroconvulsive shock (ECS) has anticonvulsant properties when injected into naive animals. The present study investigated whether the CSF of humans exposed to 1 or 10 Hz repetitive transcranial magnetic stimulation (rTMS) has similar properties. Using a 4 day rat flurothyl kindling seizure model we found that the kindling rate was significantly decreased by intraventricular injection of CSF from depressed patients exposed to 1 Hz rTMS. The CSF from patients that underwent 10 Hz rTMS showed a trend toward an increased kindling rate. These results support the similarity of ECS and rTMS and suggest that 1 Hz and 10 Hz rTMS produce distinct physiologic changes.

Publication Types:

• Research Support, U.S. Gov't, P.H.S.

PMID: 14550901 [PubMed - indexed for MEDLINE]

90: Clin Neurophysiol. 2003 Oct;114(10):1827-33.

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Suprathreshold 0.3 Hz repetitive TMS prolongs the cortical silent period: potential implications for therapeutic trials in epilepsy.

Cincotta M, Borgheresi A, Gambetti C, Balestrieri F, Rossi L, Zaccara G, Ulivelli M, Rossi S, Civardi C, Cantello R.

Unita' Operativa di Neurologia, Azienda Sanitaria di Firenze, Ospedale S. Maria Nuova, Piazza S. Maria Nuova, 1 50122, Florence, Italy. cincotta@unifi.it

OBJECTIVE: To investigate the after-effects of 0.3 Hz repetitive transcranial magnetic stimulation (rTMS) on excitatory and inhibitory mechanisms at the primary motor cortex level, as tested by single-pulse TMS variables. METHODS: In 9 healthy subjects, we studied a wide set of neurophysiological and behavioral variables from the first dorsal interosseous before (Baseline), immediately after (Post 1), and 90 min after (Post 2) the end of a 30 min long train of 0.3 Hz rTMS delivered at an intensity of 115% resting motor threshold (RMT). Variables under investigation were: maximal M wave, F wave, and peripheral silent period after ulnar nerve stimulation; RMT, amplitude and stimulus-response curve of the motor evoked potential (MEP), and cortical silent period (CSP) following TMS; finger-tapping speed. RESULTS: The CSP was consistently lengthened at both Post 1 and Post 2 compared with Baseline. The other variables did not change significantly. CONCLUSIONS: These findings suggest that suprathreshold 0.3 Hz rTMS produces a relatively long-lasting enhancement of the inhibitory mechanisms responsible for the CSP. These effects differ from those, previously reported, of 0.9-1 Hz rTMS, which reduces the excitability of the circuits underlying the MEP and does not affect the CSP. This provides rationale for sham-controlled trials aiming to assess the therapeutic potential of 0.3 Hz rTMS in epilepsy.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't

PMID: 14499744 [PubMed - indexed for MEDLINE]

91: Epilepsy Res. 2003 Sep;56(1):67-77.

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Relationship between lamotrigine oral dose, serum level and its inhibitory effect on CNS: insights from transcranial magnetic stimulation.

Tergau F, Wischer S, Somal HS, Nitsche MA, Mercer AJ, Paulus W, Steinhoff BJ.

Department of Clinical Neurophysiology, University of Göttingen, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany. f.tergau@med.uni-goettingen.de

The antiepileptic drug lamotrigine (LTG) is known to reduce cortical excitability evaluated by transcranial magnetic stimulation (TMS). We investigated the relationship between LTG oral dosages, serum levels and inhibitory effects on resting motor threshold (RMT), a parameter of motor system excitability assessed by TMS. In a randomized, placebo-controlled crossover study 16 male volunteers received 325 mg LTG as a single dose, as bi-hourly graded cumulative dose, or placebo. RMT and serum levels were measured before and after 2-8 h. With single dose, RMT elevation showed a poor but significant correlation to serum levels. With graded dose, serum levels as well as RMT increased dose-dependently with significant (P<0.0001) linear correlation. However, detailed comparison showed a high inter-individual variability in the relationship resembling a sigmoid correlation. Different mechanisms besides the sodium-channel blockage as the main mode of action of LTG are discussed to explain the diversity of individual dose-response relationships. Provided that the RMT elevation reflects the antiepileptic potential of LTG, TMS may be developed as a tool to monitor interindividual response of epilepsy patients to LTG treatment as well as to explore efficacy of other antiepileptic drugs with similar mode of action.

Publication Types:

• Clinical Trial
• Comparative Study
• Randomized Controlled Trial
• Research Support, Non-U.S. Gov't

PMID: 14529954 [PubMed - indexed for MEDLINE]

92: Seizure. 2003 Sep;12(6):373-8.

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Usefulness of magnetic motor evoked potentials in the surgical treatment of hemiplegic patients with intractable epilepsy.

Kamida T, Baba H, Ono K, Yonekura M, Fujiki M, Kobayashi H.

Department of Neurosurgery, Oita Medical University, 1-1 Idaigaoka, Hasama-machi, Oita 879-55, Japan.

Five hemiplegic patients with intractable epilepsy were studied with transcranial magnetic stimulation (TMS) before and after various surgical treatments. These patients had unilateral widespread cerebral lesions acquired at various times, including congenital, infantile and childhood injury. Motor evoked potentials (MEPs) of the abductor pollicis brevis (APB) muscles were simultaneously recorded on both sides following TMS of the motor cortex in the respective hemisphere using a figure-8 or circular coil. In all patients with congenital disease, the abolition of motor function in the affected hemisphere was estimated by magnetic MEPs, and the hemiplegia did not deteriorate after functional hemispherectomy (HS) was performed in two of them. In two patients with acquired disease, HS was not performed because it was shown by magnetic maps that the motor function in the affected hemisphere remained. Furthermore, it was shown by electric MEPs using subdural electrodes that a patient who had had encephalitis in early childhood had a reorganised motor area in the parietal cortex of the affected hemisphere. The present findings indicate that magnetic MEPs are a very useful non-invasive method of assessing whether the motor area in the affected hemisphere can be resected in hemiplegic patients with intractable epilepsy.

PMID: 12915083 [PubMed - indexed for MEDLINE]

93: Epilepsy Behav. 2003 Aug;4(4):375-85.

Related Articles, Links

Neurophysiologic correlates of psychiatric disorders and potential applications in epilepsy.

Halford JJ.

Department of Medicine, Neurology Division, Box 3678, Duke University Medical Center, Durham, NC 27710, USA. halfo001@mc.duke.edu

There is increasing interest in psychiatric assessment using neurophysiologic tools such as electroencephalography (EEG), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS). This is because these technologies have good temporal resolution, are relatively noninvasive, and (with the exception of MEG) are economical. Many different experimental paradigms and analysis techniques for the assessment of psychiatric patients involving these technologies are reviewed including conventional quantitative electroencephalography (QEEG), EEG cordance, low-resolution electromagnetic tomography (LORETA), frontal midline theta, midlatency auditory evoked potentials (P50, N100, P300), loudness dependency of the auditory evoked potential (LDAEP), mismatch negativity (MMN), contingent negative variation (CNV), and transcranial magnetic stimulation (TMS). Many of these neurophysiologic stimulus paradigms hold the promise of improving psychiatric patient care by improving diagnostic precision, predicting treatment response, and providing new phenotypes for genetic studies. Large cooperative multisite studies need to be designed to test and validate a few of these paradigms so that they might find use in routine clinical practice.

Publication Types:

• Review

PMID: 12899857 [PubMed - indexed for MEDLINE]

94: Nervenarzt. 2003 Aug;74(8):664-76.

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[Electric brain stimulation for epilepsy therapy]

[Article in German]

Kellinghaus C, Loddenkemper T, Möddel G, Tergau F, Lüders J, Lüdemann P, Nair DR, Lüders HO.

Department of Neurology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA. kelling@uni-muenster.de

Attempts to control epileptic seizures by electrical brain stimulation have been performed for 50 years. Many different stimulation targets and methods have been investigated. Vagal nerve stimulation (VNS) is now approved for the treatment of refractory epilepsies by several governmental authorities in Europe and North America. However, it is mainly used as a palliative method when patients do not respond to medical treatment and epilepsy surgery is not possible. Numerous studies of the effect of deep brain stimulation (DBS) on epileptic seizures have been performed and almost invariably report remarkable success. However, a limited number of controlled studies failed to show a significant effect. Repetitive transcranial magnetic stimulation (rTMS) also was effective in open studies, and controlled studies are now being carried out. In addition, several uncontrolled reports describe successful treatment of refractory status epilepticus with electroconvulsive therapy (ECT). In summary, with the targets and stimulation parameters investigated so far, the effects of electrical brain stimulation on seizure frequency have been moderate at best. In the animal laboratory, we are now testing high-intensity, low-frequency stimulation of white matter tracts directly connected to the epileptogenic zone (e.g., fornix, corpus callosum) as a new methodology to increase the efficacy of DBS ("overdrive method").

Publication Types:

• English Abstract
• Review

PMID: 12904868 [PubMed - indexed for MEDLINE]

95: Forensic Sci Int. 2003 Jul 29;135(1):16-26.

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The use of cyclohexanone as a "derivatizing" reagent for the GC-MS detection of amphetamines and ephedrines in seizures and the urine.

El-Haj BM, Al-Amri AM, Hassan MH, Ali HS, Bin Khadem RK.

Sharjah Police Forensic Science Laboratory, P.O. Box 29, Sharjah, United Arab Emirates.

A GC-MS method has been developed for the detection of amphetamine, methamphetamine, and the ephedrines, in seizures and the urine, based on on-GC condensation (derivatization) with cyclohexanone. The method is simple: the dried seizure material or the urine extract was mixed with cyclohexanone and injected into the GC-MS. The method was found to be superior to the methods based on acyl and trimethylsilyl (TMS) derivatization. Unlike for the acyl and TMS derivatives, the molecular and fragment ions of the cyclohexanone condensation products (cyclohexanone derivatives) were of substantial abundance, a useful property in unambiguous compound characterization. Furthermore, the high stability of the "derivatizing" reagent, cyclohexanone, compared with acyl and TMS derivatizing reagents, is a useful property in method development. The present method has proved selective and, tentatively, sensitive enough in the following areas (where methods based on acyl and TMS derivatization, as tested in this laboratory, have failed): (a) detection of amphetamine as a metabolite of methamphetamine; (b) detection of norpseudoephedrine as a metabolite of pseudoephedrine; (c) detection of amphetamine as an impurity of methamphetamine; (d) detection of cathine (norephedrine) as a constituent of Khat leaves; and (e) differentiation of Khat use from phenylpropanolamine use.

PMID: 12893131 [PubMed - indexed for MEDLINE]

96: Clin Neurophysiol. 2003 May;114(5):777-98.

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Transcranial magnetic stimulation and epilepsy.

Tassinari CA, Cincotta M, Zaccara G, Michelucci R.

Department of Neurosciences, Division of Neurology, Bellaria Hospital, Via Altura 3, 40139 Bologna, Italy. carloalberto.tassinari@ausl.bo.it

Epileptic conditions are characterized by an altered balance between excitatory and inhibitory influences at the cortical level. Transcranial magnetic stimulation (TMS) provides a noninvasive evaluation of separate excitatory and inhibitory functions of the cerebral cortex. In addition, repetitive TMS (rTMS) can modulate the excitability of cortical networks. We review the different ways that TMS has been used to investigate pathophysiological mechanisms and effects of antiepileptic drugs in patients with epilepsy and epileptic myoclonus. The safety of different TMS techniques is discussed too. Finally, we discuss the therapeutic prospects of rTMS in this field.

Publication Types:

• Review

PMID: 12738425 [PubMed - indexed for MEDLINE]

97: Magn Reson Med. 2003 May;49(5):856-63.

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Water diffusion measurements in perfused human hippocampal slices undergoing tonicity changes.

Shepherd TM, Wirth ED 3rd, Thelwall PE, Chen HX, Roper SN, Blackband SJ.

Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610, USA. tms@ufbi.ufl.edu

Diffusion MRI has the potential to probe the compartmental origins of MR signals acquired from human nervous tissue. However, current experiments in human subjects require long diffusion times, which may confound data interpretation due to the effects of compartmental exchange. To investigate human nervous tissue at shorter diffusion times, and to determine the relevance of previous diffusion studies in rat hippocampal slices, water diffusion in 20 perfused human hippocampal slices was measured using a wide-bore 17.6-T magnet equipped with 1000-mT/m gradients. These slices were procured from five patients undergoing temporal lobectomy for epilepsy. Tissue viability was confirmed with electrophysiological measurements. Diffusion-weighted water signal attenuation in the slices was well-described by a biexponential function (R(2) > 0.99). The mean diffusion parameters for slices before osmotic perturbation were 0.686 +/- 0.082 for the fraction of fast diffusing water (F(fast)), 1.22 +/- 0.22 x 10(-3) mm(2)/s for the fast apparent diffusion coefficient (ADC), and 0.06 +/- 0.02 x 10(-3) mm(2)/s for the slow ADC. Slice perturbations with 20% hypotonic and 20% hypertonic artificial cerebrospinal fluid led to changes in F(fast) of -8.2% and +10.1%, respectively (ANOVA, P < 0.001). These data agree with previous diffusion studies of rat brain slices and human brain in vivo, and should aid the development of working models of water diffusion in nervous tissue, and thus increase the clinical utility of diffusion MRI. Copyright 2003 Wiley-Liss, Inc.

Publication Types:

• Research Support, U.S. Gov't, P.H.S.

PMID: 12704768 [PubMed - indexed for MEDLINE]

98: Arq Neuropsiquiatr. 2003 Mar;61(1):146-52. Epub 2003 Apr 16.

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Comment in:

• Arq Neuropsiquiatr. 2004 Mar;62(1):185; author reply 186.

[Transcranial magnetic stimulation]

[Article in Portuguese]

Conforto AB, Marie SK, Cohen LG, Scaff M.

Divisão de Clínica Neurológica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil. abcong@yahoo.com

Transcranial magnetic stimulation (TMS) allows non-invasive study and modulation of cortical excitability in humans. Changes in cortical excitability in physiological and pathological conditions can be tracked by measurements such as motor threshold, motor evoked potentials, recruitment curves, intracortical facilitation and inhibition. The central motor conduction time can estimate neural transmission in central motor pathways. Changes in areas of representation in sensorimotor cortex can be studied with cortical mapping. Modulation of cortical processing can be used to evaluate different brain functions. Therapeutic use in depression, Parkinson's disease and epilepsy has raised great interest over the past decade. Non-invasive cortical mapping may be achieved by combining TMS to other neurophysiological/ neuroimaging techniques. TMS has great potential both as an investigational and as a therapeutical tool in Neurology and Psychiatry.

Publication Types:

• English Abstract
• Review

PMID: 12715042 [PubMed - indexed for MEDLINE]

99: Hum Brain Mapp. 2003 Mar;18(3):239-47.

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Towards understanding language organisation in the brain using fMRI.

Matthews PM, Adcock J, Chen Y, Fu S, Devlin JT, Rushworth MF, Smith S, Beckmann C, Iversen S.

Centre for Functional Magnetic Resonance Imaging of the Brain, Department of Clinical Neurology, John Radcliffe Hospital, Oxford, United Kingdom. paul@fmrib.ox.ac.uk

Functional magnetic resonance imaging (fMRI), which allows non-invasive mapping of human cognitive functions, has become an important tool for understanding language function. An understanding of component processes and sources of noise in the images is contributing to increased confidence in the reproductability of studies. This allows clinical applications, e.g., for pre-surgical lateralisation of language functions in patients with temporal lobe epilepsy. fMRI is a sensitive method for mapping regions involved in language functions. We recently have applied it to study the effect of word surface form on reading with a comparison of responses to Chinese characters or alphabetical Pinyin. Interpretation of fMRI activations must be made with caution; fMRI suggests task-associated activation, but does not independently confirm that such activity is necessary. However, complementary studies can be performed using transcranial magnetic stimulation (TMS), which can be used to interfere with brain activity in a specific region transiently for characterisation of the behavioural effects. We describe how TMS combined with fMRI has confirmed a role for the left inferior frontal cortex in semantic processing. Copyright 2003 Wiley-Liss, Inc.

Publication Types:

• Research Support, Non-U.S. Gov't
• Review

PMID: 12599283 [PubMed - indexed for MEDLINE]

100: Int J Ment Health Nurs. 2003 Mar;12(1):22-9.

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Information for assistants of repeated transcranial magnetic stimulation.

Pridmore S, Khan U, Rosa MA, George MS.

Department of Psychological Medicine, Royal Hobart Hospital, Discipline of Psychiatry, University of Tasmania, GPO Box 1061 L, Hobart 7001, Tasmania, Australia. s.pridmore@utas.edu.au

Repeated transcranial magnetic stimulation (rTMS) is an exciting new technology being used in psychiatric and neurological research in many centres around the world. rTMS has been accepted as a routine treatment of depression in Canada and Israel. To this point, it has been exclusively conducted by medical officers. As knowledge and experience grows, it is probable that professionals with other backgrounds will have the opportunity to play a role. The aim of this paper is to provide information that will be valuable to assistants. Electromagnetic principles are harnessed to deliver electric currents to localized regions of the cortex. rTMS does not involve anaesthesia or seizure. Side-effects appear to be few. Much remains uncertain, however, even including the most appropriate treatment parameters.

Publication Types:

• Review

PMID: 14685956 [PubMed - indexed for MEDLINE]

101: Suppl Clin Neurophysiol. 2003;56:33-41.

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Pulse configuration and rTMS efficacy: a review of clinical studies.

Sommer M, Paulus W.

Department of Clinical Neurophysiology, Center for Neurological Medicine, University of Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, Germany. msommer@gwdg.de

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't
• Review

PMID: 14677380 [PubMed - indexed for MEDLINE]

102: Neurology. 2002 Dec 24;59(12):1851-9.

Related Articles, Links

Transcranial magnetic stimulation techniques in clinical investigation.

Currà A, Modugno N, Inghilleri M, Manfredi M, Hallett M, Berardelli A.

Dipartimento di Scienze Neurologiche, Universita degli Studi di Roma La Sapienza, Viale dell Universita 30, 00185 Rome, Italy.

Transcranial magnetic stimulation (TMS) is a technique that can activate cortical motor areas and the corticospinal tract without causing the subject discomfort. Since TMS was introduced, numerous applications of the technique have been developed for the evaluation of neurologic diseases. Standard TMS applications (central motor conduction time, threshold and amplitude of motor evoked potentials) allow the evaluation of motor conduction in the CNS. Conduction studies provide specific information in neurologic conditions characterized by clinical and subclinical upper motor neuron involvement. In addition, they have proved useful in monitoring motor abnormalities and the recovery of motor function. TMS also gives information on the pathophysiology of the processes underlying the various clinical conditions. More complex TMS applications (paired-pulse stimulation, silent period, ipsilateral silent period, input-output curve, and evaluation of central fatigue) allow investigation into the mechanisms of diseases causing changes in the excitability of cortical motor areas. These techniques are also useful in monitoring the effects of neurotrophic drugs on cortical activity. TMS applications have an important place among the investigative tools to study patients with motor disorders.

Publication Types:

• Review

PMID: 12503582 [PubMed - indexed for MEDLINE]

103: Brain Res. 2002 Dec 6;957(1):37-41.

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The long-term high-frequency repetitive transcranial magnetic stimulation does not induce mRNA expression of inflammatory mediators in the rat central nervous system.

Okada K, Matsunaga K, Yuhi T, Kuroda E, Yamashita U, Tsuji S.

Department of Neurology, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. gion@med.uoeh-u.ac.jp

Repetitive transcranial magnetic stimulation (rTMS) has been applied for treatment of several diseases such as depression. However, the safety and biological effects of rTMS have not been fully elucidated. In this study, the effects of rTMS on the levels of inflammatory mediators in the central nervous system (CNS), which may be involved in neurodegenerative disorders, were investigated in comparison with the electric convulsive model. Long-term rTMS (1500 pulses at 30 Hz/day for series of 7 days) stimulation, which did not elicit convulsion, was given to rats (rTMS rats). Single high-frequency electrical stimulation (100 Hz, 0.5-ms pulse width, 1 s duration, 50 mA), which induced convulsion, was given to rats (ES rats). mRNA levels of interleukin (IL)-1beta, IL-6, cyclooxygenase (COX)-2 and inducible nitric oxide synthetase (iNOS) in the brain were evaluated by reverse transcription-polymerase chain reaction before and after these stimulations. mRNA of IL-1beta, IL-6 and COX-2 was induced in the brains of ES rats but not in the brains of long-term rTMS rats. mRNA of iNOS was not induced in the brain of long-term rTMS rats. These results suggest that long-term rTMS may safe and modulate neural function without up-regulation of inflammatory mediators, which may be involved in neurodegenerative disorders.

PMID: 12443977 [PubMed - indexed for MEDLINE]

104: Brain Cogn. 2002 Dec;50(3):366-86.

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Transcranial magnetic stimulation: neurophysiological applications and safety.

Anand S, Hotson J.

Department of Biological Sciences, San Jose State University, One Washington Square, San Jose, CA 95192-0100, USA. sanand@email.sjsu.edu

TMS is a non-invasive tool for measuring neural conduction and processing time, activation thresholds, facilitation and inhibition in brain cortex, and neural connections in humans. It is used to study motor, visual, somatosensory, and cognitive functions. TMS does not appear to cause long-term adverse neurological, cardiovascular, hormonal, motor, sensory, or cognitive effects in healthy subjects. Single-pulse (<1Hz) TMS is safe in normal subjects. High frequency, high-intensity repetitive TMS (rTMS) can elicit seizures even in normal subjects. Safety guidelines for using rTMS have been published.

Publication Types:

• Review

PMID: 12480484 [PubMed - indexed for MEDLINE]

105: Neurology. 2002 Oct 8;59(7):1028-33.

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Comment in:

• Neurology. 2003 Feb 11;60(3):527-8; author reply 527-8.

Reduced inhibition within primary motor cortex in patients with poststroke focal motor seizures.

Kessler KR, Schnitzler A, Classen J, Benecke R.

Department of Neurology, University of Frankfurt, Frankfurt/Main, Germany. k.kessler@em.uni-frankfurt.de

BACKGROUND: Following an ischemic brain lesion, the affected cortex undergoes structural and functional changes that may lead to increased cortical excitability or decreased inhibitory neuronal activity, resulting in the occurrence of poststroke epileptic seizures in 6 to 10% of patients with stroke. METHODS: To assess motor cortical excitability, transcranial magnetic stimulation (TMS) was used to determine the silent period (SP) duration in 84 consecutive patients with ischemic stroke. RESULTS: In a subpopulation of six patients (38 to 72 years old) a significant decrease of the SP duration (mean 116 +/- 14 msec) was detected in either the arm or the leg on the affected side as compared to the corresponding unaffected limb (mean 231 +/- 32 msec). This electrophysiologic abnormality was clinically associated with focal motor seizures in five of the six patients, whereas none of the other 76 patients with normal or prolonged SP durations developed seizures or epilepsy. CONCLUSIONS: Silent period shortening in this group reflects decreased inhibitory activity that may partly be related to functional or structural impairment of GABAergic interneurons. TMS may be of value for determining patients with stroke at risk for developing poststroke seizures.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't

PMID: 12370457 [PubMed - indexed for MEDLINE]

106: Epilepsia. 2002 Oct;43(10):1149-56.

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Topiramate selectively decreases intracortical excitability in human motor cortex.

Reis J, Tergau F, Hamer HM, Müller HH, Knake S, Fritsch B, Oertel WH, Rosenow F.

Interdisciplinary Epilepsy Center, Department of Neurology, Philipps-University, Marburg, Germany.

PURPOSE: Topiramate (TPM) is a novel drug with broad antiepileptic effect in children and adults. In vitro studies suggest activity as sodium-channel blocker, as gamma-aminobutyric acid type A (GABAA)-receptor agonist and as non-N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist. METHODS: With transcranial magnetic stimulation (TMS), we evaluated which of the mechanisms of action of TPM detected in vitro are relevant for the modulation of human motor cortex excitability. In a double-blind, placebo-controlled, crossover study design, we investigated the effect of single oral doses of 50 mg and 200 mg TPM on motor thresholds, cortical silent period (CSP), and on intracortical inhibition (ICI) and intracortical facilitation (ICF) in 20 healthy subjects. RESULTS: A significant dose-dependent increase of ICI was noticed after 200 mg TPM as compared with placebo at short interstimulus intervals of 2 to 4 ms. TPM had no effect on motor thresholds or the CSP. CONCLUSIONS: We conclude that a single dose of TPM selectively increases ICI by GABAAergic and/or glutamatergic mechanisms without a relevant influence on measures, depending on ion-channel blockade or GABAB-receptor activity. The decrease of intracortical excitability (as measured by ICI and ICF) caused by TPM may correlate with its lack of proconvulsive potential in idiopathic generalized epilepsy, because drugs without this action or with less pronounced action may exacerbate seizures in this condition.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't

PMID: 12366728 [PubMed - indexed for MEDLINE]

107: Neurology. 2002 Sep 24;59(6 Suppl 4):S56-61.

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Vagus nerve stimulation therapy: a research update.

George MS, Nahas Z, Bohning DE, Kozel FA, Anderson B, Chae JH, Lomarev M, Denslow S, Li X, Mu C.

502 North, IOP, Department of Psychiatry, Medical University of South Carolina, 67 President Street, Charleston, SC 29425, USA.

Over the past 5 years, and especially within the last year, there has been a rapid expansion of vagus nerve stimulation (VNS)-related preclinical research, as well as clinical studies in indications other than epilepsy. The research advances in understanding VNS are occurring in the midst of a blossoming of other forms of therapeutic brain stimulation, such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS). In general, improved understanding of the neurobiological effects of VNS therapy as a function of the different use parameters (frequency, intensity, pulse width, duration, dose) is beginning to guide clinical use and help determine which diseases, in addition to epilepsy, VNS might treat.

Publication Types:

• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, P.H.S.
• Review

PMID: 12270970 [PubMed - indexed for MEDLINE]

108: Neurology. 2002 Aug 27;59(4):560-2.

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Transcranial magnetic stimulation for the treatment of seizures: a controlled study.

Theodore WH, Hunter K, Chen R, Vega-Bermudez F, Boroojerdi B, Reeves-Tyer P, Werhahn K, Kelley KR, Cohen L.

Clinical Epilepsy, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. theodorw@ninds.nih.gov

OBJECTIVE: To perform a controlled trial of transcranial magnetic stimulation (TMS). METHODS: Twenty-four patients with localization-related epilepsy were randomized to blinded active or placebo stimulation. Weekly seizure frequency was compared for 8 weeks before and after 1 week of 1-Hz TMS for 15 minutes twice daily. RESULTS: When the 8-week baseline and post-stimulation periods were compared, active patients had a mean seizure frequency reduction of 0.045 +/- 0.13 and sham-stimulated control subjects -0.004 +/- 0.20. Over 2 weeks, actively treated patients had a mean reduction in weekly seizure frequency of 0.16 +/- 0.18 and sham-stimulated control subjects 0.01 +/- 0.24. Neither difference was significant. CONCLUSION: The effect of TMS on seizure frequency was mild and short lived.

Publication Types:

• Clinical Trial
• Randomized Controlled Trial

PMID: 12196649 [PubMed - indexed for MEDLINE]

109: J Psychosom Res. 2002 Aug;53(2):709-19.

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Novel physical treatments for the management of neuropsychiatric disorders.

Malhi GS, Sachdev P.

School of Psychiatry, University of New South Wales, Sydney, Australia. g.malhi@unsw.edu.au

OBJECTIVE: To briefly describe the novel non-drug physical interventions currently in use in the investigation and treatment of neuropsychiatric disorders regarding their efficacy and potential future applications. METHODS: A systematic review of the literature concerning transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), vagus nerve stimulation (VNS) and neurosurgery for mental disorders (NMD) was conducted using Medline and literature known to the authors. RESULTS: A summary of each procedure is provided giving a succinct overview of efficacy, current applications and possible future indications. CONCLUSION: Novel and innovative physical interventions are currently being used to study brain function in health and disease. In particular, TMS has quickly established itself as a useful investigational tool and is emerging as a possible antidepressant therapy. Similarly, VNS has been applied successfully in the management of intractable epilepsy and is undergoing evaluation in the management of patients with treatment-resistant depression. DBS has shown significant promise in the treatment of Parkinson's disease and may have use in the management of obsessive-compulsive disorder. Finally, neurosurgical procedures for the treatment of mental disorders have been sufficiently refined to stage a comeback, although rigorous scientific study of their efficacy and indications is still necessary.

Publication Types:

• Review

PMID: 12169345 [PubMed - indexed for MEDLINE]

110: Am J Psychiatry. 2002 Jul;159(7):1093-102.

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Comment in:

• Am J Psychiatry. 2004 May;161(5):928; author reply 928-9.

Slow transcranial magnetic stimulation, long-term depotentiation, and brain hyperexcitability disorders.

Hoffman RE, Cavus I.

Yale-New Haven Psychiatric Hospital, Yale University School of Medicine, LV 108, 20 York Street, New Haven, CT 06504, USA. ralph.hoffman@yale.edu

OBJECTIVE: Many clinical syndromes in neuropsychiatry suggest focal brain activation. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a method for selectively altering neural activity. METHOD: Studies assessing effects of "slow" rTMS, administered up to once per second, in normal people and in those with pathological conditions are reviewed. The findings are compared with those of animal studies examining long-term depression and long-term depotentiation through direct electrical stimulation of cortical tissue. RESULTS: Data suggest that slow rTMS reduces cortical excitability, both locally and in functionally linked cortical regions. Preliminary studies of patients with focal dystonia, epileptic seizures, and auditory hallucinations indicate symptom reductions following slow rTMS. Long-term depotentiation exhibits many features congruent with those of slow rTMS, including frequency dependence, spread to functionally linked cortical regions, additive efficacy, and extended duration of effects. CONCLUSIONS: Slow rTMS offers a new method for probing and possibly treating brain hyperexcitability syndromes. Further studies linking slow rTMS to animal models of neuroplasticity are indicated.

Publication Types:

• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, P.H.S.
• Review

PMID: 12091184 [PubMed - indexed for MEDLINE]

111: Acta Psychiatr Scand. 2002 May;105(5):324-40.

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The application of transcranial magnetic stimulation in psychiatry and neurosciences research.

Fitzgerald PB, Brown TL, Daskalakis ZJ.

Dandenong Psychiatry Research Centre, Department of Psychological Medicine, Monash University, PO Box 956, Dandenong, Victoria 3175, Australia. paul.fitzgerald@med.monash.edu.au

OBJECTIVE: Over recent years transcranial magnetic stimulation (TMS) has become widely applied in the study of neuropsychiatric disorders. The aim of this article is to review the application of TMS as an investigative tool and as a potential therapeutic modality in psychiatric disorders. METHOD: A comprehensive literature review. RESULTS: When applied as an investigative tool, TMS provides innovative ways to directly study the excitability of the cortex, cortical regional connectivity, the plasticity of brain responses and cognitive functioning in illness and disease states. A number of studies suggest the potential of treatment with TMS in disease states, especially in patients with depression, although difficulties exist with the interpretation of the published literature. CONCLUSION: TMS has a considerable role in neuropsychiatric research. It appears to have considerable potential as a therapeutic tool in depression, and perhaps a role in several other disorders, although widespread application requires larger trials and establishment of sustained response.

Publication Types:

• Review

PMID: 11942939 [PubMed - indexed for MEDLINE]

112: Nervenarzt. 2002 Apr;73(4):332-5.

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[Modulation of cortical excitability by transcranial direct current stimulation]

[Article in German]

Nitsche MA, Liebetanz D, Tergau F, Paulus W.

Abteilung Klinische Neurophysiolgie, Georg-August-Universität Göttingen. mnitsch1@gwdg.de

Modulation of cerebral excitability is thought to be one mechanism underlying the pharmacological treatment of neuropsychiatric diseases such as epilepsy, depression, and dystonia. Repetitive transcranial magnetic stimulation (rTMS) has been tested for several years as a nonpharmacological, noninvasive method of directly influencing patients' cortical functions. We present an overview of the more easily performed transcranial direct current stimulation (tDCS) with weak current, which produces distinctly more pronounced changes in excitability than rTMS. The basic underlying mechanism is a shift in the resting membrane potential towards either hyper- or depolarisation, depending on stimulation polarity. This in turn leads to changes in the excitability of cortical neurons. Anodic stimulation increases cortical excitability, while cathodic stimulation decreases it. These changes persist after the end of stimulation if the stimulation lasts long enough, i.e., at least several minutes. The duration of this aftereffect can be controlled through the duration and intensity of the stimulation. Transcranial direct current stimulation essentially allows a focal, selective, reversible, pain-free, and noninvasive induction of changes in cortical excitability, the therapeutic potential of which must be evaluated in clinical studies, once possible risk factors have been assessed.

Publication Types:

• English Abstract
• Research Support, Non-U.S. Gov't
• Review

PMID: 12040980 [PubMed - indexed for MEDLINE]

113: J Neurol Neurosurg Psychiatry. 2001 Dec;71(6):809-12.

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Cortical excitability and sleep deprivation: a transcranial magnetic stimulation study.

Civardi C, Boccagni C, Vicentini R, Bolamperti L, Tarletti R, Varrasi C, Monaco F, Cantello R.

Clinica Neurologica, Ospedale Maggiore, Corso Mazzini 18, 28100 Novara, Italy. c_civardi@yahoo.com

The objective was to assess the changes in cortical excitability after sleep deprivation in normal subjects. Sleep deprivation activates EEG epileptiform activity in an unknown way. Transcranial magnetic stimulation (TMS) can inform on the excitability of the primary motor cortex. Eight healthy subjects (four men and four women) were studied. Transcranial magnetic stimulation (single and paired) was performed by a focal coil over the primary motor cortex, at the "hot spot" for the right first dorsal interosseous muscle. The following motor evoked potential features were measured: (a) active and resting threshold to stimulation; (b) duration of the silent period; (c) amount of intracortical inhibition on paired TMS at the interstimulus intervals of 2 and 3 ms and amount of facilitation at interstimulus intervals of 14 and 16 ms. The whole TMS session was repeated after a sleep deprivation of at least 24 hours. After the sleep deprivation, the threshold to stimulation (in the active and resting muscle), as well as the silent period, did not change significantly. By contrast, the paired stimulus study showed a significant (p<0.05) reduction in both intracortical inhibition and facilitation. Thus, TMS showed that sleep deprivation is associated with changes in inhibition-facilitation balance in the primary motor cortex of normal subjects. These changes might have a link with the background factors of the "activating" effects of sleep deprivation.

Publication Types:

• Validation Studies

PMID: 11723210 [PubMed - indexed for MEDLINE]

PMCID: PMC1737655

114: J Neurol Neurosurg Psychiatry. 2001 Dec;71(6):772-6.

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Reduced excitability of the motor cortex in untreated patients with de novo idiopathic "grand mal" seizures.

Delvaux V, Alagona G, Gérard P, De Pasqua V, Delwaide PJ, Maertens de Noordhout A.

University Department of Neurology, Hôpital de la Citadelle, B-4000 Liège, Belgium.

OBJECTIVES: Transcranial magnetic stimulation (TMS) was used to investigate motor cortex excitability, intracortical excitatory, and inhibitory pathways in 18 patients having experienced a first "grand mal" seizure within 48 hours of the electrophysiological test. All had normal brain MRI, and were free of any treatment, drug, or alcohol misuse. Results were compared with those of 35 age matched normal volunteers. METHODS: The following parameters of responses to TMS were measured: motor thresholds at rest and with voluntary contraction, amplitudes of responses, cortical silent periods, and responses to paired pulse stimulation with interstimulus intervals of 1 to 20 ms. RESULTS: In patients, there were significantly increased motor thresholds with normal amplitudes of motor evoked potentials (MEPs), suggesting decreased cortical excitability. Cortical silent periods were not significantly different from those of normal subjects. Paired TMS with short interstimulus intervals (1-5 ms) induced normal inhibition of test MEPs, suggesting preserved function of GABAergic intracortical inhibitory interneurons. On the contrary, the subsequent period of MEP facilitation found in normal subjects (ISIs of 6-20 ms) was markedly reduced in patients. This suggests the existence of abnormally prolonged intracortical inhibition or deficient intracortical excitation. In nine patients retested 2 to 4 weeks after the initial seizure, these abnormalities persisted, although to a lesser extent. CONCLUSION: The present findings together with abnormally high motor thresholds could represent protective mechanisms against the spread or recurrence of seizures.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 11723199 [PubMed - indexed for MEDLINE]

PMCID: PMC1737654

115: Rinsho Shinkeigaku. 2001 Dec;41(12):1097-9.

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[Treatment of status epilepticus]

[Article in Japanese]

Tsuji S, Akamatsu N.

Status epilepticus (SE) is a condition requiring emergency care. There are convulsive SE, non-convulsive SE including complex partial status and absence status, non-convulsive electric SE and pseudostatus epilepticus, although convulsive SE is the most common. Diagnosis of status epilepticus of complex partial seizures (CPS) and absence seizures was significantly delayed because delays in seeking medical attention were common. The seizures were generalized convulsive SE in 84% and CPS status in 16%, and the overall mortality rate was 15% in 41 SE patients of our study. EEG monitoring is important to make or exclude the diagnosis of SE. Diazepam is the first choice medication and effective in the management of SE, and lately, lorazepam, midazolam, propofol and pentobarbital etc as emergency therapy. Phenytoin is also considered first-line agent in the emergency management of SE. Repetitive transcranial magnetic stimulation (rTMS) led to a prolonged latency for seizure induction after an intraperitoneal injection of pentylenetetrazol (PTZ) and effectively prevented the development of status epilepticus of PTZ-induced convulsions in the rats. Our data suggest that rTMS has suppressive effects on the neuronal excitability in rats. These effects are anticonvulsive and suggest the possibility of therapeutic use of rTMS in the patients with refractory seizures.

Publication Types:

• English Abstract
• Review

PMID: 12235807 [PubMed - indexed for MEDLINE]

116: Neurology. 2001 Nov 27;57(10):1793-9.

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Hyperexcitable cortical responses in progressive myoclonic epilepsy: a TMS study.

Manganotti P, Tamburin S, Zanette G, Fiaschi A.

Department of Neurological Sciences and Vision, Section of Neurological Rehabilitation, University of Verona, Italy. paolomanganotti@yahoo.com

OBJECTIVE: Transcranial magnetic stimulation (TMS) has allowed investigators to study intracortical inhibition and facilitation and sensorimotor integration in motor disorders and epilepsy. The authors used TMS to elucidate the pathophysiology of reflex myoclonus with giant somatosensory evoked potentials (SEP). METHODS: The authors studied four patients with progressive myoclonic epilepsy. All patients had giant SEP elicited by mixed and digital nerve stimulation. They studied the response to paired-pulse TMS at interstimulus intervals (ISI) ranging from 1 to 15 ms and the conditioning effect of digital electrical stimulation at ISI ranging from 10 to 100 ms on the motor evoked potential amplitude to TMS. RESULTS: Digital stimulation markedly facilitated conditioned motor evoked potentials at ISI ranging from 25 to 40 ms in all patients. This pattern was significantly different from the inhibition observed in controls (n = 12) at the same ISI. In the patients, paired-pulse TMS showed a decrease in intracortical inhibition in the motor cortex in comparison with controls. CONCLUSIONS: These findings suggest cortical and subcortical components of abnormal sensorimotor integration in addition to hyperexcitability of the sensory and motor cortex in our myoclonic patients.

PMID: 11723265 [PubMed - indexed for MEDLINE]

117: Can J Psychiatry. 2001 Oct;46(8):720-7.

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Transcranial magnetic stimulation in the treatment of mood disorder: a review and comparison with electroconvulsive therapy.

Hasey G.

Regional Mood Disorders Program, Department of Psychiatry, McMaster University, Hamilton, Ontario, Canada.

OBJECTIVE: To review repetitive transcranial magnetic stimulation (rTMS) as a mode of therapy for depression. METHOD: The following aspects of rTMS were reviewed and compared with electroconvulsive therapy (ECT): history, basic principles, technical considerations, possible mode of action, safety, adverse effects, and effects on mood in both healthy individuals and those suffering from bipolar disorder (BD) or depression. RESULTS: rTMS may selectively increase or decrease neuronal activity over discrete brain regions. As a result of this focused intervention with TMS, the potential for unwanted side effects is substantially reduced, compared with ECT. In open trials, rTMS and ECT are reported to be equally efficacious for patients having depression without psychosis, but the therapeutic benefits reported in double-blind sham-rTMS controlled trials are more modest. CONCLUSION: The antidepressant and antimanic effects of rTMS depend on technical considerations such as stimulus frequency, intensity, and magnetic coil placement, which may not yet be optimized. Biological heterogeneity among the patients treated with rTMS may also contribute to differing efficacy across clinical trials. rTMS may possess tremendous potential as a treatment for mood disorder, but this has not yet been realized. rTMS must still be regarded as an experimental intervention requiring further refinement.

Publication Types:

• Comparative Study
• Review

PMID: 11692974 [PubMed - indexed for MEDLINE]

118: Neurosci Lett. 2001 Sep 14;310(2-3):153-6.

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Decreased susceptibility to pentylenetetrazol-induced seizures after low-frequency transcranial magnetic stimulation in rats.

Akamatsu N, Fueta Y, Endo Y, Matsunaga K, Uozumi T, Tsuji S.

Department of Neurology, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. akamatn@med.uoeh-u.ac.jp

We studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure susceptibility in rats. rTMS of 1000 pulses at 0.5 Hz led to a prolonged latency for seizure development after an intraperitoneal injection of pentylenetetrazol. The rTMS effectively prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. These findings indicate that low-frequency rTMS affects the neural excitability, in the direction of anticonvulsive, and therefore, suggest the possibility of therapeutic use of rTMS in epilepsy.

PMID: 11585590 [PubMed - indexed for MEDLINE]

119: J ECT. 2001 Sep;17(3):195-7.

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Magnetic and seizure thresholds before and after six electroconvulsive treatments.

Amiaz R, Stein O, Schreiber S, Danon PN, Dolberg OT, Grunhaus L.

Psychiatry Department C, The Chaim Sheba Medical Center, Tel-Hashomer, Israel. tomrev@barak-online.net

OBJECTIVES: Electroconvulsive therapy (ECT) is a well-established treatment in psychiatry. It has been reported that in patients with nondelusional major depression, transcranial magnetic stimulation (TMS) may substitute for ECT. To explore whether ECT and TMS share mechanisms of action, we studied the effects of ECT on both seizure threshold (ST) and magnetic motor threshold (MT). METHODS: We measured ST and MT in 10 patients referred for ECT. MT was defined as the minimal power of the TMS equipment at which a motor evoked potential (MEP) response could be detected 50% of the time. ST was defined as the minimal intensity of electrical stimulation needed to elicit an adequate seizure. ECT was performed following the methods recommended by the American Psychiatric Association. All subjects signed an informed consent for participation in the research. RESULTS: We measured MT and ST in 10 patients before and after 6 ECT treatments. No changes in MT were detected from the treatment (paired t-test: t = 1.05, SD = 4.78, p = 0.25). ST, on the other hand, increased significantly with treatment (paired t-test: t = 2.99, SD = 190.20, p < 0.001). CONCLUSIONS: ECT and TMS do not share a common mechanism at least with regard to MT and ST.

Publication Types:

• Clinical Trial
• Comparative Study

PMID: 11528311 [PubMed - indexed for MEDLINE]

120: Neurology. 2001 Aug 28;57(4):706-8.

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Comment in:

• Neurology. 2002 Apr 9;58(7):1135; author reply 1135.

Prolonged cortical silent period after transcranial magnetic stimulation in generalized epilepsy.

Macdonell RA, King MA, Newton MR, Curatolo JM, Reutens DC, Berkovic SF.

Department of Neurology, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia. rmac@austin.unimelb.edu.au

Transcranial magnetic stimulation (TMS) produces a cortical silent period (CSP) during a voluntary contraction. The duration of the CSP was used to assess the level of intracortical inhibition in patients with untreated idiopathic generalized epilepsy (IGE). Mean CSP duration was assessed at three TMS stimuli in 21 patients with IGE compared with 19 normal control subjects. Mean CSP duration was increased at all stimulus intensities, indicating that intracortical inhibition is increased in patients with IGE.

PMID: 11524485 [PubMed - indexed for MEDLINE]

121: Brain. 2001 Jul;124(Pt 7):1336-49.

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Effect of multiple subpial transection on motor cortical excitability in cortical dysgenesis.

Shimizu T, Maehara T, Hino T, Komori T, Shimizu H, Yagishita A, Yokota T, Hirai S, Rossini PM.

Departments of Neurology, Neurosurgery, and Neuroradiology, Tokyo Metropolitan Neurological Hospital, Japan. TJshimizu@aol.com

We report here a 12-year-old patient with unilateral cortical dysgenesis and intractable simple partial seizure in his left arm, who underwent multiple subpial transection (MST) in the right cerebral cortex including the primary motor cortex. We investigated motor cortical excitability using multimodal transcranial magnetic stimulation (TMS) before and 1 month after MST, in which surgical cortical incisions were made with strokes 5 mm apart and 4 mm deep. Preoperative TMS studies showed hyperexcitability in the affected motor cortex as abnormally prolonged muscle responses to TMS with a wide cortical motor map, which were markedly reduced following the operation. The preoperative motor evoked potentials were large and polyphasic, and consisted of early and late components. The late component was completely abolished after MST, suggesting that this component might be due to activation of the corticospinal tract neurones by long recurrent axon branches of dysplastic excitatory pyramidal neurones, which were cut by MST, or by delayed, polysynaptic intracortical conduction with marked temporal dispersion. Intracortical inhibition in the affected motor cortex was also disrupted preoperatively and improved after MST. Postoperative recruitment order of muscle responses to TMS was bilaterally symmetrical, indicating that MST did not interfere with the function of the corticospinal tract neurones. The patient showed fair motor recovery and good seizure control after the operation. These results of TMS studies demonstrated the remarkable effectiveness of MST not only on intractable seizure but also on abnormal motor cortical organization and hyperexcitability in cortical dysgenesis.

Publication Types:

• Case Reports

PMID: 11408329 [PubMed - indexed for MEDLINE]

122: Ann N Y Acad Sci. 2001 Jun;930:179-92.

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Cerebral substrates of musical imagery.

Halpern AR.

Psychology Department, Bucknell University, Lewisburg, PA 17837, USA. ahalpern@bucknell.edu

Musical imagery refers to the experience of "replaying" music by imagining it inside the head. Whereas visual imagery has been extensively studied, few people have investigated imagery in the auditory domain. This article reviews a program of research that has tried to characterize auditory imagery for music using both behavioral and cognitive neuroscientific tools. I begin by describing some of my behavioral studies of the mental analogues of musical tempo, pitch, and temporal extent. I then describe four studies using three techniques that examine the correspondence of brain involvement in actually perceiving vs. imagining familiar music. These involve one lesion study with epilepsy surgery patients, two positron emission tomography (PET) studies, and one study using transcranial magnetic stimulation (TMS). The studies converge on the importance of the right temporal neocortex and other right-hemisphere structures in the processing of both perceived and imagined nonverbal music. Perceiving and imagining songs that have words also involve structures in the left hemisphere. The supplementary motor area (SMA) is activated during musical imagery; it may mediate rehearsal that involves motor programs, such as imagined humming. Future studies are suggested that would involve imagery of sounds that cannot be produced by the vocal tract to clarify the role of the SMA in auditory imagery.

Publication Types:

• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, Non-P.H.S.
• Review

PMID: 11458829 [PubMed - indexed for MEDLINE]

123: Prog Neuropsychopharmacol Biol Psychiatry. 2000 Nov;24(8):1251-73.

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Seizure models: anticonvulsant effects of ECT and rTMS.

Post RM, Speer AM, Weiss SR, Li H.

Biological Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda, MD 20892-1272, USA.

1. A variety of enzymes, peptides, neurotrophic factors and their receptors show complex cascades of alterations with amygdala-kindled seizure progression; some represent compensatory adaptations that could become new targets of therapeutics. 2. Non-convulsant brain stimulation with repetitive transcranial magnetic stimulation (rTMS) may be able to engage some of the neuro-adaptive effects of ECT without the necessity of inducing a seizure. 3. Data from preclinical and clinical studies raise the possibility that non-convulsant stimulation achieved by high or low frequency rTMS may be able to alter neurotransmitters, neuropeptides, and neurotrophic factors, leading to frequency- and region-dependent changes in neural excitability. 4. Individual depressed patients show differential responses to two weeks high vs. low frequency rTMS, as revealed by the inverse correlation of degree of improvement in depression achieved by these two frequencies. 5. Preliminary data from rTMS and positron emission tomography (PET) studies reveal moderately sustained differential effects of rTMS frequency on regional cerebral neural activity in depressed patients. 6. These data suggest the possibility that an individual's level of baseline rCBF or rCMRglu on PET would help predict which rTMS frequency might be the most appropriate treatment for their depression.

Publication Types:

• Review

PMID: 11125852 [PubMed - indexed for MEDLINE]

124: Neurology. 2000 Oct 10;55(7):1025-7.

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Repetitive transcranial magnetic stimulation does not replicate the Wada test.

Epstein CM, Woodard JL, Stringer AY, Bakay RA, Henry TR, Pennell PB, Litt B.

Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA. chipstein@aol.com

The authors compared inferior frontal speech arrest from repetitive transcranial magnetic stimulation (rTMS) with bilateral Wada tests in 17 epilepsy surgery candidates. Although rTMS lateralization correlated with the Wada test in most subjects, rTMS also favored the right hemisphere at a rate significantly greater than the Wada test. Postoperative language deficits were more consistent with Wada results. Available methods for inducing speech arrest with rTMS do not replicate the results of Wada tests.

PMID: 11061262 [PubMed - indexed for MEDLINE]

125: Neuroreport. 2000 Sep 28;11(14):3077-84.

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Enhanced motor cortical excitability in the unaffected hemisphere after hemispherectomy.

Shimizu T, Nariai T, Maehara T, Hino T, Komori T, Shimizu H, Hirai S, Senda M.

Department of Neurology, Tokyo Metropolitan Neurological Hospital, Fuchu, Japan.

We evaluated motor cortical excitability of the unaffected hemisphere in three patients with intractable epilepsy who underwent hemispherectomy, using transcranial magnetic stimulation (TMS) and PET. TMS of the unaffected hemisphere evoked motor responses not only in the contralateral muscles but also in the ipsilateral ones in all the patients. A PET study in one patient showed activation of the unaffected motor cortex by movement of either arm. All of these responses were enhanced after the hemispherectomy, probably due to motor cortical disinhibition by transection of the corpus callosum. The PET study also showed postoperative activation of the premotor area of the unaffected hemisphere. These phenomena indicate posthemispherectomy neuroplastic reorganization leading to preservation of the motor function after the operation.

PMID: 11043527 [PubMed - indexed for MEDLINE]

126: Epilepsy Res. 2000 Sep;41(2):179-89.

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Motor cortex excitability in patients with focal epilepsy.

Werhahn KJ, Lieber J, Classen J, Noachtar S.

Department of Neurology, University of Munich, Germany. werhahnk@ninds.nih.gov

We studied the excitability of the motor cortex using, transcranial magnetic stimulation (TMS) in patients with temporal and extratemporal epilepsy. We applied single and paired-pulse TMS to 15 patients with temporal (n = 7), extratemporal (n = 6) and focal epilepsy lateralised to one hemisphere (n = 2). Patients had no antiepileptic drugs in the last 48 h and were seizure free for 4 h prior to testing. We determined the threshold for EMG responses at rest (RMT), the cortically evoked silent period (CSSP) and intracortical inhibition (ICI, intervals of 2-4 ms) and facilitation (ICF, 7-15 ms) and compared the results to those obtained in 17 normal controls. ICI and ICF was reduced in both hemispheres (P < 0.01. ANOVA) compared to the controls. In the hemisphere of seizure origin ('abnormal') there was a reduction of ICF (P < 0.01) and normal ICI, in the 'normal' hemisphere there was a reduced ICI (P < 0.01) and a slight reduction of ICF (P < 0.05). ICF on the 'abnormal' side was reduced (P < 0.05) compared to the 'normal' hemisphere. RMT was increased in two patients, but group comparison of RMT and CSSP showed no significant differences between patients and controls. The results suggest a remote effect of epileptic activity onto the motor cortex leading to an alteration of activity in local inhibitory circuits.

PMID: 10940619 [PubMed - indexed for MEDLINE]

127: Clin Neurophysiol. 2000 Aug;111(8):1346-52.

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Cortical motor reorganization following early brain damage and hemispherectomy demonstrated by transcranial magnetic stimulation.

Kastrup O, Leonhardt G, Kurthen M, Hufnagel A.

Department of Neurology, University of Essen, Essen, Germany.

BACKGROUND: Transcranial magnetic stimulation (TMS) was utilized to study 7 patients who had undergone hemispherectomy for control of longstanding intractable epilepsy to assess cortical motor reorganization and MEP (motor evoked potentials) ipsilateral to the remaining hemisphere. Five patients were seizure-free post-operatively. All patients displayed a spastic hemiparesis, were able to walk, raise and bend the paretic arm and use the paretic hand to different degrees. METHODS: We examined MEP threshold, site of maximal response to TMS, and latency to the biceps brachii, abductor pollicis brevis and the anterior tibial muscles using a 7 and 12 cm diameter round coil. RESULTS: The following results were obtained: (1) No MEP could be induced to either side by use of the small coil. (2) When using the large coil MEP-threshold was elevated also when stimulating the non-affected hemisphere in comparison to normal controls. (3) Ipsilateral MEP were found to: be non-inducible in two patients, demonstrate largely increased latencies in 3 and be identical to contralateral MEP in two patients. (4) Ipsilateral MEP could be evoked more often in distal than proximal muscles. (5) The site of maximal ipsilateral MEP response was found approximately 2 cm anteriorly to that of the contralateral MEP to the non-affected side of the body (6) No correlation was found between the degree of hemiparesis and inducability of MEP. CONCLUSIONS: The pattern of reorganization of ipsilateral motor control following early brain damage and hemispherectomy appears to be extremely diverse and does not correlate with the degree of neurological impairment.

PMID: 10904214 [PubMed - indexed for MEDLINE]

128: Clin Neurophysiol. 2000 Aug;111(8):1340-5.

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Remote effects of cortical dysgenesis on the primary motor cortex: evidence from the silent period following transcranial magnetic stimulation.

Cincotta M, Borgheresi A, Guidi L, Macucci M, Cosottini M, Lambruschini P, Benvenuti F, Zaccara G.

Unita' Operativa di Neurologia, Azienda Sanitaria N.10 - Firenze, Ospedale S. Maria Nuova, Piazza S. Maria Nuova, 1, 50122, Firenze, Italy. cincotta@unifi.it

OBJECTIVE: In cortical dysgenesis (CD), animal studies suggested abnormal cortico-cortical connections. Cerebral areas projecting to the primary motor cortex (M1) modulate the cortical silent period (CSP) following transcranial magnetic stimulation (TMS). Therefore, we used the CSP to investigate remote effects of CD on the M1. METHODS: A detailed investigation, including single-pulse TMS and electrical nerve stimulation, was performed in 3 consecutive adults with focal CD located outside the M1 and in 18 controls. Two patients with unilateral CD were epileptic and treated with anti-epileptic drugs. One patient with focal CD on both sides had no history of seizures. Neurological examination was normal in all patients. Recordings were made from both first dorsal interosseous muscles. RESULTS: In CD patients, the CSP was significantly lengthened contralaterally to the affected hemispheres. In treated patients with unilateral CD, the interside difference of the CSP duration was also significantly increased. In contrast, excitability threshold, peripheral and corticospinal motor conduction studies, and peripheral as well as ipsilateral silent periods were not significantly modified. CONCLUSIONS: Our findings indicate that focal CD outside the M1 may produce CSP modifications, which are likely due to changes of afferent control.

Publication Types:

• Case Reports

PMID: 10904213 [PubMed - indexed for MEDLINE]

129: Clin Neurophysiol. 2000 Jun;111(6):964-74.

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Contribution of motor cortex in generation of evoked spikes in patients with benign rolandic epilepsy.

Manganotti P, Zanette G.

Department of Neurological Sciences and Vision, Neurology Section, University of Verona, Verona, Italy. manga@gorgoroma.univr.it

OBJECTIVES: Among the different kinds of rolandic epilepsy there is a form of benign epilepsy with centrotemporal spikes (BECT) presenting the peculiar characteristic of evoking rolandic paroxysmal activity, characterized by a spike followed by a slow wave, using electrical stimulation of the fingers. METHODS: We evaluated 7 patients suffering from BECT presenting evoked scalp activity by electrical stimulation of the fingers of the hand. Electrical stimulation was performed using a pair of ring electrodes applied to the thumb. The motor evoked potentials (MEPs) were elicited in hand muscles by transcranial magnetic stimulation (TMS) and were conditioned by the same electrical digital stimulation producing the evoked spikes at interstimulus intervals ranging from 10 to 200 ms. RESULTS: Digital stimulation in epileptic patients produced an increase in MEP amplitude substantially above the normal ranges. MEP facilitation showed a time course overlapping the ascending phase and peak of the evoked spike, whereas no significant MEP changes were found during the early positive peak and the descending phase of the spike, or during the following slow wave. CONCLUSIONS: Several considerations support the hypothesis that the short-lasting M1 facilitation is related to the spread of an abnormal hypersynchronous discharge of the S1 neurones to functionally related motor areas via cortico-cortical connections.

PMID: 10825702 [PubMed - indexed for MEDLINE]

130: Epilepsia. 2000 Jun;41(6):694-704.

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Cortical excitability in cryptogenic localization-related epilepsy: interictal transcranial magnetic stimulation studies.

Cantello R, Civardi C, Cavalli A, Varrasi C, Tarletti R, Monaco F, Migliaretti G.

Neurology and *Statistics Units, Department of Medical Sciences, School of Medicine, "Amedeo Avogadro" University, Novara, Italy. cantello@med.unipmn.it

PURPOSE: To assess whether single-and paired-pulse transcranial magnetic stimulation (TMS) can measure the interictal brain excitability of medicated patients with cryptogenic localization related epilepsy (CLE). Changes in the balance between excitation and inhibition are the core phenomena in focal epileptogenesis. TMS can assess this balance in the primary motor cortex. METHODS: We selected 18 patients with CLE and similar clinical features in whom we located the epileptogenic area reliably, with 11 age-and sex-matched healthy controls. For both motor cortices, we determined the threshold to TMS, the duration of the cortical silent period, and the corticocortical inhibition and facilitation curve. RESULTS: TMS was safe. The more antiepileptic drugs (AEDs) taken by the patients, the higher their threshold to TMS. The silent period duration failed to show significant changes. On paired TMS, a cluster analysis identified a homogeneous subgroup of patients (n = 7) who showed a significantly defective corticocortical inhibition and excess facilitation. With respect to the epileptogenic area, the phenomenon was bilateral in four of these patients, ipsilateral in two, and contralateral in one. The phenomenon was independent of AEDs and many other clinical variables. However, this patient group had a higher seizure frequency and a higher proportion of electroencephalograms (EEGs) showing interictal generalized epileptic discharges than the rest of the patients. CONCLUSION: Paired TMS provided a valuable pathophysiologic insight into the interictal excitatory state of the cortex in CLE. This method can potentially supply useful prognostic clinical information.

Publication Types:

• Comparative Study

PMID: 10840401 [PubMed - indexed for MEDLINE]

131: J Neurol Sci. 2000 May 1;176(1):28-36.

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Afferent and efferent excitabilities of the transcortical loop in patients with dentatorubral-pallidoluysian atrophy.

Touge T, Ichihara N, Ishibashi T, Ikeguchi M, Sasaki I, Takeuchi H.

Third Department of Internal Medicine, Kagawa Medical University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, Japan. touge@kms.ac.jp

To evaluate the excitabilities of the transcortical loop in patients with dentatorubral-pallidoluysian atrophy (DRPLA), we studied somatosensory evoked potentials (SEPs) and evoked EMG responses (V1 and V2) in 10 patients and age-matched controls. In addition, the facilitatory effects of somatosensory inputs on motor evoked potentials (MEPs) were studied in four patients and controls. We observed attenuated or prolonged cervical and subcortical potentials and prolonged middle latency components of SEPs. The amplitudes of V2 in patients were significantly lowered compared to those in the controls, while the amplitudes and latencies of V1 were similar between the two groups. Since V2 was considered as a transcortical reflex, our results suggest reduced excitabilities of the afferent pathway of the transcortical loop in patients with DRPLA. Median nerve stimulation (MNS) 25 to 30 ms preceding transcranial magnetic stimulation (TMS) facilitated MEPs in the thenar muscle in two of the four patients and in the controls. The facilitation of MEPs by MNS tended to be independent of the reduction in V2. Such a result suggests that different neural mechanisms elicit V2 and facilitate MEPs following peripheral nerve stimulation, although further studies are needed. The combination of SEPs, evoked EMG responses and MEPs may be a useful technique to detect abnormalities of input and output coordinations of the transcortical loop.

PMID: 10865089 [PubMed - indexed for MEDLINE]

132: Acta Psychiatr Scand. 2000 Mar;101(3):246-8; discussion 248-9.

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Transcranial magnetic stimulation induces 'pseudoabsence seizure'.

Conca A, König P, Hausmann A.

Department of Psychiatry I, Regional Hospital Rankweil, Austria.

OBJECTIVE: Several studies support the hypothesis of an antidepressive or mood-enhancing effect of repetitive transcranial magnetic stimulation (rTMS) on depressive patients. The most acute concern regarding rTMS is possible seizure induction; therefore, reports on seizure during rTMS are of special significance. METHOD: We describe a case in which high frequency rTMS over the left dorsolatero-prefrontal cortex (DLPC) applied as an add-on antidepressive strategy may have induced a frontal lobe complex partial seizure in a female patient affected by drug-resistant depression. RESULTS: The epileptic seizure was self-limited, and the patient did not report any physical sequelae. The psychopathological improvement, observed immediately after the incident in question, did not last. CONCLUSION: In this case train duration in rTMS, combined with drugs modulating the norepinephrine turnover, may have contributed to the occurrence of this complex partial seizure, which neuroanatomically seems to be localized in the DLPC.

Publication Types:

• Case Reports

PMID: 10721875 [PubMed - indexed for MEDLINE]

133: Epilepsia. 2000 Feb;41(2):240-2.

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Slow-frequency repetitive transcranial magnetic stimulation in a patient with focal cortical dysplasia.

Menkes DL, Gruenthal M.

Department of Neurology, University of Louisville School of Medicine, Kentucky 40292, USA.

PURPOSE: To evaluate the effect of slow-frequency repetitive transcranial magnetic stimulation (SF-rTMS) on interictal epileptiform activity and seizure frequency in a patient with medically refractory partial seizures due to focal cortical dysplasia. METHODS: A 9-cm circular coil was positioned over the area of cortical dysplasia. One hundred stimuli given at 0.5 Hz at 5% below motor threshold were given biweekly for four consecutive weeks. The EEG was recorded for 30 min before and after the first 100 stimuli. The number of seizures during the month of stimulation was compared with that of the month before stimulation. RESULTS: Stimulation was associated with a 70% reduction in the frequency of seizures and a 77% reduction in the frequency of interictal spikes. No seizures occurred during stimulation. CONCLUSIONS: SF-rTMS was safe and well tolerated in this patient. The reduction in seizures and interictal spikes associated with SF-rTMS supports the concept of SF-rTMS-induced cortical inhibition.

Publication Types:

• Case Reports

PMID: 10691123 [PubMed - indexed for MEDLINE]

134: Neurology. 1999 Oct 22;53(7):1462-7.

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Motor cortex localization using functional MRI and transcranial magnetic stimulation.

Macdonell RA, Jackson GD, Curatolo JM, Abbott DF, Berkovic SF, Carey LM, Syngeniotin A, Fabinyi GC, Scheffer IE.

Department of Neurology, Austin & Repatriation Medical Centre, Victoria, Australia.

OBJECTIVE: Congenital brain lesions producing focal seizures may be accompanied by reorganization of the areas responsible for motor and sensory functions within the brain due to a phenomenon that has been termed "neuronal plasticity." This can be studied using functional MRI (fMRI) and transcranial magnetic stimulation (TMS). Using either method, the motor cortex can be localized noninvasively, but to date there have been few studies correlating the level of agreement between the two techniques. METHODS: We used fMRI and TMS to localize the motor cortex in a young woman with intractable focal seizures, congenital left arm weakness, and a dysplastic right hemisphere on MRI. RESULTS: There was excellent agreement in the localization of motor representation for each hand. Both were predominantly located in the left hemisphere. fMRI also showed an area of posterior activation in the right hemisphere, but there was no evidence of descending corticospinal projections from this site using TMS, direct cortical stimulation, and Wada testing. CONCLUSIONS: Functional MRI (fMRI) and transcranial magnetic stimulation (TMS) were successfully used to localize cortical motor function before epilepsy surgery. Each technique demonstrated migration of motor function for the left hand to the left motor cortex. After resection of the dysplastic right precentral gyrus there was no permanent increase in weakness or disability. The two techniques are complementary; fMRI indicates all cortical areas activated by the motor task, whereas TMS identifies only those areas giving rise to corticospinal projections.

Publication Types:

• Case Reports
• Comparative Study

PMID: 10534252 [PubMed - indexed for MEDLINE]

135: Neurosci Lett. 1999 Oct 8;273(3):155-8.

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Altered seizure susceptibility after high-frequency transcranial magnetic stimulation in rats.

Ebert U, Ziemann U.

Institute of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany. uebert@pharma.tiho-hannover.de

The long-term effect of repetitive transcranial magnetic stimulation (rTMS) on the susceptibility of amygdala kindling was studied. Two weeks after a single high-frequency rTMS train (120 A/micros, 20 Hz for 3 s), the rats had a 55% higher threshold for induction of epileptic afterdischarges compared with sham-treated or control rats. However, subsequent kindling revealed no difference between rTMS-treated and control rats. Our data suggest that a single rTMS train has long-term effects on the neuronal excitability. These effects may be anticonvulsant and therefore support the safety of rTMS in clinical use.

PMID: 10515182 [PubMed - indexed for MEDLINE]

136: Neuropsychologia. 1999 May;37(5):537-44.

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Repetitive transcranial magnetic stimulation of the dominant hemisphere can disrupt visual naming in temporal lobe epilepsy patients.

Wassermann EM, Blaxton TA, Hoffman EA, Berry CD, Oletsky H, Pascual-Leone A, Theodore WH.

Office of the Clinical Director, NINDS, NIH, Bethesda, MD 20892-1428, USA.

We used repetitive transcranial magnetic stimulation (rTMS) to study visual naming in 14 patients with temporal lobe epilepsy. Ten had left hemisphere language by Wada testing and all experienced speech arrest with rTMS of the motor speech area in the left frontal lobe. One left-hander had speech arrest with stimulation of sites on both sides. Subjects were asked to name pictures or read words presented on a computer monitor. rTMS was delivered on half of the trials. Stimulation sites were the motor speech area in the left frontal lobe, the mirror site on the right, and the left and right mid superior and posterior temporal lobes. rTMS at left hemisphere sites caused more naming errors than did right hemisphere rTMS. All individual subjects, except two who had temporal lobe resections and the one with bilateral speech arrest, produced more naming errors with rTMS of left hemisphere sites. There was no significant effect on word reading. rTMS at the left hemisphere and right frontal sites produced reductions in reaction time for picture naming, but not for word reading. This was observed for both correct and incorrect responses. This study shows that left hemisphere rTMS can disrupt visual naming selectively.

PMID: 10340313 [PubMed - indexed for MEDLINE]

137: J Neurol. 1999 Apr;246(4):250-6.

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The role of the intact hemisphere in recovery of midline muscles after recent monohemispheric stroke.

Muellbacher W, Artner C, Mamoli B.

Ludwig Boltzmann Institute for Epilepsy and Neuromuscular Disorders, Second Department of Neurology, Neurological Hospital of Vienna, Austria.

Transcranial magnetic stimulation (TMS) of the motor cortex was used to study basic mechanisms of motor reorganization after major hemispheric stroke in humans. We sought to clarify the possible role of the intact hemisphere in motor recovery of the lingual muscles, and to evaluate the compensatory use of preexisting uncrossed motor pathways projecting to these midline muscles. TMS and bilateral surface recordings from the lingual muscles were carried out in six selected stroke patients who presented with a unilateral lingual paralysis after a limited monohemispheric ischemia. The first examination was performed during the symptomatic stage (t1) and was repeated after complete recovery of lingual function had been established (t2). The cortical motor output patterns were analyzed and compared with the data from 40 healthy controls. In the controls TMS of either hemisphere invariably produced contralateral and ipsilateral compound muscle action potentials (CMAPs), elicited through crossed and uncrossed central motor pathways, respectively. In most individuals an asymmetric cortical motor output pattern was found, as significantly greater mean CMAPs of shorter onset latencies were recorded from the contralateral lingual muscles than from the ipsitateral responses. In the six patients with a unilateral lingual paralysis a similar pattern was found on initial examination by stimulating the intact hemisphere, whereas TMS of the affected hemisphere failed to elicit any CMAP bilaterally. At t2 all patients had regained normal lingual function. Only one patient showed evidence of a complete recovery of the primarily affected hemisphere, as TMS now elicited normal CMAPs bilaterally. In the remaining five patients the unilateral interruption of the corticonuclear pathways persisted in spite of complete functional recovery. In these subjects the recovery of symmetric lingual movements must be attributed to the intact hemisphere. From this it is concluded that recovery of a unilateral lingual paralysis after restricted monohemispheric lesions is possible without recovery of the cortical motor projections from the affected hemisphere. In these cases the intact hemisphere is responsible for restoration of normal lingual movements, most likely by potentiating the effect of preexisting uncrossed motor pathways.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 10367692 [PubMed - indexed for MEDLINE]

138: Biol Psychiatry. 1999 Mar 15;45(6):759-63.

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Chronic treatment with repetitive transcranial magnetic stimulation inhibits seizure induction by electroconvulsive shock in rats.

Fleischmann A, Hirschmann S, Dolberg OT, Dannon PN, Grunhaus L.

Psychiatry Division, Sheba Medical Center, Ramat Gan, Israel.

BACKGROUND: Studies in laboratory animals suggest that repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive shock (ECS) increase seizure inhibition acutely. This study was designed to explore whether chronic rTMS would also have seizure inhibition properties. METHODS: To this purpose we administered rTMS (Magstim Rapid) and sham rTMS twice daily (2.5 T, 4-sec train duration, 20 Hz) to two groups of 10 rats for 16 days. The rTMS coil was a 50-mm figure-8 coil held directly over the rat's head. Raters were blind to experimental groups. On days 11, 17, and 21 (5 days after the last rTMS) ECS was administered with a Siemens convulsator using three electrical charge levels. Variables examined were the presence or absence of seizures and seizure length (measured from the initiation of the tonic contraction until the end of the limb movement). RESULTS: At day 11 rTMS had no effect on seizures, and both rTMS and sham rTMS animals convulsed equally. At day 17, however, rTMS-treated animals convulsed significantly less (both at presence/absence of seizures, and at seizure length) than sham rTMS animals. At day 21 the effects of rTMS had disappeared. CONCLUSIONS: These findings suggest that rTMS administered chronically leads to changes in seizure threshold similar to those reported for ECS and ECT; however, these effects were short-lived.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 10188006 [PubMed - indexed for MEDLINE]

139: Epilepsia. 1999 Mar;40(3):316-21.

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Cortical excitability in patients after loading doses of lamotrigine: a study with magnetic brain stimulation.

Manganotti P, Bongiovanni LG, Zanette G, Turazzini M, Fiaschi A.

Dipartimento di Scienze Neurologiche e della Visione, Universita' di Verona, Italy.

PURPOSE: Transcranial magnetic stimulation (TMS) of the brain allows the pharmacologic effects of anti-convulsant drugs (AEDs) on the excitability of motor corticospinal pathways to be evaluated in patients with epilepsy and normal subjects. However, no study has yet documented the changes in motor excitability in patients treated with lamotrigine (LTG). We aimed to study the effects of loading doses of LTG on TMS recordings in patients with epilepsy at the beginning of their treatment. METHODS: We investigated single-pulse TMS in six patients with complex partial seizures. The TMS recordings were performed in five sessions before and during 5 weeks of treatment. Motor threshold, motor-evoked potential (MEP) amplitude, cortical silent period, and peripheral conduction velocity were used as parameters of evaluation. LTG was started with a dosage of 25 mg/day until a daily maintenance dosage of 200 mg/day was reached. RESULTS: The motor threshold activation of thenar muscles was significantly increased by LTG after 2 weeks of treatment and was increased in a parallel way to the loading dose of the drug at week 3 and 5 of treatment. The MEP size recorded from the thenar muscles did not show significant changes at high- or low-intensity stimulation. The cortical silent period remained unchanged at low- and high-intensity stimulation. The absolute latency of MEPs after cortical and cervical stimulation was unchanged, as was the central motor conduction time. CONCLUSIONS: Our study documents that loading doses of LTG, administered as monotherapy, progressively increases patients' motor thresholds over short periods.

PMID: 10080512 [PubMed - indexed for MEDLINE]

140: Neuropsychologia. 1999 Feb;37(2):159-67.

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Transcranial magnetic stimulation can measure and modulate learning and memory.

Grafman J, Wassermann E.

Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1440, USA. jgr@box-j.nih.gov

The potential uses for Transcranial Magnetic Stimulation (TMS) in the study of learning and memory range from a method to map the topography and intensity of motor output maps during visuomotor learning to inducing reversible lesions that allow for the precise temporal and spatial dissection of the brain processes underlying learning and remembering. Single-pulse TMS appears to be adequate to examine motor output maps but repetitive TMS (rTMS) appears necessary to affect most cognitive processes in measurable ways. The results we have reviewed in this article indicate that rTMS may have a potential clinical application in patients with epilepsy in whom it is important to identify the lateralization of verbal memory. Single-pulse TMS can help identify changes in motor output maps during training, that may indicate improved or diminished learning and memory processes following a stroke or other neurological insult. Other evidence indicates that rTMS may even have the capability of facilitating various aspects of memory performance. From a research perspective. rTMS has demonstrated site- and time-specific effects primarily in interfering with explicit retrieval of episodic information from long-term memory. rTMS may also be able to modulate retrieval from semantic memory as evidenced by response-time and accuracy changes after rTMS. All these findings suggest that the use of transcranial magnetic stimulation in the study of learning and memory will increase in the future and that it is already a valuable tool in the cognitive neuroscientists' belt.

Publication Types:

• Review

PMID: 10080373 [PubMed - indexed for MEDLINE]

141: Clin Neurophysiol. 1999 Jan;110(1):152-7.

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Facilitation of rhythmic events in progressive myoclonus epilepsy: a transcranial magnetic stimulation study.

Valzania F, Strafella AP, Tropeani A, Rubboli G, Nassetti SA, Tassinari CA.

Divisione di Neurologia, Ospedale Bellaria, Università di Bologna, Italy.

Twelve subjects with progressive myoclonus epilepsy (PME) were studied with transcranial magnetic stimulation (TMS), using single and paired magnetic stimuli at different interstimulus intervals (ISIs), and polygraphic recording. Motor threshold (T) and silent period (SP) were normal. Paired TMS showed a loss of inhibition at 100-150 ms ISI and a marked facilitation at 50 ms ISI of conditioned motor evoked potential (MEP). Polygraphic analysis showed 20 Hz oscillatory activity over the sensorimotor area coupled to contralateral myoclonic jerks. These findings suggest a condition of increased supraspinal excitability and support the evidence of a cortical rhythm in the range of 20 Hz. No direct evidence exists that these findings are mediated by the same intracortical pathway. Furthermore, the normal SP and T suggest that the abnormal excitability is not a constant feature but is evident during rhythmic events.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 10348334 [PubMed - indexed for MEDLINE]

142: J Neurosci Methods. 1999 Jan;86(2):209-19.

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Cerebral function revealed by transcranial magnetic stimulation.

Cracco RQ, Cracco JB, Maccabee PJ, Amassian VE.

Department of Neurology, State University of New York Health Science Center at Brooklyn, 11203-2098, USA.

Although transcranial magnetic stimulation (TMS) has been introduced only recently, it is safe and provides a painless, inexpensive noninvasive method for the evaluation of brain function. Determining central motor conduction time (CMCT) permits assessment of the corticospinal pathways. Mapping the central representation of muscles provides a method for investigating the cortical reorganization that follows training, amputation and injury to the central nervous system. Such studies of human plasticity may have important implications for neurorehabilitation. TMS also provides a method whereby cortical excitability can be noninvasively evaluated, which is likely to have important implications in the study of epilepsy, movement disorders and related conditions. TMS is useful in tracking the flow of information from one brain region to another and in investigations of cognition and functional localization, thereby complementing information obtained using functional imaging techniques, which have superior spatial but inferior temporal resolution. Finally, TMS is currently being investigated as a method for establishing cerebral dominance and as a therapeutic tool in the treatment of depression. Investigations for treatment of other neurologic and psychiatric conditions are likely to be undertaken.

Publication Types:

• Review

PMID: 10065987 [PubMed - indexed for MEDLINE]

143: J Neurol Neurosurg Psychiatry. 1998 Nov;65(5):755-61.

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Motor evoked potentials in unilateral lingual paralysis after monohemispheric ischaemia.

Muellbacher W, Artner C, Mamoli B.

Ludwig Boltzmann Institute for Epilepsy and Neuromuscular Disorders, Second Department of Neurology, Neurological Hospital of Vienna, Austria.

OBJECTIVES: The occurrence of a lingual paralysis after unilateral upper motor neuron lesions is an infrequent clinical phenomenon, and the underlying pathophysiological mechanisms are poorly understood. We studied the cortical motor representations of ipsilateral and contralateral lingual muscles in healthy controls and in a selected group of stroke patients, to clarify the variable occurrence of a lingual paralysis after recent monohemispheric ischaemia. METHODS: A special bipolar surface electrode was used to record the ipsilateral and contralateral compound muscle action potentials (CMAPs) from the lingual muscles after transcranial magnetic stimulation (TMS) of the human motor cortex and peripheral electrical stimulation (PES) of the hypoglossal nerve medial to the angle of the jaw. Four patients with a lingual paralysis (group 1) and four patients with symmetric lingual movements (group 2) after monohemispheric first ever stroke were studied and compared with 40 healthy controls. RESULTS: In controls, TMS of either hemisphere invariably produces CAMPs in the ipsilateral and contralateral lingual muscles, elicited through crossed and uncrossed central motor pathways, respectively. In the 40 healthy controls, TMS of either hemisphere elicited CMAPs of significantly greater amplitudes and shorter onset latencies from the contralateral muscles compared with the ipsilateral responses (p<0.0001). In the patient groups, TMS of the affected hemisphere failed to evoke any CMAP from either lingual side; TMS of the unsevered hemisphere always produced normal ipsilateral and contralateral responses, irrespective of whether the ipsilateral muscles were paralysed or not. CONCLUSIONS: Bilateral crossed and uncrossed corticonuclear projections are invariably existent in humans. After unilateral interruption of these pathways, some people do exhibit a lingual paralysis whereas others do not. The development of a central lingual paralysis is most likely dependent on the ability of the unsevered hemisphere to utilise the pre-existent uncrossed motor projections. The variable availability of these pathways among individual subjects is in good agreement with the inconstant occurrence of a lingual paralysis after restricted monohemispheric lesions.

Publication Types:

• Comparative Study
• Research Support, Non-U.S. Gov't

PMID: 9810951 [PubMed - indexed for MEDLINE]

PMCID: PMC2170332

144: Neuropsychobiology. 1998 Oct;38(3):152-66.

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A history of the use of anticonvulsants as mood stabilizers in the last two decades of the 20th century.

Post RM, Denicoff KD, Frye MA, Dunn RT, Leverich GS, Osuch E, Speer A.

Biological Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda, MD 20892-1272, USA.

Anticonvulsants have moved into an important position as alternatives and adjuncts to lithium carbonate in the treatment of bipolar illness. Work with the nonhomologous model of kindled seizures helped in the choice of carbamazepine as a potential mood stabilizer and in the study of the mechanisms of action of the second generation anticonvulsants carbamazepine and valproate, as well as the putative third generation psychotropic anticonvulsants lamotrigine and gabapentin. Anticonvulsant neuropeptides such as TRH and nonconvulsant approaches with repeated transcranial magnetic stimulation (rTMS) also appear promising.

Publication Types:

• Historical Article

PMID: 9778604 [PubMed - indexed for MEDLINE]

145: Electroencephalogr Clin Neurophysiol. 1998 Jul;107(1):1-7.

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Interictal inhibitory mechanisms in patients with cryptogenic motor cortex epilepsy: a study of the silent period following transcranial magnetic stimulation.

Cincotta M, Borgheresi A, Lori S, Fabbri M, Zaccara G.

Unita' Operativa di Neurofisiopatologia, Azienda sanitaria N.10 Firenze, Ospedale S. Maria Nuova, Italy.

The silent period (SP) following transcranial magnetic stimulation (TMS) of the motor cortex is mainly due to cortical inhibitory mechanisms. The aim of the present study was to investigate these inhibitory phenomena in primary motor cortex epilepsy. We studied the TMS-induced SP in both the first dorsal interosseous (FDI) muscles in 8 patients who suffered from cryptogenic partial epilepsy with seizures starting with clonic movements of the right upper limb. All patients were on chronic medication with antiepileptic drugs. Therefore, besides contrasting the results with 16 age-matched normal controls, we also studied 10 patients receiving similar antiepileptic treatments who suffered from cryptogenic partial epilepsy with seizures characterised by the absence of clonic manifestations. The duration of the SP was bilaterally increased in the patients with clonic seizures when compared with the two other groups of subjects. The SP was longer in the left FDI muscle (contralateral to the side of the clonic manifestation in all the patients). Our findings likely indicate enhanced interictal inhibitory mechanisms in patients with partial epilepsy involving the primary motor cortex. The resulting inhibitory effect could be greater in the intact hemisphere rather than in the affected one, in which the hyperexcitability of the epileptic focus had to be counterbalanced.

Publication Types:

• Comparative Study

PMID: 9743265 [PubMed - indexed for MEDLINE]

146: Epilepsy Res. 1998 Mar;30(1):11-30.

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Transcranial magnetic stimulation: its current role in epilepsy research.

Ziemann U, Steinhoff BJ, Tergau F, Paulus W.

Department of Clinical Neurophysiology, University of Gottingen, Germany.

This paper reviews the current role of transcranial magnetic stimulation (TMS) in epilepsy research. After a brief introduction to the technical principles, the physiology and the safety aspects of TMS, emphasis is put on how human cortex excitability can be assessed by TMS and how this may improve our understanding of pathophysiological mechanisms in epilepsy and the mode of action of antiepileptic drugs (AEDs). Also, potential therapeutical applications of TMS are reviewed. For all aspects of this paper, a clear distinction was made between single-/paired-pulse TMS and repetitive TMS, since these two techniques have fundamentally different scopes and applications.

Publication Types:

• Research Support, Non-U.S. Gov't
• Review

PMID: 9551841 [PubMed - indexed for MEDLINE]

147: Electroencephalogr Clin Neurophysiol. 1997 Dec;105(6):415-21.

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Safety of different inter-train intervals for repetitive transcranial magnetic stimulation and recommendations for safe ranges of stimulation parameters.

Chen R, Gerloff C, Classen J, Wassermann EM, Hallett M, Cohen LG.

Human Cortical Physiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1428, USA.

Induction of a seizure in a normal subject with trains of repetitive transcranial magnetic stimulation (rTMS) applied in close succession suggested that short inter-train intervals, a parameter not considered in our previous safety studies, may not be safe. Here, we evaluate the safety of different inter-train intervals for rTMS in 10 healthy volunteers. Ten rTMS trains at 20 Hz for 1.6 s and a stimulus intensity of 110% of motor threshold (MT) were found to be safe at the inter-train interval of 5 s. However, inter-train intervals of 1 s or less were unsafe for trains of 20 Hz for 1.6 s and stimulus intensities higher than 100% of MT. Based on these results, we propose safety guidelines for inter-train intervals at different stimulus intensities. We also analyzed the stimulus parameters, used in 3 studies, that led to seizures in normal subjects. One seizure was due to short inter-train intervals, one was likely related to intense individual rTMS trains close to the limit of our previous safety recommendations, and one was likely due to a combination of these two factors. To provide an additional safety margin, we suggest reducing the duration for individual rTMS trains by 25% from our previous recommendations. Updated safety tables currently in use at our institution are provided.

Publication Types:

• Clinical Trial

PMID: 9448642 [PubMed - indexed for MEDLINE]

148: Nervenarzt. 1997 Oct;68(10):778-84.

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Comment in:

• Nervenarzt. 1998 Sep;69(9):829-31.

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]

[Article in German]

Brandt SA, Ploner CJ, Meyer BU.

Neurologische Klinik der Charité, Humboldt Universität zu Berlin.

Repetitive magnetic stimulation (rTMS) is a non-invasive, painless method to induce transient activation in circumscript regions of the human cortex. In contrast to TMS with single pulses rTMS allows a more effective stimulation of association cortex and temporary interference with the proper functioning of stimulated areas. Possible applications for examination of the functional anatomy of language lateralisation, memory functions and visual perception are discussed. Possible therapeutic for movement disorders and depression are discussed. On the basis of theoretical considerations and current experience rTMS induced epileptogenic effects are discussed and safety recommendations are given.

Publication Types:

• English Abstract
• Review

PMID: 9441249 [PubMed - indexed for MEDLINE]

149: Neurology. 1997 May;48(5):1398-403.

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Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation.

Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG.

Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.

We studied the effects of low-frequency transcranial magnetic stimulation (TMS) on motor cortex excitability in humans. TMS at 0.1 Hz for 1 hour did not change cortical excitability. Stimulation at 0.9 Hz for 15 minutes (810 pulses), similar to the parameters used to induce long-term depression (LTD) in cortical slice preparations and in vivo animal studies, led to a mean decrease in motor evoked potential (MEP) amplitude of 19.5%. The decrease in cortical excitability lasted for at least 15 minutes after the end of the 0.9 Hz stimulation. The mechanism underlying this decrease in excitability may be similar to LTD. TMS-induced reduction of cortical excitability has potential clinical applications in diseases such as epilepsy and myoclonus. Spread of excitation, which may be a warning sign for seizures, occurred in one subject and was not accompanied by increased MEP amplitude, suggesting that spread of excitation and amplitude changes are different phenomena and also indicating the need for adequate monitoring even with stimulations at low frequencies.

PMID: 9153480 [PubMed - indexed for MEDLINE]

150: Brain Dev. 1997 Mar;19(2):134-7.

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Transcranial magnetic stimulation in benign childhood epilepsy with centro-temporal spikes.

Nezu A, Kimura S, Ohtsuki N, Tanaka M.

Department of Pediatrics, Urafune Hospital of Yokohama City University, Japan.

Motor cortical excitability was studied using transcranial magnetic stimulation (TMS) in 10 age-matched controls, and 13 children with benign childhood epilepsy with centro-temporal spikes (BECT), with a mean age of 11.2 +/- 2.0 years (five untreated, and eight treated with sodium valproate (VPA) and well controlled). Motor evoked potentials (MEPs) elicited by TMS through a circular coil were recorded from the first dorsal interosseous muscle (FDI) while relaxed. There was no significant difference in latency or duration of MEPs, or central motor conduction time among controls, untreated and treated patients. The threshold intensity for TMS in the untreated patients (63.0 +/- 14.8%, mean +/- SD) was similar to that in controls (63.0 +/- 12.5%), while the threshold intensity in the treated patients (79.4 +/- 11.8%) was significantly higher than that in the other groups. A significant increase in threshold intensity (15 +/- 4.1%) was also observed in the untreated patients retested after starting VPA treatment. No adverse effects occurred during TMS in any subjects. Thus, motor cortical hyperexcitability in BECT was not recognized in the present TMS study, while VPA was confirmed to have an effect on the threshold intensity for TMS.

Publication Types:

• Clinical Trial

PMID: 9105661 [PubMed - indexed for MEDLINE]

151: J Neuropsychiatry Clin Neurosci. 1996 Fall;8(4):373-82.

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Transcranial magnetic stimulation: a neuropsychiatric tool for the 21st century.

George MS, Wassermann EM, Post RM.

Department of Psychiatry, Medical University of South Carolina, Charleston 29425, USA. georgem@musc.edu

Neuroscientists have constantly sought new methods of evaluating brain function, with progressive improvement in the last century in imaging brain structure and function. However, except for direct surgical stimulation, neuropsychiatrists can only infer causality between the signal obtained on an image and a behavior or disease. Transcranial magnetic stimulation (TMS) is a new, noninvasive technique for directly stimulating cortical neurons. It has been used to map attention, memory, movement, speech, and vision. Preliminary investigations have also used rapid-rate TMS to improve motor speed in Parkinson's disease and mood in depression. TMS is likely to be an important future neuropsychiatric tool.

Publication Types:

• Research Support, Non-U.S. Gov't
• Review

PMID: 9116472 [PubMed - indexed for MEDLINE]

152: Neuropsychologia. 1996 Aug;34(8):775-83.

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Verbal working memory components can be selectively influenced by transcranial magnetic stimulation in patients with left temporal lobe epilepsy.

Düzel E, Hufnagel A, Helmstaedter C, Elger C.

Clinic of Neurophysiology, University of Magdeburg, Germany.

The aim of this study was to investigate whether transcranial magnetic stimulation (TMS) can be used for a lateralization of verbal and non-verbal memory functions in candidates for epilepsy surgery by inducing focal, material-specific memory deficits. Twenty patients who underwent presurgical epilepsy evaluation with chronically implanted subdural strip electrodes were submitted to focal TMS over the temporal lobes and the vertex while sequences of items of the Digit Span and the Corsi Block test were presented on a computer screen. TMS was applied synchronously or 200 msec following presentation of each item. The effects of TMS on the memory span and the serial position curve were analysed in comparison to baseline levels. The following results were obtained: the quantitative effects on the verbal (Digit Span) and non-verbal (Corsi Block) memory span were not significant, but there were significant qualitative changes of serial position effects. In the group of six patients with left temporal epilepsy, TMS over the left temporal lobe induced a significant recency effect in the Digit Span test, while TMS over the vertex significantly increased the recency errors. The absolute number of errors remained unchanged. No such effects were observed in the group of nine patients with right temporal lobe epilepsy. These results suggest that in the presence of a left temporal lobe focus TMS can induce qualitative, material specific changes in verbal working memory (phonological loop) which become apparent in the serial position curve. The dissociation of TMS effects for temporal and vertex stimulation imply that TMS can selectively influence specific phonological loop components and that the phonological loop has a functionally and neuroanatomically multimodular structure.

Publication Types:

• Comparative Study

PMID: 8817507 [PubMed - indexed for MEDLINE]

153: Acta Neurol Scand. 1996 Jul;94(1):24-30.

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Transcranial magnetic stimulation in partial epilepsy: drug-induced changes of motor excitability.

Michelucci R, Passarelli D, Riguzzi P, Buzzi AM, Gardella E, Tassinari CA.

Department of Neurology, University of Bologna, Bellaria Hospital, Italy.

Single-pulse transcranial magnetic stimulation (s-TMS) with recording of motor evoked potentials (MEPs) from thenar muscles of both hands was performed on 84 patients with cryptogenic partial epilepsy and 50 healthy controls. We analyzed the cortical latency (CL), central conduction time (CCT), and threshold intensity (TI) required to elicit liminal MEPs at rest. In the patients, CL and CCT were normal, but TI was significantly higher than in the controls. Of the 84 patients, 65 were taking one or more antiepileptic drugs and 19 were untreated. The untreated patients had a significantly lower TI than the treated patients. In the treated patients, the TI increase paralleled the number of drugs taken. Additionally, in 2 subgroups of patients undergoing major modifications of antiepileptic treatment, TI dropped after partial withdrawal of medication and increased following the commencement of therapy. The results suggest that anticonvulsants depress the excitability of human motor pathways in epileptic subjects.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 8874589 [PubMed - indexed for MEDLINE]

154: Epilepsy Res. 1996 Mar;23(2):115-22.

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Repetitive transcranial magnetic stimulations of the rat. Effect of acute and chronic stimulations on pentylenetetrazole-induced clonic seizures.

Jennum P, Klitgaard H.

Department of Clinical Neurophysiology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.

Repetitive transcranial magnetic stimulation (RTMS) has been reported to induce epileptic seizures in normal control and in epileptic patients. Therefore we characterized the effect of acute or chronic stimulations with RTMS on the induction of pentylenetetrazole (PTZ)-induced clonic seizures in the rat. Male Wistar rats were stimulated with a 13-cm coil with a stimulus frequency of 50 Hz. The motor threshold (Tm) was determined by a single transcranial stimulus. Acute stimulation was performed with a stimulus intensity of 0.9 x Tm and 1.5 x Tm using a duration of the train of stimuli of five seconds. Chronic stimulation was performed with a duration of the train of stimuli of one and five seconds using a stimulus intensity of 1.8 x Tm, every day for 30 days. Time to onset of PTZ-induced clonic seizure was determined after the acute stimulation or the last stimulation in chronic RTMS. In the groups of rats receiving acute RTMS (0.9 and 1.5 x Tm) no seizures developed. No differences were observed in time to onset of clonic seizures after PTZ injection compared to control rats. In the group of rats receiving chronic RTMS some rats showed facial contractions, chewing or head movements during or immediately after the stimulations. None of the rats developed tonic or clonic seizures in relation to RTMS. Time to onset of PTZ clonic seizures was reduced in both groups receiving RTMS with a stimulus duration of one (P < 0.01) and five (P < 0.05) seconds compared to control rats. The results from this study suggest that acute suprathreshold stimulation with a stimulus frequency of 50 Hz does not affect the induction of clonic PTZ seizures, whereas chronic (daily) stimulations have a facilitatory effect. This indicates that chronic stimulation with RTMS may induce a kindling process in the rat. Chronic RTMS stimulation may therefore represent an interesting alternative non-invasively kindling model to chemical and electrical stimulations.

PMID: 8964272 [PubMed - indexed for MEDLINE]

155: Adv Neurol. 1995;67:181-97.

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Epileptic negative myoclonus.

Tassinari CA, Rubboli G, Parmeggiani L, Valzania F, Plasmati R, Riguzzi P, Michelucci R, Volpi L, Passarelli D, Meletti S, et al.

Department of Neurology, University of Bologna, Bellaria Hospital, Italy.

ENM is an etiologically heterogeneous disorder clinically evident as brief (less than 500 msec) lapses of tonic muscular contraction which seems to be related to lesions or dysfunction of different anatomofunctional levels of the CNS (Fig. 13). ENM can occur in heterogeneous epileptic disorders, ranging from benign syndromic conditions (such as BECTS) to focal static lesional epilepsy, as in neuronal migration disorders, and even to severe static or progressive myoclonic encephalopathies (PMEs). Neurophysiological studies in patients with ENM lead to the following conclusions: 1. A cortical origin of ENM is supported by EEG mapping and dipole analysis of spikes related to the ENM. In particular, our data suggest that the focal spike is a paroxysmal event involving, primarily or secondarily, the centroparietal and frontal "supplementary" motor areas. 2. A cortical inhibitory active mechanism for the genesis of ENM is supported by the occurrence of a decreased motor response to TMS, with preserved spinal excitability as demonstrated by the persistence of F waves. A "cortical motor outflow inhibition" related to spike-and-wave discharges was suggested by Gloor in his Lennox lecture (34). The cortical reflex negative myoclonus, described by Shibasaki et al. (16) in PME, is also consistent with a cortical active inhibitory mechanism. The spike associated with ENM raises new issues about the definition of "interictal" versus "ictal" EEG paroxysmal activity. A single spike on the EEG can be clinically silent (therefore, "interictal") or clinically evident as ENM (then viewed as "ictal"), depending on whether a given group of muscles is at rest or is showing tonic activity (see Fig. 4). These data, from a more general perspective, imply that the motor manifestation related to EEG paroxysmal events can depend not only on amplitude, topography, or intracortical distribution of seizure activity (35), but also on plasticity (36) and on the functional condition of the motor system (37). The variability of latency between the spike and the onset of the muscular inhibition (ranging from 15 to 50 msec, for the upper limbs), and the variability of duration of the ENM itself (from 50 to 400, or more, msec) indicate that ENM could be the result of inhibitory phenomena arising not only from a single cortical "inhibitory" area, but also from subcortical and pontine structures, as discussed by Mori et al. (this volume). The neurophysiological distinction between ENM and postmyoclonic periods of muscular suppression, mainly related to an EGG slow wave, as described by Lance and Adams (2) in the postanoxic action myoclonus is still a matter of discussion (38, 39). This is also the case for other movement disorders combining action myoclonus and epilepsy-as described in Ramsay Hunt syndrome (30), now better referred to as Unverricht-Lundborg syndrome (40) (Fig. 14). In these conditions, myoclonia and muscular silent periods are inconstantly associated with paroxysmal EEG discharges, suggesting a possible thalamocortical mechanism rather than a purely cortical one. In the most prolonged muscular inhibitions, both cortical and thalamocortical mechanisms might be implicated. Clearly, our knowledge of ENM is still very limited and gaining further insights into this complex phenomenon is a challenging problem.

Publication Types:

• Research Support, Non-U.S. Gov't
• Review

PMID: 8848969 [PubMed - indexed for MEDLINE]

156: Electroencephalogr Clin Neurophysiol. 1995 Jan;94(1):19-25.

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Epileptic seizures triggered directly by focal transcranial magnetic stimulation.

Classen J, Witte OW, Schlaug G, Seitz RJ, Holthausen H, Benecke R.

Neurologische Klinik der Heinrich-Heine-Universität, Düsseldorf, Germany.

Focal, secondarily generalizing, epileptic seizures were released by magnetic stimulation in a patient with focal epilepsy. The stimulation induced seizures had a similar clinical appearance to the patient's spontaneous seizures. They were released exclusively by an angulated "figure-of-8" coil which stimulates the brain more focally as compared to the commonly used flat round coil. The epileptic focus could be located in the left frontal cortex by electroencephalographic recordings, by magnetic resonance and by positron emission tomography imaging. Functional assessment of the motor system by transcranial magnetic stimulation (TMS) disclosed markedly prolonged electrical silence of contralesional electromyographic activity following the early excitation. This is the first EMG-documented demonstration of a focal motor seizure directly triggered by magnetic brain stimulation.

Publication Types:

• Case Reports
• Research Support, Non-U.S. Gov't

PMID: 7530636 [PubMed - indexed for MEDLINE]

157: Neurology. 1994 Sep;44(9):1697-700.

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Rapid-rate transcranial magnetic stimulation and hemispheric language dominance: usefulness and safety in epilepsy.

Michelucci R, Valzania F, Passarelli D, Santangelo M, Rizzi R, Buzzi AM, Tempestini A, Tassinari CA.

Department of Neurology, University of Bologna, Bellaria Hospital, Italy.

We performed rapid-rate transcranial magnetic stimulation (r-TMS) in 14 epileptic patients, using a coil centered over nine different positions on each side of the scalp and while the subjects counted aloud. We obtained lateralized speech arrest, concordant with the site of manual preference, in only seven patients. There was transitory homonymous hemianopia (one patient), brief jerking of one arm (two patients), and affective (crying) reaction (three patients) after the end of a train of stimuli. In our experience, r-TMS is not as sensitive as previously reported for determination of hemispheric language dominance and may have undesirable side effects.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 7936299 [PubMed - indexed for MEDLINE]

158: Epilepsy Res. 1994 Jun;18(2):167-73.

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EEG changes following repetitive transcranial magnetic stimulation in patients with temporal lobe epilepsy.

Jennum P, Winkel H, Fuglsang-Frederiksen A, Dam M.

Department of Clinical Neurophysiology, Hvidovre Hospital, University of Copenhagen, Denmark.

Transcranial magnetic stimulation (TMS) has been proposed as an epileptogenic activating procedure in the evaluation of patients with partial epilepsy. With the introduction of repetitive (rapid rate) transcranial magnetic stimulation (RTMS), it has been possible to apply cortical stimuli with a stimulus rate up to 50 Hz. This study was conducted in order to evaluate the epileptogenic effect of RTMS. Ten patients suffering from medically intractable temporal lobe epilepsy were included. As a part of the presurgical evaluation all patients were studied with ictal video-EEG scalp recordings during a period of discontinuation of the antiepileptic treatment. Eight RTMS trains were applied to left and right temporal and frontal areas, using a stimulus intensity of 1.2 x Tm (the motor threshold to a twitch in the right hand), a stimulus duration of 1 s and a stimulus frequency of 30 Hz. 50 Hz stimulations, with a stimulus duration of 1 s and a stimulus intensity of 1.2 x Tm, were applied on both anterior temporal regions, in total 10 TMS and 340 RTMS pulses to each patient. The numbers of sharp waves/spikes and low-frequency potentials were lower (P < 0.01) compared to prestimulus values and returned to prestimulation values within 10 min. In no cases paroxysmal activity was provoked and no seizures developed. The study indicates that RTMS as used in this study is not effective as an activation procedure for paroxysmal activity. As the risk of seizures may depend on the stimulus parameters, further studies are needed in order to evaluate the safety of the RTMS.

Publication Types:

• Clinical Trial

PMID: 7957039 [PubMed - indexed for MEDLINE]

159: No To Hattatsu. 1994 May;26(3):239-45.

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[Polygraphical sleep study on typical absence: relationship between the effect of sodium valproate and nigrostriatal function]

[Article in Japanese]

Hasegawa T, Shimohira M, Itoh M, Hayashi M, Kohyama J, Kumada S, Iwakawa Y.

Department of Pediatrics, Tokyo Medical and Dental University.

In order to clarify the mechanism of the effect of sodium valproate (VPA) on absence seizures, we performed sleep polygraph recordings in 10 patients with typical absence. VPA was effective in six cases (group A), partially effective in two (group B), and ineffective in two (group C). In 5 of 9 cases, the tonic sleep components were abnormal. In 4 cases, the percentage of slow wave sleep increased before administration of VPA, and did not change remarkably by its administration. In group A and B, twitch movements (TM), one of the phasic sleep components detected in the mentalis muscle on surface EMG, decreased or were unchanged after administration of VPA, especially during the REM period. In contrast, TM increased in group C. We speculate that the changes of TM (especially in the REM periods) after administration of VPA are well related to its effectiveness. Since TMs are thought to be controlled by the nigrostriatal dopaminergic pathway, the different response of basal ganglia to VPA among cases with absence epilepsy would have some relation to the different effectiveness of VPA in controlling seizures.

Publication Types:

• English Abstract

PMID: 8185977 [PubMed - indexed for MEDLINE]

160: Neurology. 1994 Feb;44(2):269-73.

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Speech localization using repetitive transcranial magnetic stimulation.

Jennum P, Friberg L, Fuglsang-Frederiksen A, Dam M.

Department of Clinical Neurophysiology, Hvidovre Hospital, Denmark.

To evaluate whether repetitive transcranial magnetic stimulation (RTMS) may be used for speech localization, we compared the results from RTMS with the intracarotid amobarbital test (IAT) in 21 patients undergoing surgical treatment (amygdalohippocampectomy or anterior temporal lobe resection) for medically intractable partial epilepsy. None of the patients had aphasia. We stimulated the temporal and frontal cortex on each side at a frequency of 30 Hz for 1 second and increased the intensity until speech was inhibited. A list of words and forward and backward counting were used to test speech function. The IAT was performed on the hemisphere of proposed surgery by unilateral injection and simultaneous regional cerebral blood flow (rCBF) recordings. In one patient, there was doubt about hemisphere dominance and a second bilateral IAT was performed. Fifteen patients had left-sided speech dominance; one, left-sided dominance and a moderate right-sided speech inhibition; two, right-sided speech dominance; and one, bilateral speech representations (bilateral injection at the IAT) with both techniques. One patient showed bilateral with right-sided speech dominance by RTMS and showed right-sided speech inhibition with right-sided injection only at the IAT procedure. One patient differed from the rest, showing bilateral representations with right-sided speech dominance with RTMS and left-sided speech inhibition by IAT with left-sided injection only. The concordance was 95%. None of the patients had seizures provoked by the procedure. We conclude that speech localization with RTMS shows a high concordance with the results from the IAT and may be useful in addition to traditional techniques in speech localization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 8309572 [PubMed - indexed for MEDLINE]

161: Acta Neurol Scand Suppl. 1994;152:93-6.

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Transcranial magnetic stimulation. Its role in the evaluation of patients with partial epilepsy.

Jennum P, Winkel H.

Department of Clinical Neurophysiology, Hvidovre Hospital, Copenhagen, Denmark.

Transcranial magnetic stimulation (TMS) is a relative new method in the evaluation of patients with various neurological diseases. With the introduction of repetitive (rapid rate) transcranial magnetic stimulators (RTMS), it has been possible to apply cortical stimuli with a stimulus rate up to 100 Hz. The preliminary results with TRMS suggest that it may be used in the study of speech lateralization. Seizures have been reported in patients with partial epilepsy during TMS. In these cases it remains uncertain whether the seizures were induced by the TMS or coincidentally with it. Minor changes in paroxysmal activity have been reported in some patients. These data suggest, that TMS is neither sensitive nor specific as an activation procedure of the epileptic focus in patients with partial epilepsy. Seizures have been provoked using RTMS, but its use as a seizure-inducing method is not yet evaluated.

PMID: 8209666 [PubMed - indexed for MEDLINE]

162: Clin Electroencephalogr. 1993 Jan;24(1):1-5.

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Transcranial magnetic stimulation (TMS) of the brain in patients with mesiotemporal epileptic foci.

Steinhoff BJ, Stodieck SR, Zivcec Z, Schreiner R, von Maffei C, Plendl H, Paulus W.

Department of Neurology, Ludwig-Maximilians-Universität, Munich, Germany.

Transcranial magnetic stimulation (TMS) of the human brain is mainly used for the diagnosis of diseases with disturbed central motor conduction. Recent studies revealed controversial results concerning the possibility of a TMS-induced specific activation of epileptogenic foci in patients with localization-related epilepsies, which would make TMS an additional diagnostic tool for the presurgical localization of the primary epileptogenic zone. We applied TMS to 19 patients with complex-partial seizures and investigated its effects and safety. In 12 patients we performed TMS during scalp electroencephalogram (EEG) recordings. The remaining 7 patients with localization-related epilepsies of mesiobasal limbic seizure origin underwent EEG with additionally implanted foramen-ovale-electrodes (FOE). We did not notice any significant spike activation and even observed bilateral reduction of epileptic activity in some patients. On the contrary, hyperventilation induced a marked activation of the epileptic focus. Our findings support that TMS is safe since adverse effects did not occur. However, due to possible safety hazards, TMS in epileptic patients still requires cautious application until more data will be available.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 8420691 [PubMed - indexed for MEDLINE]

163: J Clin Neurophysiol. 1993 Jan;10(1):111-5.

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Hyperventilation and transcranial magnetic stimulation: two methods of activation of epileptiform EEG activity in comparison.

Schüler P, Claus D, Stefan H.

Department of Neurology, University Erlangen-Nürnberg, Germany.

In a prospective study, we compared the established method for an activation of epileptiform activity in EEG, hyperventilation (HV), with the recently presented new activational technique of transcranial magnetic stimulation (TMS) in 10 patients with drug-resistant partial epilepsies. Long-term EEG recordings included subdural electrodes in the course of presurgical evaluation. Epileptiform activity was evaluated visually 500 s before, during, and 500 s after stimulation, and the results were compared statistically. TMS was not better than HV: HV caused an activation of the epileptogenic foci in 6 of 10 cases, TMS only in 3 of 10. Seizures could be induced by HV in 2 of 10, by TMS in no cases. In 2 of 10 cases, TMS even caused a significant reduction of epileptiform activity.

PMID: 8458990 [PubMed - indexed for MEDLINE]

164: Nervenarzt. 1992 Aug;63(8):492-4.

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[Transcranial magnetic stimulation of patients with a single epileptic seizure]

[Article in German]

Liepert J, Tegenthoff M.

Neurologische Klinik, BG-Krankenanstalten Bergmannsheil, Ruhruniversität Bochum.

Transcranial magnetic stimulation (TMS) was performed in 21 patients who had had loss of consciousness of unknown origin, in order to find out whether TMS could help in finding the cause of unconsciousness and to estimate the risk of provoking a seizure in patients who had single fits in the past. Furthermore, EEG recordings with hyperventilation, photostimulation, 24-hour EEG and sleep-deprivation EEG's were carried out as well as CCT or NMR investigation. In 15 patients the loss of consciousness was judged to be due to an epileptic seizure. None of the 21 patients had epileptic potentials in EEG recordings or showed an epileptic seizure during or after TMS, hyperventilation or photostimulation. One patient developed spike-wave activity in the sleep-deprivation EEG, another in the 24-hour EEG. On the basis of our results and previous reports, TMS does not seem to be helpful in the diagnosis of loss of consciousness of unknown origin. However, TMS can be used more liberally than hitherto in the study of motor pathways, in cases with a history of single epileptic seizures.

Publication Types:

• English Abstract

PMID: 1522935 [PubMed - indexed for MEDLINE]

165: Epilepsia. 1992 May-Jun;33(3):504-8.

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Lack of pathologic changes in human temporal lobes after transcranial magnetic stimulation.

Gates JR, Dhuna A, Pascual-Leone A.

Minnesota Epilepsy Group, P.A., St. Paul 55102.

Most animal studies have failed to demonstrate pathologic changes in the brain after transcranial magnetic stimulation (TMS). Nevertheless, vacuolar lesions in the cortex of rats after TMS have been reported. We report the first histopathologic studies of human brains after TMS in 2 patients with epilepsy who underwent temporal lobectomies. They had been involved in a study to determine the speech-dominant hemisphere by TMS and had received approximately 2,000 stimuli centered over the resected temporal lobe. Histologic study of the surgical specimens did not show any lesions attributable to TMS in these 2 patients.

PMID: 1592028 [PubMed - indexed for MEDLINE]

166: Neurology. 1991 Jul;41(7):1067-71.

Related Articles, Links

Comment in:

• Neurology. 1992 Jul;42(7):1429-30.

Transcranial magnetic stimulation in patients with epilepsy.

Dhuna A, Gates J, Pascual-Leone A.

Department of Neurology, University of Minnesota, Minneapolis 55455.

We studied the effects of transcranial magnetic stimulation (TMS) applied in trains of 8- to 25-Hz stimuli on electroencephalographic epileptiform activity on eight patients being evaluated for epilepsy surgery. We performed the stimulation with a round water-cooled stimulation coil held flat on the scalp and centered over different positions of the International 10-20 System. We were unable to trigger seizures or induce epileptiform discharges arising from the epileptic focus in any of the eight patients with any of the stimulation protocols. However, we induced a partial motor seizure from the contralateral hemisphere to the exclusive temporal focus in the only patient stimulated with 100% maximal intensity. Precautions have to be taken when applying rapid TMS to patients because of the risk of seizure induction. Our results do not support the view that TMS specifically activates the epileptic foci.

Publication Types:

• Comparative Study

PMID: 2067635 [PubMed - indexed for MEDLINE]

167: Neurology. 1991 May;41(5):697-702.

Related Articles, Links

Comment in:

• Neurology. 1991 Oct;41(10):1705-7.

Induction of speech arrest and counting errors with rapid-rate transcranial magnetic stimulation.

Pascual-Leone A, Gates JR, Dhuna A.

Department of Neurology, University of Minnesota, Minneapolis.

Six adult epileptic patients underwent rapid-rate transcranial magnetic stimulation (rTMS) at stimulation rates of up to 25 Hz with an 11-cm water-cooled round coil held flat on the scalp, centered over 15 different positions on each side of the scalp. The trains of stimuli were for 10 seconds while the patients counted aloud. rTMS centered over D5 or D7 induced reproducible speech arrest in all patients and counting errors in three when applied at lower intensities. There were no such speech disturbances by rTMS centered over the different positions on the right side. Intracarotid amobarbital test (IAT) demonstrated left hemispheric language dominance in all patients. Lateralization of speech arrest induced by rTMS correlated with the IAT results and may be helpful for noninvasive determination of hemispheric language dominance.

PMID: 2027485 [PubMed - indexed for MEDLINE]

168: Electroencephalogr Clin Neurophysiol Suppl. 1991;43:170-9.

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The safety of transcranial magnetic stimulation reconsidered: evidence regarding cognitive and other cerebral effects.

Bridgers SL.

CNS Medical Research Miles Inc., Pharmaceutical Division, West Haven, CT.

The potential of transcranial magnetic stimulation (TMS) to cause undesired or unexpected effects on cognition and other cerebral functions has received only limited study, although extensive clinical use has suggested that obvious problems are unlikely. Evidence so far accumulated suggests that exposure to TMS in the expected clinical situations will have no persistent effects on the electroencephalogram (EEG) or on cognitive function, although transient effects may occur. The absence of increases in either prolactin or adrenocorticotropic hormone (ACTH) in subjects undergoing TMS indicates that seizure-like events do not routinely occur, although recent evidence suggests that TMS may cause seizures or enhance the occurrence of epileptiform abnormalities in circumstances of heightened susceptibility. Despite these observations, treated seizure patients are unlikely to experience seizures with TMS. The technique is generally safe, but not entirely free from unwanted effects, and further study to define those effects is warranted.

Publication Types:

• Review

PMID: 1663448 [PubMed - indexed for MEDLINE]

169: Br J Pharmacol. 1990 Aug;100(4):800-6.

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Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: calcium current reduction.

Coulter DA, Huguenard JR, Prince DA.

Department of Neurology and Neurological Sciences, Stanford University Medical Center, CA 94305.

1. Succinimide derivatives can be either convulsant (tetramethylsuccinimide (TMS)), or anticonvulsant (ethosuximide (ES); alpha-methyl-alpha-phenylsuccinimide (MPS)). ES, an anticonvulsant succinimide, has previously been shown to block calcium currents of thalamic neurones, while the convulsant succinimide TMS blocks gamma-aminobutyric acid (GABA) responses in a similar fashion to the convulsant pentylenetetrazol (PTZ). 2. Using voltage-clamp techniques, we analysed the effects of the anticonvulsant succinimides ES and MPS and the convulsants TMS and PTZ on calcium currents of acutely isolated thalamic relay neurones of the rat. 3. MPS and ES reduced low-threshold calcium current (LTCC) in a voltage-dependent manner, without affecting steady-state inactivation. MPS was less potent than ES (IC50 of 1100 vs 200 microM) but greater in efficacy (100% maximal reduction vs 40% for ES). 4. PTZ had no effect on calcium currents, and TMS only reduced LTCC at very high concentrations, and did not occlude MPS effects when applied concurrently. 5. These results, which demonstrate that anticonvulsant, but not convulsant, succinimides block LTCC, provide additional support for the hypothesis that LTCC reduction is a mechanism of action of the anticonvulsant succinimides related to their effects in petit mal epilepsy.

Publication Types:

• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, P.H.S.

PMID: 2169941 [PubMed - indexed for MEDLINE]

PMCID: PMC1917607

170: Br J Pharmacol. 1990 Aug;100(4):807-13.

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Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: GABA current blockade.

Coulter DA, Huguenard JR, Prince DA.

Department of Neurology and Neurological Sciences, Stanford University Medical Center, CA 94305.

1. Currents evoked by applications of gamma-aminobutyric acid (GABA) to acutely dissociated thalamic neurones were analysed by voltage-clamp techniques, and the effects of the anticonvulsant succinimides ethosuximide (ES) and alpha-methyl-alpha-phenylsuccinimide (MPS) and the convulsants tetramethylsuccinimide (TMS), picrotoxin, pentylenetetrazol (PTZ), and bicuculline methiodide were assessed. 2. TMS (1 microM-10 microM) reduced responses to iontophoretically applied GABA, as did picrotoxin (0.1-100 microM), PTZ (1-100 mM) and bicuculline (1-100 microM). 3. ES, in high concentrations (1-10 mM), reduced GABA responses to a lesser extent, and also occluded the reductions in GABA-evoked currents produced by TMS, picrotoxin, and PTZ. ES did not occlude the effects of bicuculline on GABA responses. Therefore, we propose that ES acts as a partial agonist at the picrotoxin GABA-blocking receptor. 4. MPS had no effect on GABA responses (at a concentration of 1 mM), and, like ES, occluded the GABA-blocking actions of TMS, apparently acting as a full antagonist. 5. The anticonvulsant actions of ES and MPS against TMS and PTZ-induced seizures may thus involve two independent mechanisms: (1) the occlusion of TMS and PTZ GABA-blocking effects; and (2) the previously described specific effect of ES and MPS on low-threshold calcium current of thalamic neurones. The latter cellular mechanism may be more closely related to petit mal anticonvulsant activity.

Publication Types:

• In Vitro
• Research Support, Non-U.S. Gov't
• Research Support, U.S. Gov't, P.H.S.

PMID: 2119843 [PubMed - indexed for MEDLINE]

PMCID: PMC1917578

171: Neurology. 1990 Jul;40(7):1132-3.

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Transcranial magnetic stimulation in epileptic patients: usefulness and safety.

Tassinari CA, Michelucci R, Forti A, Plasmati R, Troni W, Salvi F, Blanco M, Rubboli G.

Neurological Clinic, University of Bologna School of Medicine, Italy.

We studied 58 patients with partial or generalized epilepsy who had transcranial magnetic stimulation (TMS) of the brain motor regions. Short-term monitoring disclosed that the stimulation did not provoke seizures or EEG changes in any patient. Long-term follow-up disclosed that the epileptic condition was not made worse by TMS. TMS, as currently used for monitoring conduction in central motor pathways, does not induce seizures in drug-treated epileptic patients.

Publication Types:

• Research Support, Non-U.S. Gov't

PMID: 2113205 [PubMed - indexed for MEDLINE]