Single-pulse transcranial magnetic stimulation in amyotrophic lateral sclerosis.

INTRODUCTION: Transcranial magnetic stimulation (TMS) is one of the best methods to identify changes in the corticospinal tract. We used single-pulse TMS at the beginning of the disease and in the follow-up in a group of patients with amyotrophic lateral sclerosis (ALS). METHODS: We evaluated the corticospinal tract in the bulbar, upper, and lower regions in 55 patients with ALS, and we monitored them for a period of 24 months. Data were correlated with clinical scales. RESULTS: An increase of central motor conduction time (CMCT) was the most sensitive marker of upper motor neuron involvement. The resting motor threshold, CMCT, and the central silent period increased linearly with disease duration and upper/lower motor neuron involvement. DISCUSSION: Transcranial magnetic stimulation could be an essential neurophysiological technique in the early phase of ALS because it has been shown to be useful in detecting subclinical upper motor neuron involvement. Multiple evaluations of several regions increase TMS sensitivity.

Effects of slow repetitive transcranial magnetic stimulation in patients with corticobasal syndrome.

Corticobasal syndrome is characterized by asymmetric cortical sensorimotor dysfunction and parkinsonism; an altered cortical excitability has been reported. We explored with transcranial magnetic stimulation the motor cortical excitability in corticobasal syndrome, and the effects of slow repetitive transcranial magnetic stimulation. With transcranial magnetic stimulation, we studied two corticobasal syndrome patients. We determined bilaterally from the first dorsal interosseous muscle: relaxed threshold, and contralateral and ipsilateral silent period. We also evaluated the contralateral silent period after active/sham slow repetitive transcranial magnetic stimulation on the most affected side. At T0 the silent period was bilaterally short. On the most affected side, active slow repetitive transcranial magnetic stimulation induced a short lasting prolongation of the contralateral silent period. In corticobasal syndrome, transcranial magnetic stimulation showed a reduction cortical inhibitory phenomenon potentially reversed transiently by slow repetitive transcranial magnetic stimulation.

Applications of transcranial magnetic stimulation in sleep medicine.

Transcranial magnetic stimulation (TMS) is a new method, developed nearly 20 years ago, that allows the study of cortical excitability. The whole brain undergoes profound changes in sleep. Motor evoked potentials (MEPs) have been used to trace the effects of sleep on cortical excitability and to the corticomotoneuron connections. Although in the past some technical aspects limited the application of TMS in sleep, recently we observed a new explosion of interest in this field. The main body of data was gathered on sleep physiology, but its diseases or syndromes were also studied in detail. Many single and paired pulse-TMS variables were applied. Moreover, TMS variables were investigated as a potential tool for the diagnosis or the differential diagnosis of sleep disorders. In the recent years, the advent of repetitive TMS offered some therapeutic perspectives, which are under current investigation in few of these disorders. Combining repetitive TMS with electroencephalogram (EEG) represents a new and probably useful approach to sleep. Among the main entities classified in the sleep disease group, the following were subject to TMS studies: obstructive sleep apnoea syndrome (OSAS), propriospinal myoclonus, restless legs syndrome (RLS) with periodic limb movement and narcolepsy. For each of these, we examine the applications of TMS separately.

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

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.

Corticospinal physiology in patients with Prader-Willi syndrome: a transcranial magnetic stimulation study.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic developmental disorder, mostly caused by a deletion on the paternal chromosome 15 or by a maternal uniparental disomy 15. Some PWS clinical and neurochemical features suggest an involvement of the corticospinal motor structures. OBJECTIVE: To explore the corticospinal physiology of PWS by transcranial magnetic stimulation. SETTING: A community-based hospital. METHODS: We studied motor evoked potentials in the first dorsal interosseous muscle of 21 young-adult patients with PWS. Thirteen patients had a deletion at chromosome 15; 8 had a uniparental disomy. We measured the following variables: relaxed motor threshold, central motor conduction time, duration of the central silent period, and short-interval intracortical inhibition and facilitation. We also recorded F waves in the first dorsal interosseous muscle. We had 11 normal controls. RESULTS: In the whole PWS group, motor threshold was higher as compared with controls (P<.05). The central motor conduction time, central silent period, and F waves were normal. Intracortical facilitation was reduced significantly (P<.001). Patients with PWS and a deletion had a weaker intracortical inhibition as compared with patients with PWS and a uniparental disomy (P<.05). CONCLUSIONS: Transcranial magnetic stimulation changes in patients with PWS suggested a hypo-excitability of the motor cortical areas. Defective neurogenesis of the cortical tissue and multiple transmitter alterations are the putative causes. Impaired intracortical inhibition might represent an electrical marker for a deletion defect.

Vasogenic erectile dysfunction Topiramate-induced.

Reversible erectile dysfunction due to Topiramate has been linked to the effect of this antiepileptic drug on reproductive hormones levels. We described two epileptic male patients which experienced erectile dysfunction during Topiramate treatment. Serum sexual hormones were tested during treatment and at several time intervals following drug discontinuation. Topiramate did not seem to affect plasma levels of total, free and bioavailable testosterone and sex hormone-binding globulin. Since Topiramate erectile dysfunctions could not be related to changes in reproductive hormones levels, a vasogenic mechanism must be considered.

Motor cortical organization in an adult with hemimegalencephaly and late onset epilepsy.

Hemimegalencephaly is a rare brain malformation whose physiology is largely obscure. In a single patient, we studied motor cortex using several transcranial magnetic stimulation variables testing cortical excitability, and mapping motor area. The megalencephalic hemisphere showed an enlargement of cortical motor map with abnormal axonal orientation and an excess spread of corticospinal excitation, associated with multiple defects of cortical inhibition. TMS gave new information on the anatomic/functional features and epileptogenesis in this complex and physiologically obscure syndrome.

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

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.