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

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.

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

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.

Effect of low-frequency transcranial magnetic stimulation on an affective go/no-go task in patients with major depression: role of stimulation site and depression severity.

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a therapeutic tool in major depression. However, a means to assess the effects of a single rTMS session on mood to guide subsequent sessions would be desirable. The present study examined the effects of a single rTMS session on an affective go/no-go task known to measure emotional-cognitive deficits associated with major depression. Ten patients with an acute episode of unipolar major depression and eight partially or completely remitted (improved) patients underwent 1 Hz rTMS over the left and right dorsolateral prefrontal cortex prior to task performance. TMS over the mesial occipital cortex was used as a control. We observed significantly improved performance in depressed patients following right prefrontal rTMS. This beneficial effect declined with decreasing depression severity and tended to reverse in the improved group. Left prefrontal rTMS had no significant effect in the depressed group, but it resulted in impaired task performance in the improved group. Our findings indicate that the acute response of depressed patients to rTMS varies with the stimulation site and depression severity. Further studies are needed to determine whether the present paradigm could be used to predict antidepressant treatment success or to individualize stimulation parameters according to specific pathology.

Left prefrontal repetitive transcranial magnetic stimulation impairs performance in affective go/no-go task.

Functional neuroimaging studies have associated affective go/no-go function with lateral prefrontal activation, but they have not established a causal role and have not determined whether one hemisphere is predominantly engaged. In the present study, 11 normal volunteers underwent slow repetitive transcranial magnetic stimulation of the left and right dorsolateral prefrontal cortex, and the occipital cortex prior to performance of a picture-based affective go/no-go task. We found an interfering effect of left prefrontal repetitive transcranial magnetic stimulation compared with both right prefrontal and occipital repetitive transcranial magnetic stimulation. This impairment concerned positive and negative task stimuli to a similar extent, and tended to be greater in shift compared with nonshift blocks. Our findings demonstrate a functionally relevant lateralization of the prefrontal contribution to affective go/no-go tasks.