The aim of the present study was to investigate the effects of one session of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied over the left dorsal premotor cortex (PMd) and left dorsolateral prefrontal cortex (DLPFC) on choice reaction time in a noise-compatibility task, and cognitive functions in patients with Parkinson's disease (PD). Clinical motor symptoms of PD were assessed as well. Ten patients with PD entered a randomized, placebo-controlled study with a crossover design. Each patient received 10 Hz stimulation over the left PMd and DLPFC (active stimulation sites) and the occipital cortex (OCC; a control stimulation site) in the OFF motor state, i.e. at least after 12 h of dopaminergic drugs withdrawal. Frameless stereotaxy was used to target the optimal position of the coil. For the evaluation of reaction time, we used a noise-compatibility paradigm. A short battery of neuropsychological tests was performed to evaluate executive functions, working memory, and psychomotor speed. Clinical assessment included a clinical motor evaluation using part III of the Unified Parkinson's Disease Rating Scale. Statistical analysis revealed no significant effect of rTMS applied over the left PMd and/or DLPFC in patients with PD in any of the measured parameters. In this study, we did not observe any effect of one session of high frequency rTMS applied over the left PMd and/or DLPFC on choice reaction time in a noise-compatibility task, cognitive functions, or motor features in patients with PD. rTMS applied over all three stimulated areas was well tolerated and safe in terms of the cognitive and motor effects.

fatigue. The pathophysiology of this syndrome remains unclear, although a central dopaminergic dysfunction has been proposed. There are several treatments including levodopa, dopamine agonists, benzodiazepines, and antiepileptic drugs. 1 We report a case of RLS induced by zonisamide. As far as we know there is only one case of zonisamide-induced RLS 2 and none of RLS induced by other antiepileptic drugs.We present a 50-year-old woman, hypertensive without other pathologic antecedents, diagnosed of chronic migraine according to International Headache Society criteria. 3 She had been suffering from headaches for 9 years with no response to several prophylactic drugs including propranolol, flunarizine, topiramate, valproic acid, tryptizol, and oral magnesium. She had developed an abuse of medication of triptans and antiinflammatory drugs.A regimen of zonisamide 50 mg twice daily was established for 14 days and then it was increased till 100 mg twice daily. During titration, the patient complained of an unpleasant sensation in her legs and urge to move them, especially during prolonged periods of inactivity and in the late evening and each episode lasted 20 -40 min. This discomfort was relieved by movement, resulting in motor restlessness and insomnia. She denied occurrence of any similar symptoms in the past and had no relatives with this pathology. However during the treatment with zonisamide, both the frequency and the intensity of the headache improved and there were not more adverse effects associated. Despite this, the treatment with zonisamide was suspended and the symptoms rapidly disappeared. General and neurological evaluations, including jerks were absolutely normal. Serum studies, with complete blood count, electrolytes, renal and liver functions, thyroid stimulating hormone, and serum magnesium levels were within normal levels. Ferritin was normal (73 ng/ml) and iron was in the lower limit (56 g/100 ml).Although zonisamide was originally used as a broad-spectrum antiepileptic agent, it has demonstrated effectiveness in other pathologies like impulse control disorders, chronic pain, 4 or refractory migraine. 5 It has multiple mechanisms of action, including blockage of sodium and T-type calcium channels, inhibition of carbonic anhydrase, inhibition of glutamate release, and dopaminergic activity. In the dopaminergic system, therapeutic doses of zonisamide increase intracellular and extracellular dopamine in the rat striatum. 6 On the contrary, supratherapeutic doses reduce intracellular dopamine. Thus, zonisamide has biphasic effects on the dopaminergic system. In a randomized, double-blind study, this drug has demonstrated to be effective and well tolerated at 25-100 mg/day as an adjunctive treatment in patients with Parkinson disease. 7 Many dopaminergic medications are beneficial for symptomatic relief of RLS, so the effect of zonisamide in our patient is confuse. Whether the biphasic effect may play an important role in the pathogenesis of this syndrome is unknown although other drugs with dopamine...

In addition to controlling motor symptoms, ropinirole improved both anxiety and depressive symptoms in PD patients with motor fluctuations and/or dyskinesias. Changes in mood and anxiety correlated with changes in sleep scores.

We studied whether five sessions of 10 Hz repetitive transcranial magnetic stimulation (rTMS treatment) applied over the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (MC) in advanced Parkinson's disease (PD) patients would have any effect on L-dopa-induced dyskinesias and cortical excitability. We aimed at a randomised, controlled study. Single-pulse transcranial magnetic stimulation (TMS), paired-pulse transcranial magnetic stimulation, and the Unified Parkinson's Disease Rating Scale (UPDRS parts III and IV) were performed prior to, immediately after, and one week after an appropriate rTMS treatment. Stimulation of the left DLPFC induced a significant motor cortex depression and a trend towards the improvement of L-dopa-induced dyskinesias.

Aims: The results of our pilot study suggested that one session of high frequency rTMS applied over the left dorsolateral prefrontal cortex (DLPFC) might induce measurable positive effects on executive functioning in patients with mild cognitive impairment of the vascular type without dementia (MCI-V). The aims of the current study were to replicate the results of our pilot study using a frameless stereotaxy as opposed to the standard and routinely used procedure. We also studied the effects of low frequency rTMS. Patients and method: Seven patients with MCI-V participated in a randomized, controlled, blind study with a crossover design. Each patient received 10 Hz and 1 Hz stimulation over the left DLPFC (an active stimulation site) or the motor cortex (MC; a control stimulation site). Frameless stereotaxy was used to target the DLPFC. The order of sites and frequencies was randomized. A short battery of neuropsychological tests was performed to evaluate executive function, working memory, and psychomotor speed. Results: One session of both high and low frequency rTMS was well tolerated and safe in terms of the cognitive after-effects in patients with MCI-V. We did not observe any significant frequency dependent or stimulation site-dependent cognitive effects of rTMS. Conclusion: We found neither positive nor negative significant effect of either low or high frequency rTMS applied over the DLPFC or the MC, while a mild positive site-specific effect of 10 Hz rTMS was observed in our pilot study on the Stroop interference results. These results suggested that MCI-V is a heterogeneous and poorly defined entity and, thus, rTMS might be useful in a subpopulation of this group of patients.

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