Levetiracetam in L-dopa-induced dyskinesia.

Dyskinesia To the Editor: Levetiracetam is a novel antiepi-leptic drug used in the treatment of the partial crisis as an add-on to other antiepileptic drugs. Although the underlying mechanism of action of levetirace-tam is unknown, the metabolism of GABA appears to be involved. In particular , it may counteract neuronal hyper-synchronization of the firing patterns of neurons in the substantia nigra pars reticulata and internal globus pallidus. 1 Levetiracetam has also been used in the therapy for the paroxysmal kinesigenic choreoathetosis and tardive dyskinesia. The substantia nigra pars reticulata and internal globus pallidus have been hypothesized to be critical areas in the development of dyskinesia. Levetiracetam may, through its peculiar hypersynchronization-inhibiting mechanism, play a role in the control of levodopa-induced dyskinesias, as observed in animal models of PD induced by MPTP at a dose of 60 mg/kg 4,5 as well as in parkinsonian patients (Zesiewicz et al., Paper presented at the 56th annual meeting of the American Academy of Neurology, San Francisco, 2004). Our study included 16 parkinso-nian outpatients with levodopa-induced dyskinesia (Table 1). The patients were fully informed of the aims of the study and all gave their written informed consent. This study was performed using an open-label observational design. The treatment given to the patients, optimized on each patient with the minimum effective dose of levodopa + dopaminergic agonists, was not changed for the duration of the trial. Levetiracetam was given in gradually increasing doses, starting with 125 twice daily (in the morning and in the evening). This dose was increased by 125 mg twice daily every week until a dose of 500 mg twice daily was reached. It was then increased by 500 mg every 5 days up to 2000 mg/day, or until a satisfactory result was achieved. The patients were followed for 3 months by means of monthly checkups performed by the same doctor, at the same hour of the day, and with the patient in the ON phase, using the UPDRS motor scale and AIMS each time: baseline (T0), 1 month (T1), and 3 months (T3). Moreover, the patients and their relatives recorded the presence and severity of the dyskinesia on a flowchart hourly every day and every hour. Eight patients dropped out of the trial. Seven dropped out after the first 2 weeks owing to excessive sleepiness and a sensation of dizziness and confusion. They had not, in the weeks during which they had …