Progressive Myoclonic Epilepsies.
Uthman BM, Reichl A.
University of Florida College of Medicine,
Department of Neurology and Neurosciences,
Malcom Randall Veterans Affairs Medical Center,
Neurology Service (127),
1601 SW Archer Road, Gainesville, FL 32608
Curr Treat Options Neurol 2002 Jan;4(1):3-17
Abstract
The treatment of progressive myoclonus epilepsy (PME) remains a major therapeutic challenge in neurology. Generalized convulsive seizures are often well controlled through classic antiepileptic drugs (AEDs) like valproate and clonazepam, whereas myoclonus, the main symptom that is affecting patients most in their daily life, is usually refractory to standard AEDs. Alternative therapy concepts have been and still are investigated. Among the new drugs, zonisamide and piracetam have shown the most promising results as add-on treatments. Other therapeutic approaches, like the use of antioxidants, 5-hydroxy tryptophan (5-HTP), and baclofen should also be taken into consideration for the treatment of intractable cases of PME. Non pharmacologic treatment options such as diet and physical therapy should always be considered, because they may save costs and side effects. In some instances, the occasional use of alcohol has shown beneficial effects.
Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy.
Fedi M, Reutens D, Dubeau F, Andermann E,
D’Agostino D, Andermann F. FRCP(C)
Montreal Neurological Institute and Hospital,
3801 University St, Room 127,
Montreal, Quebec, Canada H3A 2B4.
Arch Neurol 2001 May;58(5):781-6Abstract
BACKGROUND: Piracetam has been proven to be effective and well tolerated in the treatment of myoclonus in short-term studies.
OBJECTIVE: To assess its long-term clinical efficacy, 11 patients with disabling myoclonus due to progressive myoclonus epilepsy were treated with piracetam in an open-label study.
METHODS: Neurologic outcome (at the 1st, 6th, 12th, and 18th month of treatment) was assessed by an adjusted sum score of the following 3 indices: motor impairment, functional disability, and global assessment of disability due to myoclonus. Severity of other neurologic symptoms (seizure frequency and severity, dysarthria, and gait ataxia) also was assessed. Treatment with piracetam was initiated at a dose of 3.2 g/d that was gradually increased until stable benefit was noted (maximal dose in the trial was 20 g/d). Concomitant antiepileptic drugs were maintained at their previous dose.
RESULTS: Statistically significant improvement in the total rating score was observed after introduction of piracetam at the 1st, 6th, and 12th month of treatment. Severity of other neurologic symptom scores did not improve significantly. Two patients reported drowsiness during the first 2 weeks of treatment.
CONCLUSIONS: Piracetam given as add-on therapy seems to be an effective, sustained, and well-tolerated treatment of myoclonus. In patients with progressive myoclonus epilepsy, the efficacy of the drug increased during the first 12 months of treatment and then stabilized.
A pharmacological profile of piracetam (Myocalm), a drug for myoclonus
Tajima K, Nanri M.
Taiho Pharmaceutical Co.,
Ltd., Tokyo, Japan.
Nippon Yakurigaku Zasshi 2000 Oct;116(4):209-14Abstract
Myoclonus is defined as shock-like, brief involuntary abnormal movements in muscle jerking caused by external stimuli; and it arises from progressive myoclonus epilepsy, post-anoxic encephalopathy and Alzheimer’s disease, causing disabling symptoms. It is a rare syndrome but very difficult to control. Piracetam (2-oxo-1-pyrrolidineacetamide, Myocalm) was developed more than 30 years ago as a cyclic derivative of gamma-amino butyric acid (GABA); it has been used in European countries for the treatment of memory loss and other cognitive defects in patients. Some reports have suggested that piracetam has anti-myoclonus activities, but the mechanisms of myoclonus are not well-identified, and thus there have been few preclinical studies on piracetam for the treatment of myoclonus. We investigated the effect ofpiracetam and clonazepam, an anti-epileptic drug, on high dosage urea-induced myoclonus using an electromyogram in rats. The incidence of myoclonus induced by urea 4.5 g! /k! g (i.p.) was significantly reduced by piracetam at 300 mg/kg (i.p.) and by clonazepam at 0.3 mg/kg (p.o.). The co-administration of piracetam 100 mg/kg (i.p.) and clonazepam at 0.03-0.1 mg/kg (p.o.) significantly reduced the incidence of myoclonus, although separate administration was not effective. After oral administration of piracetam, it is rapidly and completely absorbed and excreted almost unchanged in the urine; however, it does show a little binding to human serum protein. Repeated oral administration of piracetam for 7 days in phase-I trials did not show any accumulation of the drug. In the placebo-controlled double-blind crossover trial ofpiracetam conducted in the UK, there was a significant improvement in cortical myoclonus. In phase-II trials,piracetam inhibited myoclonus and showed an improvement in the quality of life (QOL) of the patients. These results show that piracetam has a beneficial use in clinics for severe myoclonus patients when it is combined with anti-epileptic drugs, demonstrating an improvement in the myoclonus and QOL of patients.
Effectiveness of piracetam in cortical myoclonus.
Brown P, Steiger MJ, Thompson PD, Rothwell JC,
Day BL, Salama M, Waegemans T, Marsden CD.
MRC Human Movement and Balance Unit,
Institute of Neurology, London, England.
Mov Disord 1993;8(1):63-8Abstract
Twenty-one patients with disabling spontaneous, reflex, or action myoclonus due to various causes, who had shown apparent clinical improvement on introduction of piracetam, entered a placebo-controlled double-blind crossover trial of piracetam (2.4-16.8 g daily). All but one patient had electrophysiological evidence of cortical myoclonus. Patients were randomly allocated to a 14-day course of piracetam followed by identical placebo, or placebo followed by piracetam. Nineteen patients received piracetam/placebo in addition to their routine antimyoclonic treatment (carbamazepine, clonazepam, phenytoin, primidone, sodium valproate, or tryptophan plus isocarboxazid, alone or in combination) and two received piracetam/placebo as monotherapy. All patients were rated at the end of each treatment phase using stimulus sensitivity, motor, writing, functional disability, global assessment, and visual analogue scales. Ten of the 21 patients had to be rescued from the placebo phase of the trial because of a severe and intolerable exacerbation of their myoclonus. No patients required rescue from the piracetam phase of the double-blind trial. When the 21 patients were considered together, there was a significant improvement in motor, writing, functional disability, global assessment, and visual analogue scores during treatment with piracetam compared with placebo. The total rating score also improved significantly with piracetam, by a median of 22%. Piracetam, usually in combination with other antimyoclonic drugs, is a useful treatment for myoclonus of cortical origin.
Beneficial effect of piracetam monotherapy on post-ischaemic palatal pmyoclonus
Karacostas D, Doskas T, Artemis N, Vadicolias K, Milonas I. B.
Department of Neurology,
Aristotelian University School of Medicine,
AHEPA Hospital, Thessaloniki, Greece.
J Int Med Res 1999 Jul-Aug;27(4):201-5Abstract
A 70-year-old hypertensive woman suffered a subarachnoid haemorrhage followed by delayed vasospasm in the basal cerebral arteries. This resulted in multiple ischaemic lesions in the right middle cerebral artery region and contralateral post-ischaemic palatal myoclonus. In this setting, piracetamadministered in high doses (24-36 g/day), abolished the myoclonus observed in this patient. Although there is evidence from case reports and clinical trials of the therapeutic efficacy of piracetam in patients with skeletal myoclonus of various causes, to our knowledge this is the first report indicating the beneficial effect of piracetammonotherapy on post-ischaemic palatal myoclonus.
