Postanoxic Myoclonus Research Articles

Demonstration of the antimyoclonic effect of 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) using a new animal model

Comparatively high doses of muscimol induces myoclonic jerks in a particular strain of mice. 1-Hydroxy-3-amino-pyrrolidone-2 (HA-966) in doses of 1–10 mg/kg caused a dose-dependent blockade of this response of muscimol. Our earlier studies showed that the muscimol-induced myoclinic jerks fulfill certain criteria necessary to be considered as a valid animal model for postanoxic action myoclonus. On this basis it was concluded that HA-966 might prove to be of value in the management of this disorder.

5-Hydroxytryptamine and myoclonus induced by 1,2-di-hydroxybenzene (catechol) in the guinea-pig.

Myoclonus induced by catechol in the guinea-pig is not altered by manipulation of cerebral 5-hydroxytryptamine (5-HT). The administration of catechol does not alter brain levels of 5-HT or its metabolite 5-hydroxyindole acetic acid. This form of myoclonus therefore is not of relevance to the 5-HT-sensitive post-anoxic action myoclonus occurring in man.

Drug-Induced Yawning Successfully Treated With Pimozide

To the Editor.— We recently had a patient who had postanoxic action myoclonus (Lance-Adams syndrome). This severe movement disorder was completely suppressed with the oral administration of valproate sodium (Epilim [Britain]; Depakene, comparable US product) at a dosage of 1,000 mg daily, with corresponding serum levels of 50 to 80 μg/mL. At these serum levels and while receiving no other therapy, severe uncontrollable yawning developed. This was occurring every two to three minutes. Lowering the dosage of the valproate sodium abolished the yawning, and its reinstitution at the previous level led to its return. Pimozide (Orap), 400 mg daily, was added to the regimen of full dosage of valproate sodium, and the yawning disappeared within one day. Withdrawal of the pimozide caused the yawning to reappear. Computerized tomography of the brain demonstrated mild generalized cortical atrophy with an area of infarction in the left inferior temporal lobe. Serotonin deficiency was

Postanoxic Action Myoclonus (Lance-Adams Syndrome) Responding to Valproate

A patient with postanoxic action myoclonus (Lance-Adams syndrome) was severely disabled with this movement disorder. Valproate sodium was administered orally, with complete resolution of the myoclonus. This favorable response has been maintained for two years. Excessive yawning, the only side effect encountered, was dose related and was abolished with the addition of pimozide to the drug regimen.

Functional independence in post-anoxic myoclonus: contribution of L-5-HTP sodium valproate and clonazepam.

Functional independence in post-anoxic myoclonus: contribution of L-5-HTP sodium valproate and clonazepam.

Post-Anoxic Action Myoclonus: Improvement with Valproic Acid

Post-Anoxic Action Myoclonus: Improvement with Valproic Acid

CLINICAL, BIOCHEMICAL, AND PHYSIOLOGICAL FEATURES DISTINGUISHING MYOCLONUS RESPONSIVE TO 5-HYDROXYTRYPTOPHAN, TRYPTOPHAN WITH A MONOAMINE OXIDASE INHIBITOR, AND CLONAZEPAM

Fifteen patients with a variety of myoclonic syndromes were studied clinically, pharmacologically, and physiologically. CSF tryptophan, 5HIAA, and HVA were also measured. Of these patients, 8 were improved to varying degrees by therapy with 5HTP, tryptophan in combination with MAOI (but not tryptophan alone), and clonazepam. This group included 6 cases of post-anoxic myoclonus, one case of post-traumatic myoclonus and one undiagnosed case of non-progressive focal myoclonus and epilepsy. In this group low levels of CSF 5HIAA were found compared to non-responsive cases and controls. Two cases of dysynergia cerebellaris myoclonica, 2 cases of undiagnosed aetiology, 2 cases of essential myoclonus, and one case of palatal myoclonus failed to respond to drug therapy. However, even amongst the responsive group the improvement varied. The most dramatic responses were seen in those patients in whom physiological study suggested that myoclonus was mediated by brain-stem structures. Less dramatic responses were seen in patients in whom the myoclonus appeared to originate from cortical structures. The neurochemical basis of myoclonus responding to 5HT precursors and clonazepam is discussed. It is suggested that such myoclonus arises from a relative hypoactivity of the 5HT neuronal system which results in a release of abnormal responses to sensory stimuli which characterize this type of myoclonus.

Therapy of intention myoclonus with L-5-hydroxytryptophan and a peripheral decarboxylase inhibitor, MK 486.

Three patients with postanoxic intention myoclonus, two patients with intention tremor, and one patient with cerebral palsy were administered L-5-hydroxytryptophan (L-5HTP), the precursor of serotonin, in combination with MK 486, a peripheral amino acid decarboxylase inhibitor. L-5HTP combined with MK 486 were potent long-term therapeutic agents for postanoxic intention myoclonus, but had no effect on intention tremor or cerebral palsy. These drugs were well-tolerated by the patients, and more effective than any other known therapy for intention myoclonus. Cerebrospinal fluid concentration of 5-hydroxyindoleacetic acid, the main catabolite of serotonin, appeared low in two patients with intention myoclonus and increased markedly during drug therapy. Postanoxic intention myoclonus may be causally related to a deficiency of brain serotonin.