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mise à jour du 20 juin 2002
Arch Neurol
1979: 36; 44-45
Postanoxic action myoclonus
(Lance-Adams syndrome)
responding to valproate
Russell D. Rollinson, Bernard S. Gilligan
Department of Neurology, Bowman Gray School of Medicine, Winston-Salem and the Alfred Hospital, Melbourne
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.

Lance and Adams in 1963 described four cases of action myoclonus in chronic postanoxic states. Since that time, considerable interest has been shown in this condition, particularly since it may result in part from serotonin deficiency in the brain. These cases are clinically similar in that they demonstrate (1) a very mild intellectual deficit; (2) action myoclonus; (3) mild to moderate cerebellar ataxia; and (4) resistance to conventional forms of therapy.

REPORT OF A CASE : In November 1973, a 26-year-old woman nearly drowned in a swimming pool. When found, she had suffered a respiratory arrest and had a profound sinus bradycardia. She was successfully resuscitated, but suffered a prolonged period of anoxia. Her course was stormy. A tracheostomy was done and artificial ventilation was necessary for one week. Her recovery was slow and was severely, hampered by action myoclonus. This involuntary movement disorder prevented the patient from walking alone and she was confined to a wheelchair. The patient had been unconscious for three days postictally. In April 1974, she underwent a thoracotomy for the repair of a tracheal stenosis.

In March 1975, she was admitted to the Neurology Unit of the Alfred Hospital, Melbourne, for investigation and treatment. At that time, examination disclosed a modest, softly spoken woman with many bruises over the extremities a legacy of many falls. The striking abnormality wasthe violent jerking movements involving truncal and proximal musculature; even the muscles of respiration were not spared. These movements were absent when the patient was relaxed and supine, but appeared with anxiety-producing situations and whenever an erect, sitting, or standing posture was attempted. Any effort to walk was in vain, leading to falls, rapid labored respirations, profuse sweating, and tachycardia, and eventually terminated in physical exhaustion. These movements were absent during sleep. There was profound hypotonia of all extremities, withnormal power and symmetrical muscle stretch reflexes. The knee jerks were pendular. The plantar responses were flexor. Sensation was normal. There was mild impairment of finger-to-nose and heel-to-shin testing, and rapid alternating movements were moderately impaired. There was no clinical evidence of dementia, but according to her close friends the patient had suffered a mincir intellectual decline, and retained a period of five months postanoxic amnesia.

The following investigations gave normal findings: complete blood cell count, urinalysis, liver function tests, blood urea nitrogen level, blood glucose level, chest and skull roentgenograms, EEG, electromyography, and peripheral nerve conduction studies. Serial EEGs were not performed.

Therapy was initiated along traditional lines. The following drugs were administered singly and sequentially: diazepam,nitrazepam, carbamazepine, levodopa, and methysergide; only levodopa had a transient beneficial effect. As hydroxytryptophan was not available in this conntry, a trial of valproate sodium (Epilim [GreatBritain]; Depakene, comparable US product) was begun orally. Initially, 200 mg was given twice daily; this was gradually increased to a total of 1,600 mg in four daily doses. At this dosage, the myoclonus abated and the patient for the first time in two years was able to walk unaided. The patient was discharged on this dosage and reviewed monthly with neurological assessment, complete blood cell count, prothrombin time, and liver and renal function tests.Drug levels were also measured regularly.

The patient remained free of and became more communicative and cheerful. She attended a rehabilitation center and was generally able to care for herself. The final maintenance dose was 800mg daily; on this dosage, the serumlevels were 50 to 80 µg/mI. In February 1976, she began to yawn excessively. This proved to be a dose-related side effect. In order to maintain control of the myoclonus and to eliminate the excessive yawning, we added pimozide, 4 mg daily, to the regimen.The yawning disappeared.

In October 1976, the patient was admitted for further assessment, and the drug therapy was stopped. After the drugs had been withdrawn for 12 hours, the patient returned to her status of March 1975 with severe myoclonus. The only additional feature was a moderate degree of hypomania. After the medication had been discontinued for five days, CSF was collected for 5-hydroxyindole acetic acid(5-HIAA) estimation after 24 hours of probenecid therapy. These levels were low (less than 10 ng/ml). Valproate was again administered, with complete resolution of the myoclonus. Computerized tomography (CT) was performed (Figure). This therapeutic response has been maintained.

COMMENT : The cause of the movement disorder in the present case was undoubtedly hypoxia and this is reflected in the widespread abnormalities in the CT scan (Figure). These findings were quite unexpected. The location of the area of reduced attenuation in the anterior aspect of the left temporal lobe must have spared the language area, as at no time did this righthanded patient demonstrate any disorder of language. We have not found any previous examples of the CT findings of this condition in the literature.The pathological substrate of the Lance-Adams syndrome is not clear, although Richardson et all stated that a detailed postmortem study of their case failed to disclose any significant lesion in the midline structures of the brain stem-the site of the highest concentration of serotonin-containing structures. They postulated a functional alteration in serotoninergic activity. Lance and Adams stated that the myoclonus may be produced by the repetitive firing of thalamocortical fibers, mainly from the ventrolateral nucleus, wich is the principal relay nucleus from the cerebellum to the sensorimotor cortex. However, Lhermitte et all in a stereotactic study, were unable to verify this hypothesis. Lhermitte et all have shown that hydroxytryptophan, the precursor of serotonin was therapeutically successful in the Lance-Adams syndrome in a single patient. The CSF levels of 5-HIAA in some patients with this condition have been low. The therapeutic responses in the above cases were reflected in significant rises in the CSF of 5-HIAA after the hydroxytryptophan therapy. The following pharmacological agents have been reported to be of benefit in the Lance Adams syndrome: intravenously given hydroxytryptophan, orally given hydroxytryptophan and carbidopa,` tryptophan, trytophan and a monoamine oxidase inhibitor, levodopa, methysergide, carbamazepine, diazepam, clonazepam, chlorpromazine, and valproate.

Valproate has been found to be of benefit in many different kinds of epilepsy, particularly in the myoclonic varieties. This drug is thought to inhibit both glutamic acid decarboxylase and gamma-aminobutyric acid (GABA) alpha ketoglutarate. Tomlinson postulated that the prevention of GABA degradation might restore inhibition and provide a beneficial effect in myoclonus. The drug is administered orally; common early side effects are nausea, vomiting, and diarrhea. Transient loss of scalp hair bas also been reported. Frequently, patients demonstrate an increased mental alertness, almost hypomania as well. This has led to the suggestion that valproate may also have some effect on serotonin inetabolism. Pimozide is a useful antipsychotic agent that is thought to act as a dopa antagonist. Pimozide bas also been used in several different movement disorders. Valproate therefore may provide another less expensive, relatively safe form of therapy for this disabing condition.



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Arch Neurol
april 1979; vol 36; p253
Drug-induced yawning successfully treated with pimozide
RD Rollinson, WS Wiggins, BS Gilligan
Department of Neurology, Bowman Gray School of Medicine, Winston-Salem and the Alfred Hospital, Melbourne

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 1000 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.
Computarized tomography of the brain demonstrated mild généralized cortical atrophy with area of infarction in the left inferior temporal lobe. Serotonin deficiency was demonstrated.
This pathological yawning seemed to be a dose-related side effect of valproate sodium that has not been previously reported. Pimozide, a dopamine antagonist, was used by Mogilnicka and Klimek to reduce the yawning in rats produced by dopamine agonists; a theorical possibility is that valproate sodium led to the stimulation of dopaminergic neurons, thereby producing the yawning that in turn alleviated by administration of pimozide.