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H L Klawans

Publications and source records attributed to H L Klawans.

At least 19 recordsLinked to original sources
PubMed1992

Synaptic plasticity in the rat striatum following chronic haloperidol treatment.

Administration of the dopamine (DA) antagonist haloperidol leads to the development of behavioral hypersensitivity as well as enhanced neuronal growth when striatal extracts from these animals are incubated with mesencephalic cultures. For determining if alterations in neuronal growth also occur in vivo, the ultrastructure of the neuropil in the dorsolateral quadrant of the striatum from rats treated (24 days) with haloperidol (1.25 mg/kg) was examined by electron microscopy. Haloperidol-treated rats developed statistically significant behavioral hypersensitivity relative to vehicle-treated controls (p < 0.01). Evaluation of the neuropil revealed that haloperidol treatment enhanced, relative to vehicle-treated controls, the overall number of synaptic boutons by 9% (p < 0.01). The number of perforated synaptic profiles as well as the number of double synapses was increased by 20 and 50%, respectively, although this increase was not statistically significant. The number of myelinated axons remained unchanged, while the number of dendritic spines was increased by 21% (p < 0.05). These data suggest that chronic haloperidol treatment enhanced the growth and possible sprouting of presynaptic neurons and also induced postsynaptic plastic changes. These ultrastructural changes may contribute in part to hypersensitivity behaviors.

Animals↗
PubMed1979

Meiges disease: a clinical form of facial convulsion, bilateral and medial.

In 1910 the French neurologist Henry Meige described in detail a disorder characterized chiefly by symmetric dystonic spasms of the facial muscles, which he called "spasm facial median." Cases with this disorder are rare, and frequently misdiagnosed and inappropriately treated. We report here a translation of Meige's original description of "spasm facial median." We hope that this translation will make it easier to recognize and diagnose this disorder and that it will stimulate greater interest in this unusual syndrome.

Dystonia↗
PubMed1979

Clinical and experimental studies of phenytoin-induced hyperkinesias.

Phenytoin administration occasionally leads to the induction of hyperkinetic movement disorders. The pathophysiologic basis of this phenomena is unknown, but thought to be a toxic effect of phenytoin. Study of two cases of this disorder and a review of the literature suggest that antecedant pathologic changes in the basal ganglia are prerequisites for the development of phenytoin-induced hyperkinesias. In an animal model of tardive dyskinesia, phenytoin was found to enhance neuroleptic-induced behavioral supersensitivity but have no effect in control animals. We conclude that phenytoin induced hyperkinesias reflect a specific effect of phenytoin on an abnormal neural substrate and suggest the presence of an otherwise silent pathological alteration of the corpus striatum. The diagnostic value of an episode of phenytoin-induced hyperkinesia is discussed.

Aged↗
PubMed1979

Chorea induced by oral contraceptives.

A rare complication of oral contraceptive therapy is the induction of chorea. We here describe five cases of chorea in patients receiving low- or high-dose estrogen-containing contraceptives. All patients were nulliparous, young (average age 19 years), and became symptomatic shortly (average of 5 weeks) after initiation of contraceptive therapy. Two patients previously suffered an episode of Syndenham chorea; one experienced chorea in the course of Henoch-Schönlein purpura; and two had a history of congenital cyanotic heart disease without chorea. Dyskinesia resolved in all patients upon discontinuing the medication. Patients with preexisting striatal abnormalities appear more susceptible to oral contraceptive-induced chorea which is reversible on drug discontinuation. The mechanism of oral contraceptive-induced chorea is unknown, but clinical and experimental data suggest that it involves altered central dopaminergic activity.

Adolescent↗
PubMed1979

Dopaminergic antagonism of L-5-hydroxytryptophan-induced myoclonic jumping behavior.

We studied the effect of dopamine agonists (levodopa, apomorphine, lergotrile, and M-7 [2(dimethylamino)5,6-dihydroxytetralin] on myoclonic jumping behavior in young male guniea pigs. All these agents had a significant antagonistic effect on the frequency of this serotonin-mediated behavior. The duration of the antagonism corresponded in all cases to the duration of stereotyped chewing behavior induced by these agents alone. The dopamine antagonist haloperidol potentiated jumping behavior. Therefore myoclonic jumping behavior is influenced by dopaminergic mechanisms, and this behavior may be the result of interaction between dopaminergic and serotonergic activity. The role of dopaminergic mechanisms in human myoclonic disorders needs further clarification.

5-Hydroxytryptophan↗
PubMed1979

Calcification of the basal ganglia: computerized tomography and clinical correlation.

During a 1-year period, 4219 consecutive computerized tomograms (CT) were reviewed for basal ganglia calcification; 14 patients with such calcification were identified. Calcifications on CT scan were bilateral in 12 of these cases and unilateral in 2. All bilateral calcifications were symmetric. The globus pallidus was the site of calcification in 13 of the 14 patients. Bilateral dentate nucleus calcification was seen in one patient. Skull radiograms were normal in all but one. Patients had diverse symptoms that were often explained by other findings, suggesting that calcifications may be coincidental and that basal ganglia calcification may not be a nosologic entity. Disturbances of calcium metabolism were not found in these patients, minimizing the pathophysiologic significance of altered calcium metabolism and the need for extensive endocrinologic evaluation. The finding of basal ganglia calcification alone does not justify invasive diagnostic procedures. Extrapyramidal signs may be associated with basal ganglia calcification; parkinsonism associated with basal ganglia calcification differs from idiopathic parkinsonism in being resistant to levodopa therapy.

Adult↗
PubMed1979

Amphetamine-induced hypersensitivity in guinea pigs.

Chronic administration of d-amphetamine to young guinea pigs results in an increased behavioral response to this drug. After 6 months of daily amphetamine exposure, animals demonstrated behavioral hypersensitivity and developed full amphetamine-induced stereotyped behavior with decreased latency. The data suggest that chronic agonism with amphetamine can produce dopaminergic hypersensitivity, a behavior that contrasts with the development of drug tolerance to other pharmacologic agents. The mechanism of this induced hypersensitivity was studied by comparing brain amphetamine levels after acute and chronic amphetamine treatment. The two groups of guinea pigs showed no significant difference in amphetamine levels or drug distribution. These results suggest that altered amphetamine metabolism cannot account for the hypersensitivity seen after amphetamine exposure. Guinea pigs chronically pretreated with d-amphetamine were hypersensitive to another dopaminergic agonist whose metabolic pathway is distinct from that of amphetamine. These results have therapeutic implications in the management of clinical conditions related to chronic agonist-induced hypersensitivity.

Amphetamine↗
PubMed1979

Involuntary movement disorders--each has a meaning all its own.

Degenerative processes in the corpus striatum, neuroleptics drugs, thyroid disease, and Parkinson's disease are all causes of abnormal spontaneous movements in the elderly. Differential diagnosis is essential for selecting the proper therapy, and the patient's history often provides the key.

Aged↗
PubMed1978

Paradoxial response to dopaminergic agents in parkinsonism.

A patient with the classical stigmata of parkinsonism was treated on three separate occasions with levodopa, a combination of levodopa and carbidopa, and lergotrile mesylate, a direct-acting dopamine-receptor agonist. All three treatment regimens resulted in dose-related increases in parkinsonian features. To our knowledge, this response has not been previously described. Lergotrile did not alter CSF homovanillic acid concentration. It is suggested that this rare paradoxical motor response to dopaminergic agents may be associated with dysfunction of the postsynaptic dopamine receptor site.

Acetonitriles↗
PubMed1978

Dopamine binding following prolonged haloperidol pretreatment.

The number of binding sites for tritiated dopamine as well as the affinity of 3H-dopamine for dopamine receptors was studied in rats chronically pretreated with the neuroleptic haloperidol. The rats were given haloperidol for 14 or 21 days and were killed on day 21. It was found that 14 days of haloperidol pretreatment followed by drug withdrawal resulted in a 67% increase in the number of 3H-dopamine binding sites in the striatum and ninefold increase in the affinity constant in the striatum. The same pretreatment regimen had no effect on either the number of receptor sites or the affinity constant in the nucleus accumbens. These results are consistent with the hypothesis that chronic neuroleptic pretreatment results in receptor site hypersensitivity in the striatum, which may be a major factor in the production of tardive dyskinesia.

Animals↗