Extrapyramidal Symptomatology Research Articles

Neuroendocrinology and the extrapyramidal system

Endorphins are involved in the neuroendocrine regulation of the pituitary functioning, namely increasing the levels of prolactin and growth hormone, presumably through dopamine. This interaction of endorphins with dopamine could effect the extrapyramidal system, probably indirectly, their decrease potentially leading to an intensification of dyskinetic movements like tardive dyskinesia and an improvement of parkinsonian symptomatology. In fact, naloxone administered to 20 subjects of both sexes (10 o and 10 o) produced an increase in the intensity of tardive dyskinesia in man. In this connection, it has been reported that in rats the effect of naloxone is antagonized by prior administration of a synthetic estrogen (moxestrol) and this could explain the differential clinical response in males. Indeed, estrogens have previously been shown to possess an antidopaminergic activity. In other respects, a neuroendocrine theory has been proposed in an attempt to explain the therapeutic effect of ECT and the hypothesis that endorphins could be involved in this effect, at least in part, has already been raised to explain the mechanism of action of ECT, as well as its effect on extrapyramidal symptomatology.

Neuroleptic-induced acute dyskinesias in squirrel monkeys: correlation with propensity to cause extrapyramidal side effects.

In squirrel monkeys that had undergone repeated treatment with haloperidol at intervals of 7--14 days, subsequent acute administration of haloperidol induced dystonia and dyskinesias. This acute effect of haloperidol was dose-related and occurred at the same doses that impaired Sidman avoidance performance. Chlorpromazine, fluphenazine, metoclopramide, tetrabenazine, and Su-23397, all of which have been associated with extrapyramidal side effects, reliably elicited dyskinesias in these monkeys. Dyskinesias were less mared after thioridazine and absent after clozapine, corresponding to the reported lower incidence of extrapyramidal side effects in the clinic. The non-neuroleptics, baclofen, and diazepam, failed to elicit dyskinesias. In contrast to the dyskinetic syndrome, the incidence of catalepsy or tremor did not accurately predict propensity to elicit extrapyramidal symptomatology. The acute dyskinetic syndrome in squirrel monkeys may therefore serve as an animal model for predicting the ability of antipsychotics to cause extrapyramidal dysfunction, and may yield insight into the mechanisms of these drug-induced motor disorders.

Lesion of substantia nigra: Biochemical and behavioral effects in rats

Lesions of the substantia nigra in rats induce a marked decrease of the dopamine (DPA) content of the ipsilateral corpus striatum and a slight increase of this amine in the controlateral corpus striatum, motor disturbances but no tremor. No changes of striatal 5HT were detected under these experimental conditions. Lesions of the midbrain raphe nucleus produce an increase of motor activity and slight tremor as well as marked decrease of striatal 5HT, whereas levels of dopamine in corpora striata and in anterior part of the brain remain unchanged. It is suggested that the degenerative changes of both substantia nigra and serotoninergic fibers reaching the striatum might be responsible for the extrapyramidal symptomatology.

INTERCHANGEABLITY OF ANTIPARKINSONIAN MEDICATION.

In this study, conducted on 30 mental hospital patients manifesting extrapyramidal symptomatology, two antiparkinsonian drugs were interchanged with one another and with a placebo in a double-blind, crossover trial, and the results compared with a third antiparkinsonian drug used as a positive control. Physical and laboratory information was collected as well as ratings on psychiatric and extrapyramidal symptomatology. In all subgroups, the extrapyramidal symptom ratings were significantly higher (p>.005) when receiving placebo than when receiving promethazine, ethopropazine or trihexyphenidyl. This would indicate the effectiveness of these drugs in controlling extrapyramidal symptomatology as well as the inadequacy of placebo treatment in cases of overt extrapyramidal symptomatology. There were no significant changes in physical and laboratory measures, nor in ratings of psychiatric symptoms under any of the experimental conditions.

USES AND ABUSES OF ANTIPARKINSONIAN MEDICATION.

The antiparkinsonian medication of 30 mental hospital patients was suddenly removed. Half the patients were then placed on placebo. During the ensuing month they did not manifest any significant change in extrapyramidal symptomatology. The other half of the patients received no replacement and during the ensuing month their extrapyramidal symptoms became significantly worse (p≤.02) than during the pretrial period. In other words, it was not the withdrawal of the actual antiparkinsonian compound, but the withdrawal of the factor of non-specific psychological treatment which brought about an increase of parkinsonian manifestations. It should be added that one-third of those who received no replacement whatsoever showed no increase of parkinsonian manifestations. These results would imply that potentially toxic antiparkinsonian medication was unnecessary in the vast majority of patients, although two-thirds would require some sort of non-specific psychological treatment to keep their symptoms in check.

Epidemic encephalitis and tremor palsy. Davidenko (Vrach. Delo, 1922, No. 24—26)

Tremor palsy and similar syndromes have been the focus of neuropathologists' attention in recent years. The epidemic encephalitis with its rich extrapyramidal symptomatology has given a huge material for the study of hyperkinesias, absorbed some independent, if not nosological units, then symptom complexes and in the form of postencephalitic parkinsonism threatened the shiver palsy, dividing neuropathologists into two camps: unitarians, who denied independence of shiver palsy, and dualists, recognizing it.