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Biomedical subjects

D Chadwick

Publications and source records attributed to D Chadwick.

At least 19 recordsLinked to original sources
PubMed1979

Uraemic myoclonus: an example of reticular reflex myoclonus?

Two patients are described who developed action, reflex myoclonus during acute renal failure. In both cases the myoclonus was abolished after the intravenous administration of clonazepam. We suggest that the characteristic action myoclonus, which occurs in both acute renal failure and postanoxic encephalopathy, is caused by a disturbance of function in the lower brainstem reticular formation.

Acute Kidney Injury↗
PubMed1979

Cortical reflex myoclonus.

Three patients with a type of myoclonus produced by intention and somatosensory stimulation were studied with electrophysiologic techniques. Each jerk typically affected only a few contiguous muscles; agonist and antagonist muscles were activated simultaneously with a simple electromyographic (EMG) burst lasting 10 to 30 msec. Cranial nerve muscles were activated in an order indicating that the signal to produce the myoclonus traveled down the brainstem. In action-induced jerks a negative transient in the electroencephalogram (EEG) from the contralateral sensorimotor cortex consistently preceded the jerk with a fixed latency. In reflex-induced jerks this negative transient could be recognized as a component of the sensory evoked potential. The types of myoclonus are reviewed and it is argued that this type of myoclonus is mediated in cerebral cortex and that the negative transient represents a paroxysmal depolarization shift (PDS). The myoclonus may result from hyperactivity of a component of the long-latency stretch reflex.

Adult↗
PubMed1978

One drug for epilepsy.

We performed prospective trials of phenytoin and carbamazepine, assisted by blood level monitoring, in untreated patients newly referred with grand mal or partial seizures, or both, to a neurological clinic. At the time of follow-up (mean 28.5 months for phenytoin; 12 months for carbamazepine) 76-88% of patients were completely controlled. Twelve per cent of the patients on each drug had further seizures, despite an optimum blood level. When the blood drug concentration was in the optimum range there was a 98% reduction in grand mal attack rate and 92-93% reduction in partial seizure rate. These results suggest that polypharmacy is largely, and possibly totally, unnecessary in newly diagnosed adult epileptics.

Adolescent↗
PubMed1978

5-hydroxytryptophan-induced myoclonus in guinea pigs. A physiological and pharmacological investigations.

5-Hydroxytryptophan (5-HTP) induces a characteristic behavioural syndrome of altered motor activity with muscle jerking in guinea pigs. Myoclonic jerking occurs synchronously in forelimbs and hindlimbs and is associated with a stereotyped electromyographic (EMG) pattern of a burst of activity lasting 40-50 msec in active muscles, followed by silence lasting 50-70 msec, followed by a further variable period of muscle activity. Such myoclonus may be induced also by the administration of L-tryptophan plus a monamine oxidase inhibitor (MAOI), or by agents acting as serotonin (5-HT) receptor agonists. The 5-HTP-induced syndrome is antagonised by a central decarboxylase inhibitor (NSD-1035) and by agents which block 5-HT receptors (methysergide and cyproheptadine). 5-HTP-induced jerking is abolished below the level of a spinal cord transection, but persists in decerebrate animals. No electroencephalographic (EEG) changes are seen preceding the muscle jerks. The clinical significance of this animal model of myoclonus is discussed.

5-Hydroxytryptophan↗
PubMed1978

Functional changes in cerebral 5-hydroxytryptamine metabolism in the mouse induced by anticonvulsant drugs.

1 Acute administration of clonazepam, diazepam, and diphenylhydantoin to mice elevated cerebral 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA); chronic administration had less effect. 2 Acute administration of clonazepam and diazepam but not diphenylhydantoin raised cerebral trytophan levels; chronic administration of clonazepam caused a smaller elevation of cerebral tryptophan but chronic administration of diazepam still caused a large rise in cerebral tryptophan. 3 Neither clonazepam nor diazepam caused induction of drug metabolizing enzymes on chronic administration but diphenylhydantoin had a marked effect. 4 These data suggest that the altered 5-HT metabolism caused by these compounds is unrelated to a common action on tryptophan levels, and that the reduced effect of clonazepam and diazepam on chronic administration cannot be attributed to increased metabolism of these compounds. 5 Clonazepam induced abnormal head movements in mice in a dose-dependent manner. Pretreatment of animals with tranylcypromine increased the intensity of movement, although pargyline was without effect. Similar effects were observed with diazepam and diphenylhydantoin, suggesting that the increase in cerebral 5-HT caused by these compounds is of functional significance in stimulating 5-HT receptors.

Animals↗
PubMed1978

Manipulation of cerebral monoamines in the treatment of human epilepsy: a pilot study.

The effects of L-DOPA, L-tryptophan, monoamine oxidase inhibitor (MAOI), and MAOI plus L-tryptophan, each for 3 months, have been assessed in 10 severe, adult epileptics with placebo control. There was no overall reduction in seizure frequency, but 2 patients with minor partial seizures improved, 1 with L-DOPA, MAOI, and MAOI plus L-tryptophan, and the other with L-tryptophan and MAOI plus L-tryptophan. We have not been able to demonstrate an increased turnover of cerebral serotonin (5-HT), as measured by cerebrospinal fluid 5-hydroxyindoleacetic acid, after treatment with L-tryptophan for 3 months. This observation casts doubt on the ability of L-tryptophan to alter the long-term metabolism and functional activity of brain 5-HT. The importance of further exploration of manipulation of cerebral monoamines as a possible approach to the treatment of epilepsy is emphasized.

Adult↗
PubMed1977

Ballistic movement overflow myoclonus a form of essential myoclonus.

The clinical and electrophysiological findings in 2 cases of familial essential myoclonus are presented. The myoclonus was inherited apparently as an autosomal dominant trait, onset was in the first decade of life and the course was benign without the development of other significant neurological deficits. The electroencephalogram was unremarkable. The electromyographic appearance of the myoclonus was 50-100 ms complex bursts, usually occurring alternately in agonists and antagonists, similar to a normal ballistic movement. Muscles throughout the body were activated synchronously. In one of the cases myoclonus occurred at rest, but in both cases the myoclonus could be regularly produced by attempting a rapid movement. The myoclonic activity occurred simultaneously with the appropriate muscle activity which initiated the ballistic movement. It was as if the command to generate a ballistic movement overflowed into an excessive number of muscles. From a review of the literature it was concluded that this physiological mechanism was probably responsible for a definite sub-group of essential myoclonus. The relation of this type of myoclonus to other types of myoclonus and other involuntary movement disorders is discussed.

Adult↗
PubMed1977

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.

5-Hydroxytryptophan↗
PubMed1977

Reticular reflex myoclonus: a physiological type of human post-hypoxic myoclonus.

A patient with post-hypoxic myoclonus, sensitive to therapy with 5-hydroxytryptophan and clonazepam, was subjected to detailed electrophysiological investigation. Brief generalised jerks followed the critical stimulus of muscle stretch. The electroencephalogram showed generalised spikes that were associated with, but not time locked to, the myoclonus. The cranial nerve nuclei were activated upward. Analysis of the findings suggests that the mechanism of the myoclonus is hyperactivity of a reflex mediated in the reticular formation of the medulla oblongata.

5-Hydroxytryptophan↗
PubMed1976

One drug (phenytoin) in the treatment of epilepsy.

Thirty-one, previously untreated, adult outpatients with idiopathic or focal grand-mal and/or focal minor seizures were treated initially with phenytoin. Serum-phenytoin concentrations were monitored to achieve an optimum range of 10-20 mug/ml if necessary. With a mean duration of follow-up of 14-7 months, only three (10%) patients have required the addition of a second drug, although without the guidance of serum concentrations sixteen (54%) might have been treated with a further drug. In the optimum serum-phenytoin range only 1 grand-mal attack occurred in this series, compared with a mean pre-treatment grand-mal seizure-rate of 1-1/month. Serum phenytoin declined slowly in fourteen (45%) patients. These observations suggest that many epileptic patients could be satisfactorily treated with one drug instead of the polypharmacy which they usually receive.

Adolescent↗
PubMed1976

Anticonvulsant-induced dyskinesias: a comparison with dyskinesias induced by neuroleptics.

Anticonvulsants cause dyskinesias more commonly than has been appreciated. Diphenylhydantoin (DPH), carbamazepine, primidone, and phenobarbitone may cause asterixis. DPH, but not other anticonvulsants, may cause orofacial dyskinesias, limb chorea, and dystonia in intoxicated patients. These dyskinesias are similar to those caused by neuroleptic drugs and may be related to dopamine antagonistic properties possessed by DPH.

Adolescent↗
PubMed1975

Manipulation of brain serotonin in the treatment of myoclonus.

The response of myoclonus to oral and intravenous L-5-hydroxytryptophan (5-H.T.P.) in combination with a peripheral decarboxylase inhibitor (carbidopa) and to clonazepam has been examined in 9 patients. Moderate improvement or complete cessation of myoclonus followed treatment with one or both of these regimens in 5 patients, 1 of whom also responded to the concurrent administration of L-tryptophan and a monoamineoxidase inhibitor. The remaining 4 patients were at best only slightly improved by either 5-H.T.P. or clonazepam. The responsive group consisted of 3 patients with a history of anoxia, 1 patient with non-history of severe head injury, and 1 patient with non-progressive focal myoclonus and epilepsy. This group had low levels of 5-hydroxyindole acetic acid in the lumbar cerebrospinal fluid. It is suggested that 5-H.T.P. plus carbidopa, L-tryptophan plus a monoamine-oxidase inhibitor, and clonazepam may all act by elevating brain levels of serotonin (5-H.T.) and that some human myoclonic syndromes may be specifically related to a cerebral deficiency of 5-H.T.

5-Hydroxytryptophan↗