Striated anal sphincter function was studied electrophysiologically and radiologically in six patients with Parkinson's disease and chronic constipation. In five cases, there was paradoxic anal sphincter muscle contraction during simulated defecation straining resembling anismus-type pelvic outlet obstruction. Radiologic studies showed functional improvement of the defecatory mechanism following the administration of the dopamine receptor agonist apomorphine in four patients. Dysfunction of the striated anal sphincter musculature may be a significant cause of constipation in some parkinsonian patients, occurring as part of the generalized extrapyramidal motor disorder.

Anal Canal↗

PubMed1989

Endogenous urinary monoamine oxidase inhibitor excretion in Parkinson's disease and other neurological disorders.

In this study, urinary output of both neutral (tribulin) and basic monoamine oxidase inhibitory activity was measured in parkinsonian patients, other neurological patients and controls. No significant differences in output were found between these different groups. In general, tribulin output rose with age, in parallel with known changes in monoamine oxidase B activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1989

A double-blind, controlled study of high-dose L-deprenyl in the treatment of Parkinson's disease.

The conventional dose of deprenyl used in Parkinson's disease is 10 mg/day, having been established by in vitro platelet studies and clinical evaluation. Twelve patients with Parkinson's disease on treatment with L-dopa who showed evidence of wearing-off effects or motor oscillation were studied in a double-blind, placebo-controlled, crossover trial to compare conventional doses of deprenyl with higher doses (up to 40 mg/day) and placebo. We did not find higher doses of deprenyl to be superior to conventional doses and in 17% of cases treatment had to be withdrawn because of side effects.

Adjuvants, Pharmaceutic↗

PubMed1989

New approaches in the use of selegiline for the treatment of Parkinson's disease.

Selegiline hydrochloride (deprenyl) is a safe, useful adjuvant therapy in patients with Parkinson's disease treated with L-dopa. The optimum time for its introduction into the treatment regimen of a patient remains controversial. A multicentre long-term study being conducted by the Parkinson's Disease Research Group of the United Kingdom to attempt to answer whether selegiline improves the natural history of Parkinson's disease is discussed. In a separate study we have been unable to demonstrate that higher doses of selegiline (up to 40 mg a day) produce additional therapeutic benefit above the conventional dose of 10 mg a day in levodopa-treated patients with motor fluctuations. Preliminary data from a neuropsychological study is also presented which suggests that selegiline may have beneficial effects on the speed of psychomotor responses supporting the anecdotal clinical observations of increased mental energy and alacrity.

Adult↗

PubMed1989

Asymmetry of substantia nigra neuronal loss in Parkinson's disease and its relevance to the mechanism of levodopa related motor fluctuations.

A pathological study of 21 patients with Parkinson's disease of asymmetrical onset revealed significant asymmetry of degeneration of the substantia nigra with greater neuronal loss contralateral to the initially affected body side. It has previously been suggested that decline in duration of effectiveness of levodopa doses in Parkinsonian patients with motor oscillations is caused by loss of nigro-striatal dopaminergic terminals with consequent reduction in striatal dopamine storage capacity. If this is true, duration of levodopa motor response should be shorter on the more severely affected body side in patients with asymmetrical disease, as loss of contralateral striatal dopamine storage capacity should be greater. Serial motor evaluations in 20 patients with asymmetrical Parkinson's disease failed to reveal any such asymmetry of duration of motor response to levodopa. It is suggested that striatal dopamine storage is not an important determinant of duration of clinical response to levodopa doses.

Adult↗

PubMed1989

Sublingual apomorphine and Parkinson's disease.

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Administration, Sublingual↗

PubMed1989

Levodopa peripheral pharmacokinetics and duration of motor response in Parkinson's disease.

To assess the relative influence of central pharmacodynamic and peripheral pharmacokinetic factors on the duration of motor response to levodopa, the relationship between motor function and plasma levodopa levels was studied in 31 Parkinsonian patients. Duration of benefit from single levodopa doses while fasting depended on the degree to which the plasma levodopa level had declined over four hours; wearing off occurred when the plasma levodopa level had fallen to approximately 50% of peak concentration, irrespective of the duration of the motor response. Whilst the amplitude of motor response to levodopa is likely to be modified by alternations in dopamine receptor stimulation and sensitivity as the disease progresses, it is proposed that the duration of response is primarily determined by levodopa peripheral pharmacokinetics rather than by central pharmacodynamic factors associated with dopamine storage capacity.

Administration, Oral↗

PubMed1989

The effects of oral protein on the absorption of intraduodenal levodopa and motor performance.

Four patients with levodopa induced fluctuations in motor performance were studied during the constant intraduodenal infusion of levodopa. The results confirm that steady plasma levodopa levels with stable motor control can be achieved. However, when patients were given oral protein loads, motor performance declined despite maintenance of plasma levodopa levels. These findings suggest that competition for levodopa carrier mediated transport by amino acids, is more important at the blood-brain barrier than across the gut mucosa; thereby possibly limiting the efficacy of long-term direct intraduodenal administration of levodopa.

Aged↗

PubMed1988

Subcutaneous apomorphine in parkinsonian on-off oscillations.

Subcutaneous apomorphine, a dopamine agonist, was given by continuous infusion during the day or by repeated injections to 19 patients with Parkinson's disease disabled by severe on-off fluctuations. All patients were also given domperidone. The 11 patients treated by infusion showed marked and sustained improvement, and their mean duration of daily off periods over a period of 15 months fell by 6.3 h; similar results were obtained in 8 patients with less severe disabilities who were given repeated apomorphine injections. The therapeutic response to apomorphine was similar to that seen with intravenous levodopa; in patients treated by infusion the mean daily levodopa dose was reduced by 209 mg. These results confirm that during off periods dopamine receptors remain responsive to stimulation and provide evidence of a new, effective, and well-tolerated treatment for the most disabling complication of long-term levodopa therapy.

Adult↗

PubMed1988

Dystonia in Parkinson's disease: clinical and pharmacological features.

We studied the features of dystonia in 9 patients with untreated idiopathic Parkinson's disease and in 56 patients on sustained treatment with L-dopa. Dystonia was seen as an initial symptom in patients with both early- and late-onset Parkinson's disease and included action dystonia of the limbs and cranial dystonia. Although the coexistence of parkinsonism and dystonia suggests a common pathophysiology, antiparkinsonian drugs did not consistently influence dystonic spasms. L-dopa-induced dystonia was seen as an off-period, biphasic, or peak-dose phenomenon. Each type showed a distinctive pattern of localization of dystonic spasms, possibly reflecting neurochemical aspects of basal ganglia somatotopy. Neuropharmacological studies performed in 12 patients suggest that off-period dystonia is genuinely induced by L-dopa and best relieved by antiparkinsonian agents.

Adult↗

PubMed1988

Dystonia in homocystinuria.

Three patients with homocystinuria due to cystathionine beta-synthase deficiency who developed progressive generalised dystonia are described. Although cerebrovascular thrombosis is usually thought to be responsible for neurological dysfunction in homocystinuric patients, neuropathological studies in one case and clinical and radiological evidence in the other two suggested that dystonia was not caused by brain infarction. Movement disorder associated with homocystinuria may result from the neurochemical changes in the basal ganglia related to the inherited defect in sulphur amino acid metabolism.

Adolescent↗

PubMed1987

Vitamin E and Parkinson's disease.

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Food, Fortified↗

PubMed1987

Bradyphrenia in Parkinson's disease and psychomotor retardation in depressive illness. An experimental study.

Thirty newly diagnosed patients with Parkinson's disease and 30 patients with primary depressive illness showed slowing of response on a computerized digit symbol substitution test when compared with 30 matched normal control subjects. Significant slowing was related, in the parkinsonian patients, to structural brain disorder and affective impairment and, in the depressed patients, to motor impairment. A second computerized test, cognitively simpler but requiring the same motor response, was also administered to each subject. Both cognitive and motor slowing seemed to contribute to slowing of response in the digit symbol test in both parkinsonian and depressed patients. The tests were repeated after about six months in 12 subjects from each group. The parkinsonian patients, on dopaminergic treatment, showed neither significant change in motor or affective impairment, nor improvement in response time for the digit symbol test, but change in response time was related to change in depression rating. The depressed patients, on conventional treatment, showed significant improvement in both affective and motor impairment and improvement in response time for the digit symbol test, due to improvement in cognitive slowing. It is proposed that bradyphrenia in Parkinson's disease and psychomotor retardation in depressive illness are closely related, and that impairment of dopaminergic systems may be involved in both.

Brain↗