Radial compression neuropathy in advanced Parkinson's disease.

Radial compression neuropathy developed in four patients with advanced Parkinson's disease. Electrodiagnostic studies in two patients documented the upper middle part of the arm as the site of nerve injury. The conditions of three patients improved over four months. One markedly disabled, bradykinetic patient had a permanent flexion deformity of the wrist and hand. Radial compression neuropathy may be an initiating factor in the development of hand deformities in patients with late-stage parkinsonism.

Prevention of progression of Parkinson's disease with antioxidative therapy.

1. Oxidative mechanisms in dopaminergic neurons may contribute to cell death and the progression of Parkinson's Disease. 2. The free radical auto-toxicity concept has scientific evidence to support it. 3. Clinical trials are underway to assess the protective effect of augmenting the free radical scavenging system with vitamin E and inhibiting catecholamine oxidation with deprenyl.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), its metabolite cyperquat (MPP+) and energy transduction in mitochondria from rat striatum and liver.

In vitro studies with rat striatal and liver mitochondria have shown that the neurotoxic compound MPTP (0.5 mM) has very little effect on mitochondrial energy transduction. With pyruvate-malate (P/M), mitochondria from striatum and liver exhibited state 3 oxygen consumption rates of 101.5 +/- 21.3 and 53.6 +/- 14.8, respectively. On the other hand, MPP+ (0.5 mM) inhibited the NAD-linked substrate (P/M) oxidation in both tissue preparations. MPP+ failed to influence oxidative phosphorylation when succinate was used as the substrate. Mitochondria from liver and striatum exhibited low levels of 45Ca uptake in the absence of Mg.ADP. This was increased by about 3-fold in the presence of Mg.ADP. MPP+ under either condition had very little effect on 45Ca uptake by these organelles.

Bromocriptine: problems with low-dose de novo therapy in Parkinson's disease.

Twenty Parkinson's disease patients, who had not yet received levodopa, were treated with low-dose bromocriptine. At a mean daily bromocriptine dose of 13.2 mg, 13 patients (65%) improved and had a 32% reduction in the combined score for tremor rigidity and bradykinesia. Adverse effects were frequent, and 25% of the patients were taken off the drug because of nausea or vomiting. After 30 months follow-up, only three patients continued on bromocriptine alone. Ten patients were eventually maintained on low-dose bromocriptine and levodopa-carbidopa, and a clear synergistic effect of bromocriptine in this drug combination was documented in eight patients. Low-dose bromocriptine does not replace levodopa as initial therapy for Parkinson's disease. The potential long-term benefit of the early use of combined low-dose levodopa-dopamine agonist therapy needs to be further studied.

Bromocriptine in Parkinson's disease: results obtained with high and low dose therapy.

The results obtained with high and low dose bromocriptine therapy were compared in a review assessing the per cent of patients showing improvement (not taking account of the extent of improvement). It is concluded that the response rate with low dose bromocriptine is as good as that obtained with high dose therapy for both de novo and levodopa treated patients. The incidence of adverse effects is similar in the high and low dose treatment groups. More levodopa reduction results in a higher daily bromocriptine requirement. A statistical analysis of 61 bromocriptine-levodopa treated patients showed no positive correlation between bromocriptine dose and severity or duration of Parkinson's disease.

Method of addition of bromocriptine to the drug regime of patients with advanced Parkinson's disease.

Using a method of a gradual increase of bromocriptine with a concomitant reduction of Sinemet (levodopa 250 mg + carbidopa 25 mg), 19 patients with advanced Parkinson's disease have been treated for periods of up to 22 months and 16 of them have shown improvements of varying degrees. Eighteen patients were able to tolerate bromocriptine addition, with early transient adverse effects occurring in seven cases. In contrast to several previously reported studies, it was found necessary to withdraw bromocriptine in only one case. With the drugs currently available, bromocriptine has a role in the management of patients with advanced Parkinson's disease. The method described here may allow a greater number of patients to be given a trial with this drug.

Bromocriptine in the long-term management of advanced Parkinson's disease.

Thirty-seven patients with advanced Parkinson's disease who initially tolerated, and responded to bromocriptine therapy were followed for 12 to 50 (mean 28) months. Using a method of gradual increase of bromocriptine, with concomitant levodopa reduction, the peak effect of the drug was apparent by three months, at which time the mean daily dose of bromocriptine was 23.9 mg and Sinemet (levodopa + carbidopa) had been reduced by 34 percent. Eight patients had sustained improvement without further drug changes for an average of 29 (range 14-50) months. After periods of improvement varying between 3 and 30 months, 29 patients had a fall-off from peak effect. Peak effect was regained in 21 of these 29 patients for an average of 16 additional months by initially increasing bromocriptine or Sinemet, or by eventually increasing both drugs. The main adverse effect was a confusional state which necessitated late withdrawal of bromocriptine in four patients. The best results were in younger patients with end-of-dose deterioration and levodopa induced dyskinesias. With cautious introduction, and intermittent dosage adjustment, bromocriptine can be of long-term benefit to patients with advance Parkinson's disease. The majority of patients have a gradual late fall-off in effect which can frequently be reversed with dosage adjustment.

Antioxidant therapy in Parkinson's disease.

It is postulated that endogenous oxidative mechanisms are a major factor in the continuing death of dopaminergic neurons and the progression of Parkinson's disease. Scientific evidence in support of, and negating, the free radical auto-toxicity and dopamine toxicity concepts is reviewed. There is conflicting evidence whether free radicals are involved in the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and attempts to prevent the toxicity of MPTP with antioxidant therapy have had variable results. The oxidation of dopamine by monoamine oxidase produces toxic metabolites however animal studies with high dose longterm levodopa and MPTP have failed to show clear evidence for autoxidation. Firm supportive evidence is obtained from the monoamine oxidase B inhibitor experience which demonstrated a block of the toxicity of MPTP in animals and probable prolongation of the course of human Parkinson's disease. The scientific data available is inconclusive but there is significant hope of retarding progressive catecholaminergic neuron degenerative changes by augmenting the free radical scavenging system with antioxidants (such as Vitamin E) and slowing catecholamine oxidation by monoamine oxidase B inhibition. Careful clinical trials with these agents must be performed.

Bromocriptine in the management of end of dose deterioration in Parkinson's disease.

Thirty-three patients with advanced Parkinson's disease complicated by end of dose deterioration were treated with bromocriptine. The drug was slowly increased so that by treatment week 24 the mean daily dose of bromocriptine was 22mg and levodopa had been decreased by an average of 15 percent. The majority of improvement in daily fluctuations and Parkinsonian disability score was documented by 8 weeks, at which time the mean daily bromocriptine dose was only 12mg. End of dose deterioration was reduced in 78 percent of the patients (mean 43% improvement). Total Parkinsonian disability score was decreased by 33 percent. Adverse effects were minimal; the most common was mild transient early treatment nausea which occurred in 15 percent of the patients. The slow introduction of small doses of bromocriptine, combined with minimal levodopa reduction, can give Parkinsonian patients significant improvement in end of dose deterioration.

Neuropsychological and glucose metabolic profiles in asymmetric Parkinson's disease.

Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson's disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education, were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex, decreasing glucose metabolism was positively associated with neurobehavioral function; in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates.

Idiopathic hypoparathyroidism with impaired vitamin B 12 absorption and neuropathy.

A 68-year-old man presenting with chronic intermittent diarrhea and progressive ataxia was found to have idiopathic hypoparathyroidism. Intrinsic factor-resistant vitamin B(12) malabsorption was demonstrated. Both the diarrhea and vitamin malabsorption were reversed by correction of hypocalcemia.His neurological profile was a combination of peripheral nerve, posterior column and cerebellar deficits. He had calcifications in the dentate nuclei of the cerebellum. Possible etiological factors such as vitamin B(12) deficiency, folic acid deficiency and steatorrhea have been excluded. Posterior column and cerebellar abnormalities improved with treatment. It is postulated that hypocalcemia causes functional, reversible spinal cord and cerebellar dysfunction.