John G. Nutt

Twin study of Parkinson disease.

zero concordance for Parkinson disease was found in the first 12 monozygotic twin pairs examined in an ongoing twin study. One co-twin (subject without Parkinson disease) had essential tremor, another had cerebral vascular disease, and a third was an alcoholic. Cigarette smoking appeared to be less frequent in the probands than in the co-twins (11.9 versus 16.1 pack-years). There was also evidence of premorbid personality differences between probands and co-twins dating back to late adolescence or early adult years. These preliminary findings suggest that genetic factors do not play a major role in the etiology of Parkinson disease and point to a prodromal onset of the disease as early as late adolescence or early adult life.

Substance P in human cerebrospinal fluid Reductions in peripheral neuropathy and autonomic dysfunction

Substance P (SP), a putative peptide neurotransmitter, was measured in human lumbar cerebrospinal fluid (CSF) by radioimmunoassay. Substance P-like immunoreactivity (SPLI) was present in the CSF of 18 neurologically normal adults in concentrations ranging from 2.9 to 11.1 fmol per milliliter, with a mean of 7.0 ± 0.6 fmol per milliliter (mean ± SE). Slightly more than half of the CSF-SPLI cochromatographed with synthetic SP on Sephadex G-25. There was no apparent gradient in CSF-SPLI concentration over the first 30 ml of CSF removed by lumbar puncture. Mean concentrations of CSF-SPLI in patients with Huntington disease, parkinsonism, miscellaneous dyskinesias, progressive supranuclear palsy, myopathy, and amyotrophic lateral sclerosis did not differ significantly from normal. Patients with neuropathy or multiple-system atrophy (Shy-Drager syndrome) had significantly reduced mean CSF-SPLI concentrations. These observations suggest that lumbar CSF-SPLI arises largely from spinal cord, nerve roots, or dorsal root ganglia, and that pathologic processes affecting these structures may be reflected by reduced levels of CSF-SPLI.

Treatment of Huntington disease with a cholinergic agonist

The involuntary movements of Huntington disease may be related to cholinergic hypofunction in the striatum. For this reason, the effect of a direct cholinergic agonist, are coline, was studied in six patients with this disorder. Rather than improving the chorea, are coline tended to exacerbate the choreic movements. Arecoline did produce significant alterations of blood pressure, heart rate, and body temperature, probably by central cholinergic stimulation.

Pharmacodynamics of the hypotensive effect of levodopa in parkinsonian patients.

Blood pressure effects of i.v. levodopa were examined in parkinsonian patients with stable and fluctuating responses to levodopa. The magnitude of the hypotensive effect of levodopa was concentration dependent and was fit to an Emax model in fluctuating responders. Stable responders demonstrated a small hypotensive response. Baseline blood pressures were higher in fluctuating patients; a higher baseline blood pressure correlated with greater hypotensive effects. Antiparkinsonian effects of levodopa temporally correlated with blood pressure changes. Phenylalanine, a large neutral amino acid (LNAA) competing with levodopa for transport across the blood-brain barrier, reduced the hypotensive and antiparkinsonian effects of levodopa. We conclude that levodopa has a central hypotensive action that parallels the motor effects in fluctuating patients. The hypotensive effect appears to be related to the higher baseline blood pressure we observed in fluctuating patients relative to stable patients.

Linear Relationship between Plasma Concentration and Dosage of Sodium Valproate

Summary: Plasma valproate concentration was studied in 7 hospitalized nonepileptic patients who received sodium valproate at daily doses of up to 60 mg/kg. A linear relationship between dose and plasma concentration of valproate (r = 0.81‐0.99) was found in each patient, although the slopes of the regression lines (reflecting clearance rates) varied twofold. This suggests that if the valproate plasma concentrations at two different doses are known and the clearance of valproate is not altered by concomitant administration of other drugs, it should be possible to predict the plasma valproate concentration that will result from further dose increments.