Objectives-The United Kingdom Parkinson's Disease Research Group (UKP-DRG) trial found an increased mortality in patients with Parkinson's disease randomised to receive selegiline (10 mg/day) and levodopa compared with those taking levodopa alone. Unwanted eVects of selegiline on cardiovascular regulation have been investigated as a potential cause for the unexpected mortality finding of the UKPDRG trial. Methods-The cardiovascular responses to a range of physiological stimuli, including standing and head up tilt, were studied in patients with Parkinson's disease receiving levodopa alone and a matched group on levodopa and selegiline. Results-Head up tilt caused selective and often severe orthostatic hypotension in nine of 16 patients taking selegiline and levodopa, but was without eVect on nine patients receiving levodopa alone. Two patients taking selegiline lost consciousness with unrecordable blood pressures and a further four had severe symptomatic hypotension. The normal protective rises in heart rate and plasma noradrenaline were impaired. The abnormal response to head up tilt was reversed by discontinuation of selegiline. Drug withdrawal caused a pronounced deterioration in motor function in 13 of the 16 patients taking selegiline. Conclusion-Therapy with selegiline and levodopa in combination may be associated with severe orthostatic hypotension not attributable to levodopa alone. Selegiline also has pronounced symptomatic motor eVects in advanced Parkinson's disease. The possibilities that these cardiovascular and motor findings might be due either to non-selective inhibition of monoamine oxidase or to amphetamine and met-amphetamine are discussed.

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BackgroundNon-ataxic symptoms of spinocerebellar ataxias (SCAs) vary widely and often overlap with various types of SCAs. Duration and severity of the disease and genetic background may play a role in such phenotypic diversity. We conducted the study in order to study clinical characteristics of common SCAs in Thailand and the factors that may influence their phenotypes.Methods131 (49.43%) out of 265 Thai ataxia families with cerebellar degeneration had positive tests for SCA1, SCA2, Machado-Joseph disease (MJD) or SCA6. The study evaluated 83 available families including SCA1 (21 patients), SCA2 (15), MJD (39) and SCA6 (8). Comparisons of frequency of each non-ataxic sign among different SCA subtypes were analysed. Multivariate logistic regression analyses were undertaken to analyze parameters in association with disease severity and size of CAG repeat.ResultsMean ages at onset were not different among patients with different SCAs (40.31 ± 11.33 years, mean ± SD). Surprisingly, SCA6 patients often had age at onset and phenotypes indistinguishable from SCA1, SCA2 and MJD. Frequencies of ophthalmoparesis, nystagmus, hyperreflexia and areflexia were significantly different among the common SCAs, whilst frequency of slow saccade was not. In contrast to Caucasian patients, parkinsonism, dystonia, dementia, and facial fasciculation were uncommon in Thai patients. Multivariate logistic regression analysis demonstrated that ophthalmoparesis (p < 0.001) and sensory impairment (p = 0.025) were associated with the severity of the disease.ConclusionsWe described clinical characteristics of the 4 most common SCAs in Thailand accounting for almost 90% of familial spinocerebellar ataxias. There were some different observations compared to Caucasian patients including earlier age at onset of SCA6 and the paucity of extrapyramidal features, cognitive impairment and facial fasciculation. Severity of the disease, size of the pathological CAG repeat allele, genetic background and somatic heterogeneity of pathological alleles may influence clinical expressions of these common SCAs.