149 previously untreated patients with Parkinson's disease were recruited over a three year period and randomly allocated to either low dose levodopa-carbidopa

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One hundred de novo patients with Parkinson's disease (PD) were classified into two groups according to age of onset of symptoms. Seventy two patients were under 70 years and 28 were 70 years and over. All patients were given neurological and neuropsychological assessments, and the severity of the signs was rated on a modified Columbia scale. The neuropsychological assessment was also administered to 50 age-and-education-matched controls. The neuropsychological test battery included tests of verbal learning, visual memory, verbal fluency, visuospatial skill, simple and choice reaction time, language and maze learning. The late-onset patients had significant impairment in nonverbal reasoning, auditory verbal learning, visual memory and choice reaction time in contrast to early-onset patients and controls. A relationship was found between bradykinesia and widespread cognitive impairment. Severity of tremor was found to be significantly correlated with impairment in auditory verbal learning, visual memory and increased choice reaction time, while rigidity was found to be associated with cognitive impairment in verbal fluency and visuospatial skill. Using DSM II criteria, 39% of the late-onset and 8% of the early-onset group were classified as demented. Dementia was more common in patients with bilateral symmetrical disease and in those patients with marked tremor and bradykinesia. The pattern of cognitive impairment in PD was consistent with that associated with a subcortical dementia. This study confirms that the expression of PD is markedly influenced by the age of onset.

SUMMARY One hundred and twenty nine de novo patients with idiopathic Parkinson's disease are being followed over a 5 year period in a double-blind multicentre study comparing low-dose bromocriptine (< 30 mg/day) with low-dose levodopa-carbidopa (< 600/150 mg/day). Sixty six patients have been randomised to bromocriptine and 63 patients to levodopa-carbidopa. Improvement has been greater in the levodopa-carbidopa group than in the bromocriptine group. Involuntary movements have so far only occurred in patients on levodopa-carbidopa, the incidence being much lower than is usually described with conventional doses. Mild, end-of-dose failure has occurred in both treatment groups; however, no patient has developed the "on-off' phenomenon. Low-dose levodopa-carbidopa appears to be a more effective anti-Parkinsonian treatment than lowdose bromocriptine but more prone to cause dyskinesia.The value of levodopa in the long-term treatment of Parkinson's disease is limited by the emergence of dyskinesia and the "on-of' phenomenon.'-3 Attempts to reduce the incidence of these problems by giving levodopa in low dosage have met with limited success.45 Dyskinesia has rarely been observed and the "on-off" phenomenon has not been described in patients treated with bromocriptine alone.'5 Nausea, postural hypotension and confusion limit the use of bromocriptine in up to 35% of patients using conventional doses.>" Several studies have shown that these side-effects can be minimised by giving bromocriptine in low dosage.'1213The aim of this study is to compare the efficacy and side-effects of low dose bromocriptine (< 30 mg/day) with low-dose levodopa-carbidopa (< 600/150 mg/ day) over a 5 year period in de novo patients. We report the results ofthe first 3 years of the study during which patients were recruited. MethodsOne hundred and forty nine patients with idiopathic Parkinson's disease were recruited over a 3 year period from neurologists and general practitioners in the Sydney area.

Inter- and intrarater reliability in scoring the signs of Parkinson's disease using the original Columbia scale and a modified version of this, the Sydney scale, were assessed in five neurologists participating in a long-term study of Parkinson's disease. Scoring was done on video recordings of 41 patients whose disability ranged from mild to severe. Although all the neurologists were familiar with the scales and had received training designed to produce uniformity of scoring, interrater reliability was poor. The mean score for the Columbia scale varied from 18.6 to 30 and for the Sydney scale from 15.2 to 23.2. By contrast, intrarater reliability was good. This study highlights the limitations of clinical rating scales in Parkinson's disease when more than one rater is used. In designing clinical trials, every effort should be made to ensure that the same patient is always assessed by the same rater.

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SUMMARY Acute and delayed effects of embollring cerebral surface vessels with cholesterol crystals were studied by direct observation in anesthetized rats and rabbits, using an open-skull technique, and by histologicai examination of brains at intervals of one day and one week following embolization. The number and size spectrum of crystals, w ich were infused into the ipsiiaterai Internal carotid artery, were believed to approximate those released by a rupturing large atheromatous plaque in man, but the other lipid materials contained in such plaques were intentionally excluded. It was found that cholesterol crystals had only limited ability to impede blood flow in the 20-80/* diameter arteries in view. They were also inert within the lumen, causing no vessel wall reaction even after a week; nor was any evidence seen of a thrombogenic effect. Local caliber changes in the containing artery were reproducibly seen, with dilatation of the arterial segment proximal to the embolus and narrowing of the segment in front. These changes appeared to represent an active response of the vessel wall, rather than a passive response to alterations in intraluminal pressure. The difficulty in subsequently locating cholesterol emboli histologically was confirmed. Possible therapeutic implications for atheroembolic cerebral infarction in man were discussed.Stroke, Vol II, No 2, 1980

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