ABSTRACT:Clinical diagnosis of Parkinson's syndrome (PS) is reasonably easy in most cases but the distinction between different variants of PS may be difficult in early cases. The correct diagnosis is not only important for counselling and management of patients but also in conducting pharmacological and epidemiological studies. There is very little critical literature on the pathological verification of the clinical diagnosis in PS. We report our 22 year experience to address that issue. Between 1968 and 1990, 65 PS patients came to autopsy. Complete data are available in 59 (M- 50, F-19) cases. The initial diagnosis made by a qualified neurologist was idiopathic Parkinson's disease (IPD) in 43 cases. Of those 28 (65%) had Lewy body pathology. After a mean duration of 12 years the final diagnosis was IPD in 41 cases which was confirmed in 31 (76%). The IPD could not be clinically distinguished from cases with severe substantia nigra neuronal loss without inclusions or from those with neurofibrillary tangle inclusions and neuronal loss at the anatomical sites typically involved in IPD. All progressive supra-nuclear palsy, olivopontocerebellar atrophy, Jakob-Creutzfeldt's disease and the majority of the multiple system atrophy cases were diagnosed correctly during life. The correct clinical diagnosis in most non-IPD variants of PS was possible within 5 years of onset (range: 2 months to 18 years). We recommend that studies aimed at including only the IPD cases restrict the enrollment to those cases that have had PS motor manifestations for five years or longer duration.

We sought to determine the continued benefit and the pattern of motor complications of long-term levodopa treatment in Parkinson's disease. Patients were evaluated between 1968 and 1996. Only those who had an adequate levodopa trial and in whom autopsy revealed Lewy body Parkinson's disease were included. Total levodopa and mean daily dose were calculated in each case. Dyskinesia, wearing-off and on-off were collectively classified as motor adverse effects and reported as cumulative incidence. Forty-two patients (male, 30; female, 12) with mean 15.9 years of illness and 9.1 years follow-up received on average 500-mg levodopa daily over 9.8 years. Seventeen of 21 patients assessed during the last 18 months of life reported some motor benefit. Adverse effects were seen in 71.4% of patients. The most common was dyskinesia, in 61.9%; wearing-off in 35.7%; and on-off in 16.7% of patients. The earliest adverse effect was dyskinesia and the last to emerge was on-off. Isolated dyskinesia was seen in 35.7% and wearing-off in 7.1% of patients; 15.5% of patients developed dyskinesia after 2.6 years and 31% after 6.4 years on levodopa. We concluded that levodopa benefit declined and adverse effects increased with time. Dyskinesia was the earliest and the most common isolated adverse effect.

We evaluated 16 (15 men, 1 woman) autopsy-verified progressive supranuclear palsy (PSP) cases during 31 years (1969-2000) for clinical diagnosis and the course of the disease. The onset was gait difficulty or postural instability in 9 (56.3%), general motor slowing in 3 (18.8%), and tremor in 2. One case had onset with cognitive decline and 1 as hemidystonia. Four cases had supranuclear ophthalmoplegia (SNO) at the first assessment and were diagnosed as PSP. By last assessment, PSP diagnosis was made in 4 additional cases, but in 8 (50%) who never manifested ophthalmoplegia (mean 9.8 years after onset), PSP diagnosis was not made. Other manifestations included bulbar symptoms in 13 (81.3%), and cognitive impairment in 10 (62.5%) during the course of illness. Fifteen cases received levodopa, amantadine, anticholinergics, dopamine agonists, and selegiline in different combinations with symptomatic benefit in 9 of 15 (60%). Five had some improvement on levodopa alone and 3 showed more improvement when a dopamine agonist was added to levodopa. In general, the benefit was minimal and occurred only early in the course of illness. The mean age at onset was 63.7 (range, 53-85) years. Mean duration at PSP diagnosis was 4.8 (range, 2-11) years. Mean survival was 8.6 (range, 3-24) years and mean age at death was 72.3 (range, 60-89) years. When the different diagnostic criteria recommended in the literature were used, the accuracy of clinical diagnosis did not improve substantially.

SYNOPSIS Necropsy studies were done on six patients with idiopathic paralysis agitans, one with multiple system atrophy including features of Parkinsonism, and one control. Autonomic functions had been evaluated during life to a varying degree. Intra-arterial blood pressure studies were carried out on two patients with paralysis agitans (cases 4 and 6) and the one with multiple system atrophy (case 7). Lewy bodies with or without cell loss were seen in the sympathetic ganglia of five cases of paralysis agitans. Three of these had orthostatic hypotension and the severity of the lesion approximately correlated with the degree of hypotension. It is concluded that the lesions of the sympathetic ganglia may play a major role in the production oforthostatic hypotension in idiopathic paralysis agitans.Autonomic dysfunction in Parkinson's disease was first reported in 1817 by James Parkinson himself. Abnormalities of salivation, sweating, bladder and bowel function are common features of the disease he described, and orthostatic hypotension, though less common, is perhaps the most disturbing form of dysautonomia. Parkinsonism features may also occur in multiple system atrophy of which progressive autonomic failure may be a predominant feature. Parkinson's disease and multiple system atrophy can be distinguished clinically (Bannister and Oppenheimer, 1972). In multiple system atrophy the pathological basis of autonomic failure, including orthostatic hypotension, is loss of cells in the intermediolateral column in the spinal cord (Johnson et al., 1966;Schwartz, 1967;Chokroverty et al., 1969;Bannister and Oppenheimer, 1972 One patient who suffered from brain tumour was used as a control. All patients were admitted to hospital. A detailed history of onset and progression of symptoms was obtained and an inquiry into constipation, urinary retention or incontinence, anal sphincter problem, sexual impotence, unusual sweating, seborrhoea, sialorrhoea, oculogyric crisis, and postural dizziness was made in each case. The severity of major manifestations of Parkinsonism-tremor, rigidity, and bradykinesia-was graded by the criteria of Webster (1968). Global disability was measured using the criteria of Hoehn and Yahr (1967

Parkinsonian features, notably resting tremor may be seen in some essential tremor patients but the significance of those is unknown. The reported risk of parkinsonism in essential tremor patients varies from being unchanged to 35 times higher than expected. We studied 9 patients with essential tremor who had autopsies. In 6 of the 9 (66%) resting tremor was noted and in 3 (33%) cases fully developed parkinsonism was noted. The parkinsonism was consequent to neuroleptic usage in 2 and to basal ganglia status lacunaris and cribrosus in one case but no consistent abnormalities were noted in 3 essential tremor only and 3 essential tremor plus resting tremor cases. We conclude that resting tremor is an age-related natural evolution in some essential tremor patients. We recommend that the additional diagnosis of parkinsonism in the essential tremor be made only when resting tremor, bradykinesia and rigidity are all evident. The risk of ideopathic Parkinson's disease in essential tremor cases is similar to the general population. RESUME: Signification des manifestations parkinsoniennes dans les cas de tremblement essentiel. Des manifestations parkinsoniennes (PS), particulierement le tremblement de repos (TR), peuvent etre observees chez certains patients souffrant de tremblement essentiel (TE), mais leur signification est inconnue. Selon la litterature, le risque de parkinsonisme (PS) chez les patients souffrant de TE varie de identique a 35 fois celui de la population en general. Nous avons procede a l'autopsie de 9 patients souffrant de TE. Chez 6 des 9 patients (66%), un TR avait ete note et chez 3 (33%), un PS evident avait ete note. Le PS etait consecutif a ('utilisation de neuroleptiques chez 2 et a I'etat lacunaire et crible des noyaux gris centraux chez un cas. Cependant, aucune anomalie constante n'a ete notee chez 3 patients atteints de TE seulement et chez 3 patients avec TE et TR. Nous concluons que le TR est une evolution naturelle, en relation avec I'age, chez certains patients atteints de TE. Nous recommandons que le diagnostic additionnel de PS chez le patient atteint de TE ne soit pose que Iorsque le tremblement de repos, la bradycinesie et la rigidite sont tous evidents. Le risque de maladie de Parkinson idiopathique chez les cas de TE est le meme que celui de la population en general.Can. J. Neurol. Sci. 1993; 20: 114-117 Essential tremor (ET) is the most common pathological tremor in man 1 and Parkinson syndrome (PS) is a common neurological disorder in the elderly population. 2 ' 6 Therefore these two conditions may coexist in some individuals. Essential tremor may first manifest in childhood, young adult or old age but PS is concentrated in the later age. When an individual suffers from both ET and PS the usual sequence is an earlier onset of ET and subsequent emergence of PS. Considering that pattern of evolution there is now an active debate on the risk of parkinsonism in the ET patients. 712 The presence of parkinsonian features in the ET cases may indicate: (1) a natural evolu...