BROMOCRIPTINE VERSUS PLACEBO IN LEVODOPA TREATED PATIENTS WITH PARKINSON''S DISEASE

Twenty patients with idiopathic parkinsonism who had been on optimal levodopa therapy for at least 3 months prior to the investigation and where effect of the treatment was decreasing or side effects were increasing, were treated with bromocriptine in a double-blind crossover trial during a 12 + 12 weeks period. Reduction in disability scores was found significant. Hyperkinesia was more frequent in the bromocriptine period than in the placebo period, but reduction of dose in six patients for this reason was not followed by deterioration. Both hyperkinesia and other side effects disappeared after dose reduction. Doses were 2.5 mg-40 mg. Bromocriptine seems a valuable supplement to previous therapy in these patients.     

BRAIN ACETYLCHOLINESTERASE IN PARKINSON''S DISEASE

The activity of acetylcholinesterase was studied in various autopsy brain samples of nine parkinsonian patients and eight control subjects without extrapyramidal disorders. Putamen and caudate nucleus showed the highest activities of acetylcholinesterase when different brain areas were compared. Acetylcholinesterase values expressed per wet weight or protein were somewhat lower in the extrapyramidal brain regions of parkinsonian patients than in those of controls. When values were calculated per desoxyribonucleic acid (DNA) it was found that extrapyramidal brain regions, especially substantia nigra, showed higher activities in parkinsonian material than in controls. This difference is due to the decrease of DNA which in the substantia nigra mainly reflects the loss of dopaminergic substantia nigra neurons. Furthermore, analyses of dopamine from the same tissue samples showed many times increased acetylcholinesterase-dopamine ratio in parkinsonian brain than in controls. Levodopa alone or combined with a decarboxylase inhibitor did not have any significant effect on the activity of acetylcholinesterase. It is concluded that the cholinergic mechanisms in the extrapyramidal system of parkinsonian brain are not so severely affected as the dopaminergic ones leading to relative and functional cholinergic dominance.     

DISTURBANCES of MICTURITION IN PARKINSON''S DISEASE

During the years 1970-1974, a total of 44 patients referred by neurologists to the Urological Laboratory were classified in the following groups: paralysis agitans (27), postencephalitic parkinsonism (5), cerebral arteriosclerosis and parkinsonism (7) and cerebral arteriosclerosis and parkinsonism, suspected (5). Bladder function was assessed on the basis of cystometry and urodynamic investigation. A high frequency of supranuclear bladder paresis (SNP) was found, although unequally distributed in the different diagnostic groups. Stereotactic operations on the thalamic nuclei seemed to be correlated with SNP. The question was raised whether SNP was part of the parkinsonian syndrome or merely signs and symptoms related to ageing.     

EPIDEMIOLOGY of PARKINSON''S DISEASE IN FINLAND

This investigation was conducted to clarify the epidemiology of Parkinson's disease in Finland. A community survey was made in a selected area in southwest Finland in addition to an analysis of Finnish mortality statistics for Parkinson's disease. The annual mortality rate from Parkinson's disease was found to average 2 per 100,000 population. Almost 70 per cent of the deaths occurred between 65-79 years of age. The total and age-specific mortality rates for males were greater than those for females whereas the proportionate mortality rates were almost identical. This was considered to indicate that suggestions of greater male prevalence, based on mortality statistics, do not appear justified. On prevalence day, Dec. 31st, 1971, 484 patients with Parkinson's disease (of which 444 were personally examined) lived in the area of investigation (population 402,988), the prevalence rate being 120.1 per 100,000 population. The highest annual incidence rate was 16.6 per 100,000 population. The age-specific prevalence rates showed a rapid increase after the 50th year of age. The greatest prevalence was shown by the age group 70-79 years of age in which almost 0.8 per cent of the population are affected. Age-specific incidence rates also displayed an increase after the 50th year of age. The greatest incidence was observed in the age group 70-79 years of age in which almost 1 per 1,000 of the population are annually affected by the disease. A difference between the sexes was demonstrable in the prevalence and incidence rates showing greater values for females, but in the age-specific frequencies the differences were reduced. This probably reflects the difference between the age structures of the male and female populations, suggesting that both sexes have a similar risk of being affected by the disease. The permanent age structure shown by idiopathic patients in comparison with previous investigations as well as the increased mean age and proportionate decrease of postencephalitic patients was found to be in disagreement with the cohort theory according to which all parkinsonian patients are previously victims of encephalitis lethargica.     

BLINK REFLEX IN HUNTINGTON''S CHOREA AND PARKINSON''S DISEASE

The electrically-evoked late response (R2) of the blink reflex has been determined in 8 well-documented cases of Huntington's chorea and in 19 Parkinsonian patients. The results obtained from the two groups are compared with those from 10 normal subjects. A statistically significant difference of some components of the blink reflex was obtained when the three groups were compared. In both pathological conditions, the habituation index, latency and differential latency can be considered to represent the opposite extremes from the same scale, providing further evidence of the neurophysiological antagonism between the two disease states. The blink reflex pattern in Huntington's chorea probably reflects a diminished brain-stem interneurone basal activity through an over-inhibition of dopaminergic receptors in the striatum. The electrophysiological analysis of the blink reflex in incipient Huntington's chorea can provide an objective diagnostic assessment. It might be an effective method of detection for dopaminergic-activated carriers asking for genetic counseling.     

IDIOPATHIC PARKINSON''S DISEASE AND THE LEWY BODY DISORDERS

A common clinical manifestation of idiopathic Lewy body disease is levodopa responsive idiopathic Parkinson's disease. Infrequently features such as dementia or autonomic failure predominate. The Lewy body is also reported; as an incidental finding in 7-10% of normal individuals mostly over the age of 60 as an incidental sporadic finding in Parkinson's syndrome from other causes, mostly over the age of sixty; in an additional group of degenerative disorders at a younger age, some with familial inheritance. The incidental finding of Lewy bodies can precede clinical Parkinson's disease. It is though they do not occur as an age-related feature, although this cannot be stated with certainty. Current evidence suggests that about 10% of the population may possess the pathological substratum for idiopathic Parkinson's disease.     

帕金森综合征的多巴胺能营养因子转基因治疗的展望

帕金森综合征（ＰＤ）作为一种多因素引起的中枢神经系统（ＣＮＳ）退行性疾病，其主要特征为中脑黑质多巴胺（ＤＡ）能神经通路的退化，纹状体内ＤＡ能神经减少，目前还没有很好的治疗措施。常用的药物治疗及脑移植方法均不能产久地减缓疾病的进程，并有不同程度的副作用，长期疗效不好，神经营养因子（ＮＴＦｓ）作为一类肽类活性物质除可促进神经的分化外，还能促进成年动物神经的存活和刺激神经的再生，ＮＴＦｓ中的许多成员如Ｂ     

THE SIGNIFICANCE OF THE LEWY BODY IN THE DIAGNOSIS OF IDIOPATHIC PARKINSON''S DISEASE

A retrospective study of 269 patients with a clinical diagnosis of Parkinson's syndrome was carried out. Seventy-eight were selected as cases of Parkinson's disease on the basis of generally accepted criteria. Of these, 73 were found to have Lewy bodies and cell loss in the substantia nigra, two had the pathological changes of striatonigral degeneration, two had extensive neurofibrillary tangles and nigral cell loss compatible with post-encephalitic parkinsonian syndrome, and one had Lewy bodies and striatonigral degeneration. Pathological examination of the remaining brains revealed Lewy bodies with cell loss in the nigra, a different pathological diagnosis, or normal basal ganglia. No unclassifiable 'senile' patients, or cases with neurofibrillary tangle degeneration or extranigral pathology of unknown cause were found. As a result of these findings clinico-pathological diagnostic criteria for Parkinson's disease are proposed. All patients with this diagnosis had Lewy bodies in surviving neurons of two unilateral 7 microns sections of the mid-part of the substantia nigra. The frequency of Lewy bodies in multiple system atrophy, Steele-Richardson-Olszewski syndrome and Alzheimer's disease was low and similar to that in age-matched 'normal' controls. Pathological findings were compatible with the notion that these individuals have preclinical or coincidental Parkinson's disease.     

Anti-depressive treatment in Parkinson's disease A CONTROLLED TRIAL OF THE EFFECT OF NORTRIPTYLINE IN PATIENTS WITH PARKINSON'S DISEASE TREATED WITH L-DOPA

Nineteen patients with L-DOPA treated parkinsonism involving depressive symptoms, the therapeutic effect of nortriptyline was compared to placebo in a controlled trial. The depressive and neurological symptoms were evaluated by rating scales. Nortriptyline had a clinical significant effect with regard to the depressive symptoms, whereas the neurological parameters were unchanged. The authors suggest the depression in Parkinson's disease to be of both reactive and endogenous origins.     

PIRIBEDIL (ET 495) IN THE TREATMENT OF PARKINSON'S DISEASE COMBINED WITH AMANTADINE OR LEVODOPA

The further therapeutic benefit of piribedil when combined with amantadine or Levodopa was studied by a double-blind, cross-over trial in 15 patients with Parkinson's disease. A significant improvement at the 5 per cent level for akinesia, gait, speech disorder and facial expression occurred when piribedil was added to Levodopa; and a more highly significant improvement at the 1 per cent level for akinesia, facial expression and finger dexterity occurred with piribedil and amantadine. No significant improvement occurred for special timed tests. Improvement was associated with side effects in both groups of patients. Side effects occurred with both placebo and active piribedil. Only nausea during piribedil and Levodopa treatment reached statistical significance when compared with the placebo. Piribedil did not give rise to any haematological or biochemical complications. Our findings suggest that piribedil is of further therapeutic benefit when added to amantadine or Levodopa. It was suggested that the improvement which occurred together with amantadine could be due to the combined action of both drugs on dopamine receptors.     

MYASTHENIA GRAVIS AND MYASTHENIC SYNDROMES TREATED WITH PREDNISONE

Prednisone treatment resulted in a complete or almost complete remission in 10 of 13 courses in 6 of 7 patients with myasthenia gravis or a myasthenic syndrome. In none of the patients did an initial exacerbation occur. If prednisone was withdrawn a relapse followed in a few weeks. 3 patients have been almost free from symptoms for 3½1/2–5 years on a maintenance medication. The average age of the patients was very high and perhaps prednisone has special value in the treatment of older myasthenic patients. Prednisone is probably superior to ACTH in the treatment of myasthenic patients refractory to anticholinesterase medication, because an initial exacerbation of symptoms is rare and maintenance therapy is more convenient.