CLINICAL AND PATHOLOGICAL AND BIOCHEMICAL STUDIES OF THE MECHANISM UNDERLYING DYSKINESIA AND FROZEN GAIT - PATHHOPHYSIOLOGICAL STUDY USING AUTOPSIED BRAINS OF PARKINSONIAN PATIENTS IN ADVANCED STAGES

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With the long duration of Parkinson's disease, and problems encountered during its therapy, such as motor response fluctuations, dyskinesia, and levodopa-unresponsive symptoms, e.g., frozen gait, dementia develops. Although the pathophysiology of these symptoms has been described in reports of several animal experiments, the pathophysiology in parkinsonian patients has not been clarified. In this study, we analyzed biochemical markers in autopsied brains of patients with Parkinson's disease and correlated their activities or concentrations with their clinical symptoms, in order to investigate the pathophysiology of parkinsonism in humans. The biochemical markers examined in this study were tyrosine hydroxylase (TH) or dopamine (DA) as a marker of dopaminergic nerve terminals, norepinephrine (NE), GABA and glutamate (Glu) and neuropeptide (dynorphin). The brain regions in which the activity or concentrations of the above-mentioned substances were measured were the caudate nucleus and nucleus accumbens, putamen, substantia nigra, pallidum interna, pallidum externa, subthalamic nucleus. The obtained data were correlated with the clinical data of each patient ; that is, dyskinesia and wearing-off phenomenon were correlated with TH activity and levels of amino acids and dynorphin in the striatum, and frozen gait and dementia were correlated with DA and NE contents in the nucleus accumbens. There is no correlation between frozen gait, dementia and reduction in catecholamine content in the nucleus accumbens. Dyskinesia and the wearing-off phenomenon tended to correlate with a marked reduction in TH activity in the middle and caudal parts of the putamen. Results indicate that a marked reduction in dopaminaergic nerve terminals from the middle to caudal part of the putamen was a significant factor in the development of motor complications.