Lancet neurology
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Review
Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms.
A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. ⋯ These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
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To date, there have been few systematic attempts to provide a standard operating procedure for the neuropathological diagnosis of Parkinson's disease (PD). Pathological examination cannot classify the clinical syndrome with certainty; therefore, the neuropathological diagnosis is, at best, a probability statement. The neuropathological diagnosis of parkinsonism has become increasingly based on fundamental molecular underpinnings, with recognition that the genetics of parkinsonism is heterogeneous and includes disorders that are associated with and without Lewy bodies. ⋯ In this Review we discuss the diagnostic criteria for the neuropathological assessment of PD. These criteria are provisional and need to be validated through an iterative process that could help with their refinement. Additionally, we suggest future directions for neuropathology research on PD.