Epidémiologie, étiologie, physiopathologie, diagnostic et troubles cognitifs de la maladie de Parkinson.

PARKINSON'S disease; DOPAMINERGIC mechanisms; BRAIN diseases

Epidemiology, Aetiology, Pathophysiology, Diagnosis and Cognitive Disorders in Parkinson's Disease The definition of Parkinson's disease is evolving, from the classical description of a neurodegenerative disease of unknown aetiology with selective degeneration of the nigrostriatal dopaminergic (DA) pathway to a more complex picture, including genetic background and multiple subcortical abnormalities. Brain-imaging studies in twins have demonstrated a better concordance of DA depletion in asymptomatic homozygotic twins than in heterozygotic ones. Molecular studies have focused on mutations of the alpha-synuclein and parkin genes on chromosomes 4 and 6. New findings support the hypothesis that recessive forms of Parkinson's disease are related to deletions or mutations of the parkin gene. The segregation of DA neurons in the brainstem according to the density of astroglial cells, which provide the protective enzyme glutathione peroxidase, may be related to the heterogeneity of lesions in Parkinson's disease. This also supports the hypothesis of neuronal death secondary to a metabolic dysfunction of cell energy metabolism, and may be related to the toxic hypothesis of Parkinson's disease. Case control studies have recently suggested exposure to rotenone and other pesticides as a risk factor. The pathophysiology of motor symptoms remains largely unknown, even if overactivity of the subthalamic nucleus (STN) and internal pallidum is observed in akinetic patients. A differential effect of the disease and of DA drugs on the segregated D and D pathways may partly explain the levodopa-induced dyskinesias. Other pathways may be involved in the appearance of motor symptoms of Parkinson's disease, such as thalamic intralaminar or pedunculopontine nucleus lesions. Many subcortical lesions, which are mainly non-dopaminergic, can account for the cognitive impairment in Parkinson's disease, in the same way as lesions of the autonomic CNS nuclei can account for vegetative disturbances. Diagnosis of idiopathic Parkinson's disease depends mainly on clinical data: akinesia and/or tremor at rest and rigidity; unilateral or asymmetric motor disturbances; absence of a known cause of extrapyramidal disorder, and of other neurological or psychiatric signs; and long term efficacy of dopaminergic treatments. Biological analyses and brain imaging are useful only in atypical parkinsonian cases. Brain imaging by positron emission tomography (PET) or single-photon emission computed tomography (SPECT) are performed mainly in research protocols, but may become useful for preclinical diagnosis. Cognitive impairment is described as ‘subcortical’, and includes memory disturbances, attentional deficits and other deficits of executive function. Striatal, thalamic and aminergic pathways would appear to be involved. Cortical disturbances are rare, and may be correlated with the amount of Lewy bodies and/or neurofibrillary tangles in cortical neurons. Résumé La maladie de Parkinson devient moins “idiopathique” que par le passé. Des avancées importantes concernent la génétique, avec un rôle grandissant attribué aux mutations du gène parkine, et l'identification de possibles facteurs de risque exogène, comme les pesticides. La physiopathologie analyse les anomalies fonctionnelles qui sous-tendent les troubles moteurs, leur évolution et leur traitement médical ou chirurgical, les troubles végétatifs et cognitifs. L'imagerie par résonance magnétique permet d'aborder des lésions neurochimiques par spectroscopie, et les troubles de l'activation corticale, tout comme la tomographie par émission de positons. L'imagerie pourrait jouer un rôle dans la détection préclinique de la maladie, et permettre de mieux comprendre également les troubles cognitifs. [ABSTRACT FROM AUTHOR]

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