Neuropathology and Pathogenesis of Extrapyramidal Movement Disorders: A Critical Update. II. Hyperkinetic Disorders

J Neural Transm (Vienna). 2019 Aug;126(8):997-1027. doi: 10.1007/s00702-019-02030-y. Epub 2019 Jun 24.


Extrapyramidal movement disorders comprise hypokinetic-rigid and hyperkinetic or mixed forms, most of them originating from dysfunction of the basal ganglia (BG) and their information circuits that have been briefly reviewed in part 1 of the papers on neuropathology and pathogenesis of extrapyramidal movement disorders. The classification of hyperkinetic forms distinguishes the following: (1) chorea and related syndromes; (2) dystonias (dyskinesias); (3) tics and tourette disorders; (4) ballism; (5) myoclonic and startle disorders; and (6) tremor syndromes. Recent genetic and molecular classification distinguishes the following: (1) polyglutamine disorders (Huntington's disease and related disorders); (2) pantothenate kinase associated neurodegeneration; (3) Wilson's disease and related disorders; and (4) other hereditary neurodegenerations without hitherto detected genetic or specific markers. The diversity of phenotypes is related to the deposition of pathologic proteins in distinct cell populations, causing neurodegeneration due to genetic and environmental factors, but there is frequent overlap between various disorders. Their etiopathogenesis is still poorly understood but is suggested to result from an interaction between genetic and environmental factors, multiple etiologies, and noxious factors (protein mishandling, mitochondrial dysfunction, oxidative stress, excitotoxicity, energy failure, chronic neuroinflammation), being more likely than one single factor. Current clinical consensus criteria have increased the diagnostic accuracy of most neurodegenerative movement disorders, but for their definite diagnosis, histopathological confirmation is required. A timely overview of the neuropathology and pathogenesis of the major hyperkinetic movement disorders is presented.

Keywords: Chorea syndromes; Dystonias; Genetics; Movement disorders; Neuropathology; PKAN; Pathophysiology; Polyglutamine repeat disorder; Proteinopathies; Tics; Tremor syndromes; Wilson’s disease.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't