Neurodegenerative disorders with extrapyramidal features--a neuropathological overview.

Although neuropathological examination is the "gold standard" for the diagnosis of neurodegenerative disorders with extrapyramidal features, difficulties may arise in the morphological differentiation of some of these disorders. They are all associated with major structural pathology within or directly affecting the basal ganglia and related neuronal loops. In addition to progressive neuronal loss and gliosis involving specific subcortico-cortical systems or multiple circuits, many of these disorders are characterized by intracellular neuronal and/or glial inclusions indicating cytoskeletal dysmetabolism that may serve as important diagnostic signposts, whereas in other disorders, e.g. Huntington's disease, pallidal or other multisystem degenerations, no such cytopathological hallmarks have been described. The neuropathological diagnostic criteria for the major neurodegenerative disorders with extrapyramidal features based on structural cytoskeletal features and morphological lesion patterns are reviewed, and the difficulties in nosological differentiation between some groups of disorders are discussed. Although current post mortem diagnostic criteria with additional clinical information are useful in the differentiation of these disorders, in view of many clinicopathological overlaps and the lack of in vivo markers, further standardization of criteria is warranted for their exact classification order to provide further insight into their pathophysiology and pathogenesis as a basis for future therapeutic strategies.