Expanding the spectrum of neuronal pathology in multiple system XXXX .

@entity1 @entity8095 @entity304 @entity73 @entity9576 @entity1833 @entity194 @entity76 @entity6447 @entity528 @entity11460
@entity9576 is a sporadic alpha-synucleinopathy that typically affects @entity1 in their sixth decade of life and beyond. The defining clinical features of the disease include @entity11460 , @entity304 , and @entity6447 leading to significant disability. Pathologically, multiple system @entity194 is characterized by glial cytoplasmic inclusions containing filamentous @entity8095 . @entity528 also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 @entity1 with multiple system @entity194 (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of @entity1 , not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. @entity528 also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system @entity194 followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of @entity1 with multiple system @entity194 , including a @entity1 with @entity1833 . Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal @entity8095 pathology, was associated with @entity73 (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, @entity76 ) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho >=  0.6) in pathologic glial and @entity528 burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system @entity194 .
