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1/1. A novel grading scale for striatonigral degeneration (multiple system atrophy).

    striatonigral degeneration (SND) is commonly thought to represent the neuropathological substrate of L-Dopa unresponsive parkinsonism in patients with multiple system atrophy (MSA). Other neuropathological hallmarks of MSA include olivopontocerebellar atrophy (OPCA) and preganglionic sympathetic spinal cord lesions. Clinicopathological evaluation of MSA patients recruited into ongoing natural history studies or neuroprotective intervention trials will require standardized grading of MSA pathology. Based on 25 autopsy cases of MSA, we propose a novel SND grading scale which allows semiquantitative assessment of lesion severity based on neuronal loss, astrogliosis and presence of alpha-synuclein positive glial cytoplasmic inclusions (GCIs) in substantia nigra, putamen, caudate nucleus, and globus pallidus. SND grade I is defined as degeneration of the substantia nigra pars compacta (SNC) with relative preservation of the striatum except for minimal gliosis and GCIs in the posterior putamen ("minimal change MSA"). SND grade II is characterized by neuronal loss, astrogliosis and presence of GCIs in SNC and posterior/dorsolateral putamen. caudate nucleus and external globus pallidus may exhibit slight gliosis. Striatal pathology is severe and extends to anterior ventromedial subregions in SND grade III. There is neuronal loss in caudate nucleus and globus pallidus. GCIs are more abundant in grade II than grade III SNC and putamen. Preliminary clinicopathologic correlation studies suggest milder parkinsonian disability and better initial L-Dopa responsiveness in SND grade I and II cases compared to grade III cases. Prospective clinicopathologic studies are required to validate the proposed SND grading scale and may result in further subdivisions, particularly of SND grade III.
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