Brainstem in multiple system atrophy: clinicopathological correlations

1. Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that manifests with parkinsonism, cerebellar ataxia, and autonomic failure in various combinations. 2. Orthostatic hypotension, neurogenic bladder, laryngeal stridor and sleep apnea, and rapid eye movement (REM) sleep behavior disorder are prominent manifestations of MSA. 3. In MSA, there is severe depletion of catecholaminergic neurons of the C1 and A1 areas in the ventrolateral medulla, and this may contribute to orthostatic hypotension and endocrine disturbances in this disorder, respectively. 4. Loss of corticotrophin-releasing factor (CRF) neurons in the pontine micturition area may contribute to neurogenic bladder dysfunction. 5. Respiratory abnormalities may reflect loss of cholinergic neurons in the arcuate nucleus of the ventral medulla. 6. Loss of cholinergic mesopontine neurons, in the setting of loss of locus ceruleus neurons and preservation of rostral raphe neurons, may contribute to REM sleep abnormalities in MSA.