Cerebrovascular pathology and misdiagnosis of multiple system atrophy: An autopsy study

Background: Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by a combination of dysautonomia, parkinsonism, and cerebellar ataxia. Other disorders can mimic MSA, but it is unknown whether cerebrovascular pathology, so-called "vascular parkinsonism," can mimic MSA. This study aimed to determine the clinicopathological features and red flags for vascular parkinsonism masquerading as MSA.

Methods: Using a brain bank database, we screened 270 patients with an antemortem diagnosis of MSA, who did not have pathologic evidence of MSA, but rather cerebrovascular pathology, including leukoencephalopathy, lacunar infarcts, and microinfarcts. Histologic sections from the neocortex, basal ganglia, thalamus, brainstem, and cerebellum were reviewed. Medical records were reviewed to characterize the clinical features. The probability of a clinical diagnosis of MSA was assigned retrospectively, guided by current consensus criteria.

Results: Four patients had cerebrovascular pathology without neurodegenerative processes. Chronic ischemic changes in periventricular white matter, subcortical leukoencephalopathy, lacunar infarcts, or microinfarcts were detected in basal ganglia of all patients. Cerebrovascular pathology that might contribute to autonomic failure was not identified. Clinically, two patients were diagnosed with possible MSA-parkinsonism, one with probable MSA-parkinsonism, and one with possible MSA-cerebellar type; however, they also had one or more non-supporting features of MSA (e.g., onset >75-years of age, dementia), vascular risk factors, and other etiologies (e.g., autonomic neuropathy) that could cause autonomic failure.

Conclusions: When combined with cerebrovascular risk factors and comorbidities, cerebrovascular pathology may masquerade as MSA. The important lesson from this study is that the diagnosis of MSA requires exclusion of other causes, including cerebrovascular disease.