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Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy
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Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy
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Journal Article
Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy
2018
Overview
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterised by a variable combination of autonomic failure, levodopa-unresponsive parkinsonism, cerebellar ataxia and pyramidal symptoms. The pathological hallmark is the oligodendrocytic glial cytoplasmic inclusion (GCI) consisting of α-synuclein; therefore, MSA is included in the category of α-synucleinopathies. MSA has been divided into two clinicopathological subtypes: MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia, which generally correlate with striatonigral degeneration and olivopontocerebellar atrophy, respectively. It is increasingly recognised, however, that clinical and pathological features of MSA are broader than previously considered.In this review, we aim to describe recent advances in neuropathology of MSA from a review of the literature and from information derived from review of nearly 200 definite MSA cases in the Mayo Clinic Brain Bank. In light of these new neuropathological findings, GCIs and neuronal cytoplasmic inclusions play an important role in clinicopathological correlates of MSA. We also focus on clinical diagnostic accuracy and differential diagnosis of MSA as well as candidate biomarkers. We also review some controversial topics in MSA. Cognitive impairment, which has been a non-supporting feature of MSA, is considered from both clinical and pathological perspectives. The cellular origin of α-synuclein in GCI and a ‘prion hypothesis’ are discussed. Finally, completed and ongoing clinical trials targeting disease modification, including immunotherapy, are summarised.
Publisher
BMJ Publishing Group LTD
Subject
/ Ataxia
/ Atrophy
/ Cerebellar Ataxia - physiopathology
/ Cognitive Dysfunction - physiopathology
/ Disease
/ Humans
/ Inclusion Bodies - metabolism
/ Inclusion Bodies - pathology
/ Multiple System Atrophy - metabolism
/ Multiple System Atrophy - pathology
/ Multiple System Atrophy - physiopathology
/ Multiple System Atrophy - therapy
/ Oligodendroglia - metabolism
/ Parkinsonian Disorders - physiopathology
/ Positron-Emission Tomography
/ Prions
/ Rodents
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