TY - JOUR
T1 - Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy
AU - Koga, Shunsuke
AU - Dickson, Dennis W.
N1 - Funding Information:
Funding This research is supported by NiH grant P50 NS072187 and a Jaye F and Betty F Dyer Foundation Fellowship in progressive supranuclear palsy research.
Publisher Copyright:
© 2018 Article author(s) (or their employer(s) unless otherwise stated in the text of the article). All rights reserved.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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 â € prion hypothesis' are discussed. Finally, completed and ongoing clinical trials targeting disease modification, including immunotherapy, are summarised.
AB - 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 â € prion hypothesis' are discussed. Finally, completed and ongoing clinical trials targeting disease modification, including immunotherapy, are summarised.
KW - clinical neurology
KW - cognition
KW - movement disorders
KW - multisystem atrophy
KW - neuropathology
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U2 - 10.1136/jnnp-2017-315813
DO - 10.1136/jnnp-2017-315813
M3 - Review article
C2 - 28860330
AN - SCOPUS:85047248927
VL - 89
SP - 175
EP - 184
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
SN - 0022-3050
IS - 2
ER -