TY - JOUR
T1 - Clinical features of autopsy-confirmed multiple system atrophy in the Mayo Clinic Florida brain bank
AU - Koga, Shunsuke
AU - Cheshire, William P.
AU - Tipton, Philip W.
AU - Driver-Dunckley, Erika D.
AU - Wszolek, Zbigniew K.
AU - Uitti, Ryan J.
AU - Graff-Radford, Neill R.
AU - van Gerpen, Jay A.
AU - Dickson, Dennis W.
N1 - Funding Information:
Dr. Uitti receives research support from Advanced Neuromodulation Systems, Inc./St. Jude Medical.
Funding Information:
We would like to thank the patients and their families who donated brains to help further the scientific understanding of neurodegeneration. The authors would also like to acknowledge Virginia Phillips and Jo A. Landino Garcia for histologic support, and Monica Castanedes-Casey and Ariston L. Librero (Mayo Clinic, Jacksonville) for immunohistochemistry support. We also acknowledge the assistance of Ms. Audrey J. Strongosky, C.C.R.C. (Mayo Clinic, Jacksonville) for her assistance in obtaining the provisional consent for the autopsies and for her involvement in providing the assistance to families of deceased patients with procedural requirements. Supported by Rainwater Charitable Foundation , CurePSP and a Jaye F. and Betty F. Dyer Foundation Fellowship in progressive supranuclear palsy research.
Funding Information:
Dr. Dickson receives support from the NIH ( P50-NS110435 , ).
Funding Information:
Although RBD is not a red flag for MSA in the current criteria [1], RBD is often associated with ?-synucleinopathies, including PD, DLB, and MSA [25]. A multicenter study by Palma et al. reported that the frequency of clinically-suspected RBD and polysomnography-confirmed RBD in patients with probable MSA was 76% and 81%, respectively [26]. The frequency of RBD in our cohort was 48%, which was lower than their findings, but close to the result of other autopsy series with 40%?41%, probably due to the nature of brain bank-based retrospective studies [5,24]. We also found that RBD was one of the most common initial symptoms in MSA (12%), and it could precede other motor or autonomic symptoms (9%). This finding is consistent with a study based on clinically-diagnosed MSA patients [27]. The presence of RBD might be useful to support a clinical diagnosis of MSA, especially for differentiating it from non- ?-synucleinopathies, such as PSP [4]. Even within ?-synucleinopathies, idiopathic RBD, or pure autonomic failure and RBD, with preserved olfactory function, strongly predicted to progression to MSA rather than PD and DLB [28,29]. Taken together, our results, as well as the results from other studies, support the inclusion of RBD as a supportive feature for MSA in the context of differential diagnosis between MSA and non-synucleinopathies, such as PSP and idiopathic late-onset cerebellar ataxia.Dr. Cheshire receives support from NIH, Autonomic Rare Diseases Clinical Research Consortium.Dr. Wszolek is partially supported by the Mayo Clinic Center for Regenerative Medicine, Mayo Clinic in Florida Focused Research Team Program, the gifts from The Sol Goldman Charitable Trust, and the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson's Research Foundation. He serves as PI or Co-PI on Biogen, Inc. (228PD201), Biohaven Pharmaceuticals, Inc.(BHV4157-206 and BHV3241-301), and Neuraly, Inc. (NLY01-PD-1) grants. He serves as Co-PI of the Mayo Clinic APDA Center for Advanced Research.Dr. Graff-Radford has taken part in multicenter studies supported by grants from Eli Lilly, AbbVie and Biogen. He has received payment for writing a chapter in UpToDate.Dr. Dickson receives support from the NIH (P50-NS110435, ).We would like to thank the patients and their families who donated brains to help further the scientific understanding of neurodegeneration. The authors would also like to acknowledge Virginia Phillips and Jo A. Landino Garcia for histologic support, and Monica Castanedes-Casey and Ariston L. Librero (Mayo Clinic, Jacksonville) for immunohistochemistry support. We also acknowledge the assistance of Ms. Audrey J. Strongosky, C.C.R.C. (Mayo Clinic, Jacksonville) for her assistance in obtaining the provisional consent for the autopsies and for her involvement in providing the assistance to families of deceased patients with procedural requirements. Supported by Rainwater Charitable Foundation, CurePSP and a Jaye F. and Betty F. Dyer Foundation Fellowship in progressive supranuclear palsy research.
Funding Information:
Dr. Wszolek is partially supported by the Mayo Clinic Center for Regenerative Medicine , Mayo Clinic in Florida Focused Research Team Program, the gifts from The Sol Goldman Charitable Trust, and the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson's Research Foundation . He serves as PI or Co-PI on Biogen, Inc. (228PD201), Biohaven Pharmaceuticals, Inc.(BHV4157-206 and BHV3241-301), and Neuraly, Inc. (NLY01-PD-1) grants. He serves as Co-PI of the Mayo Clinic APDA Center for Advanced Research.
Funding Information:
Dr. Cheshire receives support from NIH , Autonomic Rare Diseases Clinical Research Consortium.
Publisher Copyright:
© 2021
PY - 2021/8
Y1 - 2021/8
N2 - Background: Multiple system atrophy (MSA) presents with various combinations of autonomic dysfunction, parkinsonism, and cerebellar ataxia. Although clinical diagnostic criteria have been widely used, the sensitivity and specificity are suboptimal. This study aims to provide evidence supporting the revision of the current diagnostic criteria for MSA. Methods: Medical records of 171 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank were reviewed with regard to their clinical features and diagnoses. Pathologic features, including concomitant pathologies (i.e., Alzheimer-related and Lewy-related pathologies), were also assessed. Results: The cohort included 133 MSA-parkinsonian type, 36 MSA-cerebellar type, and 2 unclassified MSA patients who did not show significant motor symptoms. Twenty-three patients (13%) were not clinically diagnosed with MSA, but instead with progressive supranuclear palsy, Parkinson's disease (PD), PD with dementia (PDD), or dementia with Lewy bodies (DLB). Three patients with PDD and DLB also had concomitant Lewy body pathology. Six patients had late-onset MSA, with an age of onset greater than 75 years. Erectile dysfunction was frequent in male patients (60/63; 95%) in all age ranges. REM sleep behavior disorder (RBD) was present in 82 patients (48%) and was the initial symptom in 13 patients. Cognitive impairment was present in 60 patients (35%), but was an initial symptom in only two patients. Conclusions: Our findings support the conclusion that late-onset presentation should not exclude MSA. The findings of this large autopsy-based cohort provides valuable insights for improving clinical criteria for MSA.
AB - Background: Multiple system atrophy (MSA) presents with various combinations of autonomic dysfunction, parkinsonism, and cerebellar ataxia. Although clinical diagnostic criteria have been widely used, the sensitivity and specificity are suboptimal. This study aims to provide evidence supporting the revision of the current diagnostic criteria for MSA. Methods: Medical records of 171 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank were reviewed with regard to their clinical features and diagnoses. Pathologic features, including concomitant pathologies (i.e., Alzheimer-related and Lewy-related pathologies), were also assessed. Results: The cohort included 133 MSA-parkinsonian type, 36 MSA-cerebellar type, and 2 unclassified MSA patients who did not show significant motor symptoms. Twenty-three patients (13%) were not clinically diagnosed with MSA, but instead with progressive supranuclear palsy, Parkinson's disease (PD), PD with dementia (PDD), or dementia with Lewy bodies (DLB). Three patients with PDD and DLB also had concomitant Lewy body pathology. Six patients had late-onset MSA, with an age of onset greater than 75 years. Erectile dysfunction was frequent in male patients (60/63; 95%) in all age ranges. REM sleep behavior disorder (RBD) was present in 82 patients (48%) and was the initial symptom in 13 patients. Cognitive impairment was present in 60 patients (35%), but was an initial symptom in only two patients. Conclusions: Our findings support the conclusion that late-onset presentation should not exclude MSA. The findings of this large autopsy-based cohort provides valuable insights for improving clinical criteria for MSA.
KW - Cognitive impairment
KW - Dementia with lewy bodies
KW - Diagnostic accuracy
KW - Erectile dysfunction
KW - Late-onset MSA
KW - Multiple system atrophy
KW - Neuropathology
KW - Parkinson's disease
KW - Progressive supranuclear palsy
KW - REM sleep Behavior disorder
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U2 - 10.1016/j.parkreldis.2021.07.007
DO - 10.1016/j.parkreldis.2021.07.007
M3 - Article
C2 - 34303202
AN - SCOPUS:85110665281
SN - 1353-8020
VL - 89
SP - 155
EP - 161
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -