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Ozawa M, Saito R, Konno T, Kuroha Y, Ikeda T, Yokoseki A, Tani T, Sato T, Idezuka J, Koide R, Fujimoto S, Onodera O, Tada M, Kakita A. Late-onset multiple system atrophy: Neuropathological features associated with slow disease progression. Brain Pathol 2025:e70016. [PMID: 40389287 DOI: 10.1111/bpa.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 04/29/2025] [Indexed: 05/21/2025] Open
Abstract
Patients with late-onset (LO) multiple system atrophy (MSA), whose initial symptoms appear at age 75 years or older, are more common than previously assumed, but their clinicopathological characteristics remain unclear. We aimed to clarify the clinicopathological features of LO-MSA. Of 102 patients with autopsy-confirmed MSA, 5 were identified as having LO-MSA and 24 as having usual-age-onset MSA (UO-MSA) with a similar disease duration. On the basis of previous reports, we defined UO-MSA as the appearance of initial symptoms between the ages of 55 and 65 years. We compared the clinical pictures of the two groups and assessed their histopathological features using quantitative and semi-quantitative methods. The investigated features included the severity of degeneration in the striatonigral (StrN) and olivopontocerebellar (OPC) systems, the numbers of neurons in the brainstem autonomic and spinal intermediolateral nuclei, and the density of α-synuclein-immunopositive inclusions in the putamen, inferior olivary nucleus, and ventrolateral medulla (VLM). Most patients with both LO-MSA and UO-MSA exhibited the MSA-olivopontocerebellar atrophy (OPCA) subtype (3/5 and 18/24, respectively). The median disease duration for LO-MSA patients was 5.5 years, which was comparable to that for patients in our cohort who had developed symptoms below 75 years of age. Pathologically, degeneration of the StrN and OPC systems in LO-MSA was less severe than that observed in UO-MSA. Quantitative analysis revealed better preservation of neuron numbers in the brainstem autonomic nuclei in LO-MSA than in UO-MSA, with a significantly higher number of serotonergic neurons in the VLM (p = 0.013). The density of α-synuclein-positive inclusions in the putamen was significantly lower in LO-MSA than in UO-MSA (p < 0.001). Neuronal degeneration in LO-MSA may progress more slowly than in UO-MSA. Accordingly, the prognosis of LO-MSA may not necessarily be less favorable than that of MSA generally, especially with appropriate care.
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Affiliation(s)
- Misato Ozawa
- Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
- Division of Neurology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Rie Saito
- Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
| | - Takuya Konno
- Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
- Horikawa Clinic of Internal Medicine and Neurology, Niigata, Japan
| | - Yasuko Kuroha
- Department of Neurology, NHO Nishi-Niigata Chuo National Hospital, Niigata, Japan
| | - Tetsuhiko Ikeda
- Department of Neurology, NHO Niigata National Hospital, Kashiwazaki, Niigata, Japan
| | - Akio Yokoseki
- Department of Neurology, Brain Disease Center, Agano Hospital, Agano, Niigata, Japan
| | - Takashi Tani
- Department of Neurology, NHO Nishi-Niigata Chuo National Hospital, Niigata, Japan
| | - Tomoe Sato
- Department of Neurology, Saiseikai Niigata Kenoh Kikan Hospital, Sanjo, Niigata, Japan
| | - Jiro Idezuka
- Department of Neurology, Ojiya Sakura Hospital, Ojiya, Niigata, Japan
| | - Reiji Koide
- Division of Neurology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Shigeru Fujimoto
- Division of Neurology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Osamu Onodera
- Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan
| | - Mari Tada
- Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
| | - Akiyoshi Kakita
- Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan
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Ren G, Wang Y, Tian H, Zhang K, Zhang H, Liu X, Chen Z. Multiple system atrophy related neurogenic bladder: mechanism and treatment. Neurol Sci 2025; 46:1965-1976. [PMID: 39875674 DOI: 10.1007/s10072-025-08002-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 01/09/2025] [Indexed: 01/30/2025]
Abstract
BACKGROUND Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by its aggressive nature. Its main clinical features include autonomic dysfunction, Parkinson's disease, and cerebellar ataxia. METHODS We conducted a comprehensive review of the existing literature, exploring studies and reports related to the mechanisms and treatment of multiple system atrophy related neurogenic bladder. Our aim is to provide a detailed and up-to-date overview of its underlying pathophysiology and current therapeutic strategies. RESULTS AND CONCLUSION Neurogenic bladder, a common manifestation of MSA, often goes untreated or mistreated, significantly affecting patients' quality of life. Early-stage bladder dysfunction is frequent in MSA patients and correlates with disease severity. The mechanisms of MSA related neurogenic bladder are related to the autonomic nervous system, somatic nerves, frontal cortex, brainstem, and sacral medulla center. Currently, treatment for MSA related neurogenic bladder is mainly symptomatic, and specific drugs are lacking. Further in-depth research is needed to develop more effective therapeutic options that improve patients' quality of life and reduce the risk of complications.
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Affiliation(s)
- Gengqing Ren
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Yao Wang
- Tsinghua University, Beijing, 100084, China
| | - Hao Tian
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Kaige Zhang
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Han Zhang
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xiaoxu Liu
- Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Zhigang Chen
- Neurology Department One, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6, Fangxingyuan Community, Fangzhuang, Fengtai District, Beijing, 100078, People's Republic of China.
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Giannini G, Baldelli L, Provini F, Cani I, Baiardi S, Sambati L, Magliocchetti F, Guaraldi P, Parchi P, Cortelli P, Calandra-Buonaura G. Early onset sleep disorders predict severity, progression and death in multiple system atrophy. J Neurol 2025; 272:239. [PMID: 40025376 PMCID: PMC11872749 DOI: 10.1007/s00415-025-12969-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 02/08/2025] [Accepted: 02/11/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Early stridor onset (≤ 3 years from disease onset) is a predictor of shorter survival in Multiple System Atrophy (MSA), but its role on disease progression is not yet established. In MSA, previous studies on trajectories of disease did not include stridor and REM sleep behavior disorder (RBD) as clinical variable. The aims of the study were: (1) to investigate disease progression in MSA patients with early stridor onset and with early stridor and/or RBD onset; (2) to assess cerebrospinal fluid (CSF) levels of neurofilament light chain protein (NfL) in MSA patients with early onset sleep disorders. METHODS This is a retrospective and prospective cohort study including 208 (120 males) MSA patients. Occurrence of symptoms/signs, milestones of disease progression, and their latency from disease onset were collected. RBD and stridor were video-polysomnography (VPSG)-confirmed. CSF NfL levels were analyzed. Survival data and predictors of mortality were calculated. RESULTS Out of 208 MSA patients (157 deceased), 91 were diagnosed with stridor and 160 with VPSG-confirmed RBD. Patients with early stridor onset (n = 41) and with early stridor and/or RBD onset (n = 132) showed an early autonomic involvement, developed a more progressive and severe disease and presented higher CSF NfL than those with late stridor and RBD onset. Early stridor and early RBD were independent risk factors on MSA survival. CONCLUSIONS The evidence of a more rapid and severe disease progression and of high CSF NfL levels in patients who early developed sleep disorders could define a different MSA phenotype with a widespread impairment of central-brainstem circuits.
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Affiliation(s)
- Giulia Giannini
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Luca Baldelli
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Federica Provini
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Ilaria Cani
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Simone Baiardi
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Luisa Sambati
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy
| | - Franco Magliocchetti
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy
| | - Pietro Guaraldi
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy
| | - Piero Parchi
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Pietro Cortelli
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy
- Department of Biomedical and Neuromotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Giovanna Calandra-Buonaura
- IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy.
- Department of Biomedical and Neuromotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy.
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Liu M, Cai Y, Pan J, Wang T, Li Y, Yu Q, Mao W, Chan P. Serum neurofilament light chain as a diagnostic and prognostic biomarker in multiple system atrophy: a prospective cohort study. J Neurol 2024; 272:74. [PMID: 39680179 DOI: 10.1007/s00415-024-12784-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 10/10/2024] [Accepted: 10/13/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND Neurofilament light chain (NFL) in blood has been identified as a valuable biomarker in multiple system atrophy (MSA), but data regarding its utility in the early diagnosis and prognosis of MSA remain limited. OBJECTIVE To investigate serum NFL's diagnostic and prognostic value in patients with MSA in a prospective clinical cohort. METHODS Two hundred twenty-eight participants were enrolled, including ninety-eight with MSA, seventeen with uncertain MSA at inclusion, fifty-nine with Parkinson's disease (PD), and fifty-four healthy controls (HCs). Patients with MSA and uncertain diagnoses were followed up. Serum NFL levels were measured with electrochemiluminescence immunoassay at baseline. RESULTS Patients with MSA and uncertain diagnoses underwent repeated clinical assessments with a median follow-up period of 1.43 years. The final diagnoses included 102 MSA, 62 PD, and 54 HCs. Serum NFL levels were significantly higher in MSA and PD than in HCs. Serum NFL levels, with cutoff values of 223.5 and 218.0 pg/mL, could discriminate between patients with MSA and PD (AUC = 0.930) in the early disease stages, and between MSA-parkinsonism subtypes and PD (AUC = 0.878). Higher serum NFL levels were independently associated with a shorter median time to poor prognosis and death. In addition, reduced levodopa responsiveness was correlated with poor outcomes, and orthostatic hypotension (OH) was linked to a higher risk of death. CONCLUSION Serum NFL levels can not only differentiate between MSA, MSA-P, and PD in the early stages of the disease but also serve as a reliable independent predictor of poor prognosis and survival time in MSA.
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Affiliation(s)
- Min Liu
- Department of Neurology, Neurobiology and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing Institute of Geriatrics, 45 Changchun Street, Xicheng District, Beijing, 100053, China
- Department of Neurology, Beijing Longfu Hospital, Beijing, China
| | - Yanning Cai
- Department of Neurobiology, Clinical Center for Parkinson's Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Xuanwu Hospital of Capital Medical University, Beijing, China
| | - Jing Pan
- Department of Neurology, Neurobiology and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing Institute of Geriatrics, 45 Changchun Street, Xicheng District, Beijing, 100053, China
| | - Ting Wang
- Department of Neurobiology, Clinical Center for Parkinson's Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Xuanwu Hospital of Capital Medical University, Beijing, China
| | - Yuan Li
- Department of Neurology, Neurobiology and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing Institute of Geriatrics, 45 Changchun Street, Xicheng District, Beijing, 100053, China
| | - Qian Yu
- School of Health Professions, Stony Brook University, Stony Brook, New York, USA
| | - Wei Mao
- Department of Neurology, Neurobiology and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing Institute of Geriatrics, 45 Changchun Street, Xicheng District, Beijing, 100053, China.
- Department of Neurobiology, Clinical Center for Parkinson's Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Xuanwu Hospital of Capital Medical University, Beijing, China.
| | - Piu Chan
- Department of Neurology, Neurobiology and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing Institute of Geriatrics, 45 Changchun Street, Xicheng District, Beijing, 100053, China.
- Department of Neurobiology, Clinical Center for Parkinson's Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Xuanwu Hospital of Capital Medical University, Beijing, China.
- Collaborative Innovation Center for Brain Disorders, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.
- Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
- National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, China.
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Sekiya H, Tipton PW, Kawazoe M, Koga S, Murakami A, Maier AR, Uitti RJ, Cheshire WP, Wszolek ZK, Dickson DW. Current Landscape of Clinical Diagnosis in Multiple System Atrophy: A 15-Year Analysis From 2008 to 2022. Neurology 2024; 103:e210021. [PMID: 39531604 DOI: 10.1212/wnl.0000000000210021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Clinical diagnosis of multiple system atrophy (MSA) is challenging. In 2022, new diagnostic criteria for MSA were proposed. We hypothesized that the positive predictive value (PPV) of clinical diagnosis of MSA improved because of advanced diagnostic tools, including brain MRI. This study aimed to understand temporal changes in PPV of MSA. METHODS We conducted a retrospective analysis of patients clinically diagnosed with MSA whose brains were examined in the Mayo Clinic brain bank from 2008 to 2022. PPV was compared between 2 periods (2008-2017 and 2018-2022) and successively with a 4-year moving average. PPV for each clinical subtype (parkinsonism type [MSA-P] and cerebellar type [MSA-C]) was assessed. RESULTS This study included 321 patients (136 women, age at death 68 ± 9 years) with a clinical diagnosis of MSA. Among them, 225 were pathologically confirmed as MSA, resulting in an overall PPV of 70%. The remaining 30% had alternative pathologic diagnoses including Lewy body disease (18%), progressive supranuclear palsy (4%), cerebrovascular disease (1%), corticobasal degeneration (1%), and others (6%). PPV improved from 63% in 2008-2017 to 78% in 2018-2022 (odds ratio [OR] 2.0 [1.2-3.5], p = 0.005). Linear analysis also demonstrated increased PPV over time (r = 0.66 [0.14-0.89], p = 0.02). Brain MRI scans were more frequently performed in 2018-2022 compared with 2008-2017 (91% vs 80%; OR 2.4 [1.2-5.0], p = 0.012). PPV was higher in patients with brain MRI compared with those without (73% vs 52%; OR 2.5 [1.3-4.9], p = 0.0057). PPV for MSA-C was similar in both groups (87% in 2008-2017 and 93% in 2018-2022), while that for MSA-P improved from 59% in 2008-2017 to 72% in 2018-2022 (OR 1.8 [1.0-3.2], p = 0.04). DISCUSSION This study demonstrates an improvement in the PPV of MSA in recent years, potentially attributed to the increased use of brain MRI. Nevertheless, it also highlights that it remains difficult to make a correct diagnosis for some patients based on their clinical presentation. These findings provide a baseline for future clinicopathologic research on MSA.
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Affiliation(s)
- Hiroaki Sekiya
- From the Department of Neuroscience (H.S., M.K., S.K., A.M., A.R.M., D.W.D.), and Department of Neurology (P.W.T., R.J.U., W.P.C., Z.K.W.), Mayo Clinic, Jacksonville, FL
| | - Philip W Tipton
- From the Department of Neuroscience (H.S., M.K., S.K., A.M., A.R.M., D.W.D.), and Department of Neurology (P.W.T., R.J.U., W.P.C., Z.K.W.), Mayo Clinic, Jacksonville, FL
| | - Miki Kawazoe
- From the Department of Neuroscience (H.S., M.K., S.K., A.M., A.R.M., D.W.D.), and Department of Neurology (P.W.T., R.J.U., W.P.C., Z.K.W.), Mayo Clinic, Jacksonville, FL
| | - Shunsuke Koga
- From the Department of Neuroscience (H.S., M.K., S.K., A.M., A.R.M., D.W.D.), and Department of Neurology (P.W.T., R.J.U., W.P.C., Z.K.W.), Mayo Clinic, Jacksonville, FL
| | - Aya Murakami
- From the Department of Neuroscience (H.S., M.K., S.K., A.M., A.R.M., D.W.D.), and Department of Neurology (P.W.T., R.J.U., W.P.C., Z.K.W.), Mayo Clinic, Jacksonville, FL
| | - Alexia R Maier
- From the Department of Neuroscience (H.S., M.K., S.K., A.M., A.R.M., D.W.D.), and Department of Neurology (P.W.T., R.J.U., W.P.C., Z.K.W.), Mayo Clinic, Jacksonville, FL
| | - Ryan J Uitti
- From the Department of Neuroscience (H.S., M.K., S.K., A.M., A.R.M., D.W.D.), and Department of Neurology (P.W.T., R.J.U., W.P.C., Z.K.W.), Mayo Clinic, Jacksonville, FL
| | - William P Cheshire
- From the Department of Neuroscience (H.S., M.K., S.K., A.M., A.R.M., D.W.D.), and Department of Neurology (P.W.T., R.J.U., W.P.C., Z.K.W.), Mayo Clinic, Jacksonville, FL
| | - Zbigniew K Wszolek
- From the Department of Neuroscience (H.S., M.K., S.K., A.M., A.R.M., D.W.D.), and Department of Neurology (P.W.T., R.J.U., W.P.C., Z.K.W.), Mayo Clinic, Jacksonville, FL
| | - Dennis W Dickson
- From the Department of Neuroscience (H.S., M.K., S.K., A.M., A.R.M., D.W.D.), and Department of Neurology (P.W.T., R.J.U., W.P.C., Z.K.W.), Mayo Clinic, Jacksonville, FL
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Wada T, Shimizu T, Asano Y, Kaneko T, Kawazoe T, Bokuda K, Nakata Y, Naito R, Tobisawa S, Nagaoka U, Sugaya K, Takahashi K. Early-onset dysphagia predicts short survival in multiple system atrophy. J Neurol 2024; 271:6715-6723. [PMID: 39158732 DOI: 10.1007/s00415-024-12623-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND The prognostic impact of dysphagia in multiple system atrophy (MSA) remains controversial. This study aimed to investigate the relationship between dysphagia severity and survival in MSA and to elucidate whether this impact differs between MSA-cerebellar ataxia (MSA-C) and MSA-parkinsonism (MSA-P). METHODS This retrospective study included 297 patients with MSA: 251 met criteria for clinically established MSA and 46 for clinically probable MSA. Among them, 171 had MSA-C and 126 had MSA-P. We evaluated symptomatic dysphagia within 3 years of onset and quantified dysphagia severity using the Hyodo score (0 to 12) through fibreoptic endoscopic evaluation of swallowing (FEES) and clinical features, including autonomic dysfunction and vocal cord paralysis. Patients were followed up until death or tracheostomy, and survival factors were analysed using the log-rank test and multivariate Cox proportional hazards model. RESULTS Ninety patients developed symptomatic dysphagia within 3 years of onset, and 75 were evaluated for dysphagia severity using FEES. Survival from onset was shorter in patients with dysphagia within 3 years compared to those without (median: 4.2 years vs. 7.3 years; p < 0.001). Symptomatic dysphagia within 3 years of onset was an independent predictor of shorter survival in the multivariate Cox analysis. While the Hyodo score was higher in MSA-P than in MSA-C patients (p = 0.048), the Hyodo score was associated with survival in both MSA-C and MSA-P patients (log-rank p < 0.001 and p = 0.046, respectively). CONCLUSION Symptomatic dysphagia within 3 years of onset predicts shorter survival in MSA-C and MSA-P patients.
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Affiliation(s)
- Takahide Wada
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH), 2-6-1 Musashidai, Fuchu, Tokyo, 183-0042, Japan.
| | - Toshio Shimizu
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH), 2-6-1 Musashidai, Fuchu, Tokyo, 183-0042, Japan
| | - Yuri Asano
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH), 2-6-1 Musashidai, Fuchu, Tokyo, 183-0042, Japan
| | - Tetsuji Kaneko
- Department of Clinical Trial, Clinical Research Support Center, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan
| | - Tomoya Kawazoe
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH), 2-6-1 Musashidai, Fuchu, Tokyo, 183-0042, Japan
| | - Kota Bokuda
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH), 2-6-1 Musashidai, Fuchu, Tokyo, 183-0042, Japan
| | | | - Rie Naito
- Department of Neurotology, TMNH, Tokyo, Japan
| | - Shinsuke Tobisawa
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH), 2-6-1 Musashidai, Fuchu, Tokyo, 183-0042, Japan
| | - Utako Nagaoka
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH), 2-6-1 Musashidai, Fuchu, Tokyo, 183-0042, Japan
| | - Keizo Sugaya
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH), 2-6-1 Musashidai, Fuchu, Tokyo, 183-0042, Japan
| | - Kazushi Takahashi
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH), 2-6-1 Musashidai, Fuchu, Tokyo, 183-0042, Japan
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Pérez-Soriano A, Painous C, Segura B, Martí MJ. Revisiting sex-gender disparities in MSA: An unfinished narrative. Parkinsonism Relat Disord 2024:107159. [PMID: 39322469 DOI: 10.1016/j.parkreldis.2024.107159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 09/16/2024] [Accepted: 09/21/2024] [Indexed: 09/27/2024]
Affiliation(s)
- Alexandra Pérez-Soriano
- Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, FCRB-IDIBAPS, CIBERNED CB06/05/0018, European Reference Network for Rare Neurological Diseases - Project ID No 739510, University of Barcelona, Barcelona, Catalonia, Spain; Sinapsi Neurologia-UParkinson, Institut Neurociences, Centre Mèdic Teknon, Quiron-Salud, Spain
| | - Celia Painous
- Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, FCRB-IDIBAPS, CIBERNED CB06/05/0018, European Reference Network for Rare Neurological Diseases - Project ID No 739510, University of Barcelona, Barcelona, Catalonia, Spain
| | - Barbara Segura
- Medical Psychology Unit, Department of Medicine, Institute of Neurosciences, University of Barcelona, Faculty of Medicine, Clínic Campus, FCRB-IDIBAPS, CIBERNED: CB06/05/0018-ISCIII, Spain
| | - Maria José Martí
- Parkinson's Disease and Movement Disorders Unit, Neurology Service, ICN, Hospital Clínic, FCRB-IDIBAPS, CIBERNED CB06/05/0018, European Reference Network for Rare Neurological Diseases - Project ID No 739510, University of Barcelona, Barcelona, Catalonia, Spain.
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Leys F, Eschlböck S, Campese N, Mahlknecht P, Peball M, Goebel G, Sidoroff V, Krismer F, Granata R, Kiechl S, Poewe W, Seppi K, Wenning GK, Fanciulli A. Sex-related differences in the clinical presentation of multiple system atrophy. Clin Auton Res 2024; 34:253-268. [PMID: 38630378 PMCID: PMC11127878 DOI: 10.1007/s10286-024-01028-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 03/20/2024] [Indexed: 05/26/2024]
Abstract
PURPOSE To investigate sex-related differences in the clinical presentation of multiple system atrophy (MSA) through a literature review and an analysis of a retrospective cohort. METHODS The PubMed database was searched for articles including sex-related information in MSA. In a retrospective Innsbruck cohort, we investigated the baseline to last available follow-up clinical-demographic differences between men and women with MSA in a univariate fashion, followed by multivariable binary regression analysis. RESULTS The literature search yielded 46 publications with sex-related information in MSA. Most studies found comparable survival rates between the sexes, while some recent reports suggested a potential survival benefit for women, possibly due to initial motor onset and overall less severe autonomic failure compared to men. The retrospective Innsbruck MSA cohort comprised 56 female and 60 male individuals with a comparable median follow-up of 27 months. At baseline, female sex was independently associated with depression (odds ratio [OR] 4.7; p = 0.007) and male sex with severe orthostatic hypotension (OR 5.5; p = 0.016). In addition, at last follow-up, female sex was associated with the intake of central nervous system-active drugs (OR 4.1; p = 0.029), whereas male sex was associated with the presence of supine hypertension (OR 3.0; p = 0.020) and the intake of antihypertensive medications (OR 8.7; p = 0.001). Male sex was also associated with initiation of antihypertensive medications over the observation period (OR 12.4; p = 0.004). CONCLUSION The available literature and findings of the present study indicate sex-related differences in the clinical presentation of MSA and its evolution over time, highlighting the importance of considering sex in symptom exploration, therapeutic decision-making, and future clinical trial design.
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Affiliation(s)
- Fabian Leys
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Sabine Eschlböck
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
- Department of Neurology, Hochzirl-Natters Hospital, Zirl, Austria
| | - Nicole Campese
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Philipp Mahlknecht
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Marina Peball
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Georg Goebel
- Institute of Medical Statistics and Informatics, Medical University of Innsbruck, Innsbruck, Austria
| | - Victoria Sidoroff
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Florian Krismer
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Roberta Granata
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Kiechl
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Werner Poewe
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Klaus Seppi
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
- Department of Neurology, Provincial Hospital of Kufstein, Kufstein, Austria
| | - Gregor K Wenning
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
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9
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Badihian N, Savica R, Adler CH, Wszolek ZK, Jackson LM, Benarroch EE, Sandroni P, Low PA, Singer W, Coon EA. Clinical Characteristics and Outcomes in Young-Onset Multiple System Atrophy. Mov Disord Clin Pract 2024; 11:220-226. [PMID: 38468536 PMCID: PMC10928343 DOI: 10.1002/mdc3.13925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Revised: 09/22/2023] [Accepted: 10/29/2023] [Indexed: 03/13/2024] Open
Abstract
BACKGROUND Young-onset multiple system atrophy (YOMSA) is defined as the onset of multiple system atrophy (MSA) before the age of 40 years old. YOMSA is rare and there is much uncertainty of the phenotype and natural history in patients with YOMSA. OBJECTIVE The objective is to evaluate the characteristics and disease course of patients with YOMSA. METHODS We retrospectively reviewed medical records of patients with MSA who were evaluated at all Mayo Clinic sites from 1998 to 2021. We identified patients with YOMSA and evaluated clinical characteristics, autonomic function testing results, and disease course. RESULTS Of 1496 patients with a diagnosis of clinically probable or clinically established MSA, 20 patients had YOMSA. The median age of onset was 39.1 (interquartile range [IQR] = 37.1, 40.1) years; 13 patients (65%) were male. MSA-parkinsonism was the most common subtype (65%). The median duration of symptom onset to YOMSA diagnosis was 4.9 (IQR = 3.7, 9) years. At the time of medical record review, 17 patients were deceased with a median survival of 8.3 (IQR = 7, 10.9) years. Univariate analysis showed that initial onset of autonomic failure predicted unfavorable survival (hazard ratio = 2.89, P = 0.04) compared to those who presented with motor impairment only at onset. At the time of YOMSA diagnosis, composite autonomic severity score was available in 19 patients with a median of 5 (IQR = 4, 6.5). CONCLUSIONS YOMSA resembles MSA in most aspects including phenotype and prognosis, although the diagnosis is usually delayed. The presence of autonomic failure at symptom onset may be a poor predictor for survival.
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Affiliation(s)
- Negin Badihian
- Department of Neurology, Mayo ClinicRochesterMinnesotaUSA
| | - Rodolfo Savica
- Department of Neurology, Mayo ClinicRochesterMinnesotaUSA
| | - Charles H. Adler
- Department of Neurology, Mayo Clinic College of MedicineScottsdaleArizonaUSA
| | | | | | | | - Paola Sandroni
- Department of Neurology, Mayo ClinicRochesterMinnesotaUSA
| | - Phillip A. Low
- Department of Neurology, Mayo ClinicRochesterMinnesotaUSA
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10
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Ndayisaba A, Pitaro AT, Willett AS, Jones KA, de Gusmao CM, Olsen AL, Kim J, Rissanen E, Woods JK, Srinivasan SR, Nagy A, Nagy A, Mesidor M, Cicero S, Patel V, Oakley DH, Tuncali I, Taglieri-Noble K, Clark EC, Paulson J, Krolewski RC, Ho GP, Hung AY, Wills AM, Hayes MT, Macmore JP, Warren L, Bower PG, Langer CB, Kellerman LR, Humphreys CW, Glanz BI, Dielubanza EJ, Frosch MP, Freeman RL, Gibbons CH, Stefanova N, Chitnis T, Weiner HL, Scherzer CR, Scholz SW, Vuzman D, Cox LM, Wenning G, Schmahmann JD, Gupta AS, Novak P, Young GS, Feany MB, Singhal T, Khurana V. Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping. CEREBELLUM (LONDON, ENGLAND) 2024; 23:31-51. [PMID: 36190676 PMCID: PMC9527378 DOI: 10.1007/s12311-022-01471-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 08/26/2022] [Indexed: 11/30/2022]
Abstract
Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson's disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal "n-of-few" clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA.
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Affiliation(s)
- Alain Ndayisaba
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
- Division of Clinical Neurobiology, Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria
| | - Ariana T Pitaro
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Andrew S Willett
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Kristie A Jones
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Claudio Melo de Gusmao
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Abby L Olsen
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Jisoo Kim
- Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
| | - Eero Rissanen
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Jared K Woods
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
| | - Sharan R Srinivasan
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
- Department of Neurology, University of Michigan, Ann Arbor, MI , 48103, USA
| | - Anna Nagy
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Amanda Nagy
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Merlyne Mesidor
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Steven Cicero
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Viharkumar Patel
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
| | - Derek H Oakley
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | - Idil Tuncali
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Katherine Taglieri-Noble
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Emily C Clark
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Jordan Paulson
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Richard C Krolewski
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Gary P Ho
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Albert Y Hung
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
- Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | - Anne-Marie Wills
- Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | - Michael T Hayes
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Jason P Macmore
- Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | | | - Pamela G Bower
- The Multiple System Atrophy Coalition, Inc., 7918 Jones Branch Drive, Suite 300, McLean, VA, 22102, USA
| | - Carol B Langer
- The Multiple System Atrophy Coalition, Inc., 7918 Jones Branch Drive, Suite 300, McLean, VA, 22102, USA
| | - Lawrence R Kellerman
- The Multiple System Atrophy Coalition, Inc., 7918 Jones Branch Drive, Suite 300, McLean, VA, 22102, USA
| | - Christopher W Humphreys
- Department of Pulmonary, Sleep and Critical Care Medicine, Salem Hospital, MassGeneral Brigham, Salem, MA, 01970, USA
| | - Bonnie I Glanz
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Elodi J Dielubanza
- Department of Urology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
| | - Matthew P Frosch
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | - Roy L Freeman
- Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02115, USA
| | - Christopher H Gibbons
- Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02115, USA
| | - Nadia Stefanova
- Division of Clinical Neurobiology, Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria
| | - Tanuja Chitnis
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Howard L Weiner
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Clemens R Scherzer
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Sonja W Scholz
- Laboratory of Neurogenetics, Disorders and Stroke, National Institute of Neurological, National Institute of Neurological Disorders and Stroke, Bethesda, MD, 20892, USA
- Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, 21287, USA
| | - Dana Vuzman
- Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
- Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA
| | - Laura M Cox
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Gregor Wenning
- Division of Clinical Neurobiology, Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria
| | - Jeremy D Schmahmann
- Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | - Anoopum S Gupta
- Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | - Peter Novak
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Geoffrey S Young
- Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
| | - Mel B Feany
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA
| | - Tarun Singhal
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA
| | - Vikram Khurana
- Department of Neurology, Building for Transformative Medicine Room 10016L, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, Boston, 02115, USA.
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11
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Palma JA, Thijs RD. Non-Pharmacological Treatment of Autonomic Dysfunction in Parkinson's Disease and Other Synucleinopathies. JOURNAL OF PARKINSON'S DISEASE 2024; 14:S81-S92. [PMID: 37694308 PMCID: PMC11380254 DOI: 10.3233/jpd-230173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
Abstract
Symptoms of autonomic dysfunction are prevalent and can be very debilitating, reducing the quality of life in patients with Parkinson's disease (PD) and other synucleinopathies such as dementia with Lewy bodies and multiple system atrophy. Non-pharmacological therapies are key to effective management and are frequently used alone in patients with mild autonomic symptoms, or in combination with pharmacological therapies in patients with moderate and severe symptoms. This article focuses on non-pharmacological approaches. Our objective was to review the non-drug and non-surgical approaches to treating autonomic symptoms in patients with PD and other synucleinopathies, focusing on cardiovascular, gastrointestinal, and genitourinary autonomic dysfunction. Evidence supporting the effectiveness of non-pharmacological treatment for the management of neurogenic orthostatic hypotension, supine hypertension, constipation, and bladder and sexual dysfunction is available. High-quality prospective trials are scarce, yet some non-pharmacological interventions (e.g., physical counter maneuvers) can be evaluated relatively quickly on an individual basis and often seem effective. The emerging variety of clinical presentations advocates for a stepwise, individualized, and non-pharmacological approach for the management of autonomic symptoms. Often, the first step is to reduce or discontinue drugs that cause or aggravate autonomic symptoms followed by lifestyle measures. While non-pharmacological and non-surgical treatments are available and, in many cases, effective to improve symptoms of autonomic dysfunction in PD and other synucleinopathies, they are often overlooked. Large randomized trials testing and comparing non-pharmacological approaches are warranted.
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Affiliation(s)
- Jose-Alberto Palma
- Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA
| | - Roland D Thijs
- Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
- Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands
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12
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Katunina EA, Shipilova NN, Farnieva IA, Isaeva ZS, Dzugaeva FK, Belikova LP, Batsoeva DO. [Cognitive impairment in multiple system atrophy - exclusion criteria or an integral part of the clinical picture?]. Zh Nevrol Psikhiatr Im S S Korsakova 2024; 124:86-91. [PMID: 38696156 DOI: 10.17116/jnevro202412404286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/23/2024]
Abstract
Multiple system atrophy (MSA) is a severe, orphan disease characterized by a steady increase in symptoms of parkinsonism, cerebellar disorders, and autonomic failure. In addition to autonomic failure, which is considered the defining symptom of this type of atypical parkinsonism, there are a range of other non-motor clinical manifestations, such as sleep disorders, pain syndrome, anxiety-depressive disorders, cognitive impairment (CI). CI, especially severe CI, has long been considered as a distinctive feature of MCA. Recently, there have been many clinical studies with pathomorphological or neuroimaging confirmation, indicating a high prevalence of cognitive disorders in MCA. In this article, we discuss the pathogenetic mechanisms of the development of MCA and CI in MCA, as well as the range of clinical manifestations of cognitive dysfunction.
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Affiliation(s)
- E A Katunina
- Federal center of brain research and neurotechnologies, Moscow, Russia
- Pirogov Russian National Research Medical University Moscow, Russi, Pirogov Russian National Research Medical University Moscow, Russia
| | - N N Shipilova
- Federal center of brain research and neurotechnologies, Moscow, Russia
- Pirogov Russian National Research Medical University Moscow, Russi, Pirogov Russian National Research Medical University Moscow, Russia
| | - I A Farnieva
- North Caucasian Multidisciplinary Medical Center, Beslan, Russia
| | - Z S Isaeva
- Pirogov City Clinical Hospital No. 1, Moscow, Russia
| | - F K Dzugaeva
- North Caucasian Multidisciplinary Medical Center, Beslan, Russia
| | - L P Belikova
- Pirogov City Clinical Hospital No. 1, Moscow, Russia
| | - D O Batsoeva
- North Caucasian Multidisciplinary Medical Center, Beslan, Russia
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13
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Eschlboeck S, Goebel G, Eckhardt C, Fanciulli A, Raccagni C, Boesch S, Djamshidian A, Heim B, Mahlknecht P, Mair K, Nachbauer W, Scherfler C, Stockner H, Poewe W, Seppi K, Kiechl S, Wenning G, Krismer F, and the EMSA‐SG NHS Investigators. Development and Validation of a Prognostic Model to Predict Overall Survival in Multiple System Atrophy. Mov Disord Clin Pract 2023; 10:1368-1376. [PMID: 37772304 PMCID: PMC10525072 DOI: 10.1002/mdc3.13822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/05/2023] [Accepted: 06/14/2023] [Indexed: 09/30/2023] Open
Abstract
Background Multiple system atrophy (MSA) is a devastating disease characterized by a variable combination of motor and autonomic symptoms. Previous studies identified numerous clinical factors to be associated with shorter survival. Objective To enable personalized patient counseling, we aimed at developing a risk model of survival based on baseline clinical symptoms. Methods MSA patients referred to the Movement Disorders Unit in Innsbruck, Austria, between 1999 and 2016 were retrospectively analyzed. Kaplan-Meier curves and multivariate Cox regression analysis with least absolute shrinkage and selection operator penalty for variable selection were performed to identify prognostic factors. A nomogram was developed to estimate the 7 years overall survival probability. The performance of the predictive model was validated and calibrated internally using bootstrap resampling and externally using data from the prospective European MSA Study Group Natural History Study. Results A total of 210 MSA patients were included in this analysis, of which 124 patients died. The median survival was 7 years. The following clinical variables were found to significantly affect overall survival and were included in the nomogram: age at symptom onset, falls within 3 years of onset, early autonomic failure including orthostatic hypotension and urogenital failure, and lacking levodopa response. The time-dependent area under curve for internal and external validation was >0.7 within the first 7 years of the disease course. The model was well calibrated showing good overlap between predicted and actual survival probability at 7 years. Conclusion The nomogram is a simple tool to predict survival on an individual basis and may help to improve counseling and treatment of MSA patients.
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Affiliation(s)
| | - Georg Goebel
- Department of Medical Statistics Informatics and Health EconomicsInnsbruck Medical UniversityInnsbruckAustria
| | - Christine Eckhardt
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
- Department of AnesthesiaInnsbruck Medical UniversityInnsbruckAustria
| | | | - Cecilia Raccagni
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
- Department of Neurology, Provincial Hospital of BolzanoTeaching hospital of Paracelsus Medical Private UniversityBolzano‐BozenItaly
| | - Sylvia Boesch
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
| | | | - Beatrice Heim
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
| | | | - Katherina Mair
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
| | | | | | - Heike Stockner
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
| | - Werner Poewe
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
| | - Klaus Seppi
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
- Department of NeurologyProvincial Hospital of KufsteinKufsteinAustria
| | - Stefan Kiechl
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
| | - Gregor Wenning
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
| | - Florian Krismer
- Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
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14
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Peng L, Wan L, Liu M, Long Z, Chen D, Yuan X, Tang Z, Fu Y, Zhu S, Lei L, Wang C, Peng H, Shi Y, He L, Yuan H, Wan N, Hou X, Xia K, Li J, Chen C, Qiu R, Tang B, Chen Z, Jiang H. Diagnostic and prognostic performance of plasma neurofilament light chain in multiple system atrophy: a cross-sectional and longitudinal study. J Neurol 2023; 270:4248-4261. [PMID: 37184660 DOI: 10.1007/s00415-023-11741-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/22/2023] [Accepted: 04/24/2023] [Indexed: 05/16/2023]
Abstract
BACKGROUND The longitudinal dynamics of neurofilament light chain (NfL) in multiple system atrophy (MSA) were incompletely illuminated. This study aimed to explore whether the plasma NfL (pNfL) could serve as a potential biomarker of clinical diagnosis and disease progression for MSA. METHODS We quantified pNfL concentrations in both a large cross-sectional cohort with 214 MSA individuals, 65 PD individuals, and 211 healthy controls (HC), and a longitudinal cohort of 84 MSA patients. Propensity score matching (PSM) was used to balance the age between the three groups. The pNfL levels between groups were compared using Kruskal-Wallis test. Linear mixed models were performed to explore the disease progression-associated factors in longitudinal MSA cohort. Random forest model as a complement to linear models was employed to quantify the importance of predictors. RESULTS Before and after matching the age by PSM, the pNfL levels could reliably differentiate MSA from HC and PD groups, but only had mild potential to distinguish PD from HC. By combining linear and nonlinear models, we demonstrated that pNfL levels at baseline, rather than the change rate of pNfL, displayed potential prognostic value for progression of MSA. The combination of baseline pNfL levels and other modifiers, such as subtypes, Hoehn-Yahr stage at baseline, was first shown to improve the diagnosis accuracy. CONCLUSIONS Our study contributed to a better understanding of longitudinal dynamics of pNfL in MSA, and validated the values of pNfL as a non-invasive sensitive biomarker for the diagnosis and progression. The combination of pNfL and other factors is recommended for better monitoring and prediction of MSA progression.
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Affiliation(s)
- Linliu Peng
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Linlin Wan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 410008, Hunan, China
- Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National International Collaborative Research Center for Medical Metabolomics, Central South University, Changsha, 410008, Hunan, China
| | - Mingjie Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Neurology, the Affiliated Nanhua Hospital, University of South China, Hengyang, 421002, Hunan, China
| | - Zhe Long
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China
| | - Daji Chen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xinrong Yuan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Zhichao Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - You Fu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Sudan Zhu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Lijing Lei
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Chunrong Wang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Huirong Peng
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Yuting Shi
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Lang He
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Hongyu Yuan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Na Wan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xuan Hou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Kun Xia
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008, Hunan, China
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, 410008, Hunan, China
| | - Jinchen Li
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Chao Chen
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008, Hunan, China
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, 410008, Hunan, China
| | - Rong Qiu
- School of Computer Science and Engineering, Central South University, Changsha, 410083, Hunan, China
| | - Beisha Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
| | - Zhao Chen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China.
| | - Hong Jiang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Department of Neurology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China.
- National International Collaborative Research Center for Medical Metabolomics, Central South University, Changsha, 410008, Hunan, China.
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15
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Raheel K, Deegan G, Di Giulio I, Cash D, Ilic K, Gnoni V, Chaudhuri KR, Drakatos P, Moran R, Rosenzweig I. Sex differences in alpha-synucleinopathies: a systematic review. Front Neurol 2023; 14:1204104. [PMID: 37545736 PMCID: PMC10398394 DOI: 10.3389/fneur.2023.1204104] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 06/13/2023] [Indexed: 08/08/2023] Open
Abstract
Background Past research indicates a higher prevalence, incidence, and severe clinical manifestations of alpha-synucleinopathies in men, leading to a suggestion of neuroprotective properties of female sex hormones (especially estrogen). The potential pathomechanisms of any such effect on alpha-synucleinopathies, however, are far from understood. With that aim, we undertook to systematically review, and to critically assess, contemporary evidence on sex and gender differences in alpha-synucleinopathies using a bench-to-bedside approach. Methods In this systematic review, studies investigating sex and gender differences in alpha-synucleinopathies (Rapid Eye Movement (REM) Behavior Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) from 2012 to 2022 were identified using electronic database searches of PubMed, Embase and Ovid. Results One hundred sixty-two studies were included; 5 RBD, 6 MSA, 20 DLB and 131 PD studies. Overall, there is conclusive evidence to suggest sex-and gender-specific manifestation in demographics, biomarkers, genetics, clinical features, interventions, and quality of life in alpha-synucleinopathies. Only limited data exists on the effects of distinct sex hormones, with majority of studies concentrating on estrogen and its speculated neuroprotective effects. Conclusion Future studies disentangling the underlying sex-specific mechanisms of alpha-synucleinopathies are urgently needed in order to enable novel sex-specific therapeutics.
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Affiliation(s)
- Kausar Raheel
- Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
| | - Gemma Deegan
- Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
- BRAIN, Imaging Centre, CNS, King’s College London, London, United Kingdom
| | - Irene Di Giulio
- Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
- School of Basic and Medical Biosciences, Faculty of Life Science and Medicine, King’s College London, London, United Kingdom
| | - Diana Cash
- Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
- BRAIN, Imaging Centre, CNS, King’s College London, London, United Kingdom
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
| | - Katarina Ilic
- Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
- BRAIN, Imaging Centre, CNS, King’s College London, London, United Kingdom
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
| | - Valentina Gnoni
- Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
- Center for Neurodegenerative Diseases and the Aging Brain, University of Bari Aldo Moro, Lecce, Italy
| | - K. Ray Chaudhuri
- Movement Disorders Unit, King’s College Hospital and Department of Clinical and Basic Neurosciences, Institute of Psychiatry, Psychology and Neuroscience and Parkinson Foundation Centre of Excellence, King’s College London, London, United Kingdom
| | - Panagis Drakatos
- School of Basic and Medical Biosciences, Faculty of Life Science and Medicine, King’s College London, London, United Kingdom
- Sleep Disorders Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
| | - Rosalyn Moran
- Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
| | - Ivana Rosenzweig
- Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, United Kingdom
- Sleep Disorders Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
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16
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Bailey ES, Hooshmand SJ, Badihian N, Sandroni P, Benarroch EE, Bower JH, Low PA, Singer W, Coon EA. Sex and Gender Influence Urinary Symptoms and Management in Multiple System Atrophy. J Mov Disord 2023; 16:196-201. [PMID: 37258281 DOI: 10.14802/jmd.23016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 03/24/2023] [Indexed: 06/02/2023] Open
Abstract
OBJECTIVE Multiple system atrophy (MSA) is characterized by urinary dysfunction, yet the influence of sex and gender on urinary symptoms and treatment is unclear. We sought to characterize sex and gender differences in the symptomatology, evaluation, and management of urinary dysfunction in patients with MSA. METHODS Patients with MSA evaluated at our institution were reviewed and stratified by sex. RESULTS While the prevalence of urinary symptoms was similar in male and female patients, incontinence was more common in females. Despite this, males and females underwent postvoid residual (PVR) measurement at similar rates. While catheterization rates were similar when PVR was measured, males were more than twice as likely to be catheterized than females in the absence of PVR measurement. CONCLUSION Urinary symptoms are common in MSA, but their presentation differs between males and females. The difference in catheterization rates may be driven by a gender disparity in referrals for PVR, which can guide treatment.
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Affiliation(s)
| | | | - Negin Badihian
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | - Paola Sandroni
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | | | - James H Bower
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | - Phillip A Low
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
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17
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Shi Z, Zhang J, Zhao P, Li X, Liu S, Wu H, Jia P, Ji Y. Characteristics of Mild Cognitive Impairment and Associated Factors in MSA Patients. Brain Sci 2023; 13:brainsci13040582. [PMID: 37190547 DOI: 10.3390/brainsci13040582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/24/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023] Open
Abstract
Mild cognitive impairment (MCI) in multiple-system atrophy (MSA) patients is common but remains poorly characterized, and the related factors are unclear. This retrospective study included 200 consecutive patients with a clinical diagnosis of possible or probable MSA, 102 MSA patients with MCI (MSA-MCI), and 98 MSA patients with normal cognition (MSA-NC). Cognitive profiles were compared between MSA-MCI and MSA-NC patients using the MoCA. In addition, demographic as well as major motor and nonmotor symptom differences were compared between MSA-MCI and MSA-NC patients. The median MMSE score was 26 points. Overall, MSA-MCI was observed in 51% of patients, with predominant impairment in visuospatial, executive, and attention functions compared with MSA-NC patients. MSA-MCI patients were older (p = 0.015) and had a later onset age (p = 0.024) and a higher frequency of hypertension, motor onset, and MSA with the predominant parkinsonism (MSA-P) phenotype than MSA-NC patients. The positive rate of orthostatic hypotension (OH) in MSA-MCI patients was significantly decreased and depression/anxiety was significantly increased compared with MSA-NC patients (p = 0.004). Multivariate logistic analysis showed that motor onset was independently associated with MCI in MSA patients. MSA-MCI patients had impairment in visuospatial, executive, and attention functions. More prominent memory impairment was observed in MSA-P than in MSA-C patients. Motor onset was independently associated with MCI in MSA patients. MCI was commonly presented in MSA with more prominent memory impairment in MSA-P. Future follow-up studies are warranted to identify more factors that influence cognitive impairment in MSA.
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18
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Goh YY, Saunders E, Pavey S, Rushton E, Quinn N, Houlden H, Chelban V. Multiple system atrophy. Pract Neurol 2023; 23:208-221. [PMID: 36927875 DOI: 10.1136/pn-2020-002797] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/16/2023] [Indexed: 03/18/2023]
Abstract
This is a practical guide to diagnosing and managing multiple system atrophy (MSA). We explain the newly published Movement Disorders Society Consensus Diagnostic Criteria, which include new 'Clinically Established MSA' and 'Possible Prodromal MSA' categories, hopefully reducing time to diagnosis. We then highlight the key clinical features of MSA to aid diagnosis. We include a list of MSA mimics with suggested methods of differentiation from MSA. Lastly, we discuss practical symptom management in people living with MSA, including balancing side effects, with the ultimate aim of improving quality of life.
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Affiliation(s)
- Yee Yen Goh
- Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK
| | | | | | | | - Niall Quinn
- Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK
| | - Henry Houlden
- Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK
| | - Viorica Chelban
- Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK .,Neurobiology and Medical Genetics Laboratory, "Nicolae Testemitanu" State University of Medicine and Pharmacy, Chisinau, Moldova
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19
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Ali N, Nesspor V, Bang J, Scholz SW, Pantelyat A. Factors impacting quality of life in multiple system atrophy. Front Neurol 2023; 14:1111605. [PMID: 36970533 PMCID: PMC10036583 DOI: 10.3389/fneur.2023.1111605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 02/13/2023] [Indexed: 03/12/2023] Open
Abstract
BackgroundMultiple system atrophy (MSA) is an atypical parkinsonian disorder marked by autonomic dysfunction, parkinsonism, cerebellar dysfunction, and poor response to dopaminergic medications such as levodopa. Patient-reported quality of life is an important benchmark for clinicians and clinical trials. The Unified Multiple System Atrophy Rating Scale (UMSARS) allows healthcare providers to rate and assess MSA progression. The MSA-QoL questionnaire is a health-related quality of life scale intended to provide patient-reported outcome measures. In this article, we investigated inter-scale correlations between the MSA-QoL and UMSARS to determine factors impacting the quality of life of patients with MSA.MethodsTwenty patients at the Johns Hopkins Atypical Parkinsonism Center's Multidisciplinary Clinic with a diagnosis of clinically probable MSA and who filled out the MSA-QoL and UMSARS questionnaires within 2 weeks of each other were included. Inter-scale correlations between MSA-QoL and UMSARS responses were examined. Linear regressions were also performed to examine relationships between both scales.ResultsSignificant inter-scale correlations were found between the MSA-QoL and UMSARS, both between MSA-QoL total score and UMSARS Part I subtotal scores and for individual scale items. There were no significant correlations between MSA-QoL life satisfaction rating and UMSARS subtotal scores or any specific UMSARS items. Linear regression analysis found significant associations between MSA-QoL total score and UMSARS Part I and total scores, and between MSA-QoL life satisfaction rating and UMSARS Part I, Part II, and total scores (after adjustment for age).ConclusionsOur study demonstrates significant inter-scale correlations between MSA-QoL and UMSARS, particularly relating to activities of daily living and hygiene. MSA-QoL total score and UMSARS Part I subtotal scores, which assess patients' functional status, were significantly correlated. The lack of significant associations between MSA-QoL life satisfaction rating and any UMSARS item suggests there may be aspects to quality of life that are not fully captured by this assessment. Larger cross-sectional and longitudinal analyses utilizing UMSARS and MSA-QoL are warranted and modification of the UMSARS should be considered.
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Affiliation(s)
- Nabila Ali
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Vanessa Nesspor
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Jee Bang
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Sonja W. Scholz
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
| | - Alexander Pantelyat
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- *Correspondence: Alexander Pantelyat
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20
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Zhang J, Han J, Shi Z, Zhang J, Zhou Z, Liu J, Yang G, Sun Y, Gu P, Zhao P, Ma L, Gong Z, Zhao J, Liu S, Liu C, Zhai X, Shang W, Chen Z, Gan J, Ma L, Hu W, Zhu H, Ji Y. The characteristic of nonmotor symptoms with different phenotypes and onsets in multiple system atrophy patients. J Clin Neurosci 2023; 109:1-5. [PMID: 36634471 DOI: 10.1016/j.jocn.2022.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 11/26/2022] [Accepted: 12/13/2022] [Indexed: 01/11/2023]
Abstract
OBJECTIVES The characteristic of nonmotor symptoms in patients with multiple system atrophy (MSA) has varied among previous studies. The objective was to investigatethe nonmotor characteristics in MSA patients with different phenotypes, sex and different onset patterns. METHODS We performed a retrospective review of 1492 MSA patients. All cases were evaluatedby neurologists and assessed with motormanifestations, nonmotor symptoms, auxiliary examinationand brain MRI scans. RESULTS Multiple system atrophy-cerebellar ataxia (MSA-C) was the predominant phenotype in 998 patients. Average age of onset (56.8 ± 9.2 years) was earlier, the disease duration (2.4 ± 2.2 year) was shorter and brain MRI abnormalities (49.2 %) were more frequently in MSA-C (P < 0.001). Multiple system atrophy-parkinsonism (MSA-P) patients were more likely to have nonmotor symptoms. After adjusted significant parameters, urinary dysfunction (OR 1.441, 95 %CI = 1.067-1.946, P = 0.017), constipation (OR 1.482, 95 %CI = 1.113-1.973, P = 0.007), cognitive impairment (OR 1.509, 95 %CI = 1.074-2.121, P = 0.018) and drooling (OR 2.095, 95 %CI = 1.248-3.518, P = 0.005) were associated with the MSA-P phenotype. Males were more likely to have orthostatic hypotension, urinary dysfunction, sexual dysfunction, drooling and females in constipation and probable RBD. In different onset patterns, constipation (59.2 %) and probable RBD (28.4 %) were more frequently in autonomiconset pattern. CONCLUSIONS MSA-C is the predominant phenotype in Chinese patients, while many nonmotor symptoms are more common in MSA-P phenotype. Patients with different sex and onset patterns have different nonmotor characteristics. The different clinical features identified could help the physician counseling of MSA patients more easily and more accurately.
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Affiliation(s)
- Jinhong Zhang
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin 300070, China; Department of Neurology, Cangzhou People's Hospital, Cangzhou, Hebei 061000, China
| | - Jiuyan Han
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Zhihong Shi
- Tianjin Key Laboratory of Cerebrovascular and of Neurodegenerative Diseases, Tianjin 300350, China; Tianjin Dementia Institute, Department of Neurology, Tianjin Huan hu Hospital, Tianjin 300350, China
| | - Jiewen Zhang
- Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450003, China
| | - Zhi Zhou
- Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Junyan Liu
- Department of Neurology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei 050051, China
| | - Gaiqing Yang
- Department of Neurology, Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450007, China
| | - Yongan Sun
- Department of Neurology, Peking University First Hospital, Beijing 100034, China
| | - Ping Gu
- Department of Neurology, Hebei Medical University First Affiliated Hospital, Shijiazhuang, Hebei 050030, China
| | - Ping Zhao
- Department of Neurology, Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Lili Ma
- Department of Neurology Ward 3, Kaifeng Central Hospital, Kaifeng, Henan 475001, China
| | - Zhongying Gong
- Department of Neurology, Tianjin First Central Hospital, Tianjin 300190, China
| | - Jingxia Zhao
- Department of Neurology, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, Hebei 050011, China
| | - Shuai Liu
- Tianjin Key Laboratory of Cerebrovascular and of Neurodegenerative Diseases, Tianjin 300350, China; Tianjin Dementia Institute, Department of Neurology, Tianjin Huan hu Hospital, Tianjin 300350, China
| | - Chunyan Liu
- Department of Neurology, Beijing Aerospace General Hospital, Beijing 100012, China
| | - Xiaoyan Zhai
- Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei 050051, China
| | - Wanyu Shang
- Department of Neurology, Second Affiliated Hospital of Hebei, Shi Jiazhuang, Hebei 050000, China
| | - Zhichao Chen
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Jinghuan Gan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Lingyun Ma
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Wenzheng Hu
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
| | - Hongcan Zhu
- Department of Neurology, Zhengzhou University First Affiliated Hospital, Zhengzhou, Henan 450052, China.
| | - Yong Ji
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin 300070, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Tianjin Key Laboratory of Cerebrovascular and of Neurodegenerative Diseases, Tianjin Dementia Institute, Department of Neurology, Tianjin Huan hu Hospital, Tianjin 300350, China.
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21
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Chen D, Wan L, Chen Z, Yuan X, Liu M, Tang Z, Fu Y, Zhu S, Zhang X, Qiu R, Tang B, Jiang H. Serum vitamin levels in multiple system atrophy: A case-control study. Front Aging Neurosci 2023; 14:1105019. [PMID: 36688152 PMCID: PMC9849558 DOI: 10.3389/fnagi.2022.1105019] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 12/16/2022] [Indexed: 01/24/2023] Open
Abstract
Aim There is increasing evidence suggesting that vitamins may play important roles in the pathogenesis of multiple system atrophy (MSA). The purpose of this study was to detect the changes of serum vitamin levels and investigate their correlation with disease severity in MSA patients. Methods In this cross-sectional study, 244 MSA patients, 200 Parkinson's disease (PD) patients and 244 age-gender matched healthy controls were recruited. Serum vitamin levels were measured, including vitamin A, B1, B2, B9 (folate), B12, C, D, and E. Relevant clinical scales were used to assess the disease severity of MSA patients. Results Compared with the healthy controls, decreased serum folate levels and increased serum vitamin A and C levels were detected in MSA patients. Similar differences were also observed in the gender-based subgroup analysis. There were no differences detected between MSA and PD patients. In MSA patients, significant correlation was found between vitamin A, folate, or vitamin C and relevant clinical scales or laboratory findings. In addition, ROC analysis showed potential diagnostic value of the combination of vitamin A, folate, and vitamin C in distinguishing MSA patients from healthy controls. Conclusion There were significant changes in the blood vitamin spectrums of MSA patients, suggesting that dysregulation of vitamins homeostasis might play an important role in the pathogenesis of MSA.
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Affiliation(s)
- Daji Chen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Linlin Wan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China,Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China,Department of Radiology, Xiangya Hospital, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
| | - Zhao Chen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China,Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Xinrong Yuan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Mingjie Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Zhichao Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - You Fu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Sudan Zhu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Xuewei Zhang
- Health Management Center, Xiangya Hospital, Central South University, Changsha, China
| | - Rong Qiu
- School of Computer Science and Engineering, Central South University, Changsha, China
| | - Beisha Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China,Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Hong Jiang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China,Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China,Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China,School of Basic Medical Science, Central South University, Changsha, China,National International Collaborative Research Center for Medical Metabolomics, Central South University, Changsha, China,*Correspondence: Hong Jiang, ✉
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22
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Du J, Cui S, Huang P, Gao C, Zhang P, Liu J, Li H, Huang M, Shen X, Liu Z, Chen Z, Tan Y, Chen S. Predicting the Prognosis of Multiple System Atrophy Using Cluster and Principal Component Analysis. JOURNAL OF PARKINSON'S DISEASE 2023; 13:937-946. [PMID: 37522217 PMCID: PMC10578219 DOI: 10.3233/jpd-225127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/03/2023] [Indexed: 08/01/2023]
Abstract
BACKGROUND Multiple system atrophy (MSA) is an intractable neurodegenerative disorder with poorly understanding of prognostic factors. OBJECTIVE The purpose of this retrospective longitudinal study was to explore the main predictors of survival of MSA patients with new clinical subtypes based on cluster analysis. METHODS A total of 153 Chinese MSA patients were recruited in our study. The basic demographic data and motor and nonmotor symptoms were assessed. Cluster and principal component analysis (PCA) were used to eliminate collinearity and search for new clinical subtypes. The multivariable Cox regression was used to find factors associated with survival in MSA patients. RESULTS The median survival time from symptom onset to death (estimated using data from all patients by Kaplan-Meier analysis) was 6.3 (95% CI = 6.1-6.7) years. The survival model showed that a shorter survival time was associated with motor principal component (PC)1 (HR = 1.71, 95% CI: 1.26-2.30, p < 0.001) and nonmotor PC3 (HR = 1.68, 95% CI: 1.31-2.10, p < 0.001) through PCA. Four clusters were identified: Cluster 1 (mild), Cluster 2 (mood disorder-dominant), Cluster 3 (axial symptoms and cognitive impairment-dominant), and Cluster 4 (autonomic failure-dominant). Multivariate Cox regression indicated that Cluster 3 (HR = 4.15, 95% CI: 1.73-9.90, p = 0.001) and Cluster 4 (HR = 4.18, 95% CI: 1.73-10.1, p = 0.002) were independently associated with shorter survival time. CONCLUSION More serious motor symptoms, axial symptoms such as falls and dysphagia, orthostatic hypotension, and cognitive impairment were associated with poor survival in MSA via PCA and cluster analysis.
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Affiliation(s)
- Juanjuan Du
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shishuang Cui
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Lab for Translational Research of Neurodegenerative Diseases, Shanghai Institute for Advanced Immunochemical Studies (SIAIS), Shanghai Tech University, Shanghai, China
| | - Pei Huang
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chao Gao
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Pingchen Zhang
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jin Liu
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hongxia Li
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Maoxin Huang
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xin Shen
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zixian Liu
- Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zilu Chen
- Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuyan Tan
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shengdi Chen
- Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Jiang Q, Zhang L, Lin J, Wei Q, Li C, Hou Y, Ou R, Liu K, Yang T, Xiao Y, Zhao B, Wu Y, Shang H. Orthostatic Hypotension in Multiple System Atrophy: Related Factors and Disease Prognosis. JOURNAL OF PARKINSON'S DISEASE 2023; 13:1313-1320. [PMID: 38143372 PMCID: PMC10741317 DOI: 10.3233/jpd-230095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/21/2023] [Indexed: 12/26/2023]
Abstract
BACKGROUND Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by Parkinsonism, ataxia, and autonomic nervous failure. Orthostatic hypotension (OH) is the main feature of central vascular autonomic failure in MSA. OBJECTIVE The study aimed elucidate the effects of OH on cognitive function, disease milestones, and survival. METHODS A total of 444 patients with clinically established MSA were enrolled. Mild and severe OH were defined as a decrease in systolic blood pressure (SBP)/diastolic blood pressure (DBP) >20/10 mmHg and SBP/DBP ≥30/15 mmHg, respectively. RESULTS In this study, 215 MSA patients presented without OH, 88 had mild OH, and 141 had severe OH. The proportion of MSA-C in the severe OH subgroup was significantly higher than that in the subgroup without OH (95/46 vs. 113/102, p = 0.021). The UMSARS I score and the frequency of supine hypertension (SH) in patients with OH were significantly higher than those in patients without OH (16.22 vs. 16.89 vs. 14.60, p < 0.001; 77/64 vs. 29/59 vs. 32/183, p < 0.001). Factors related to the severity of OH included sex (OR, 0.65; p = 0.031), onset age (OR, 0.98; p = 0.029), and SH (OR, 0.21; p < 0.001). The median survival time of patients with severe OH was significantly lower than that of patients without OH (6.79 vs. 8.13 years, p = 0.001). Consistently, Cox survival analysis found that compared with patients without OH, patients with severe OH had a significantly increased risk of death (OR, 2.22; p < 0.001). CONCLUSION Our large cohort study of MSA provides additional evidence for the negative impact of severe OH on survival.
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Affiliation(s)
- Qirui Jiang
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lingyu Zhang
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Junyu Lin
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qianqian Wei
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chunyu Li
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yanbing Hou
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ruwei Ou
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Kuncheng Liu
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tianmi Yang
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yi Xiao
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bi Zhao
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ying Wu
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Huifang Shang
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Lamotte G, Singer W. Synucleinopathies. HANDBOOK OF CLINICAL NEUROLOGY 2023; 196:175-202. [PMID: 37620069 DOI: 10.1016/b978-0-323-98817-9.00032-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/26/2023]
Abstract
The α-synucleinopathies include pure autonomic failure, multiple system atrophy, dementia with Lewy bodies, and Parkinson disease. The past two decades have witnessed significant advances in the diagnostic strategies and symptomatic treatment of motor and nonmotor symptoms of the synucleinopathies. This chapter provides an in-depth review of the pathophysiology, pathology, genetic, epidemiology, and clinical and laboratory autonomic features that distinguish the different synucleinopathies with an emphasis on autonomic failure as a common feature. The treatment of the different synucleinopathies is discussed along with the proposal for multidisciplinary, individualized care models that optimally address the various symptoms. There is an urgent need for clinical scientific studies addressing patients at risk of developing synucleinopathies and the investigation of disease mechanisms, biomarkers, potential disease-modifying therapies, and further advancement of symptomatic treatments for motor and nonmotor symptoms.
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Affiliation(s)
- Guillaume Lamotte
- Department of Neurology, University of Utah, Salt Lake City, UT, United States
| | - Wolfgang Singer
- Department of Neurology, Mayo Clinic, Rochester, MN, United States.
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25
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Fabbri M, Foubert-Samier A, Pavy-le Traon A, Rascol O, Meissner WG. Atrofia multisistemica. Neurologia 2022. [DOI: 10.1016/s1634-7072(22)47094-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
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26
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Sekiya H, Koga S, Otsuka Y, Chihara N, Ueda T, Sekiguchi K, Yoneda Y, Kageyama Y, Matsumoto R, Dickson DW. Clinical and pathological characteristics of later onset multiple system atrophy. J Neurol 2022; 269:4310-4321. [PMID: 35305144 PMCID: PMC10315173 DOI: 10.1007/s00415-022-11067-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 03/01/2022] [Accepted: 03/04/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND In the current consensus criteria, onset after age 75 is considered as non-supporting for diagnosis of multiples system atrophy (MSA); however, some MSA patients present after age 75. Clinical and pathological characteristics of such later onset MSA (LO-MSA) compared to usual onset MSA (UO-MSA) remain poorly understood. METHODS The clinical cohort included patients from Kobe University Hospital and Amagasaki General Medical Center Hospital, while the autopsy cohort was from the brain bank at Mayo Clinic Florida. We identified 83 patients in the clinical cohort and 193 patients in the autopsy cohort. We divided MSA into two groups according to age at onset: UO-MSA (≤ 75) and LO-MSA (> 75). We compared clinical features and outcomes between the two groups in the clinical cohort and compared the findings to the autopsy cohort. RESULTS LO-MSA accounted for 8% in the clinical cohort and 5% in the autopsy cohort. The median time from onset to death or to life-saving tracheostomy was significantly shorter in LO-MSA than in UO-MSA in both cohorts (4.8 vs 7.9 years in the clinical cohort and 3.9 vs 7.5 years in the autopsy cohort; P = 0.043 and P < 0.0001, respectively). The median time from diagnosis to death was less than 3 years in LO-MSA in the clinical cohort. CONCLUSIONS Some MSA patients have late age of onset and short survival, limiting time for clinical decision making. MSA should be considered in the differential diagnosis of elderly patients with autonomic symptoms and extrapyramidal and/or cerebellar syndromes.
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Affiliation(s)
- Hiroaki Sekiya
- Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
- Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
| | - Shunsuke Koga
- Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Yoshihisa Otsuka
- Department of Neurology, Hyogo Prefectural Amagasaki General Medical Center Hospital, Amagasaki, Hyogo, Japan
| | - Norio Chihara
- Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Takehiro Ueda
- Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Kenji Sekiguchi
- Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Yukihiro Yoneda
- Department of Neurology, Hyogo Prefectural Amagasaki General Medical Center Hospital, Amagasaki, Hyogo, Japan
| | - Yasufumi Kageyama
- Department of Neurology, Hyogo Prefectural Amagasaki General Medical Center Hospital, Amagasaki, Hyogo, Japan
| | - Riki Matsumoto
- Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
| | - Dennis W Dickson
- Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
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27
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Bagchi AD. Multiple System Atrophy. J Nurse Pract 2022. [DOI: 10.1016/j.nurpra.2022.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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28
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Kühnel L, Raket LL, Åström DO, Berger A, Hansen IH, Krismer F, Wenning GK, Seppi K, Poewe W, Molinuevo J, the EMSA‐SG Natural History Study Investigators. Disease Progression in Multiple System Atrophy-Novel Modeling Framework and Predictive Factors. Mov Disord 2022; 37:1719-1727. [PMID: 35668573 PMCID: PMC9540561 DOI: 10.1002/mds.29077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 04/21/2022] [Accepted: 05/02/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Multiple system atrophy (MSA) is a rare and aggressive neurodegenerative disease that typically leads to death 6 to 10 years after symptom onset. The rapid evolution renders it crucial to understand the general disease progression and factors affecting the disease course. OBJECTIVES The aims of this study were to develop a novel disease-progression model to estimate a population-level MSA progression trajectory and predict patient-specific continuous disease stages describing the degree of progress into the disease. METHODS The disease-progression model estimated a population-level progression trajectory of subscales of the Unified MSA Rating Scale and the Unified Parkinson's Disease Rating Scale using patients in the European MSA natural history study. The predicted disease continuum was validated via multiple analyses based on reported anchor points, and the effect of MSA subtype on the rate of disease progression was evaluated. RESULTS The predicted disease continuum spanned approximately 6 years, with an estimated average duration of 51 months for a patient with global disability score 0 to reach the highest level of 4. The predicted continuous disease stages were shown to be correlated with time of symptom onset and predictive of survival time. MSA motor subtype was found to significantly affect disease progression, with MSA-parkinsonian (MSA-P) type patients having an accelerated rate of progression. CONCLUSIONS The proposed modeling framework introduces a new method of analyzing and interpreting the progression of MSA. It can provide new insights and opportunities for investigating covariate effects on the rate of progression and provide well-founded predictions of patient-level future progressions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Line Kühnel
- H. Lundbeck A/SCopenhagenDenmark
- Department of Mathematical SciencesUniversity of CopenhagenCopenhagenDenmark
| | - Lars Lau Raket
- H. Lundbeck A/SCopenhagenDenmark
- Clinical Memory Research Unit, Department of Clinical SciencesLund UniversityLundSweden
| | | | | | | | - Florian Krismer
- Department of NeurologyMedical University InnsbruckInnsbruckAustria
| | | | - Klaus Seppi
- Department of NeurologyMedical University InnsbruckInnsbruckAustria
| | - Werner Poewe
- Department of NeurologyMedical University InnsbruckInnsbruckAustria
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29
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Oyeyinka BO, Afolayan AJ. Suitability of Banana and Plantain Fruits in Modulating Neurodegenerative Diseases: Implicating the In Vitro and In Vivo Evidence from Neuroactive Narratives of Constituent Biomolecules. Foods 2022; 11:foods11152263. [PMID: 35954031 PMCID: PMC9367880 DOI: 10.3390/foods11152263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 12/12/2021] [Accepted: 12/14/2021] [Indexed: 12/04/2022] Open
Abstract
Active principles in plant-based foods, especially staple fruits, such as bananas and plantains, possess inter-related anti-inflammatory, anti-apoptotic, antioxidative, and neuromodulatory activities. Neurodegenerative diseases affect the functionality of the central and peripheral nervous system, with attendant cognitive deficits being hallmarks of these conditions. The dietary constitution of a wide range of bioactive compounds identified in this review further iterates the significance of the banana and plantain in compromising, halting, or preventing the pathological mechanisms of neurological disorders. The neuroprotective mechanisms of these biomolecules have been identified by using protein expression regulation and specific gene/pathway targeting, such as the nuclear and tumor necrosis factors, extracellular signal-regulated and mitogen-activated protein kinases, activator protein-1, and the glial fibrillary acidic protein. This review establishes the potential double-edged neuro-pharmacological fingerprints of banana and plantain fruits in their traditionally consumed pulp and less utilized peel component for human nutrition.
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30
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Kermorgant M, Fernagut PO, Meissner WG, Arvanitis DN, N'Guyen D, Senard JM, Pavy-Le Traon A. Age and Gender Differences in Cardiovascular Autonomic Failure in the Transgenic PLP-syn Mouse, a Model of Multiple System Atrophy. Front Neurol 2022; 13:874155. [PMID: 35720100 PMCID: PMC9201283 DOI: 10.3389/fneur.2022.874155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/11/2022] [Indexed: 12/02/2022] Open
Abstract
Multiple system atrophy (MSA) is a rare and progressive neurodegenerative disorder. Autonomic failure (AF) is one main clinical feature which has a significant impact on health-related quality of life. The neuropathological hallmark of MSA is the abnormal accumulation of α-synuclein in oligodendrocytes forming glial cytoplasmic inclusions. Only little is known about gender and age differences in AF in MSA. This study was carried out in 6 and 12 months old transgenic PLP-α-syn and WT male and female mice. Heart rate variability (HRV) was assessed both in time, frequential and non-linear domains. Baroreflex sensitivity (BRS) was estimated by the sequence method. Duration of ventricular depolarization and repolarization (QT/QTc intervals) were evaluated from the ECG signals. Three-way ANOVA (genotype x gender x age) with Sidak's method post-hoc was used to analyze data. BRS was significantly changed in PLP-α-syn mice and was age-dependent. QT and QTc intervals were not significantly modified in PLP-α-syn mice. An impaired HRV was observed at 12 months of age in PLP-α-syn female but not in male mice, indicative of cardiovascular AF.
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Affiliation(s)
- Marc Kermorgant
- INSERM DR Midi-Pyrénées Limousin, Institute of Cardiovascular and Metabolic Diseases (I2MC) UMR1297, University Hospital of Toulouse, Toulouse, France
- French Reference Center for Multiple System Atrophy, Neurology Department, University Hospital of Toulouse, Toulouse, France
- *Correspondence: Marc Kermorgant
| | - Pierre-Olivier Fernagut
- Univ. Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France
- Laboratoire de Neurosciences Expérimentales et Cliniques INSERM U1084, University of Poitiers, Poitiers, France
| | - Wassilios G. Meissner
- Univ. Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France
- CRMR AMS, Service de Neurologie - Maladies Neurodégénératives, CHU de Bordeaux, Bordeaux, France
- Department of Medicine, University of Otago, Christchurch, New Zealand
- New Zealand Brain Research Institute, Christchurch, New Zealand
| | - Dina N. Arvanitis
- INSERM DR Midi-Pyrénées Limousin, Institute of Cardiovascular and Metabolic Diseases (I2MC) UMR1297, University Hospital of Toulouse, Toulouse, France
| | - Du N'Guyen
- INSERM DR Midi-Pyrénées Limousin, Institute of Cardiovascular and Metabolic Diseases (I2MC) UMR1297, University Hospital of Toulouse, Toulouse, France
| | - Jean-Michel Senard
- INSERM DR Midi-Pyrénées Limousin, Institute of Cardiovascular and Metabolic Diseases (I2MC) UMR1297, University Hospital of Toulouse, Toulouse, France
- Department of Clinical Pharmacology, University Hospital of Toulouse, Toulouse, France
| | - Anne Pavy-Le Traon
- INSERM DR Midi-Pyrénées Limousin, Institute of Cardiovascular and Metabolic Diseases (I2MC) UMR1297, University Hospital of Toulouse, Toulouse, France
- French Reference Center for Multiple System Atrophy, Neurology Department, University Hospital of Toulouse, Toulouse, France
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Pharyngolaryngeal semiology and prognostic factors in multiple system atrophy. Eur Arch Otorhinolaryngol 2022; 279:4473-4483. [PMID: 35513505 PMCID: PMC9363394 DOI: 10.1007/s00405-022-07410-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 04/17/2022] [Indexed: 11/30/2022]
Abstract
Introduction Multiple system atrophy (MSA) is a rare degenerative neurological disorder in adults. It induces parkinsonian and/or cerebellar syndrome associated with dysautonomia. Pharyngolaryngeal symptoms are common. Our aim is to describe the Pharyngolaryngeal semiology on one hand, and to ascertain whether the presence of these symptoms represents a prognostic factor for MSA on the other. Methods Thus, we carried out a retrospective, single-centre study, on a cohort receiving care at the centre of reference for MSA. The patients were referred for otorhinolaryngology assessment. The data was collected over the year 2020 with the help of computer software from the university hospital centre (UHC). Firstly, we described the Pharyngolaryngeal semiology specific to MSA by questioning patients, and by the results of nasofibroscopic examinations and swallowing tests. We then used multivariate analysis of variance to describe the prognostic factors of MSA progression (in UMSARS I and II points per month of progression) and survival (number of years between the first symptoms and death). Results This study included a hundred and one patients and made it possible to define a Pharyngolaryngeal semiology profile of MSA, which is: a reduction in laryngeal mobility (primarily vocal cord abduction defects), abnormal movements (particularly at rest or when initiating a movement) and a defect in the protection mechanisms of the upper airways. The swallowing difficulties are moderate and the main mechanisms are delayed pharyngeal swallow and/or an oro-pharyngeal transport defect. In the multivariate analyses, the contributing factors are laryngeal anomalies, modification of solid food to fluid food and nutritional complication. Conclusion ENT specialists should pay close attention to problems in the Pharyngolaryngeal dynamic and then consider a neurological cause. They can also itemize the clinical factors that could have a negative effect on the prognosis of the patient with MSA. Indeed, early detection makes it possible to provide care for respiratory and nutritional complications.
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Giannini G, Provini F, Cani I, Cecere A, Mignani F, Guaraldi P, Di Mirto CVF, Cortelli P, Calandra-Buonaura G. Tracheostomy is associated with increased survival in multiple system atrophy patients with stridor. Eur J Neurol 2022; 29:2232-2240. [PMID: 35384153 PMCID: PMC9545543 DOI: 10.1111/ene.15347] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 04/02/2022] [Indexed: 11/29/2022]
Abstract
Background and purpose Stridor treatment in multiple system atrophy (MSA) mainly comprises tracheostomy or continuous positive airway pressure (CPAP), but guidelines for the use of these treatments are lacking. The aim of the study was to evaluate the predictive value of stridor treatment in an MSA cohort. Methods This is a retrospective and prospective monocentric cohort study including MSA patients evaluated at least once a year during the disease course. Stridor was video‐polysomnography confirmed. The time of stridor treatment (CPAP or tracheostomy) and latency from stridor onset were collected. Survival and predictors of survival were calculated. Results A total of 182 (107 males, mean age at disease onset 57.3 ± 8.4 years) MSA patients were included in the study; 141 were deceased at the time of study. Of the total sample, 75 patients were diagnosed with stridor: 22 patients were treated with tracheostomy and 29 with CPAP, whilst 24 patients did not receive treatment. Treatment with tracheostomy showed longer survival compared with both treatment with CPAP or no treatment (incidence rate of death 12 vs. 21 vs. 23 per 100 person‐years, respectively). Tracheostomy remained an independent factor associated with longer survival (hazard ratio 0.38, p = 0.029), also after adjustment for other confounders and latency for stridor treatment. Conclusions This is the largest monocentric and long‐term follow‐up study comparing survival between tracheostomy and CPAP in MSA patients with stridor. Treatment with tracheostomy showed longer survival compared with both treatment with CPAP or no treatment. A careful multidisciplinary approach is required for the management of MSA patients with stridor.
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Affiliation(s)
- Giulia Giannini
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy.,Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Italy
| | - Federica Provini
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy.,Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Italy
| | - Ilaria Cani
- Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Italy
| | - Annagrazia Cecere
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy
| | - Francesco Mignani
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy
| | - Pietro Guaraldi
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy
| | | | - Pietro Cortelli
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy.,Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Italy
| | - Giovanna Calandra-Buonaura
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy.,Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Italy
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Todisco M, Cosentino G, Scardina S, Fresia M, Prunetti P, Pisani A, Alfonsi E. Diagnostic and Prognostic Value of External Anal Sphincter
EMG
Patterns in Multiple System Atrophy. Mov Disord 2022; 37:1069-1074. [PMID: 35122320 PMCID: PMC9305564 DOI: 10.1002/mds.28938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 01/06/2022] [Accepted: 01/09/2022] [Indexed: 11/08/2022] Open
Abstract
Background It is debated whether external anal sphincter (EAS) electromyography can distinguish between multiple system atrophy (MSA) and Parkinson's disease (PD), whereas its usefulness for MSA prognosis is unknown. Objectives We explored the diagnostic and prognostic value and clinical correlations of EAS electromyography patterns in MSA. Methods We collected clinical data and EAS electromyography findings in 72 patients with MSA and 21 with PD. Results We identified four EAS patterns. The normal pattern was frequently observed in PD and associated with prolonged survival when identified in MSA. Abnormal patterns were predominant in MSA. The most severe pattern was associated with the highest likelihood of MSA diagnosis and with the worst prognosis in the MSA cohort. MSA patients with EAS abnormalities often showed urogenital symptoms and fecal incontinence. Conclusions The increasing severity of EAS electromyography patterns paralleled diagnostic accuracy and survival in MSA, and correlated with prevalence of bladder and bowel symptoms. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
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Affiliation(s)
- Massimiliano Todisco
- Translational Neurophysiology Research Unit IRCCS Mondino Foundation Pavia Italy
- Movement Disorders Research Center IRCCS Mondino Foundation Pavia Italy
- Department of Brain and Behavioral Sciences University of Pavia Pavia Italy
| | - Giuseppe Cosentino
- Translational Neurophysiology Research Unit IRCCS Mondino Foundation Pavia Italy
- Department of Brain and Behavioral Sciences University of Pavia Pavia Italy
| | - Serena Scardina
- Department of Biomedicine, Neuroscience and advanced Diagnostics (BIND) University of Palermo Palermo Italy
| | - Mauro Fresia
- Translational Neurophysiology Research Unit IRCCS Mondino Foundation Pavia Italy
| | - Paolo Prunetti
- Translational Neurophysiology Research Unit IRCCS Mondino Foundation Pavia Italy
| | - Antonio Pisani
- Movement Disorders Research Center IRCCS Mondino Foundation Pavia Italy
- Department of Brain and Behavioral Sciences University of Pavia Pavia Italy
| | - Enrico Alfonsi
- Translational Neurophysiology Research Unit IRCCS Mondino Foundation Pavia Italy
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Cao B, Liang Y, Zhang LY, Hou YB, Ou RW, Wei QQ, Shang H. The Cold Hand Sign in Multiple System Atrophy: Frequency-Associated Factors and Its Impact on Survival. Front Aging Neurosci 2022; 13:767211. [PMID: 34987378 PMCID: PMC8722673 DOI: 10.3389/fnagi.2021.767211] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 11/18/2021] [Indexed: 02/05/2023] Open
Abstract
Background: Few studies have focused on the cold hand sign (CHS), a red flag symptom, in multiple system atrophy (MSA). Objective: This study aimed to investigate the frequency and correlative factors of CHS in patients with MSA and the impact of its early occurrence on the survival of these patients. Methods: A total of 483 patients with MSA were enrolled in this study, and the motor and non-motor symptoms between patients with MSA with and without CHS were compared. Moreover, patients with disease duration ≤ 3 years at baseline were followed, and the association between CHS and survival of patients with MSA was examined. Results: The frequencies of CHS in patients with MSA were 20, 15.4, and 25.3% in MSA, MSA-parkinsonian subtype (MSA-P), and MSA-cerebellar subtype (MSA-C), respectively. Higher Unified Multiple System Atrophy Rating Scale (UMSARS) scores and higher Non-Motor Symptom Scale (NMSS) scores at baseline were associated with CHS in MSA. CHS was associated with shorter survival after adjusting for baseline diagnosis subtype, age at onset, sex, orthostatic hypotension, disease duration, autonomic onset, UMSARS total score, and NMSS score (p = 0.001; HR = 3.701; 95% CI = 1.765–7.760). Conclusion: CHS is not rare in patients with MSA. Greater disease severity and more severe non-motor symptoms were associated with CHS in patients with MSA. Patients with early occurrence of CHS had a poor prognosis.
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Affiliation(s)
- Bei Cao
- Laboratory of Neurodegenerative Disorders, Department of Neurology, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Yan Liang
- Laboratory of Neurodegenerative Disorders, Department of Neurology, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Ling-Yu Zhang
- Laboratory of Neurodegenerative Disorders, Department of Neurology, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Yan-Bing Hou
- Laboratory of Neurodegenerative Disorders, Department of Neurology, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Ru-Wei Ou
- Laboratory of Neurodegenerative Disorders, Department of Neurology, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Qian-Qian Wei
- Laboratory of Neurodegenerative Disorders, Department of Neurology, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Huifang Shang
- Laboratory of Neurodegenerative Disorders, Department of Neurology, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
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35
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Nishida K, Sakashita K, Yamasaki H, Futamura N. Impact of tracheostomy invasive ventilation on survival in Japanese patients with multiple system atrophy. Parkinsonism Relat Disord 2022; 97:107-111. [DOI: 10.1016/j.parkreldis.2022.01.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/13/2021] [Accepted: 01/08/2022] [Indexed: 01/09/2023]
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Gong D, Wang W, Yuan X, Yu H, Zhao M. Long-Term Clinical Efficacy of Human Umbilical Cord Blood Mononuclear Cell Transplantation by Lateral Atlanto-Occipital Space Puncture (Gong's Puncture) for the Treatment of Multiple System Atrophy. Cell Transplant 2022; 31:9636897221136553. [PMID: 36354017 DOI: 10.1177/09636897221136553] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2024] Open
Abstract
Multiple system atrophy (MSA) is a sporadic, progressive neurodegenerative disease characterized by autonomic nervous dysfunction with parkinsonism or cerebellar ataxia. Mesenchymal stem cell therapy or transplantation of human umbilical cord blood mononuclear cells (hUCB-MCs) may inhibit progression in MSA, but long-term studies are lacking. In addition, injection of stem cells via lateral atlanto-occipital space puncture (LASP, or Gong's puncture) may efficiently target areas of brain injury and avoid the disadvantages of other methods. This prospective study investigated the long-term clinical efficacy of transplantation of hUCB-MCs via LASP for the treatment of MSA. Seven patients with MSA who received hUCB-MC transplantation via LASP were followed for 3 to 5 years. Neurological function was evaluated before (baseline), at 3, 6, and 12 months, and annually after the first transplantation using the Unified MSA Rating Scale (UMSARS); a lower score indicated improvement. Adverse events were recorded. The best therapeutic effect was observed 3 to 6 months after the first hUCB-MC transplantation. The total UMSARS score at the timepoint of best effect (25.71 ± 11.87) was significantly lower than the score before treatment (42.57 ± 7.96; P = 0.001), but also significantly lower than at the end of follow-up (35.14 ± 18.21; P = 0.038). The UMSARS II score (findings on neurological examination) at the timepoint of best effect was significantly lower than before treatment (P = 0.001). There were no serious adverse events. In conclusion, transplantation of hUCB-MCs via LASP is a safe and effective treatment for MSA.
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Affiliation(s)
- Dianrong Gong
- Department of Neurology, Liaocheng People's Hospital, Liaocheng District, China
| | - Weifei Wang
- Department of Neurology, Liaocheng People's Hospital, Liaocheng District, China
| | - Xiaoling Yuan
- Department of Neurology, Liaocheng People's Hospital, Liaocheng District, China
| | - Haiyan Yu
- Department of Neurology, Liaocheng People's Hospital, Liaocheng District, China
| | - Min Zhao
- Department of Neurology, Liaocheng People's Hospital, Liaocheng District, China
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37
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Lo R. Epidemiology of atypical parkinsonian syndromes. Tzu Chi Med J 2022; 34:169-181. [PMID: 35465274 PMCID: PMC9020244 DOI: 10.4103/tcmj.tcmj_218_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 09/10/2020] [Accepted: 09/15/2020] [Indexed: 11/04/2022] Open
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Zhang L, Cao B, Hou Y, Gu X, Wei Q, Ou R, Zhao B, Luo C, Shang H. Neurofilament Light Chain Predicts Disease Severity and Progression in Multiple System Atrophy. Mov Disord 2021; 37:421-426. [PMID: 34719813 DOI: 10.1002/mds.28847] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/09/2021] [Accepted: 10/13/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Neurofilament light chain (NFL), a potential biomarker of multiple system atrophy (MSA), has been reported in several studies. OBJECTIVES The objective of this study was to investigate whether plasma NFL levels are correlated with the progression of motor and cognition function in MSA. METHODS Patients with MSA were part of a prospective cohort study with assessments at baseline and after 1 year. Plasma NFL was quantified using ultrasensitive Simoa technology. RESULTS A total of 91 patients with MSA and 60 healthy controls (HCs) were enrolled. NFL levels increased from baseline to 1-year follow-up (P = 0.010). Baseline plasma NFL levels were significantly associated with motor severity and progression in patients with MSA (P < 0.05) but not with cognitive progression (P > 0.05). CONCLUSIONS Plasma NFL is a reliable biomarker for the disease severity of MSA and monitoring the progression of MSA, but not the progression of cognition. © 2021 International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Lingyu Zhang
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Bei Cao
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Yanbing Hou
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaojing Gu
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Qianqian Wei
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Ruwei Ou
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Bi Zhao
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Chunyan Luo
- Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Huifang Shang
- Department of Neurology, Laboratory of Neurodegenerative Disorders, Rare Diseases Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
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Fukushima K, Nakamura A, Takei YI, Oguchi K, Itagaki H, Ohara S, Yamada M. Elderly-Onset Multiple System Atrophy with Lewy Body Pathology: A Case Report. Case Rep Neurol 2021; 13:613-619. [PMID: 34703451 PMCID: PMC8460921 DOI: 10.1159/000515973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 03/09/2021] [Indexed: 11/19/2022] Open
Abstract
An 81-year-old woman presented with a 2-year history of progressive dysarthria and gait disturbance. Subsequently, she developed orthostatic hypotension, obstructive sleep apnea, right-sided resting tremor, and rigidity. Together with characteristic findings of imaging studies, she was diagnosed with multiple system atrophy (MSA). Despite progressive dysphagia and repeated choking episodes, the patient elected not to use artificial feeding or tracheostomy. She died suddenly at age 91 after 12 years of illness. The autopsy revealed neuropathological features of both MSA and of Parkinson's disease. The peripheral autonomic ganglia revealed both pre- and postganglionic involvement by synucleinopathy, which may have underscored the sudden death of the patient. The patient survived 10 years after onset, despite the presence of multiple poor prognostic factors in MSA including the onset of old age and early appearance of orthostatic hypotension and falls, in addition to the complication of PD pathology found by autopsy. Multidisciplinary team approach and her preserved cognitive function may have been contributory to the long-term survival.
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Affiliation(s)
- Kazuhiro Fukushima
- Department of Neurology, National Hospital Organization, Matsumoto Medical Center, Matsumoto, Japan
| | - Akinori Nakamura
- Department of Neurology, National Hospital Organization, Matsumoto Medical Center, Matsumoto, Japan
| | - Yo-Ichi Takei
- Department of Neurology, National Hospital Organization, Matsumoto Medical Center, Matsumoto, Japan
| | - Kenya Oguchi
- Department of Neurology, National Hospital Organization, Matsumoto Medical Center, Matsumoto, Japan
| | - Hiroko Itagaki
- Department of Diagnostic Pathology, National Hospital Organization, Matsumoto Medical Center, Matsumoto, Japan
| | - Shinji Ohara
- Department of Neurology, National Hospital Organization, Matsumoto Medical Center, Matsumoto, Japan.,Department of Neurology, Iida Hospital, Iida, Japan
| | - Mitsunori Yamada
- Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Japan
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Malfertheiner K, Stefanova N, Heras-Garvin A. The Concept of α-Synuclein Strains and How Different Conformations May Explain Distinct Neurodegenerative Disorders. Front Neurol 2021; 12:737195. [PMID: 34675870 PMCID: PMC8523670 DOI: 10.3389/fneur.2021.737195] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 09/08/2021] [Indexed: 12/27/2022] Open
Abstract
In the past few years, an increasing amount of studies primarily based on experimental models have investigated the existence of distinct α-synuclein strains and their different pathological effects. This novel concept could shed light on the heterogeneous nature of α-synucleinopathies, a group of disorders that includes Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, which share as their key-molecular hallmark the abnormal aggregation of α-synuclein, a process that seems pivotal in disease pathogenesis according to experimental observations. However, the etiology of α-synucleinopathies and the initial events leading to the formation of α-synuclein aggregates remains elusive. Hence, the hypothesis that structurally distinct fibrillary assemblies of α-synuclein could have a causative role in the different disease phenotypes and explain, at least to some extent, their specific neurodegenerative, disease progression, and clinical presentation patterns is very appealing. Moreover, the presence of different α-synuclein strains might represent a potential biomarker for the diagnosis of these neurodegenerative disorders. In this regard, the recent use of super resolution techniques and protein aggregation assays has offered the possibility, on the one hand, to elucidate the conformation of α-synuclein pathogenic strains and, on the other hand, to cyclically amplify to detectable levels low amounts of α-synuclein strains in blood, cerebrospinal fluid and peripheral tissue from patients. Thus, the inclusion of these techniques could facilitate the differentiation between α-synucleinopathies, even at early stages, which is crucial for successful therapeutic intervention. This mini-review summarizes the current knowledge on α-synuclein strains and discusses its possible applications and potential benefits.
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Affiliation(s)
- Katja Malfertheiner
- Laboratory for Translational Neurodegeneration Research, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Nadia Stefanova
- Laboratory for Translational Neurodegeneration Research, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Antonio Heras-Garvin
- Laboratory for Translational Neurodegeneration Research, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
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41
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Eschlböck S, Kiss G, Krismer F, Fanciulli A, Kaindlstorfer C, Raccagni C, Seppi K, Kiechl S, Panicker JN, Wenning GK. Urodynamic Evaluation in Multiple System Atrophy: A Retrospective Cohort Study. Mov Disord Clin Pract 2021; 8:1052-1060. [PMID: 34631941 PMCID: PMC8485589 DOI: 10.1002/mdc3.13307] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 06/13/2021] [Accepted: 06/27/2021] [Indexed: 12/19/2022] Open
Abstract
Background Urological dysfunction in patients with multiple system atrophy (MSA) is one of the main manifestations of autonomic failure. Urodynamic examination is clinically relevant since underlying pathophysiology of lower urinary tract (LUT) dysfunction can be variable. Objective Evaluation of the pathophysiology of urological symptoms and exploration of differences in urodynamic patterns of LUT dysfunction between MSA-P and MSA-C. Methods Retrospective study of patients with possible and probable MSA who were referred for urodynamic studies between 2004 and 2019. Demographic data, medical history, physical examination and urodynamic studies assessing storage and voiding dysfunction were obtained. Results Seventy-four patients were included in this study (MSA-P 64.9% n = 48; median age 62.5 (IQR 56.8-70) years). Detrusor overactivity during filling phase was noted in 58.1% (n = 43) of the patients. In the voiding phase, detrusor sphincter dyssynergia and detrusor underactivity were observed in 24.6% (n = 17) and in 62.1% (n = 41) of the patients, respectively. A postmicturition residual volume of over 100 ml was present in 71.4% (n = 50) of the patients. Comparison of MSA subtypes showed weaker detrusor contractility in MSA-P compared to MSA-C [pdetQmax 26.2 vs. 34.4 cmH20, P = 0.04]. In 56.2% (n = 41) of patients pathophysiology of LUT dysfunction was deemed to be neurogenic and consistent with the diagnosis of MSA. In 35.6% (n = 26) urodynamic pattern suggested other urological co-morbidities. Conclusion Urodynamic evaluation is an important tool to analyze the pattern of LUT dysfunction in MSA. Impaired detrusor contractility was seen more in MSA-P which needs to be investigated in further studies.
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Affiliation(s)
- Sabine Eschlböck
- Department of Neurology Medical University of Innsbruck Innsbruck Austria
| | - Gustav Kiss
- Division of Neurourology, Department of Urology Medical University of Innsbruck Innsbruck Austria
| | - Florian Krismer
- Department of Neurology Medical University of Innsbruck Innsbruck Austria
| | | | | | - Cecilia Raccagni
- Department of Neurology Medical University of Innsbruck Innsbruck Austria.,Department of Neurology Regional General Hospital Bolzano Italy
| | - Klaus Seppi
- Department of Neurology Medical University of Innsbruck Innsbruck Austria
| | - Stefan Kiechl
- Department of Neurology Medical University of Innsbruck Innsbruck Austria
| | - Jalesh N Panicker
- Department of Uro-Neurology The National Hospital for Neurology and Neurosurgery, and UCL Queen Square Institute of Neurology London United Kingdom
| | - Gregor K Wenning
- Department of Neurology Medical University of Innsbruck Innsbruck Austria
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Marsili L, Giannini G, Cortelli P, Colosimo C. Early recognition and diagnosis of multiple system atrophy: best practice and emerging concepts. Expert Rev Neurother 2021; 21:993-1004. [PMID: 34253122 DOI: 10.1080/14737175.2021.1953984] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Introduction: Multiple system atrophy (MSA) is a progressive degenerative disorder of the central and autonomic nervous systems characterized by parkinsonism, cerebellar ataxia, dysautonomia, and pyramidal signs. The confirmatory diagnosis is pathological, but clinical-diagnostic criteria have been developed to help clinicians. To date, the early diagnosis of MSA is challenging due to the lack of reliable diagnostic biomarkers.Areas covered: The authors reappraised the main clinical, neurophysiological, imaging, genetic, and laboratory evidence to help in the early diagnosis of MSA in the clinical and in the research settings. They also addressed the practical clinical issues in the differential diagnosis between MSA and other parkinsonian and cerebellar syndromes. Finally, the authors summarized the unmet needs in the early diagnosis of MSA and proposed the next steps for future research efforts in this field.Expert opinion: In the last decade, many advances have been achieved to help the correct MSA diagnosis since early stages. In the next future, the early diagnosis and correct classification of MSA, together with a better knowledge of the causative mechanisms of the disease, will hopefully allow the identification of suitable candidates to enroll in clinical trials and select the most appropriate disease-modifying strategies to slow down disease progression.
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Affiliation(s)
- Luca Marsili
- Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA
| | - Giulia Giannini
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica NeuroMet, Ospedale Bellaria, Bologna, Italy.,Dipartimento di Scienze Biomediche e Neuromotorie, Università Bologna, Bologna, Italy
| | - Pietro Cortelli
- IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica NeuroMet, Ospedale Bellaria, Bologna, Italy.,Dipartimento di Scienze Biomediche e Neuromotorie, Università Bologna, Bologna, Italy
| | - Carlo Colosimo
- Department of Neurology, Santa Maria University Hospital, Terni, Italy
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Giannini G, Provini F, Cortelli P, Calandra-Buonaura G. REM Sleep Behaviour Disorder in Multiple System Atrophy: From Prodromal to Progression of Disease. Front Neurol 2021; 12:677213. [PMID: 34194385 PMCID: PMC8238043 DOI: 10.3389/fneur.2021.677213] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 05/04/2021] [Indexed: 12/25/2022] Open
Abstract
A higher frequency of motor and breathing sleep-related disorders in multiple system atrophy (MSA) populations is reported. REM sleep behaviour disorder (RBD) is one of the most robust markers of an underlying alpha-synucleinopathy. Although a large corpus of literature documented the higher prevalence of RBD in MSA, few studies have systematically investigated the prevalence of RBD as mode of disease onset and its role in disease progression. Moreover, there has been increasing interest in phenoconversion into synucleinopathies of cohorts of patients with isolated RBD (iRBD). Finally, some studies investigated RBD as predictive factor of conversion in isolated autonomic failure, a synucleinopathy presenting with autonomic failure as the sole clinical manifestation that could convert to a manifest central nervous system synucleinopathy. As the field of neurodegenerative disorders moves increasingly towards developing disease-modifying therapies, detecting individuals in the prodromal stage of these synucleinopathies becomes crucial. The aims of this review are to summarise (1) the prevalence of RBD during the course of MSA and as presenting feature of MSA (iRBD), (2) the RBD features in MSA, (3) MSA progression and prognosis in the subgroup of patients with RBD predating disease onset, and (4) the prevalence of MSA conversion in iRBD cohorts. Moreover, we summarise previous results on the role of RBD in the context of isolated autonomic failure as marker of phenoconversion to other synucleinopathies and, in particular, to MSA.
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Affiliation(s)
- Giulia Giannini
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Unità Operativa Complessa (UOC) Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy.,Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Federica Provini
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Unità Operativa Complessa (UOC) Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy.,Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Pietro Cortelli
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Unità Operativa Complessa (UOC) Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy.,Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Giovanna Calandra-Buonaura
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Unità Operativa Complessa (UOC) Clinica Neurologica Rete Metropolitana NEUROMET, Bologna, Italy.,Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Alma Mater Studiorum - University of Bologna, Bologna, Italy
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Yoo HS, Chung SJ, Lee YH, Ye BS, Sohn YH, Kwon H, Lee PH. Urate is closely linked to white matter integrity in multiple system atrophy. Ann Clin Transl Neurol 2021; 7:1029-1039. [PMID: 32588990 PMCID: PMC7318089 DOI: 10.1002/acn3.51073] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 05/07/2020] [Accepted: 05/11/2020] [Indexed: 12/13/2022] Open
Abstract
Objective We aimed to investigate the association of the serum urate level with cortical thickness and white matter integrity in multiple system atrophy (MSA). Methods We recruited 75 MSA patients and 42 controls who underwent brain MRI and measured serum urate level at baseline. Using cortical thickness and tract‐based spatial statistics analyses, we investigated the correlation between serum urate levels and cortical thickness or diffusion tensor imaging (DTI) measures in controls and MSA patients. Interaction effects were analyzed to find different patterns of correlation according to sex and clinical subtype. We evaluated the relationship between serum urate levels, DTI measures, and total UMSARS score, using path analysis. Results Serum urate levels showed a positive correlation with FA values in the corpus callosum and a negative correlation with MD values in widespread regions including cerebellar, brainstem, and cerebral white matter in patients with MSA. Both sexes showed a negative correlation between serum urate levels and MD values without significant interaction effect. In subgroup analysis according to subtype, patients with cerebellar subtype showed a negative correlation. Serum urate levels did not correlated with cortical thickness. Path analysis showed that MD values in middle and inferior cerebellar peduncle mediated the association between serum urate level and total UMSAR score. Interpretation The present study demonstrated that serum urate levels played a pivotal role in white matter disintegrity and clinical disability in MSA. It would provide an evidence of the role of urate as a potential neuroprotective factor against white matter neurodegeneration in MSA.
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Affiliation(s)
- Han Soo Yoo
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
| | - Seok Jong Chung
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
| | - Yang Hyun Lee
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
| | - Byoung Seok Ye
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
| | - Young H Sohn
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea
| | - Hunki Kwon
- Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Phil Hyu Lee
- Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.,Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea
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Coon EA, Ahlskog JE. My Treatment Approach to Multiple System Atrophy. Mayo Clin Proc 2021; 96:708-719. [PMID: 33673922 DOI: 10.1016/j.mayocp.2020.10.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 08/07/2020] [Accepted: 10/13/2020] [Indexed: 11/28/2022]
Abstract
Multiple system atrophy (MSA) is a neurodegenerative disorder primarily characterized by autonomic failure plus parkinsonism or cerebellar ataxia. The diagnosis may be challenging and is usually made at a tertiary care center. The long-term management issues are equally challenging and frequently require collaboration with the patient's local care providers. Whereas there is currently no cure for MSA, treatment focuses on the most problematic symptoms experienced by the patient. Autonomic symptoms may include severe orthostatic hypotension with syncope, urinary symptoms culminating in incontinence, constipation, anhidrosis, and erectile dysfunction. Motor symptoms include parkinsonism, cerebellar ataxia, and falls. Although certain motor symptoms may respond partially to medications, some of these medications may exacerbate autonomic problems. In this manuscript, we seek to bridge the gap between tertiary care providers and the patient's local care providers to provide multidisciplinary care to the MSA patient. Patients are often best served by management of their chronic and evolving complex problems with a team approach involving their primary care providers and subspecialists. Treatment guidelines typically list myriad therapeutic options without clarifying the most efficacious and simplest treatment strategies. Herein, we provide a guideline based on what has worked in our MSA clinic, a clinic designed to provide care throughout the disease course with subspecialty integration with the goal of empowering a partnership with the patient's home primary care providers.
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Gurevich T, Merkin L, Rozenberg A, Fisher A, Atanasova Mishkova-Serafimova E, Klepikov D, Giladi N, Peretz C. Interrelationships between Survival, Sex, and Blood Pressure in Patients with Multiple System Atrophy. Neuroepidemiology 2021; 55:1-6. [PMID: 33601380 DOI: 10.1159/000512697] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 10/25/2020] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE The aim of this study is to estimate survival among patients with multiple system atrophy-parkinsonian type (MSA-P) or cerebellar type MSA (MSA-C) in relation to blood pressure (BP) measurements, by sex. METHODS A cohort of 99 MSA patients was studied retrospectively. Their BP measurements were obtained during prolonged (40 min, vertical position) drug-free tilt testing. We used K-M survival curves and Cox regression to calculate adjusted (to age of onset) hazard ratios (HRs) of BP measurements on time to death by MSA subtype and sex. RESULTS Fifty-two MSA patients were males and 47 were females. Sixty-three of them had MSA-P and 36 had MSA-C. The mean age at motor symptom onset was 61.1 ± 10.4 years, and mean disease duration at the time of BP assessment was 8.0 ± 4.7 years. The 2 study groups (MSA-P and MSA-C) did not differ significantly in age at MSA onset, sex ratio, or disease duration. Survival time did not differ between the groups {medians: 12 years (95% confidence interval [CI]: 8-28) and 10 years (95% CI: 8-13), respectively}. The MSA-P group showed a trend towards better survival for males (log-rank p = 0.0925). The maximal diastolic orthostatic BP decline during tilt testing had a borderline positive association with death risk among MSA-C males (adjusted HR = 1.18, p = 0.0665), and systolic BP after 10 min in a supine position had a significant positive association with death risk among MSA-P males (adjusted HR = 1.06, p = 0.0354). CONCLUSIONS The findings of a sex-based difference in the effect of BP on death risk may be important for adjusting the therapeutic approach to MSA patients.
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Affiliation(s)
- Tanya Gurevich
- Movement Disorders Unit and Neuroautonomic Service, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel,
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel,
- Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel,
| | - Ludmila Merkin
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Alina Rozenberg
- School of Public Health, Tel-Aviv University, Tel-Aviv, Tel-Aviv, Israel
| | - Ariel Fisher
- Diagnostic Radiology Department University of Rochester Medical Center, Rochester, New York, USA
| | | | - Dina Klepikov
- Movement Disorders Unit and Neuroautonomic Service, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Nir Giladi
- Movement Disorders Unit and Neuroautonomic Service, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel
| | - Chava Peretz
- Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- School of Public Health, Tel-Aviv University, Tel-Aviv, Tel-Aviv, Israel
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Cheshire WP, Freeman R, Gibbons CH, Cortelli P, Wenning GK, Hilz MJ, Spies JM, Lipp A, Sandroni P, Wada N, Mano A, Ah Kim H, Kimpinski K, Iodice V, Idiáquez J, Thaisetthawatkul P, Coon EA, Low PA, Singer W. Electrodiagnostic assessment of the autonomic nervous system: A consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology. Clin Neurophysiol 2020; 132:666-682. [PMID: 33419664 DOI: 10.1016/j.clinph.2020.11.024] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 11/02/2020] [Accepted: 11/28/2020] [Indexed: 12/17/2022]
Abstract
Evaluation of disorders of the autonomic nervous system is both an art and a science, calling upon the physician's most astute clinical skills as well as knowledge of autonomic neurology and physiology. Over the last three decades, the development of noninvasive clinical tests that assess the function of autonomic nerves, the validation and standardization of these tests, and the growth of a large body of literature characterizing test results in patients with autonomic disorders have equipped clinical practice further with a valuable set of objective tools to assist diagnosis and prognosis. This review, based on current evidence, outlines an international expert consensus set of recommendations to guide clinical electrodiagnostic autonomic testing. Grading and localization of autonomic deficits incorporates scores from sympathetic cardiovascular adrenergic, parasympathetic cardiovagal, and sudomotor testing, as no single test alone is sufficient to diagnose the degree or distribution of autonomic failure. The composite autonomic severity score (CASS) is a useful score of autonomic failure that is normalized for age and gender. Valid indications for autonomic testing include generalized autonomic failure, regional or selective system syndromes of autonomic impairment, peripheral autonomic neuropathy and ganglionopathy, small fiber neuropathy, orthostatic hypotension, orthostatic intolerance, syncope, neurodegenerative disorders, autonomic hyperactivity, and anhidrosis.
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Affiliation(s)
- William P Cheshire
- Department of Neurology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, Florida 32224, USA
| | - Roy Freeman
- Department of Neurology, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215-5400, USA
| | - Christopher H Gibbons
- Department of Neurology, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215-5400, USA
| | - Pietro Cortelli
- DIBINEM - University of Bologna, Bologna, Italy; IRCCS Istituto di Scienze Neurologiche, Bologna, Italy
| | - Gregor K Wenning
- Section of Clinical Neurobiology, Department of Neurology, Medical University of Innsbruck, Anichstraße 35, A-6020 Innsbruck, Austria
| | - Max J Hilz
- Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, Erlangen 91054, Germany
| | - Judith M Spies
- Department of Neurology, Level 8 East, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia
| | - Axel Lipp
- Park-Klinik Weißensee, Schönstraße 80, Berlin 13086, Germany
| | - Paola Sandroni
- Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, Minnesota 55905, USA
| | - Naoki Wada
- Department of Renal and Urologic Surgery, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa 078-8510, Japan
| | - Akiko Mano
- Department of Cardiothoracic Surgery, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-Cho Itabashi-ku, Tokyo 173-0015, Japan
| | - Hyun Ah Kim
- Department of Neurology, Keimyung University Dongsan Hospital, 2800 Dalgubeol Daero, Dalseo-gu, Daegu, South Korea
| | - Kurt Kimpinski
- School of Kinesiology, Western University, London, Ontario, Canada; Department of Clinical Neurological Sciences, University Hospital, London Health Sciences Centre, London, Ontario, Canada; Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
| | - Valeria Iodice
- Autonomic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, Division of Clinical Neurology, Institute of Neurology, University College London, WC1N 3BG London, United Kingdom
| | - Juan Idiáquez
- Department of Neurologia, Facultad de Medicina, University of Valparaíso, 7 Norte 1122, Valparaíso, 2531094, Chile
| | - Pariwat Thaisetthawatkul
- Department of Neurological Sciences, 988435 University of Nebraska Medical Center, Omaha, Nebraska 68198-8435, USA
| | - Elizabeth A Coon
- Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, Minnesota 55905, USA
| | - Phillip A Low
- Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, Minnesota 55905, USA.
| | - Wolfgang Singer
- Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, Minnesota 55905, USA.
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Abstract
PURPOSE OF REVIEW This article reviews the α-synucleinopathies pure autonomic failure, multiple system atrophy, dementia with Lewy bodies, and Parkinson disease with respect to autonomic failure. RECENT FINDINGS The pattern and severity of autonomic involvement in the synucleinopathies is related to differences in cellular deposition and neuronal populations affected by α-synuclein aggregation, which influences the degree and manifestation of autonomic failure. Clinical and laboratory autonomic features distinguish the different synucleinopathies based on pattern and severity. These features also determine which patients are at risk for evolution from pure autonomic failure to the synucleinopathies with prominent motor involvement, such as multiple system atrophy, dementia with Lewy bodies, or Parkinson disease. SUMMARY Autonomic failure is a key feature of the synucleinopathies, with varying type and degree of dysfunction from predominantly peripheral involvement in the Lewy body disorders to central involvement in multiple system atrophy.
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Sleep-related symptoms in multiple system atrophy: determinants and impact on disease severity. Chin Med J (Engl) 2020; 134:690-698. [PMID: 33234871 PMCID: PMC7989985 DOI: 10.1097/cm9.0000000000001211] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background: Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity. Methods: This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS). Results: The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA. Conclusions: Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.
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Tseng FS, Deng X, Ong YL, Li HH, Tan EK. Multiple System Atrophy (MSA) and smoking: a meta-analysis and mechanistic insights. Aging (Albany NY) 2020; 12:21959-21970. [PMID: 33161394 PMCID: PMC7695394 DOI: 10.18632/aging.104021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 08/19/2020] [Indexed: 11/25/2022]
Abstract
BACKGROUND The association between cigarette smoking and multiple system atrophy (MSA) has been debated. We conducted a systematic review and a meta-analysis to investigate this link. RESULTS We identified 161 articles from database searching and bibliographic review. Five case-control studies satisfied the inclusion and exclusion criteria, and 435 and 352 healthy controls and MSA patients were examined. The prevalence of MSA amongst ever smokers was lower compared to never smokers (aOR=0.57; 95% CI, 0.29-1.14), although this result did not reach statistical significance. This was also observed for current and former smokers, with a stronger association for current smokers (aOR=0.63 vs aOR=0.96). CONCLUSIONS There is a suggestion that smoking protects against MSA. Prospective studies in larger patient cohorts are required to further evaluate the cause-effect relationship and functional studies in cellular and animal models will provide mechanistic insights on their potential etiologic links. METHODS PubMed and Cochrane Library were searched from inception to July 7, 2019 to identify case-control studies that analyzed smoking as an environmental risk or protective factor for MSA. Two authors independently extracted data and performed risk-of-bias and quality assessment. The random-effects model was assumed to account for between-study variance when pooling the crude and adjusted odds ratios.
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Affiliation(s)
- Fan-Shuen Tseng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Xiao Deng
- Department of Neurology, National Neuroscience Institute, Singapore 169856, Singapore
| | - Yi-Lin Ong
- Department of Neurology, National Neuroscience Institute, Singapore 169856, Singapore
| | - Hui-Hua Li
- Department of Clinical Research, Singapore General Hospital, Singapore 169856, Singapore
| | - Eng-King Tan
- Department of Neurology, National Neuroscience Institute, Singapore 169856, Singapore.,Duke-NUS Medical School, Singapore 169857, Singapore
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