多系统萎缩自主神经功能障碍研究的新进展

正多系统萎缩(MSA)是一种成年后发病、散发、快速进展的神经系统变性疾病,临床特征为帕金森综合征,以及小脑、自主神经、锥体束等功能障碍的不同组合~([1-3])。自主神经功能障碍是MSA的重要特征,维持心血管、呼吸、泌尿生殖、胃肠和排汗等功能的中枢和外周自主神经均可受累,且相关症状常可先于运动症状出现;早期自主神经功能衰竭成为疾病快速进展和不良预后的独立预测因素。因此,正确评估自主神经     

多系统萎缩合并睡眠呼吸障碍与快速眼动睡眠行为障碍1例报道

正多系统萎缩(multiple system atrophy,MSA)是一种成年起病、进展性的神经系统变性疾病,表现为不同程度的自主神经功能障碍、对左旋多巴类药物反应不良的帕金森综合征、小脑性共济失调及锥体束征等临床特征。由于起病时累及3个系统的先后不同,临床表现复杂,可出现尿失禁、体位性低血压、运动迟缓、行走不稳等症状,还可能出现精神情感障碍[1],但合并特殊类型睡眠障碍患者少见。随着病程进展,最     

多系统萎缩的临床特点分析

目的探讨多系统萎缩(MSA)的临床表现特点。方法回顾性分析18例多系统萎缩患者的一般资料、临床表现、重要辅助检查及治疗转归等。结果 18例患者中,最常见的症状是帕金森综合征和小脑性共济失调,最常见的首发症状为自主神经功能障碍。MSA好发于成年,以缓慢起病为主,逐渐进展;直立倾斜实验、肛门括约肌肌电图有助于发现亚临床病变;磁共振(MRI)检查阳性率高;临床定位以双侧小脑半球、延髓腹外侧面、脑桥小脑受累最常见。目前尚无特效治疗方法,只能对症治疗。结论根据临床特点,结合直立倾斜试验、肌电图、影像学等检查能大大提高MSA的临床诊断率。     

多系统萎缩与散发性橄榄脑桥小脑萎缩及其他类型的特发性晚发小脑萎缩的关系

多系统萎缩(MSA)是一种散发性进展性原因不明的神经变性疾病,临床特征为合并存在小脑、锥体束、锥体外系和自主神经障碍。许多患者先出现锥体外系症状后出现自主神经障碍或/及小脑体征;或以自主神经障碍起病;或先表现为小脑体征后出现自主神经或锥体外系症状。仅有锥体外系和自主神经障碍的患者经神经病理证实多数也存在小脑和脑干变性。MSA包     

多系统萎缩的昼夜节律异常

正多系统萎缩(multiple system atrophy,MSA)是一种罕见的、致命的神经退行性疾病,成人发病,缓慢起病,逐渐进展。临床表现为自主神经功能障碍、帕金森综合征和小脑性共济失调等多个系统功能障碍的不同组合~([1])。近年来多个研究发现MSA患者在血压心率、尿量、皮质醇分泌、胃肌电以及睡眠等方面存在昼夜节律异常,这些昼夜节律异常可能对MSA临床症状特点的分析判断,对MSA发病机制的深入理解有所帮助。在此综述中,将简述MSA患者的昼夜节律异常。1.多系统萎缩机制多系统萎缩是一种特殊的神经胶质变性疾病,其神经病理     

多系统萎缩的认知障碍研究进展

<正>多系统萎缩(multiple system atrophy,MSA)于1969年被首次命名,是一种中老年起病,表现为进展性自主神经功能障碍,伴小脑性共济失调症状、帕金森症状、及锥体束征为主要临床特征的神经系统退行性疾病~([1])。病理学涉及橄榄脑桥小脑(olivopontocerebellar,OPCA)和纹状体黑     

多系统萎缩诊断标准中国专家共识(2022)

多系统萎缩(MSA)是一种成年起病的进展性神经退行性疾病, 其病因不明, 临床主要表现为自主神经功能障碍、帕金森综合征和小脑综合征等多种组合, 早期诊断相对困难, 预后不佳。为了更好地规范我国临床医师对MSA的诊断和鉴别, 中华医学会神经病学分会帕金森病及运动障碍学组和中国医师协会神经内科医师分会帕金森病及运动障碍学组的相关专家以国内外MSA最新的临床研究结果为依据, 结合我国临床实际, 对我国MSA诊断标准专家共识进行内容上的更新, 以期提高临床医师对MSA诊断的正确率, 减少漏诊与误诊。     

多系统萎缩患者52例的自主神经功能障碍与肛门括约肌肌电图的关系

目的探讨肛门括约肌肌电图(EAS-EMG)在评价多系统萎缩(MSA)患者自主神经功能障碍方面的作用。方法对52例临床诊断MSA(可能MSA 9例,拟诊MSA 43例)的患者进行自主神经功能障碍的临床特点分析(膀胱直肠功能、卧立位血压、性功能)和EAS-EMG检查,并分析两者的关系。结果44例(84.6%)患者早期出现自主神经功能障碍,但仅少数患者(38.5%)因此就诊。12例无卧立位血压异常的患者均有不同程度的尿便障碍和性功能障碍。EAS-EMG结果全部异常。尿频、尿失禁、排尿困难、夜尿增多患者的EAS-EMG指标异常均不同程度地高于无相应症状的患者,部分指标异常的差异有统计学意义。卧立位血压异常的有无并未造成EAS-EMG各项指标的显著性差异。EAS-EMG的平均时限在阳痿早期出现的患者[(13.30±0.14)m s]明显长于后期出现者[(15.31±2.50)m s,P=0.000]。结论MSA患者的自主神经功能障碍多数早于其他症状出现。卧立位血压的异常和尿失禁均非最早出现的自主神经功能障碍,对早期出现的各种难以解释的自主神经功能障碍均应加以重视。EAS-EMG对于临床怀疑MSA而无卧立位血压异常的患者更具诊断价值,有尿失禁等排尿障碍的患者更易出现EAS-EMG的异常。     

多系统萎缩的影像学特征

多系统萎缩(MSA)是一种散发的、迅速进展的神经系统变性疾病,临床表现为自主神经功能障碍和帕金森病样症状、小脑性共济失调的不同组合。对此疾病早期识别的研究进展导致了诊断标准的修订,包含首次将神经影像学特征列入诊断标准。例如MRI显示壳核、小脑中脚、脑桥、小脑萎缩;FDG-PET显示壳核、脑干、小脑代谢减退;SPECT或PET显示突触前黑质纹状体多巴胺能失神经支配。MSA的影像学特征可以作为临床生物学标记物用于早期识别MSA。     

多系统萎缩(附12例临床分析)

目的　探讨多系统萎缩 (MSA)的神经系统症状、体征和神经影像学表现与诊断的关系。方法　分析 12例MSA患者的症状、体征、影像学表现 ,并按诊断标准诊断。结果　 12例中橄榄桥脑小脑萎缩(OPCA) 7例 ,纹状体黑质变性 (SND) 4例 ,特发性直立性低血压 (Shy -Dragersyndrome ,SDS) 1例。 结论　中老年起病隐袭 ,进展缓慢 ,有小脑性共济失调、帕金森综合征、自主神经功能障碍三大症状 ,影像学有脑干、小脑萎缩的直接或间接征象 ,排除其它疾病 ,则可诊断多系统萎缩     

Early development of autonomic dysfunction may predict poor prognosis in patients with multiple system atrophy

BACKGROUND: Multiple system atrophy (MSA) is diverse in clinical phenotype, disease progression, and prognosis. Sudden death is a leading cause of death in patients with MSA. OBJECTIVE: To determine what clinical factors affect the progression and survival prognosis of those with MSA. DESIGN: A retrospective review of the medical records of 49 consecutive Japanese patients with pathologically confirmed MSA (29 men and 20 women; mean +/- SD age at onset, 59.8 +/- 6.5 years). Cox proportional hazards models were used to compare the risks of being in a wheelchair-bound state, being in a bedridden state, and having a shorter survival. RESULTS: Thirty-one patients were diagnosed as having cerebellar type MSA, and 18 were diagnosed as having parkinsonian type MSA. Twenty-nine patients with cerebellar type MSA and 17 patients with parkinsonian type MSA had autonomic dysfunction. The median times from disease onset to being in a wheelchair-bound state, being in a bedridden state, death, and the development of autonomic dysfunction were 3.5, 5.0, 7.0, and 2.5 years, respectively. Patients with an early development of autonomic dysfunction (within 2.5 years from the onset of MSA) had significantly higher risks of being in a wheelchair-bound state (multivariate-adjusted hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.04-9.15), being in a bedridden state (HR, 3.87; 95% CI, 1.77-8.48), having a shorter survival (HR, 3.40; 95% CI, 1.61-7.15), and sudden death (HR, 7.22; 95% CI, 1.49-35.07). CONCLUSION: The early development of autonomic dysfunction is an independent predictive factor for rapid disease progression and shorter survival in patients with MSA.     

Progression and prognosis in pure autonomic failure (PAF): comparison with multiple system atrophy

OBJECTIVE: To clarify the progression of autonomic symptoms and functional deterioration in pure autonomic failure (PAF), particularly in comparison with multiple system atrophy (MSA). METHODS: The investigation involved eight patients with PAF (M/F = 7/1; mean age at onset, 57 years) and 22 with probable MSA matched for age at onset (M/F = 14/8; onset 56 years). Subjects were followed up for neurological symptoms, activities of daily living, and autonomic function for more than seven years. Autonomic functional tests were carried out. RESULTS: In PAF, fainting or sudomotor dysfunction occurred first, followed by constipation and syncope. Urinary dysfunction developed late, and respiratory dysfunction was not evident. This clinical course contrasted sharply with that in MSA, where early urinary dysfunction usually proceeded to sudomotor dysfunction or orthostatic hypotension (p = 0.004), followed by respiratory dysfunction (p = 0.0004). Results of pharmacological tests also distinguished PAF from MSA. Progression and prognosis in patients with PAF did not worsen, unlike the steady progressive autonomic dysfunction in MSA (p < 0.0001, p < 0.0001, p = 0.0009, and p = 0.003, for progression to modified Rankin scale grade III, IV, V, and death, respectively). CONCLUSIONS: The time course and pattern of progression of autonomic failure differed significantly between PAF and MSA. Patients with PAF had slower functional deterioration and a better prognosis.     

Evolution of sporadic olivopontocerebellar atrophy into multiple system atrophy

OBJECTIVE: To determine the percentage of sporadic olivopontocerebellar atrophy (sOPCA) patients who later develop multiple system atrophy (MSA). METHODS: Observations of the course of 51 sOPCA patients 20 years of age or older initially evaluated in an ataxia clinic over 14 years and followed at 3- to 6-month intervals for 3 months to 10 years (median 2.5 years, interquartile range 5 months to 4 years). RESULTS: Seventeen patients evolved to develop MSA, whereas the remaining 34 manifested only progressively worsening cerebellar ataxia. The features of the MSA cases included autonomic failure and parkinsonism in 10 patients, autonomic failure without parkinsonism in six, and parkinsonism without autonomic failure in one. Using survival analysis methods, the authors estimated that 24% of subjects in this population will evolve to MSA within 5 years of the onset of sOPCA symptoms (95% CI 10% to 36%). An older age at onset of symptoms and a shorter time from onset of symptoms to first presentation in a neurology specialty clinic were both highly predictive of evolution to MSA. Six of the 17 patients who evolved to MSA died 4 months to 5 years after they had met diagnostic criteria for MSA. The estimated median survival time from time of transition was 3.5 years. In contrast, death occurred in only one of the 34 patients with sOPCA who did not evolve to MSA. Autopsy examination of all six patients with MSA who died confirmed the diagnosis. CONCLUSIONS: Approximately one-fourth of sporadic olivopontocerebellar atrophy patients will evolve to multiple system atrophy within 5 years, and this transition carries a poor prognosis for survival. Older age at onset of ataxia and earlier presentation in a neurologic specialty clinic predicted transition to MSA.     

Progression of parkinsonism in multiple system atrophy

BACKGROUND: Progression of parkinsonian motor impairment is usually rapid and relentless in multiple system atrophy (MSA). However, it may also be subject to considerable variation. Prospective natural history studies using validated rating scales are required to accurately determine the progression of parkinsonism in MSA. OBJECTIVE: To assess the progression of parkinsonism in patients with the Parkinson variant of MSA. METHODS: Parkinsonian motor impairment was assessed on regular therapy at two time points (mean follow-up 11.8 months, SD 1.4) using the Hoehn and Yahr scale (H&Y), the Schwab and England ADL scale (SES) and the motor examination section of the UPDRS (UPDRS-III) in 38 patients with clinically probable MSA-P. RESULTS : We examined 38 patients with probable MSA-P (mean age 63.2 years, SD 7.4; mean disease duration 4.1 years, SD 3.0). The mean difference of UPDRS-III between baseline and follow-up was 10.8 (95% CI 8.6-12.9), consistent with an average annual 28.3 % increase of UPDRS-III baseline scores. Several variables were associated with faster progression of parkinsonism including low baseline global motor disability as assessed by H&Y and SES, low baseline UPDRS-III score, and short disease duration. UPDRS-III progression was unrelated to gender, age at symptom onset, and age at baseline visit. CONCLUSION: This is the first observational study on UPDRS rates of decline in MSA. The observed 28.6% annual increase of UPDRS-III scores illustrates the rapid progression of motor impairment in MSA. Furthermore, motor progression appeared to be accelerated during the early disease stages.Our data allow sample size calculations that may be helpful for the planning of future therapeutic trials.     

Recent developments in multiple system atrophy

Multiple system atrophy (MSA) is a rare late onset neurodegenerative disorder which presents with autonomic failure and a complicated motor syndrome including atypical parkinsonism, ataxia and pyramidal signs. MSA is a glial alpha-synucleinopathy with rapid progression and currently poor therapeutic management. This paper reviews the clinical features, natural history and novel diagnostic criteria for MSA as well as contemporary knowledge on pathogenesis based on evidence from neuropathological studies and experimental models. An outline of the rationale for managing symptomatic deterioration in MSA is provided together with a summary of novel experimental therapeutic approaches to decrease disease progression.     

Non-motor multiple system atrophy associated with sudden death: pathological observations of autonomic nuclei

Multiple system atrophy (MSA) manifests as a combination of dysautonomia and motor symptoms/signs. However, rare cases presenting with autonomic failures in absence of motor symptoms/signs until their deaths have been reported and are referred to as non-motor MSA. To clarify pathological findings underlying non-motor MSA patients, we analyzed consecutively autopsied 161 patients with MSA. In results, four patients were identified as having non-motor MSA, who showed isolated autonomic disorders throughout their lives and had minimal pathological changes in the motor systems. We also identified two patients with pathologically minimal MSA, who had minimal pathological involvement in the motor systems and presented with definite parkinsonism and dysautonomia. Survival durations of the non-motor MSA patients were much shorter (1.3–2.0 years) than those of the classical MSA patients (3.0–7.0 years), and the causes of death were all sudden death. The medullary serotonergic neurons were severely involved in the non-motor MSA patients in comparison with the classical MSA patients. Also, one of the pathologically minimal MSA patients had died suddenly and exhibited marked involvement of the medullary serotonergic neurons. The involvement of the medullary catecholaminergic or cholinergic neurons did not differ in severities among the groups. We conclude that non-motor MSA may be a pathological variant of MSA that preferentially involves the medullary serotonergic neurons and autonomic systems in association with poor prognosis.     

Multiple system atrophy with prolonged survival: is late onset of dysautonomia the clue?

Multiple system atrophy (MSA) is a neurodegenerative disease characterised by cardiovascular autonomic failure and/or urinary dysfunctions, associated with parkinsonism, cerebellar and/or corticospinal signs, usually leading to death after an average of 7 years. We describe the disease course of five patients diagnosed with probable MSA (4 with predominant parkinsonism and 1 with predominant cerebellar ataxia) who survived for more than 15 years and were followed throughout the disease course at our department. Cardiovascular autonomic dysfunction of any severity occurred late (mean latency from disease onset 9.4 ± 5 years) in this subgroup of MSA patients. The time of involvement of the urogenital system was more variable (from 0 to 14 years after disease onset) and manifested with symptoms of storage disorders (urinary urgency, frequency and incontinence) and erectile dysfunction in men. Conversely complains suggestive of urinary voiding dysfunction (incomplete bladder emptying and urinary retention) were not recorded and patients required catheterization only late in the disease course. In conclusion, our study showed that late onset of both cardiovascular autonomic failure and urinary voiding disorders may be positive prognostic factors in MSA irrespective of the MSA subtype.     

Multiple system atrophy: Prognostic indicators of survival

Neurological and autonomic presentation in multiple system atrophy (MSA) may predict early mortality. Quantification of early autonomic failure as a mortality predictor is lacking. Early neurological and autonomic clinical features were retrospectively reviewed in 49 MSA cases (median age at onset, 56.1 years; 16 women) confirmed by autopsy at Mayo Clinic. When available, the 10‐point composite autonomic severity score derived from the autonomic reflex screen provided quantification of the degree of autonomic failure and thermoregulatory sweat test quantitated body surface anhidrosis. Symptoms at onset were autonomic in 50%, parkinsonian in 30%, and cerebellar in 20% of cases. Survival (median [95% confidence interval]) was 8.6 [6.7‐10.2] years. Survival was shorter in patients with early laboratory evidence of generalized (composite autonomic severity score ≥ 6) autonomic failure (7.0 [3.9‐9.8] vs. 9.8 [4.6‐13.8] years; P = 0.036), and early requirement of bladder catheterization (7.3 [3.1‐10.2] vs. 13.7 [8.5‐14.9] years; P = 0.003) compared with those without these clinical features. On Cox proportional analysis, prognostic indicators of shorter survival were older age at onset (hazard ratio [95% confidence interval], 1.04 [1.01‐1.08]; P = 0.03), early requirement of bladder catheterization (7.9 [1.88‐38.63]; P = 0.004), and early generalized (composite autonomic severity score ≥ 6) autonomic failure (2.8 [1.01‐9.26]; P = 0.047). Gender, phenotype, and early development of gait instability, aid‐requiring ambulation, orthostatic symptoms, neurogenic bladder, or significant anhidrosis (thermoregulatory sweat test ≥ 40%) were not indicators of shorter survival. Our data suggest that early development of severe generalized autonomic failure more than triples the risk of shorter survival in patients with MSA. © 2014 International Parkinson and Movement Disorder Society     

Assessment of the Scopa-Aut questionnaire in multiple system atrophy: relation to UMSARS scores and progression over time

Autonomic failure is a key feature of multiple system atrophy (MSA). Moreover, early autonomic failure is an independent predictive factor for rapid disease progression and shorter survival. The assessment of autonomic failure is therefore important for both, the diagnosis and prognosis of MSA. Here, we evaluate autonomic dysfunction in MSA patients by the Scopa-Aut questionnaire. Potential associations between the Scopa-Aut questionnaire and established markers of disease progression - that is the Unified MSA Rating Scale (UMSARS) - were further assessed. The results confirm early and prominent autonomic failure in MSA patients. Relative scores were highest for the sexual and urinary subdomains. Surprisingly, relative scores in the cardiovascular subdomain were lowest suggesting that the Scopa-Aut questionnaire is suboptimal for the screening and evaluation of cardiovascular symptoms in MSA. A multivariate regression showed an association between total Scopa-Aut and UMSARS I scores. No significant changes in Scopa-Aut scores were observed during follow-up except for the urinary subdomain, while UMSARS I, II and IV scores significantly increased over time. In conclusion, Scopa-Aut can be used as a simple auto-questionnaire for the screening of autonomic symptoms in multiple system atrophy. It seems not useful as endpoint for disease-modification or neuroprotection trials.     

Multiple system atrophy presenting as parkinsonism: clinical features and diagnostic criteria.

To evaluate the possibility that parkinsonian signs may be the only presenting feature of multiple system atrophy (MSA), parkinsonian patients were studied who had no atypical clinical signs and had no symptoms of autonomic dysfunction, but who reported that they had not experienced the anticipated good response to dopaminergic treatment. These stringent criteria identified 20 patients from a series of 298 consecutive parkinsonian outpatients. The following clinical pointers were analysed: (a) rate of disease progression; (b) symmetry of parkinsonian symptoms and signs; (c) occurrence of resting tremor during the first three years from onset. In addition, all patients underwent (d) acute and chronic challenge with dopaminergic drugs; (e) cardiovascular reflex autonomic function tests; (f) high field MRI. Rapid progression of disease was seen in 45% of patients, onset was symmetric in 25%, tremor was absent at onset in 70%, response to dopaminergic drug challenges was inadequate in 40%, abnormal cardiovascular reflexes occurred in 50%, and some abnormal MRI finding occurred in 35% of cases. Each of these features was equally weighted by giving to each patient a 0 to 6 point score corresponding to the number of abnormal findings. Fifteen patients scoring higher than 1 were considered at risk for having MSA: five of them were classified as clinically possible (score 2), six as clinically probable (score 3-4), and four patients were classified as clinically definite multiple system atrophy (score 5). The six pointers considered were variably combined in each patient, none of them being universally abnormal in patients with high scores. The patients were followed up for a mean 2.1 (SEM 0.65) years. All but one of the 10 patients prospectively classified as probable or definite MSA developed unequivocal clinical signs of fully symptomatic MSA. A receiver operator characteristic cure was plotted for the prospective score based on follow up diagnosis. The best compromise for trade off between sensitivity and specificity was a cut off value at a score of 3. The sensitivity and specificity of the individual pointers considered to predict fully symptomatic MSA varied considerably, and no single item could predict whether patients presenting with just parkinsonian signs went on during the two year follow up period to develop fully symptomatic MSA. Instead, the number of abnormalities offered a predictive value for the clinical prognosis of these parkinsonian patients.