External anal sphincter electromyography in multiple system atrophy:implications for diagnosis,clinical correlations,and novel insights into prognosis

Multiple system atrophy is a sporadic,progressive,adult-onset,neurodegenerative disorder characte rized by autonomic dysfunction symptoms,parkinsonian features,and cerebellar signs in va rious combinations.An early diagnosis of multiple system atrophy is of utmost impo rtance for the proper prevention and management of its potentially fatal complications leading to the poor prognosis of these patients.The current diagnostic criteria incorporate several clinical red flags and magnetic resonance imaging marke rs supporting diagnosis of multiple system atrophy.Nonetheless,especially in the early disease stage,it can be challenging to differentiate multiple system atrophy from mimic disorders,in particular Parkinson’s disease.Electromyography of the external anal sphincter represents a useful neurophysiological tool for diffe rential diagnosis since it can provide indirect evidence of Onuf’s nucleus degeneration,which is a pathological hallmark of multiple system atrophy.However,the diagnostic value of external anal sphincter electromyography has been a matter of debate for three decades due to controve rsial reports in the literature.In this review,after a brief ove rview of the electrophysiological methodology,we first aimed to critically analyze the available knowledge on the diagnostic role of external anal sphincter electromyography.We discussed the conflicting evidence on the clinical correlations of neurogenic abnormalities found at external anal sphincter electro myography.Finally,we repo rted recent prognostic findings of a novel classification of electromyography patterns of the external anal sphincter that could pave the way toward the implementation of this neurophysiological technique for survival prediction in patients with multiple system atrophy.

Elevated serum growth differentiation factor 15 in multiple system atrophy patients:A case control study

BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.

Regional gray matter atrophy and neuropsychologcal problems in relapsing-remitting multiple sclerosis

In multiple sclerosis, gray matter atrophy is extensive, and cognitive deficits and mood disorders are frequently encountered. It has been conjectured that focal atrophy is associated with emotional decline. However, conventional MRI has revealed that the pathological characteristics cannot fully account for the mood disorders. Moreover, there is no correlation between cognitive disorders and MRI results in clinically isolated syndromes or in cases of definite multiple sclerosis. In this casecontrol study, voxel-based morphometric analysis was performed on 11 subjects with relapsing-remitting multiple sclerosis, and the results show that these patients exhibit gray matter atrophy. Moreover, the gray matter atrophy in the superior and middle gyri of the right frontal lobe in patients with multiple sclerosis was correlated with scores from the Hamilton Anxiety Rating Scale. The scores obtained with the Repeatable Battery for the Assessment of Neuropsychological Status were associated with gray matter atrophy in the middle gyrus of the left frontal lobe, the superior and middle gyrus of the right frontal lobe, the middle gyrus of the left cingulate, the superior and middle gyri of the left frontal lobe, and the triangular area of the left frontal lobe. However, there was no statistical significance. These findings suggest that the cingulate and frontal cortices of the dominant hemisphere are the most severely atrophic regions of the brain, and this atrophy is correlated with cognitive decline and emotional abnormalities.

Coenzyme Q10 in neurodegenerative disorders: Potential benefit of Co Q10 supplementation for multiple system atrophy

Coenzyme Q10(Co Q10) is an essential cofactor in the mitochondrial respiratory pathway and also functions as a lipid-soluble antioxidant. Co Q10 deficiency has been implicated in many clinical disorders and aging. Primary Co Q10 deficiency is a group of recessively inherited diseases caused by mutations in any gene involved in the Co Q10 biosynthesis pathway. Although primary Co Q10 deficiency is rare, its diagnosis is important because it is potentially treatable with exogenous Co Q10. Multiple system atrophy(MSA) was recently shown to be linked to mutations in the COQ2 gene, one of the genes involved in the Co Q10 biosynthesis pathway. MSA is relatively common in adult-onset neurodegenerative diseases characterized by Parkinsonism, cerebellar ataxia and autonomic failures. Because COQ2 mutations are associated with an increased risk of MSA, oral Co Q10 supplementation may be beneficial for MSA, as for other primary Co Q10 deficiencies. Statins are 3-hydroxy-3-methylglutaryl coenzyme A inhibitors that inhibit the biosynthesis of cholesterol, as well as the synthesis of mevalonate, a critical intermediate in cholesterol synthesis. Statin therapy has been associ-ated with a variety of muscle complaints from myalgia to rhabdomyolysis. Statin treatment carries a potential risk of Co Q10 deficiency, although no definite evidence has implicated CQ10 deficiency as the cause of statinrelated myopathy.

New advances in multiple system atrophy

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by a variable combination of autonomic failure, parkinsonism with poor response to levodopa, cerebellar ataxia and pyramidal symptoms. The pathological hallmark of MSA is the oligodendrocytic glial cytoplasmic inclusions (GCIs) consisting of α-synuclein, and so MSA, together with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), is an α-synucleinopathy. Currently few effective biomarkers have been identified for the diagnosis or prognosis of MSA, and there is no established therapy to delay its progression. In this review, we discuss the epidemiology, neuropathology, genetics, clinical presentation and diagnostic biomarkers of MSA, as well as recent advances in its treatment.

Pathogenic roles of alpha-synuclein in Parkinson’s disease and multiple system atrophy

Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these diseases there exist abnormal accumulation of alpha-synuclein(α-syn)aggregates in nerve tissues,the pathological lesions formed byα-syn aggregates and their cellular locations are quite different.In PD and DLB,the hallmark pathological lesions are Lewy bodies(LBs)and Lewy neurites(LNs),which are localized in the neuronal somata and processes.In MSA,the characteristic pathologic structures are glial cytoplasmic inclusions,which are deposited in the cytoplasm of oligodendrocytes.The fact that PD and MSA have distinct pathologicalα-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases.In this review article,we compare the clinical manifestations and pathological features of PD and MSA,the two common synucleinopathies,and discuss the potential mechanisms for the formation ofα-syn aggregates and their pathologic roles in PD and MSA.

Correlation between white matter damage and gray matter lesions in multiple sclerosis patients

We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe（superior frontal, middle frontal, precentral, and orbital gyri）, right parietal lobe（postcentral and inferior parietal gyri）, right temporal lobe（caudate nucleus）, right occipital lobe（middle occipital gyrus）, right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.

郝风玲教授杞菊六味汤治疗MSA-C型多系统萎缩1例

多系统萎缩是一种神经系统变性疾病,临床表现为自主神经功能障碍、帕金森综合征、小脑性共济失调等症状,并分为MSA-P型和MSA-C型2个亚型。当前此病西医病因及发病机制尚不明确,现代医学尚无针对性治疗方法;中医学对此病的辨证论治不完全相同,但都能有效缓解其发病症状。此文报道郝风玲教授以杞菊六味汤加减治疗MSA-C型多系统萎缩1例。

Longitudinal Study of Iron Deposition and Volume in the Precentral Gyrus in Patients with Relapse-Remitting Multiple Sclerosis

Objective: To longitudinally assess dynamic changes of iron deposition and volume of the precentral gyrus and its correlation with clinical manifestations of Relapse-Remitting Multiple Sclerosis(RRMS) by using 3D enhanced T2* weighted angiography(ESWAN). Methods: Thirty RRMS patients and thirty age- and sex-matched healthy controls were recruited and underwent ESWAN and 3D T1WI twice interval of one year with the same parameters. The mean phase values (MPVs) and volumes in precentral gyrus gray matter (PGM) were measured, and change of iron content and its correlation with volume, clinical manifestations were analyzed. Results: Compared with controls, the RRMS had higher iron deposition in both single-time measurements, but the volume decreased. Comparing to the first scan, we found significant difference in MPVs between the two times (P rs = 0.764, P rs = 0.592, P rs = 0.582, P rs = -0.399, P rs = -0.745, P rs = -0.367, P Conclusions: With the disease progression, the content of iron in PGM in RRMS patients is increasing, while the volume has no obvious change, suggesting that the iron deposition may precede or develop faster than cerebral atrophy.

Structure Sorting of Multiple Macromolecular States in Heterogeneous Cryo-EM Samples by 3D Multivariate Statistical Analysis

Heterogeneity of biological samples is usually considered a major obstacle for three-dimensional (3D) structure determination of macromolecular complexes. Heterogeneity may occur at the level of composition or conformational variability of complexes and affects most 3D structure determination methods that rely on signal averaging. Here, an approach is described that allows sorting structural states based on a 3D statistical approach, the 3D sampling and classification (3D-SC) of 3D structures derived from single particles imaged by cryo electron microscopy (cryo-EM). The method is based on jackknifing & bootstrapping of 3D sub-ensembles and 3D multivariate statistical analysis followed by 3D classification. The robustness of the statistical sorting procedure is corroborated using model data from an RNA polymerase structure and experimental data from a ribosome complex. It allows resolving multiple states within heterogeneous complexes that thus become amendable for a structural analysis despite of their highly flexible nature. The method has important implications for high-resolution structural studies and allows describing structure ensembles to provide insights into the dynamics of multi-component macromolecular assemblies.

DTI在MSA诊断中的应用价值和研究进展

多系统萎缩(MSA)是一种病因不详、多系统受累的进行性神经系统变性疾病,神经影像学技术是诊断与鉴别诊断MSA的有力手段。近年,弥散张量成像(DTI)在MSA的诊断、治疗和研究中的作用日益重要。本文对DTI在MSA的诊断及其与帕金森病、其他帕金森叠加综合征的鉴别诊断中的应用价值和研究进展进行综述。

多系统萎缩中医认识及中医药治疗现状

多系统萎缩(MSA)是一种中枢神经退行性疾病,起病具有隐匿性、散发性、进行性加重的特点。现代医学对其病因及发病机制认识尚不清晰,且治疗方法较为匮乏,中医学对MSA治疗却具有显著优势。现梳理近五年中医药治疗MSA相关文献,从病因病机和辨证论治方面总结其中医药治疗现状,认为MSA多由情志内伤和正虚体弱所致,病机总属肝肾脾亏虚,气、血、水湿运化功能失调。中医药临床多从肝肾亏虚证、脾肾亏虚证和痰瘀互阻证论治,可有效改善自主神经功能障碍、认知功能障碍和躯体运动障碍,并能够延缓MSA中枢神经老化和调节脑内微环境异常,以期为今后中医药治疗MSA提供临床依据和参考。

多系统萎缩合并尿潴留的临床特征及危险因素分析

目的探讨多系统萎缩(multiple system atrophy,MSA)患者并发尿潴留的临床特征以及发生尿潴留的影响因素。方法纳入2021年9月至2022年12月于北京中医药大学东方医院门诊就诊的MSA患者100例,根据膀胱残余尿量将患者分为无尿潴留组(残余尿量<100 mL)和尿潴留组(残余尿量≥100 mL),分析两组患者间性别、年龄、受教育年限、既往病史、病程、临床分型、临床诊断等级、直立性低血压、卧位高血压、性功能障碍以及相关量表评分差异。采用二元Logistic回归筛选影响MSA患者发生尿潴留的危险因素。结果MSA患者发生尿潴留47例(47.0%)。与无尿潴留组比较,尿潴留组很可能的MSA患者占比更高(P<0.05),统一MSA评分量表(UMSARS)-Ⅰ、日间尿频、尿急、急迫性尿失禁评分均更高(均P<0.05)。急迫性尿失禁是MSA患者发生尿潴留的独立危险因素(OR=1.995,P=0.010)。结论MSA患者发生尿潴留较为普遍,其中急迫性尿失禁是MSA伴发尿潴留的独立危险因素。

UMSARS-Ⅰ量表在MSA患者病情评价中的应用

目的检验统一的多系统萎缩评分量表第一部分(UMSARS-Ⅰ),在多系统萎缩(MSA)患者病情严重程度评价中的可靠性。方法对46例MSA患者进行UMSARS-Ⅰ回顾性分析及前瞻性随访评分,同时对患者进行日常生活自理能力和病情严重程度分级,以对该量表在评价MSA病情严重程度中的价值进行信度、效度和反应度的检测。结果UMSARS-Ⅰ在MSA病情评价中具有很高的内部一致性信度(标准Crohnbach’sα=0.88)和良好的内容、标准、结构和区分效度,对病情进展评价显示较好的反应度(效应尺度=0.61)。结论UMSARS-Ⅰ量表是评价MSA病情严重程度和病程进展的全面和可靠的临床半定量量表。

求解MSA问题的新型单亲遗传算法

多序列联配(MSA)在生物信息学研究中占有重要地位,MSA问题是一个典型的NP问题,遗传算法是求解NP完全问题的一种理想方法。文章针对MSA问题,提出了一种新型单亲遗传算法(PGA),不使用交叉算子,只使用变异和选择算子。并根据群体的多样性自适应调节变异概率,有效消除了算法中的欺骗性条件,使用灾变算子来确保算法的搜索能力。整个算法模拟了自然界进化的周期性,较好地解决了群体的多样性和收敛深度的矛盾。算法的分析和测试表明,该算法是有效的。

多系统萎缩患者体位性低血压的危险因素分析

目的探讨多系统萎缩(MSA)患者体位性低血压(OH)的危险因素。方法共纳入199例MSA患者,根据OH的严重程度将患者分组,比较各组间临床资料的差异,并用有序Logistic回归分析MSA患者出现OH的危险因素。结果不同OH等级患者在性别、糖尿病病史、疾病等级、晕厥、卧位高血压、疲劳、脑保护药物方面,差异有统计学意义(均P<0.05)。有序Logistic回归分析发现,疾病等级(很可能的MSA)、晕厥、卧位高血压、疲劳是MSA患者发生OH的独立危险因素(均P<0.05)。结论OH在MSA患者中普遍存在,其严重程度受多方面影响。其中疾病等级(很可能的MSA)、晕厥、卧位高血压、疲劳是MSA伴发OH的独立危险因素。

基于肛门括约肌临检的多系统萎缩病症分析

分析了多系统萎缩患者临床特点和肛门括约肌肌电图特征,探讨了肛门括约肌肌电图对多系统萎缩早期临床诊断的价值。回顾性分析多系统萎缩患者26例,采集患者一般资料、日常生活活动能力评分、肛门括约肌肌电图结果。以是否出现卫星电位、是否存在尿便障碍、是否有体位性低血压分别进行分组比较,比较组间患者的年龄、病程、日常生活活动能力评分、肛门括约肌肌电图结果。同时分析病程、肛门括约肌肌电图运动单位动作电位平均时限、日常生活活动能力评分和病程的相关性。26例多系统萎缩患者中最常见症状依次为尿便障碍、走路不稳及睡眠障碍;最常见体征依次为肌张力障碍、体位性低血压及共济失调;26例患者运动单位动作电位平均时限为11.6 ms(范围为10.1~14.5 ms),平均波幅为876.5μV(范围为740.8~1135.8μV),多相波百分比为27.4%(范围为13.3%~53.6%);卫星电位组比无卫星电位组运动单位动作电位平均时限长、多相波百分比高、日常生活活动能力评分低(P<0.05);体位性低血压组比无体位性低血压组日常生活活动能力评分低(P<0.05);多系统萎缩患者的病程与日常生活活动能力评分呈显著负相关(r=-0.695,P=0.000),病程与运动单位动作电位平均时限无明显相关性,日常生活活动能力评分与运动单位动作电位平均时限无明显相关性。多系统萎缩患者病程越长,病情越重,出现卫星电位或出现体位性低血压病情更重,肛门括约肌肌电图有利于无尿便障碍多系统萎缩患者早期诊断。

MRI联合交感皮肤反应及经颅超声诊断帕金森病与多系统萎缩P型的研究

目的 探讨头部常规磁共振(MRI)联合交感神经皮肤反应(SSR)及经颅超声成像(TCS)用于诊断帕金森病(PD)与多系统萎缩P型(MSA-P型)的价值。方法 收集2019-01—2022-06郑州大学第五附属医院临床确诊且具有完整资料的22例MSA-P型患者和29例PD患者,均行头部常规MRI、SSR和TCS检查,采用ROC曲线评价头部MRI、SSR和TCS诊断MSA-P型和PD患者的临床价值。结果 壳核裂隙征具有影像特异性,MSA-P型组远高于PD组(P<0.05)。MSA-P型组上、下肢SSR平均起始潜伏期延长,平均波幅降低与PD组比较差异有统计学意义(P<0.01)。2组黑质强回声面积、黑质强回声总面积与中脑总面积比值比较差异有统计学意义(P<0.01)。ROC曲线下壳核裂隙征有高特异性(96.8%),SSR上肢潜伏期有高敏感性(88.2%),SN强回声面积诊断价值最高,曲线下面积(AUC)为0.881;头部MRI联合SSR、TCS用于预测两种疾病的敏感度为72.1%,AUC为0.913。结论 分析头部MRI检查结果,早期进行SSR、TCS检查可提高对MSA-P型与PD患者的诊断率。

多元统计分析结合HS-GC-MS对单粮复合香型白酒挥发性特征差异的分析

采用感官定量描述分析法(SQDA)对A(JA1~JA3)、B(JB1~JB3)、C(JC1~JC3)三组复合香型白酒9个样品的风味结构进行分析,结果表明:三组复合香型白酒在香气评分上差异不显著,粮香、焦香、麦芽香突出,在口感评分上差异显著,A组白酒各维度口感评分高于其他两组。采用顶空-气相色谱质谱联用技术(HS-GC-MS)对3种白酒挥发性化合物组成进行检测分析,共检测到148种挥发性物质。相关性分析结果显示,异丁醛、3-甲基呋喃、二甲基二硫醚、巴豆酸、环氧丙烷、丙烯醛和草酸只在A组白酒中被检测出来,丁酸乙酯在B组白酒中含量最高,JA3中含量偏低,表明3组白酒样品间存在明显的风味物质种类和含量差异。同步结合特征差异代谢物分析挖掘出74个VIP>1的潜在差异代谢物,A vs B组、A vs C组、B vs C组分别有14种、7种、4种化合物呈现极显著性差异(p<0.01),这些含量具有显著差异性的化合物可能与复合香型白酒风味特征的差异具有重要联系。综上所述,本研究采用两种技术协同分析,获得了3种白酒更全面的挥发性风味信息,解析了三组复合香型白酒的风味结构特征及差异,为深入研究复合香型白酒风味形成的机理奠定了基础。

QSM与DTI在多系统萎缩中的应用

多系统萎缩(multiple system atrophy,MSA)属于α-突触核蛋白病,病理改变是α-突触核蛋白在少突胶质细胞中球状聚集,形成胶质细胞胞质包涵体,导致神经纤维束的损伤。另外,铁的过量沉积可以通过产生自由基对神经元细胞造成伤害。两者的病理改变可以间接用扩散张量成像(diffusion tensor imaging,DTI)及定量磁敏感成像(quantitative susceptibility mapping,QSM)以影像学的方式表现出来。目前,MSA的诊断主要依靠临床,但MRI在辅助诊断方面也扮演着重要的角色。本文就QSM与DTI序列在MSA中的应用进行综述。