MSA多系统萎缩PPT课件.ppt

Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Company Logo,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,多系统萎缩,Multiple System Atrophy,2013-01-08,定义,(definition),多系统萎缩,(Multiple system atrophy,，,MSA),，是,原因不明,的累及,锥体外系、锥体系、小脑和自主神经系统,等多部位的,神经系统变性病,。,MSA depicts a group of disorders characterized by,neuronal degeneration,mainly in the,substantia nigra,striatum,autonomic nervous system,and,cerebellum,.,Company,Logo,3,2026/1/7 周三,.,一、病例介绍,(case description),李,XX,，男，,47,岁，国家公务员。,2002,年，右手静止性震颤（轻度），不影响工作；,2003-2004,年，右侧上肢活动不灵活，伴右下肢行走拖步（轻），仍能工作；,2005-2007,年，左侧上下肢也出现活动不灵活，动作慢，仍坚持工作；,2008,年初，出现讲话不清，流口水，小便频及淋沥不尽，因四肢活动僵硬，行走困难，头晕，病休。,4,2026/1/7 周三,.,病例介绍,(case description),既往：否认脑外伤、脑炎、一氧化碳中毒；否认类似家族史、否认药物中毒及过敏史。,2002,年诊断帕金森病？,2003,年开始服药，曾服药苯海索、金刚烷胺、多巴丝肼、吡呗地尓，症状略有改善。,2007,年诊断帕金森叠加综合征？,5,2026/1/7 周三,.,病例介绍,(case description),2009,年,3,月复诊。,查体：神清，面具脸,;,构音不清，时流口水；眼动好，其他颅神经正常。四肢张力高，双上肢以齿轮样增高为主、右侧为著；未见静止性震颤。,双手轮替笨拙，双下肢跟膝试验不稳；,右下肢病理征阳性；,自行站立、行走困难；感觉正常，生活不能自理。,卧立位血压：卧位,120/60 mmHg,立位,90/50 mmHg,6,2026/1/7 周三,.,MRI(2009),7,2026/1/7 周三,.,病例特点：中年男性，隐匿起病，病程缓慢进展,(7,年,),，无家族史。,临床表现：帕金森样症状，小脑性共济失调，自主神经功能障碍，皮质脊髓束损害。,脑,MRI,：脑干，小脑萎缩。,诊断：多系统萎缩。,8二、相关概念,(Related Notion),3 SYMPTOMS,SND,(,striatonigral,degeneration),OPCA,(,olivopontocerebellar atrophy,),SDS,(Shy-Drager syndrome),2026/1/7 周三,.,Graham,和,Oppenheimer,（,1969,）,9,2026/1/7 周三,.,（一）流行病学（,epidemiology,）,年发病率估计为,0.6,/10,万人，,50,岁以上年发病率,3-5,/10,万人，平均发病年龄,54,岁，以,男性,为多；,MSA,进展较,PD,快,；,80%,的患者出现运动障碍后,5,年内瘫痪；,20%,的患者存活期超过,12,年；,平均病程,5-6,年。,10,2026/1/7 周三,.,（二）病因（,etiology,）,病因不明,。,1989,年发现,少突胶质细胞包涵体,在发病过程中起重要作用,它的分布、密度与病变的严重程度呈正相关。,少突胶质细胞包涵体在,MSA,的不同亚型中均有发现，具有较强的特异性，它从病理学上证实了,SND,，,OPCA,及,SDS,是具有不同临床表现的同一组疾病，,现已成为,MSA,的一个病理学指标,。,MSA,还可能与神经元凋亡或酶代谢异常有关。,病因学研究目前已从细胞和分子水平探讨，期望有所突破,11,2026/1/7 周三,.,（三）病理,(pathology),基本病理表现主要是,神经元缺失,，,胶质细胞增生,。主要发生在下橄榄核、脑桥、小脑、黑质、纹状体和脊髓的中间外侧细胞柱和迷走神经核。,(autopsy),少突胶质细胞包涵体是确诊多系统萎缩的病理学指标。该包涵体的核心成分为,-synuclein,(-,突触蛋白,),。,-synuclein,也是,Lewy-body,的主要成分，因此，,MSA,和,PD,、,Lewy,体痴呆、,Down,综合症等病一起被归为,突触核蛋白病,(-synucleinopathy).,。,12,2026/1/7 周三,.,13,2026/1/7 周三,.,（四）临床表现,(clinical feature),Autonomic failure,Motor disorder,Other features,14,Autonomic failure,OH(Orthostatic hypotension),A reduction of systolic blood pressure by at least,30,mm Hg,or,of diastolic blood pressure by at least,15,mmHg,(3min heart rate),asymptomatic or symptomatic,syncope,GD(Genitourinary dysfunction),earliest symptom male patients erectile dysfunction impotence,urinary symptoms,urinary urgency or retetion,urinary or fecal incontinence,Other symptoms,loss of sweating,dry mouth,miosis,Vocal cord palsy is an important and sometimes initial manifestation of the disorder;it may cause dysphonia or stridor and airway obstruction,2026/1/7 周三,.,15,2026/1/7 周三,.,Motor disorder,Parkinsonism,90%,Cerebellar ataxia,54%,corticospinal disorder 49%,16,Parkinsonism,bradykinesia,with,rigidity,tremor,or,postural instability,The tremor is usually,irregular,and,postural/action,often incorporating myoclonus,but a classic pill-rolling rest tremor is uncommon.,The parkinsonism can be,asymmetric,.,Postural instability,occurs,earlier,and progresses,more rapidly,than in PD.,Parkinsonism usually responds,poorly,to chronic,levodopa therapy,;up to 30%of patients show a clinically significant,but usually waning,；,The lack of L-dopa effect is probably attributable to the loss of striatal,dopamine receptors,.,2026/1/7 周三,.,17,Cerebellar ataxia,Ataxia,of gait,limb ataxia,cerebellar dysarthria,cerebellar oculomotor dysfunction,gaze-evoked nystagmus,2026/1/7 周三,.,18,corticospinal disorder,Babinski sign with hyperreflexia,2026/1/7 周三,.,19,2026/1/7 周三,.,Other features,Sleep disorders(REM),Inspiratory sighs,Severe dysphonia,New or increased snoring,Cold hands and feet,Pathologic laughter or crying,postural/action tremor,20,2026/1/7 周三,.,（五）临床分型,(Clinical classification),三组亚型,依据：临床症状,MSA-P,型,MSA-C型,MSA-A,型,SND,OPCA,SDS,21,2026/1/7 周三,.,（六）辅助检查,(auxiliary examination),卧立位血压,：先测卧位血压，站立时血压下降,20-40 mmHg,或以上，而心率无明显变化为阳性。,正电子发射计算机体层扫描（,PET,）,：能发现纹状体、黑质、橄榄、脑桥和小脑出现代谢降低区。,肌电图,：,MSA,患者的尿道括约肌或肛门括约肌,EMG,检查发现为神经元性受损。,血液生化检查,：血浆去甲肾上腺素含量测定、,24,小时尿儿茶酚胺含量测定有明显降低。,22,2026/1/7 周三,.,影像学检查,头颅,CT,和,MRI,：可见脑干、小脑萎缩，环池及第 四脑室扩大；,MRI,有相对特征的表现：,T1,像壳核、小脑、脑干萎缩，呈稍低信号；,T2,像壳核、小脑、脑干萎缩，呈稍高信号；,脑桥十字征：是在,T2WI,上脑桥十字形异常高信号影，其出现机制可能与脑桥核及脑桥横行纤维变性，胶质增生致含水量增加，而由齿状核发出构成小脑上脚的纤维和锥体束未损害有关。不具有特征性。,23,2026/1/7 周三,.,MRI,24,2026/1/7 周三,.,三、诊断,(Diagnosis),临床上根据成年期缓慢起病、无家族史、临床表现为进展的小脑性共济失调、自主神经功能不全和帕金森样等症状及体征，应考虑本病。,25,2008 Second consensus statement on the diagnosis of multiple system atrophy,Autonomic dysfunction,:orthostatic hypotension;urinary urgency,frequency or urinary incontinence,incomplete bladder emptying,erectile dysfunction in males;,Parkinsonism,:bradykinesia with rigidity,tremor,or postural instability;,Cerebellar syndrome,:gait ataxia with cerebellar dysarthria,limb ataxia,or cerebellar oculomotor dysfunction;,Corticospinal disorder,:B,abinski sign with hyperreflexia,2026/1/7 周三,.,4 Clinical features,26,Criteria for MSA,Definite criteria,Probable criteria,Possible criteria,2026/1/7 周三,.,27,Criteria for possible MSA,A sporadic,progressive,adult(30y)-onset disease characterized by,Parkinsonism,or,Cerebellar syndrome,and,At least one feature suggesting autonomic dysfunction,and,At least one of additional features,Company,Logo,28,additional features of possible MSA,Possible MSA-P or MSA-C,Babinski sign with hyperreflexia,Stridor,Company,Logo,29,Possible MSA-P,Rapidly,progressive parkinsonism,Poor,response to levodopa,Postural instability,within 3y of motor onset,Gait,ataxia,cerebellar dysarthria,limb ataxia,or cerebellar oculomotor dysfunction,Dysphagia,within 5y of motor onset,Atrophy on,MRI,of putamen,middle cerebellar peduncle,pons,or cerebellum,Hypometabolism,on PET in putamen,brainstem,or cerebellum,Company,Logo,30,Possible MSA-C,Parkinsonism,(bradykinesia and rigidity),Atrophy on,MRI,of putamen,middle cerebellar peduncle,or pons,Hypometabolism,on PET in putamen,Company,Logo,31,Criteria for probable MSA,A sporadic,progressive,adult(30y)-onset disease characterized by,Autonomic failure,and,Poorly levodopa-responsive parkinsonism,or,A cerebellar syndrome,Company,Logo,32,Criteria for definite MSA,A sporadic,progressive,adult(30y)-onset disease characterized by,Neuropathologic,Glial cytoplasmic inclusions,with,neurodegenerative changes,in striatonigral or olivopontocerebellar structures.,2026/1/7 周三,.,33,Nonsupporting features,Classic pill-rolling rest tremor,Clinically significant neuropathy,Hallucinations not induced by drugs,Onset before age 30y or after age 75y,Family history of ataxia or parkinsonism,Dementia,White matter lesions suggesting multiple sclerosis,2026/1/7 周三,.,34,conclusion,Possible MSA,requires a sporadic,progressive adult-onset disease including parkinsonism,or,cerebellar ataxia,and,at least one feature suggesting autonomic dysfunction,plus,one other feature that may be a clinical or a neuroimaging abnormality.,Probable MSA,requires a sporadic,progressive adult-onset disorder including rigorously defined autonomic failure,and,poorly levodoparesponsive parkinsonism,or,cerebellar ataxia.,Definite MSA,requires,neuropathologic,demonstration of CNS,-synucleinpositive,glial cytoplasmic inclusions,with neurodegenerative changes in striatonigral or olivopontocerebellar structures.,2026/1/7 周三,.,35,2026/1/7 周三,.,（四）鉴别诊断,1.,帕金森病,伴有自主神经功能不全的帕金森病的特点为严重的直立性低血压,餐后低血压,对去甲肾上腺素很敏感,为节后交感神经病变,常在疾病的中晚期出现；,MSA,虽有帕金森样症状,但以肢体僵直为主而少有震颤；,MSA,对多巴胺制剂反应差。,2.,症状性、直立性低血压,老年人常见,为单纯的自主神经系统功能障碍,不伴有帕金森样症状和小脑症状。常见于药物性,(,三环类抗抑郁药、降压药、利尿药、氯丙嗪等镇静药,),；贫血及血容量不足；老年人长期卧床后突然起立和排尿性等低血压反应诱发。,36,2026/1/7 周三,.,鉴别诊断,3.,进行性核上性麻痹（,PSP,）,肢体僵硬，活动减少，肢体及躯干的肌张力增高，站立及行走易摔倒；,双眼注视性麻痹,，以下视麻痹多见；语言含糊,吞咽困难,可合并,认知功能障碍,。,MRI:,中脑顶盖和四叠体区明显萎缩。,37,Comparison,PD,PSP,2026/1/7 周三,.,38,2026/1/7 周三,.,鉴别诊断,4.,皮层基底节变性（,CBD,）,好发于,60-80,岁。,不对称性,的帕金森样表现、构音障碍和智能减退；失用、异己手（肢）综合征，肌张力不全、肌阵挛、强握反射等。,头颅,CT,或,MRI,：非对称性的皮层萎缩。,39,2026/1/7 周三,.,四、治疗,无特效治疗方法,主要对症治疗,。,运动障碍的治疗：,左旋多巴,(,美多芭,/,息宁,),；,多巴胺受体激动剂,(,吡呗地尓,),；,单胺氧化酶抑制剂,(,司来吉林,),。,自主神经功能障碍的治疗,：,直立性低血压的治疗,:,口服,盐酸米多君,（,a-,受体激动剂）,通过提高外周阻力升高血压,改善头晕，每次,2.5 mg,，一日,2-3,次；,穿高筒弹力裤，紧身衣，倾斜台面练习；适当高盐饮食，多饮水增加血容量；避免快速体位变动，避免久站不动。,40,2026/1/7 周三,.,五、预后,由于直立性低血压，可反复发生晕厥，导致头及四肢的外伤和骨折；,由于肢体僵硬，活动受限，生活不能自理；,后期睡眠呼吸暂停，导致突发呼吸、心跳骤停，危及生命；,平均存活时间,5-6,年（,3-9,年）；,MSA,对自主神经系统的损害越重，对黒质纹状体系统的损害越轻，患者的预后越差。,41,2026/1/7 周三,.,小结,1.,成年期缓慢起病，没有家族史，临床表现为进展的小脑性的共济失调，自主神经功能不全和帕金森样症状及体征。,2.,少突胶质细胞包涵体是确诊多系统萎缩的病理学指标。,3.,临床上分为三个亚型。,4.,没有特效的治疗方法，目前只能对症治疗，预后不良。,42,Thank you,43,Thank You!,谢谢大家！,2026/1/7 周三,46,.,