1、LOGO多系统萎缩多系统萎缩Multiple System Atrophy 2013-01-08LOGO定义(definition)v 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。v MSA depicts a group of disorders characterized by neuronal degeneration mainly in the substantia nigra, striatum, autonomic nervous system, and Company Logo
2、32022-7-12.一、病例介绍一、病例介绍(case description)v李XX，男，47岁，国家公务员。v2002年，右手静止性震颤（轻度），不影响工作；v2003-2004年，右侧上肢活动不灵活，伴右下肢行走拖步（轻），仍能工作；v2005-2007年，左侧上下肢也出现活动不灵活，动作慢，仍坚持工作；v2008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。 42022-7-12.病例介绍病例介绍(case description)v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。v2002年诊断帕金森病？v2003
3、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。v2007年诊断帕金森叠加综合征？ 52022-7-12.病例介绍病例介绍(case description)v 2009年3月复诊。v 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。v 双手轮替笨拙，双下肢跟膝试验不稳；v 右下肢病理征阳性；v 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 mmHg62022-7-12.MRI(2009)72022-7-12.v病例特点：中年男性，隐匿起病
4、，病程缓慢进展(7年)，无家族史。v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。v脑MRI：脑干，小脑萎缩。v诊断：多系统萎缩。8二、相关概念(Related Notion)3 SYMPTOMS SND(striatonigraldegeneration) OPCA(olivopontocerebellar atrophy)SDS(Shy-Drager syndrome)2022-7-12.Graham和Oppenheimer（1969）92022-7-12.（一）流行病学（一）流行病学（epidemiology）v年发病率估计为0.6 /10万人，50 岁以上年
5、发病率3-5/10万人，平均发病年龄54 岁，以男性为多；vMSA进展较PD快；v80%的患者出现运动障碍后5 年内瘫痪；v20%的患者存活期超过12 年；v平均病程5-6年。102022-7-12.（二）病因（二）病因（etiology） v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。v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。vMSA还可能与神经元凋亡或酶代谢异常有关。v病因学研究目前已从细胞和分子
6、水平探讨，期望有所突破112022-7-12.（三）病理（三）病理 (pathology)v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) v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)。v- 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).。 122022-7-12.132022-7-12.（四）临床表现(clinical
7、 feature) Autonomic failureMotor disorderOther features14Autonomic failurevOH(Orthostatic hypotension)v 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)v asymptomatic or symptomatic v syncopevGD(Genitourinary dysfunction)
8、v earliest symptom male patients erectile dysfunction impotencevurinary symptomsv urinary urgency or retetion, urinary or fecal incontinencevOther symptomsv loss of sweating,dry mouth, miosis, v Vocal cord palsy is an important and sometimes initial manifestation of the disorder; it may cause dyspho
9、nia or stridor and airway obstruction2022-7-12.152022-7-12.Motor disorderParkinsonism 90%Cerebellar ataxia 54%corticospinal disorder 49%16Parkinsonismvbradykinesia with rigidity, tremor, or postural instabilityv The tremor is usually irregular and postural/action, often incorporating myoclonus, but
10、a classic pill-rolling rest tremor is uncommon.v The parkinsonism can be asymmetric.v Postural instability, occurs earlier and progresses more rapidly than in PD. v Parkinsonism usually responds poorly to chronic levodopa therapy; up to 30% of patients show a clinically significant, but usually wani
11、ng； The lack of L-dopa effect is probably attributable to the loss of striatal dopamine receptors.2022-7-12.17Cerebellar ataxiavAtaxia of gait vlimb ataxiavcerebellar dysarthria vcerebellar oculomotor dysfunction gaze-evoked nystagmus2022-7-12.18corticospinal disordervBabinski sign with hyperreflexi
12、a2022-7-12.192022-7-12.Other featuresvSleep disorders(REM)v Inspiratory sighsvSevere dysphoniavNew or increased snoringvCold hands and feetvPathologic laughter or cryingvpostural/action tremor202022-7-12. （五）临床分型（五）临床分型(Clinical classification)三组亚型三组亚型依据：临床症状依据：临床症状MSA-P型型MSA-C型型MSA-A型型SNDOPCASDS212
13、022-7-12.（六）辅助检查（六）辅助检查(auxiliary examination) v卧立位血压卧立位血压：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。v正电子发射计算机体层扫描（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。v肌电图肌电图：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。v血液生化检查血液生化检查：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。222022-7-12.影像学检查v头颅CT和MRI：可见脑干、小脑萎缩，环池及第 四脑室扩大；vMRI有相对特征
14、的表现：v T1像壳核、小脑、脑干萎缩，呈稍低信号；v T2像壳核、小脑、脑干萎缩，呈稍高信号；v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。232022-7-12.MRI242022-7-12.三、诊断(Diagnosis) v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。252008 Second consensus statement on the diagnosis of mul
15、tiple system atrophyAutonomic 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 dysar
16、thria,limb ataxia,or cerebellar oculomotor dysfunction;Corticospinal disorder:Babinski sign with hyperreflexia2022-7-12.4 Clinical features26Criteria for MSADefinite criteriaProbable criteriaPossible criteria 2022-7-12.27Criteria for possible MSAvA sporadic,progressive,adult(30y)-onset disease chara
17、cterized byvParkinsonism or vCerebellar syndrome andvAt least one feature suggesting autonomic dysfunction andvAt least one of additional features Company Logo28additional features of possible MSAvPossible MSA-P or MSA-CvBabinski sign with hyperreflexiavSCompany Logo29Possible MSA-PvRapidly progress
18、ive parkinsonismvPoor response to levodopavPostural instability within 3y of motor onsetvGait ataxia,cerebellar dysarthria,limb ataxia,or cerebellar oculomotor dysfunctionvDysphagia within 5y of motor onsetvAtrophy on MRI of putamen,middle cerebellar peduncle,pons,or cerebellumvHypometabolism on PET
19、 in putamen,brainstem,or Company Logo30Possible MSA-CvParkinsonism(bradykinesia and rigidity)vAtrophy on MRI of putamen,middle cerebellar peduncle,or ponsvHypometabolism on PET in Company Logo31Criteria for probable MSAv A sporadic,progressive,adult(30y)-onset disease characterized byvAutonomic fail
20、ure andvPoorly levodopa-responsive parkinsonism orvA cerebellar Company Logo32Criteria for definite MSAv A sporadic,progressive,adult(30y)-onset disease characterized byvNeuropathologic vGlial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structures.
21、2022-7-12.33Nonsupporting featuresvClassic pill-rolling rest tremorvClinically significant neuropathyvHallucinations not induced by drugsvOnset before age 30y or after age 75yvFamily history of ataxia or parkinsonismvDementiavWhite matter lesions suggesting multiple sclerosis2022-7-12.34conclusionPo
22、ssible 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
23、 disorder including rigorously defined autonomic failure and poorly levodopa-responsive parkinsonism or cerebellar ataxia. Definite MSA requires neuropathologic demonstration of CNS -synucleinpositive glial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebella
24、r structures. 2022-7-12.352022-7-12.（四）鉴别诊断v 1.帕金森病v 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。v 2. 症状性、直立性低血压v 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。362022-7-12.鉴别诊断v3.进行性
25、核上性麻痹（PSP）v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。vMRI:中脑顶盖和四叠体区明显萎缩。37ComparisonvPDvPSP2022-7-12.382022-7-12.鉴别诊断v4. 皮层基底节变性（CBD）v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。v头颅CT或MRI：非对称性的皮层萎缩。392022-7-12.四、治疗v无特效治疗方法,主要对症治疗。v运动障碍的治疗：运动障碍的治疗：v 左旋多巴(美多芭/
26、息宁)；v 多巴胺受体激动剂(吡呗地尓)；v 单胺氧化酶抑制剂(司来吉林)。v自主神经功能障碍的治疗自主神经功能障碍的治疗：v 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；v 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。402022-7-12.五、预后v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；v由于肢体僵硬，活动受限，生活不能自理；v后期睡眠呼吸暂停，导致突发呼吸、心跳骤停，危及生命；v平均存活时间5-6年（3-9年）；vMSA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。412022-7-12.小结v1.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。v2.少突胶质细胞包涵体是确诊多系统萎缩的病理学指标。v3.临床上分为三个亚型。v4.没有特效的治疗方法，目前只能对症治疗，预后不良。42Thank youLOGO LOGO2022-7-1246.
