《MSA多系统萎缩(PPT45页).ppt》由会员分享，可在线阅读，更多相关《MSA多系统萎缩(PPT45页).ppt（45页珍藏版）》请在taowenge.com淘文阁网|工程机械CAD图纸|机械工程制图|CAD装配图下载|SolidWorks_CaTia_CAD_UG_PROE_设计图分享下载上搜索。
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、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。 Company Logo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年开始服药，曾服药苯
3、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？ Company Logo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 mmHCompany LogoMRI(2009)Company Logov病例特点：中年男性，隐匿起病，病程缓慢进展(
4、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。二、相关概念(Related Notion)3 SYMPTOMS SND(striatonigraldegeneration) OPCA(olivopontocerebellar atrophy)SDS(Shy-Drager syndrome)Graham和Oppenheimer（1969）Company Logo（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 岁以上年发病率3-5/10万人，平均发病年龄
5、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。Company Logo（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水平探讨，期望有所突破Company
6、 Logo（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).。 Company LCompany Logo（四）临床表现(clinical feature) Autonomic f
7、ailureMotor disorderOther featuresAutonomic 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)v earliest symptom male
8、 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 dysphonia or stridor and airw
9、ay Company LCompany LogoMotor disorderParkinsonism 90%Cerebellar ataxia 54%corticospinal disorder 49%Parkinsonismvbradykinesia with rigidity, tremor, or postural instabilityv The tremor is usually irregular and postural/action, often incorporating myoclonus, but a classic pill-rolling rest tremor is
10、 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 waning； The lack of L-dopa effect is prob
11、ably attributable to the loss of striatal dopamine Company LogoCerebellar ataxiavAtaxia of gait vlimb ataxiavcerebellar dysarthria vcerebellar oculomotor dysfunction gaze-evoked Company Logocorticospinal disordervBabinski sign with Company LCompany LogoOther featuresvSleep disorders(REM)v Inspirator
12、y sighsvSevere dysphoniavNew or increased snoringvCold hands and feetvPathologic laughter or cryingvpostural/action Company Logo （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SNDOPCASDSCompany Logo（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-
13、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。Company Logo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
14、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。Company LogoMRICompany Logo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。2008 Second consensus statement on the diagnosis of multiple system atrophyAutonomic dysfunction: orthostatic hypotension; urinary ur
15、gency,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:
16、Babinski sign with Company Logo4 Clinical featuresCriteria for MSADefinite criteriaProbable criteriaPossible criteria Company LogoCriteria for possible MSAvA sporadic,progressive,adult(30y)-onset disease characterized byvParkinsonism or vCerebellar syndrome andvAt least one feature suggesting autono
17、mic dysfunction andvAt least one of additional features additional features of possible MSAvPossible MSA-P or MSA-CvBabinski sign with hyperreflexiavStridorPossible MSA-PvRapidly progressive parkinsonismvPoor response to levodopavPostural instability within 3y of motor onsetvGait ataxia,cerebellar d
18、ysarthria,limb ataxia,or cerebellar oculomotor dysfunctionvDysphagia within 5y of motor onsetvAtrophy on MRI of putamen,middle cerebellar peduncle,pons,or cerebellumvHypometabolism on PET in putamen,brainstem,or cerebellumPossible MSA-CvParkinsonism(bradykinesia and rigidity)vAtrophy on MRI of putam
19、en,middle cerebellar peduncle,or ponsvHypometabolism on PET in putamenCriteria for probable MSAv A sporadic,progressive,adult(30y)-onset disease characterized byvAutonomic failure andvPoorly levodopa-responsive parkinsonism orvA cerebellar syndromeCriteria for definite MSAv A sporadic,progressive,ad
20、ult(30y)-onset disease characterized byvNeuropathologic vGlial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structures. Company LogoNonsupporting featuresvClassic pill-rolling rest tremorvClinically significant neuropathyvHallucinations not induced b
21、y drugsvOnset before age 30y or after age 75yvFamily history of ataxia or parkinsonismvDementiavWhite matter lesions suggesting multiple Company LogoconclusionPossible MSA requires a sporadic, progressive adult-onset disease including parkinsonism or cerebellar ataxia and at least one feature sugges
22、ting 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 levodopa-responsive parkinsonism or cerebellar ataxia. Definite MSA req
23、uires neuropathologic demonstration of CNS -synucleinpositive glial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structures. Company LCompany Logo（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
24、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。Company Logo鉴别诊断v3.进行性核上性麻痹（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。ComparisonvPDvPSPCompany LCompany Logo鉴别诊断v
25、4. 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。Company Logo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/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
26、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。Company Logo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。Company Logo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。Thank youLOGO LOGO