MSA多系统萎缩

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,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。,,Company Logo,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？,,Company Logo,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,,Company Logo,MRI(2009),,Company Logo,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。,二、相关概念(Related Notion),,Graham和Oppenheimer（1969）,,Company Logo,（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。,,Company Logo,（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,,Company Logo,（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).。,,Company Logo,,Company Logo,（四）临床表现(clinical feature),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 syncopeGD(Genitourinary dysfunction)earliest symptom male patients erectile dysfunction impotenceurinary symptomsurinary urgency or retetion, urinary or fecal incontinenceOther symptomsloss 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,,Company Logo,,Company Logo,Motor disorder,Parkinsonism,bradykinesia with rigidity, tremor, or postural instabilityThe 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.,,Company Logo,Cerebellar ataxia,Ataxia of gait limb ataxiacerebellar dysarthria cerebellar oculomotor dysfunction gaze-evoked nystagmus,,Company Logo,corticospinal disorder,Babinski sign with hyperreflexia,,Company Logo,,Company Logo,Other features,Sleep disorders(REM) Inspiratory sighsSevere dysphoniaNew or increased snoringCold hands and feetPathologic laughter or cryingpostural/action tremor,,Company Logo,（五）临床分型(Clinical classification),,Company Logo,（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。,,Company Logo,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。,,Company Logo,MRI,,Company Logo,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。,2008 Second consensus statement on the diagnosis of multiple system atrophy,,Company Logo,4 Clinical features,Criteria for MSA,,Company Logo,Criteria for possible MSA,A sporadic,progressive,adult(30y)-onset disease characterized byParkinsonism or Cerebellar syndrome andAt least one feature suggesting autonomic dysfunction andAt least one of additional features,additional features of possible MSA,Possible MSA-P or MSA-CBabinski sign with hyperreflexiaStridor,Possible MSA-P,Rapidly progressive parkinsonismPoor response to levodopaPostural instability within 3y of motor onsetGait ataxia,cerebellar dysarthria,limb ataxia,or cerebellar oculomotor dysfunctionDysphagia within 5y of motor onsetAtrophy on MRI of putamen,middle cerebellar peduncle,pons,or cerebellumHypometabolism on PET in putamen,brainstem,or cerebellum,Possible MSA-C,Parkinsonism(bradykinesia and rigidity)Atrophy on MRI of putamen,middle cerebellar peduncle,or ponsHypometabolism on PET in putamen,Criteria for probable MSA,A sporadic,progressive,adult(30y)-onset disease characterized byAutonomic failure andPoorly levodopa-responsive parkinsonism orA cerebellar syndrome,Criteria for definite MSA,A sporadic,progressive,adult(30y)-onset disease characterized byNeuropathologic Glial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structures.,,Company Logo,Nonsupporting features,Classic pill-rolling rest tremorClinically significant neuropathyHallucinations not induced by drugsOnset before age 30y or after age 75yFamily history of ataxia or parkinsonismDementiaWhite matter lesions suggesting multiple sclerosis,,Company Logo,conclusion,,Company Logo,,Company Logo,（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。,,Company Logo,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。,Comparison,PD,PSP,,Company Logo,www.theme