SECTION1第一部分
A51-year-oldwomanpresentedtotheneuromuscularclinicforevaluationofpredominantlyproximalbilaterallowerlimbweaknessthathadslowlyprogressedfor5years.However,herhusbandnotedthatforatleast20–30yearsshehashadawaddlinggait.Shedeniedupperlimbweakness,ptosis,diplopia,bulbarsymptoms,andfluctuationsoftheweakness.Therewasnohistoryofmyalgia,cramps,orurinediscoloration.Shehadnosensorysymptoms,cognitivechanges,orcardiorespiratorysymptoms.
51岁女患，就诊于神经肌肉门诊，主诉双侧下肢近端为主缓慢进展性无力5年。然而，患者的丈夫注意到，患者蹒跚步态至少已经有20到30年。患者否认有上肢无力、上睑下垂、复视、延髓症状，肢体无力症状无波动。无肌肉疼痛、痛性痉挛或尿颜色变化等病史，无感觉障碍、认知改变或心肺症状。
Thepatientwastheproductofanormalpregnancyandhadnormalmotordevelopment.Shewasabletokeepupwithherpeersingymclass.Hermedicalhistorywasunremarkable.Thefamilyhistorywasrelevantforlegweaknessresultingindifficultyclimbingstairsinhermothersinceher50s.Twobrothers(ages41and47years)and2sons(ages26and30years)hadnoweakness.Therewasnofamilyhistoryofcardiomyopathy,cardiacarrhythmia,cataracts,orearlydisability.
患者属于正常分娩，并且运动发育正常。在体育课上与同龄人表现相仿。既往史无明显异常。家族史中，相关的家族史：她的母亲从50岁开始因为腿部无力，出现爬楼梯困难，两个兄弟（分别41岁和47岁）和两个儿子（分别26岁和30岁）现无肢体无力症状。家族中无心肌病、心律失常、白内障和早年残疾病史。
Onexamination,shehadmoderatetomarkedpredominantlyproximallowerlimbmuscleweakness(MedicalResearchCouncil[MRC]grade2–3)andmilderproximalmorethandistalupperlimbweakness(MRCgrade3–4).Theweaknesswasrelativelysymmetric(rightminimallyworsethanleft).Tendonreflexeswereabsent,exceptforbicepsbilaterallyandleftkneejerk,whichwerepresentbuthypoactive.Shehadawaddlinggaitandcouldnotwalkonheelsortoes.Shewasunabletorisefromachairwithoutpushingonitwithherhands.Shehadmildhyperlordosis,paraspinalmuscleatrophy,andspinalrigidityinthecervicalregion.Shealsohadlaxityoftheleftmetacarpophalangealanddistalinterphalangesjointsofboththumbs.Therestoftheneurologicexaminationwasnormal,and,inparticular,shehadnoweaknessoftheextraocularorfacialmuscles.Herbloodpressureandheartratewerenormal.
查体：中到重度近端为主的下肢肌无力（MRC分级2-3级），上肢无力较轻，近端重于远端(MRC分级3-4级)。双侧肢体无力比较对称（右侧无力略重于左侧）。双侧肱二头肌反射、左侧膝腱反射存在但减弱，其他腱反射消失。患者蹒跚步态，不能用脚跟或脚趾走路。如果不借助双手支撑椅子，患者无法从椅子上站起来。轻度脊柱前凸畸形，椎旁肌萎缩，颈部脊椎强直。左侧掌指关节和双拇指远端指间关节松弛。余神经系统检查正常，值得注意的是，患者无眼外肌和面肌无力表现。患者血压和心率正常。
Questionsforconsideration:
1.Whatisyourdifferentialdiagnosisatthispoint?
2.Whattestswouldyouconsidertohelpnarrowyourdifferentialdiagnosis?
思考问题：
1.此时，你考虑哪些鉴别诊断？
2.你想做哪些检查来帮助缩小鉴别诊断范围？
SECTION2第二部分
Thepatientpresentedwithslowlyprogressivelowergreaterthanupperlimbweakness,withbothproximalanddistalmuscleinvolvement.Paraspinalmuscleatrophyandspinalrigiditywerenotable.Sensorysymptomswereabsentandtherewasnosensoryloss.Thereforethisisapuremotorsyndromethatcouldlocalizetotheanteriorhorncells,neuromuscularjunction,ormuscle.Apolyradiculopathycouldexplainproximalanddistalweakness,buttheabsenceofsensoryfeatureswouldbeatypicalforit.Althoughthepatientonlynotedsymptomsfor5years,itwasclearfromherhusbandthathergaitwasabnormalfor20–30years.Thelongstandingminimallyandveryslowlyprogressivecourseofhersymptomswouldfavoraninheritedetiology,asopposedtoanacquireddisease(suchasinflammatoryorimmune-mediateddisordersofthemuscle,neuromuscularjunction,ornerveroots).
该患者表现缓慢进展的肢体无力，下肢重于上肢，双侧近端和远端肌肉同时受累。椎旁肌萎缩及颈椎强直症状明显。无感觉症状，没有感觉缺失。因此，该病是纯运动综合症，可定位在脊髓前角细胞、神经肌肉接头或肌肉。多发性神经根病能够解释肢体远端和近端无力，但没有感觉障碍症状对该病来说表现不典型。尽管患者注意到症状只有5年，但从他的丈夫那里明确患者步态异常已有20-30年。患者长期轻微的症状、非常缓慢进展的过程支持遗传病因，不支持获得性疾病（如炎症或免疫介导的肌肉疾病、神经肌肉接头或神经根疾病）。
Theevaluationincludedcreatinekinase(CK)ofU/L(normal,U/L)andnormalbloodcount,erythrocytesedimentationrate,andthyroid-stimulatinghormone.Acetylcholinereceptoranti-bodieswereabsent.Nerveconductionstudiesshowednormalperoneal,tibial,andulnarnervemotorstudies,andnormalsuralandmedialnervesensorystudies.2-Hzrepetitivenervestimulationofthefacialandspinalaccessorynerveswasnormal.NeedleEMGofthebicepsbrachii,triceps,infraspinatus,medialgastrocnemius,gluteusmedius,tibialisanterior,vastuslateralis,andlumbarparaspinalmusclesrevealedshort-durationlow-amplitudepolyphasicmotorunitpotentialswithrapidrecruitmentespeciallyinthebicepsandtriceps.Fibrillationpotentialsandmyotonicdischargeswereabsent.
检验提示肌酸激酶U/L（正常值U/L），血细胞计数、血沉和促甲状腺激素正常。乙酰胆碱受体抗体阴性。神经传导测定显示腓神经、胫神经、尺神经运动传导速度正常，腓肠神经、正中神经感觉传导速度正常。2Hz重复神经刺激示面神经和副神经正常。针肌电图显示肱二头肌、肱三头肌、岗下肌、内侧腓肠肌、臀中肌、胫骨前肌、股外侧肌、腰椎椎旁肌出现短时限、低波幅为特点的多相运动单位电位伴早期募集相，肱二头肌与肱三头肌最为显著，未见纤颤电位与肌强直性放电。
Questionsforconsideration:
1.Whatisyourdifferentialdiagnosisbasedonthisinformation?
2.Whattestingcouldyouconsiderperformingatthistime?
思考问题：
1.根据这些信息，你考虑哪些鉴别诊断？
2.此时你考虑做哪些检查？
SECTION3第三部分
TheEMGfindingsarehighlysuggestiveofamyopathy,andruleoutdisordersoftheanteriorhorncells,nerveroots,andneuromuscularjunction.Thedifferentialdiagnosisforageneralizedmyopathyisbroad.Thelongstanding,slowlyprogressivecoursepointsawayfromacquiredmyopathiesandfavorsahereditarymyopathy.Thehistoryofweaknessinthepatient’smothersuggestsanautosomaldominantdisease.Thenear-normalCKvaluedoesnotruleoutamyopathy,sincemanyinheritedmyopathies(e.g.,congenitalmyopathies)mayhaveanormaloronlyminimallyelevatedCKvalue.
肌电图所见高度提示肌肉病，排除了脊髓前角细胞、神经根及神经肌肉接头疾病。广义肌肉病的鉴别诊断有许多。长期、缓慢进展过程不支持获得性肌病，倾向遗传性肌病。该患者的母亲有肌无力病史提示该病为常染色体显性遗传病。肌酶值接近正常不能除外肌病，因为许多遗传性肌病（如先天性肌病）可以出现肌酶正常或只是轻微升高。
Onefeaturethatmayhelpnarrowthedifferentialdiagnosisisthepresenceofparaspinalmuscleatrophyandspinalrigidity.Spinalrigidity,characterizedbylimitedrangeofmotionofthecervical,thoracic,orlumbosacralspinalsegments,hassometimesbeenreferredtoastherigidspinesyndrome(RSS).RSScanac