病例报告岁女性伴下肢麻木无力.ppt

CaseReport,病例：53岁女性伴下肢麻木无力2019年06月发表于新英格兰杂志资料来源于麻省总医院,A53-year-oldwomanwithrheumatoidarthritis.Thepatienthadbeeninherusualhealthuntil4monthsbeforethisadmission,whenhypoesthesiadevelopedinthelateralaspectoftheleftfoot.,PresentationofCase,53岁女性，有类风湿关节炎病史。首发症状为左足外侧感觉减退。病史4个月。,病例介绍,Duringthefollowing2daysThehypoesthesiaspreadtoinvolvethetoesandmidfoot;chroniclow-backpain,whichradiatedtothebuttocks,hadincreasedinintensity,buttherewasnopaininthelegs,fever,weightloss,orbowelorbladderchanges.Examination:Perceptionoflighttouchandpinprickwasabsentonthelefttoesandleftforefoot;theremainderoftheexaminationwasnormal.Lab:ESR,VB12,glycatedhemoglobin,thyrotropinwerenormal.,PresentationofCase,病例介绍,首次症状出现后2天：症状：感觉减退逐渐发展到左足趾及左脚掌，同时存在慢性背痛，并放射到臀部，且程度加强，无双下肢疼痛，无发热，无体重减轻，无大小便异常。查体：左足趾及左脚掌浅感觉及针刺觉缺失，余查体未见明显异常。检查化验：血沉、维生素B12、糖化血红蛋白、促甲状腺素未见异常。,Duringthenext5dayshypoesthesiaprogressedtoinvolvetheproximalportionoftheleftfoot,aswellastheankleandthelaterallowerleg,butnopainorbowelorbladderincontinence.Examination:cranial-nerveexaminationswerenormal.Strengthwas4+outof5duringflexionandextensionofthetoesontheleftfoot,dorsiflexionandplantarflexionoftheleftankle,eversionandinversionoftheleftfoot,andflexionoftheleftknee.Perceptionofvibrationwasmarkedlydiminishedatthelefthallux.Perceptionoflighttouchandpinprickwasdecreasedontheleftfootandtheleftlateralleg.Deep-tendonreflexesofthearmsandlegswerenormal.Theplantarreflexwasflexorontherightsideandabsentontheleftside.,PresentationofCase,病例介绍,此后的5天：症状：感觉减退逐渐进展至整个左脚、左脚踝、左小腿外侧，但无肢体疼痛及大小便失禁。查体：颅神经查体未见异常。左足趾屈伸运动、左踝关节趾屈和背屈、左足内外翻、左膝关节屈曲肌力检查4+级。左足趾震动觉明显减退。左足、左小腿触觉、针刺觉减退。四肢腱反射正常。左侧足跖反射消失，右侧正常。,7dayslater(3monthsbeforethisadmission)Thesensoryandmotorresponseswerenormalandsymmetric.F-waveminimallatenciesinthetibialnerveswerenormal.H-reflexwasabsentattheleftsoleusandnormalattherightsoleus.Needleelectromyographyoftheleftlegshoweddiminishedrecruitmentoflong-duration,polyphasicmotor-unitpotentialsinproximalanddistalmusclesoftheL5myotome.Resultsofelectromyographyoftherightlegwerenormal.,Nerve-conductionstudies,神经传导速度,7天后（本次入院前3个月）：感觉、运动神经传导速度正常、对称。胫神经F波潜伏期正常。左侧胫神经H反射消失，右侧正常。针肌电图显示左下肢长时程募集相及腰5神经支配肌肉的多相运动电位减低，右下肢未见异常。,Imaging,L3-S1,T1-weighted,showclumped,thickened,andenhancingcaudaequinanerverootsinthelumbarspinalcanal,影像,腰椎MRI+强化：平扫显示腰椎间盘突出、黄韧带增厚、小关节病，可见L4-L5水平椎间孔、L5-S1水平椎间孔狭窄。箭头处所示L3-S1水平神经根增粗，强化。背根神经节及周围神经，对称未见强化。,CSFanalysis,Oligoclonalbandingwasnot.Cytologicstudiesshowedincreasedlymphocytesthatwerepolymorphousandoccasionallyreactiveandappearedtobebenign.ImmunophenotypicevaluationdidnotrevealevidenceofamonoclonalB-cellorunusualT-cellpopulation.,脑脊液分析,寡克隆带(-)。淋巴细胞增多，呈多形性表现，考虑反应增多是良性表现。脑脊液免疫表型未见单克隆B细胞或T细胞数量异常。葡萄糖轻度减低为41mg/dl（正常值50-75mg/dl），蛋白为207mg/dl（正常值5-55mg/dl）。巨细胞及EB病毒检测阴性。,CIDP,Provisionaldiagnosis,Intravenousimmuneglobulinwasadministered4weeksand1weekbeforethepatientwasadmittedtothishospital.,初步诊断,慢性炎症性脱髓鞘性多发性神经根神经病分别于本次入院前4周、1周给予丙种球蛋白治疗,Despitetheadministrationofintravenousimmuneglobulin,symptomsintheleftlegdidnotimprove,andhypoesthesiaandweaknessdevelopedintherightlegandprogressedcentripetally.Thepatienthadseveralfallsathomeandbegantouseacane,thenawalker,andultimatelyawheelchair.Thepatientreportedepisodesofbowelandbladderincontinencethatsheattributedtolegweaknessinterferingwithherabilitytowalktothebathroomquickly.,Admission,入院情况,在接受丙种球蛋白治疗后，患者左下肢症状未见改善，且无力及感觉减退进展到右下肢，并向心性发展。患者曾在家多次跌倒，并开始使用拐杖，后改用助力器，最终患者因病情只能借助轮椅活动。患者此次就诊于急诊，表诉存在大小便失禁，但患者认为是因为下肢无力症状而妨碍她去往卫生间。,Shereportednofevers,weightloss,ornightsweats.Rheumatoidarthritishadbeendiagnosed18monthsbeforethisadmission,andtherapywithmethotrexateandprednisonehadbeeninitiated.Becauseofpersistentdiseaseactivity,therapywithetanerceptwasinitiated7monthsbeforethisadmission,afteraninterferon-releaseassayforMycobacteriumtuberculosishadbeennegative.,Admission,入院情况,患者无发热、体重减轻、盗汗。患者于本次入院前18个月确诊类风湿关节炎，并接受甲氨蝶呤、强的松治疗，因疾病仍处于活动期，在进行结核分枝杆菌干扰素释放实验阴性后，加用伊那西普治疗。,CTofthechest:thereweresubcentimeterpulmonarynodulesinthebilaterallowerlobesthathadremainedunchangedoveraperiodof4years.Resultsofroutinescreeningmammographyperformed1monthbeforethisadmissionwerenormal.,Admission,入院情况,肺CT显示双肺底可见小结节，4年内肺CT比较未见明显改变。入院前1个月乳腺X线检查未见明显异常。,Medication:omeprazole,methotrexate,prednisone,folicacid,gabapentin,andduloxetine.Thepatienthadrecentlystoppedtakingetanercept,becauseshethoughtherprogressivesymptomscouldberelatedtothatmedication.Medicalhistory:gastroesophagealrefluxdisease,uterinefibroids,and-thalassemiaminor.Personalhistory:Shewasacurrentsmoker,anddidnotdrinkalcoholoruseillicitdrugs.Familyhistory:Hersisterhadmultiplesclerosis;therewasnofamilyhistoryofcancer.,Admission,入院情况,服用药物：奥美拉唑、甲氨蝶呤、强的松、叶酸、加巴喷丁、和度洛西汀。患者认为疾病进展与药物相关，自行停用依那西普。既往史：反流性食管炎、子宫肌瘤、地中海贫血。个人史：吸烟，无饮酒及违禁药品应用史。家族史：患者姐姐患有多发性硬化，家族中无肿瘤病史。,Onexamination,T36.3C,BP168/78mm/Hg,P90beatsperminute,R18breathsperminute,SPO2100%whilethepatientwasbreathingambientair.Motorstrengthwas4outof5inbothlegsand4+outof5onbothsidesduringhipflexion;theremainderofthemotorexaminationwasnormal.Perceptionofvibrationandtemperaturewasmarkedlydiminishedinbothlegsfromthetoestoabovetheknees.Deep-tendonreflexeswere1+andsymmetricatthepatellaeandwereabsentatthesoleus.Theplantarreflexwasabsentonbothsides.Twofirm,nontendersubcutaneousnodules(approximately1cmindiameter)withoverlyingexcoriationswerepresentintheleftsubmandibulararea.,入院查体,T36.3C,BP168/78mm/Hg,P90次/分,R18次/分，SPO2100%。双下肢肌力4级，双侧髋关节屈曲肌力4+级，余未见明显异常。双下肢从足趾到膝关节震动觉、温度觉明显减低。双侧膝腱反射减弱（+）对称，双侧跟膝胫反射消失。双侧足跖反射消失。左下颌抓痕处可见两个无痛性硬性结节（小于1cm）。,Urinaryretention,absenceofrectaltone,andsaddleanesthesia(lossofsensationintheareaofthebuttocksandperineum)developed.Thepatientwasunabletostandwithoutassistance.,Onexamination,入院查体,患者存在尿潴留、肠鸣音消失、鞍区麻痹（臀部和会阴区域的感觉丧失）。患者无辅助工具不能站立。,Onexamination,Bloodlevelsofelectrolytes,glucose,CRP,andangiotensin-convertingenzymeandresultsofkidney-andliver-functiontestswerenormal.Withtheexceptionofthepresenceofastablemicrocyticanemia,thecompletebloodcountandwhite-celldifferentialcountwerenormal.BloodtestsforHIVtype1p24antigen,HIVtype1andtype2antibodies,andTreponemapallidumwerenegative.,检查,血电解质、血糖、C反应蛋白、血管紧张素转换酶、肝肾功能示正常。存在稳定小细胞低色素贫血，血液细胞计数及白细胞分类计数示正常。血HIV1型p24抗原、HIV1型2型抗体、梅毒螺旋体检测阴性。,Fine-needleaspirationofoneofthesubmandibularnoduleswasperformedbutyieldedinsufficientmaterialforpathologicalevaluation.Threeinduced-sputumsampleswerenegativeforacid-fastbacteria.CTofthechestrevealednoclinicallysignificantchangeinthepreviouslyidentifiedpulmonarynodulesandnolymphadenopathy.,Onexamination,检查,左下颌结节处针刺活检，但病理检测材料不足。三次诱导痰标本抗酸染色阴性。肺CT示双肺小结节较前无明显改变，未见淋巴结肿大。,Imaging,Sagittalandaxialcontrast-enhanced,T1-weighted,fat-saturatedimagesofthelumbarspine(PanelsAandB,respectively)showgradualprogressionoftheclumping,thickening,andenhancementofthecaudaequinanerveroots(arrows),alongwithcompleteobliterationofthethecalsacandmasseffectonthelowerthoracicspinalcordandconus(PanelA,arrowhead).,影像,腰椎MRI+强化：病变发展到T10水平，椎管内可见脊髓弥漫异常强化，考虑存在轻度脊髓肿胀，马尾显示不清。脊髓神经根强化明显。箭头所指处可见占位效应明显，硬膜囊消失。,Imaging,Anaxial,T2-weightedfluid-attenuatedinversionrecoveryimageoftheheadobtainedatthelevelofthefrontoparietalconvexities(PanelC)showshyperintensityinthecerebralsulci(arrow).Anaxialcontrast-enhanced,T1-weightedimageofthehead(PanelD)showspatchy,illdefinedenhancementintheperiventricularwhitematteralongthelateralventricles(arrow)thatisgreaterontherightsidethanontheleft.,影像,头MRI+强化：脑沟可见弥漫的异常高信号，但软脑膜未见强化。双侧侧脑室旁可见片状异常强化，右侧较左侧明显。,Nerve-conductionstudiesrevealedasymmetricattenuationintheamplitudesofsensoryandmotorresponses(whichwasworseontheleftsidethanontheright)andnoevidenceofprimarydemyelination.Electro-myographyshowedabnormalspontaneousactivityinthebilateralthoracicparaspinalmusclesatthelevelofT8andinthebilateralgluteusmaximus,tensorfasciaelatae,lateralgastrocnemius,andrighttibialisanteriormuscles.Diffuselydiminishedrecruitmentofnormal-appearingmotor-unitpotentialswasobservedinallthemusclestestedinbothlegs.,Nerve-conductionstudies,肌电图及神经传导速度,神经传导速度：感觉和运动神经反应振幅不对称性衰减（左侧较右侧明显），未发现原发性脱髓鞘的证据。肌电图：T8水平的双侧棘旁肌、双侧臀大肌、阔筋膜张肌、腓肠肌、右侧胫前肌可见异常的自发性肌电活动。双下肢所检测肌肉均可见正常运动电位的减少。,CSFanalysis,Immuno-phenotypicevaluationoftheCSFrevealedBcellswithindeterminatesurfaceandcytoplasmicexpressionofkappaandlambdaimmunoglobulinlightchains.,脑脊液分析,淋巴细胞增多，体积增大，但没有确定的临床意义。免疫表型评价显示B细胞表面不稳定，可见胞浆k和免疫球蛋白轻链表达。葡萄糖明显减低为2mg/dl（正常值50-75mg/dl），蛋白显著升高为4620mg/dl（正常值5-55mg/dl）。,Differentialdiagnosis,SarcoidosisTuberculosisCancer,鉴别诊断,结节病肺结核肿瘤,SarcoidosisSarcoidosisisanimportantconsiderationinthispatientwithpulmonarynodules.Thebloodtestforangiotensin-convertingenzymewasnegative.TheincreasedcellularityandelevatedproteinlevelintheCSFweremoreseverethanwouldtypicallybeexpectedinapatientwithsarcoidosis.Thispatientpresentedwithmarkedhypoesthesiaandnopain.Involvementoftheperipheralnervoussystemisrareinsarcoidosis,butwhenitispresent,itistypicallypainful,andthepainismorepronouncedthanweaknessandsensoryloss.,结节病与结节病鉴别的一个重要考虑因素：肺结节。排除因素：血液检测血管紧张素转换酶为阴性。CSF分析细胞数和蛋白水平的增高，比典型结节病严重。患者存在明显的感觉减退但是不伴有疼痛。结节病中周围神经系统受累罕见，但出现时，伴随典型疼痛，且疼痛比无力和感觉减退更为明显。,TuberculosisTuberculosisisanimportantconsiderationinthisimmunosuppressedpatientwithpulmonarynodules.Shedoesnotliveinanareainwhichthediseaseisendemic.Aninterferon-releaseassaywasnegativebeforetheinitiationofetanercept,andthreeinduced-sputumspecimenswerenegativeforacid-fastbacteria.Theincreasedcellularity,elevatedproteinlevel,anddiminishedglucoselevelintheCSFweremoreseverethanwouldtypicallybeexpectedinapatientwithtuberculousmeningitis.Theabsenceofconstitutionalsymptomsandheadachewouldalsobeunusual.,肺结核与肺结核鉴别的重要考虑因素：应用免疫抑制剂、肺结节。排除因素：患者未在流行区域内。在应用依那西普开始之前干扰素-释放试验检测阴性，痰标本抗酸染色阴性。虽然均缺乏敏感性，但联合阴性结果不支持结核病的诊断。脑脊液分析中细胞数升高、蛋白升高、糖降低水平均较典型结核性脑膜炎患者严重。结核性脑膜炎患者通常有全身症状及头痛。,CancerOfthepossiblediagnosesinthiscase,meningitisrelatedtoacanceristhemostlikely.Therapidextensionofdiseaseintothethoracicnerverootsanddorsal-rootgangliasuggestsanaggressive,infiltrativeprocess,suchascarcinomatousmeningitisduetometastasisfromaremotesolidtumor,leukemicmeningitis,orlymphomatousmeningitis.,癌症对于这个病例，最可能的诊断为肿瘤。疾病在胸神经到背根神经的快速进展，显示疾病侵袭浸润，例如癌组织转移的脑膜炎、白血病或淋巴瘤性脑膜炎。,Onserialimagingstudiesofthechest,pulmonarynoduleshadbeenstableovera4-yearperiod;thisfindingarguesagainstaprimarylungcancerormetastasistothelung.Althoughanoccultsolidtumorisapossibility,imagingstudiesoftheabdomenandpelvisdidnotrevealanysuspiciouslesions,andresultsofrecentscreeningmammographywerenormal.Theunremarkableperipheral-bloodcountsmakeleukemiaunlikely.Themostlikelydiagnosisinthiscaseisisolatedlymphomatousmeningitis.Mostpatientswithlymphomatousmeningitispresentwithfeaturesofsystemicdisease,suchasfever,weightloss,andnightsweats.Thispatientdidnothavethesefeatures,whichsuggeststhatshehashighlycompartmentalizeddisease.,Cancer,癌症肺CT的连续检查，显示肺结节4年内未见明显改变，故除外肺癌及肺癌转移。虽然隐匿性实体肿瘤是可能的，但腹部和骨盆的影像学检查并没有发现任何可疑的病灶，最近的乳房X光检查结果正常。外周血计数排除白血病可能。目前最可能的诊断是孤立的淋巴瘤性脑膜炎。大多数淋巴瘤性脑膜炎的患者伴随全身症状，例如发热、体重减轻、盗汗。但本例患者未伴随这些症状，故考虑特殊类型的肿瘤疾病。,Myeloradiculoneuropathyduetocancer.,ClinicalDiagnosis,Lymphomatousmeningitis,mostlikelyduetoprimaryleptomeningeallymphoma.,临床诊断：肿瘤相关的脊髓神经根型神经病淋巴瘤性脑膜炎，最有可能是原发性脑膜淋巴瘤病,PathologicalDiscussion,病理活检,A图HE染色显示淋巴细胞浸润神经根。箭头所指可见有丝分离的体积较大的肿瘤淋巴细胞。B图免疫组化染色神经：显示肿瘤细胞的浸润性。C图CD20染色：棕染为B淋巴细胞，强调非典型的淋巴细胞增多。Ki-67染色是一种在分裂细胞中特异表达的蛋白，显示了癌细胞的高度增殖性，并支持病变为恶性的理论。,马尾神经根病理活检,散瞳检查及全身PET，这些检查没有发现其他疾病的证据。,DiffuselargeB-celllymphomaconsistentwithneurolymphomatosis.,诊断：弥漫性大B细胞淋巴瘤符合神经淋巴瘤病,Treatment,Shereceivedchemotherapywithhigh-dosemethotrexate,rituximab,andtemozolomide.Aftershehadreceived10dosesofmethotrexate,MRIshowedclinicallysignificantimprovement,whichindicatedthatshehadachievedacompleteresponse(i.e.,completeresolutionofallenhancingdisease).Inaddition,thestrengthandsensationinherlegsimproved.Afterthepatienthadachievedacompleteresponse,sheunderwentautologou