病例報告歲女性伴下肢麻木無力

1、Case Report,病例：53歲女性伴下肢麻木無力2017年06月發(fā)表于新英格蘭雜志資料來源于麻省總醫(yī)院,A 53-year-old woman with rheumatoid arthritis.The patient had been in her usual health until 4 months before this admission, when hypoesthesia developed in the

2、 lateral aspect of the left foot.,,Presentation of Case,53歲女性，有類風濕關(guān)節(jié)炎病史。首發(fā)癥狀為左足外側(cè)感覺減退。病史4個月。,,病例介紹,During the following 2 daysThe hypoesthesia spread to involve the toes and midfoot; chronic low-back pain, which ra

3、diated to the buttocks, had increased in intensity, but there was no pain in the legs, fever, weight loss, or bowel or bladder changes. Examination: Perception of light touch and pinprick was absent on the left toes an

4、d left forefoot; the remainder of the examination was normal.Lab: ESR, VB12, glycated hemoglobin, thyrotropin were normal.,,Presentation of Case,,病例介紹,首次癥狀出現(xiàn)后2天：癥狀：感覺減退逐漸發(fā)展到左足趾及左腳掌，同時存在慢性背痛，并放射到臀部，且程度加強，無雙下肢疼痛，無發(fā)熱，無體

5、重減輕，無大小便異常。查體：左足趾及左腳掌淺感覺及針刺覺缺失，余查體未見明顯異常。檢查化驗：血沉、維生素B12、糖化血紅蛋白、促甲狀腺素未見異常。,During the next 5 dayshypoesthesia progressed to involve the proximal portion of the left foot, as well as the ankle and the lateral lower l

6、eg, but no pain or bowel or bladder incontinence.Examination: cranial-nerve examinations were normal. Strength was 4+ out of 5 during flexion and extension of the toes on the left foot, dorsiflexion and plantar flexi

7、on of the left ankle, eversion and inversion of the left foot, and flexion of the left knee. Perception of vibration was markedly diminished at the left hallux. Perception of light touch and pinprick was decreased on t

8、he left foot and the left lateral leg. Deep-tendon reflexes of the arms and legs were normal. The plantar reflex was flexor on the right side and absent on the left side.,,Presentation of Case,,病例介紹,此后的5天：癥狀：感覺減退逐漸進展

9、至整個左腳、左腳踝、左小腿外側(cè)，但無肢體疼痛及大小便失禁。查體：顱神經(jīng)查體未見異常。左足趾屈伸運動、左踝關(guān)節(jié)趾屈和背屈、左足內(nèi)外翻、左膝關(guān)節(jié)屈曲肌力檢查4+級。左足趾震動覺明顯減退。左足、左小腿觸覺、針刺覺減退。四肢腱反射正常。左側(cè)足跖反射消失，右側(cè)正常。,7 days later (3 months before this admission)The sensory and motor responses were

10、normal and symmetric.F-wave minimal latencies in the tibial nerves were normal.H-reflex was absent at the left soleus and normal at the right soleus. Needle electromyography of the left leg showed diminished recrui

11、tment of long-duration, polyphasic motor-unit potentials in proximal and distal muscles of the L5 myotome. Results of electromyography of the right leg were normal.,,Nerve-conduction studies,,神經(jīng)傳導速度,7天后（本次入院前3個月）：感覺、運動

12、神經(jīng)傳導速度正常、對稱。脛神經(jīng)F波潛伏期正常。左側(cè)脛神經(jīng)H反射消失，右側(cè)正常。針肌電圖顯示左下肢長時程募集相及腰5神經(jīng)支配肌肉的多相運動電位減低，右下肢未見異常。,,Imaging,L3-S1,T1-weighted, show clumped, thickened, and enhancing cauda equina nerve roots in the lumbar spinal canal,,影像,腰椎MRI+強化：

13、平掃顯示腰椎間盤突出、黃韌帶增厚、小關(guān)節(jié)病，可見L4-L5水平椎間孔、L5-S1水平椎間孔狹窄。箭頭處所示L3-S1水平神經(jīng)根增粗，強化。背根神經(jīng)節(jié)及周圍神經(jīng)，對稱未見強化。,,CSF analysis,,Oligoclonal banding was not. Cytologic studies showed increased lymphocytes that were polymorphous and occasion

14、ally reactive and appeared to be benign. Immunophenotypic evaluation did not reveal evidence of a monoclonal B-cell or unusual T-cell population.,,腦脊液分析,寡克隆帶(-)。淋巴細胞增多，呈多形性表現(xiàn)，考慮反應增多是良性表現(xiàn)。腦脊液免疫表型未見單克隆B細胞或T細胞數(shù)量異常。葡

15、萄糖輕度減低為41mg/dl（正常值 50-75mg/dl），蛋白為207mg/dl（正常值 5-55mg/dl）。巨細胞及EB病毒檢測陰性。,CIDP,,,Provisional diagnosis,Intravenous immune globulin was administered 4 weeks and 1 week before the patient was admitted to this hospital.,,初步

16、診斷,慢性炎癥性脫髓鞘性多發(fā)性神經(jīng)根神經(jīng)病分別于本次入院前4周、1周給予丙種球蛋白治療,Despite the administration of intravenous immune globulin, symptoms in the left leg did not improve, and hypoesthesia and weakness developed in the right leg and progresse

17、d centripetally. The patient had several falls at home and began to use a cane, then a walker, and ultimately a wheelchair. The patient reported episodes of bowel and bladder incontinence that she attributed to leg w

18、eakness interfering with her ability to walk to the bathroom quickly.,,,Admission,,,入院情況,在接受丙種球蛋白治療后，患者左下肢癥狀未見改善，且無力及感覺減退進展到右下肢，并向心性發(fā)展。患者曾在家多次跌倒，并開始使用拐杖，后改用助力器，最終患者因病情只能借助輪椅活動?；颊叽舜尉驮\于急診，表訴存在大小便失禁，但患者認為是因為下肢無力癥狀而妨礙她去往

19、衛(wèi)生間。,She reported no fevers, weight loss, or night sweats. Rheumatoid arthritis had been diagnosed 18 months before this admission, and therapy with methotrexate and prednisone had been initiated. Because of persistent

20、 disease activity, therapy with etanercept was initiated 7 months before this admission, after an interferon-γ release assay for Mycobacterium tuberculosis had been negative.,,,Admission,,,入院情況,患者無發(fā)熱、體重減輕、盜汗?；颊哂诒敬稳朐呵?8

21、個月確診類風濕關(guān)節(jié)炎，并接受甲氨蝶呤、強的松治療，因疾病仍處于活動期，在進行結(jié)核分枝桿菌γ干擾素釋放實驗陰性后，加用伊那西普治療。,CT of the chest: there were subcentimeter pulmonary nodules in the bilateral lower lobes that had remained unchanged over a period of 4 years. Results o

22、f routine screening mammography performed 1 month before this admission were normal.,,,Admission,,,入院情況,肺CT顯示雙肺底可見小結(jié)節(jié)，4年內(nèi)肺CT比較未見明顯改變。入院前1個月乳腺X線檢查未見明顯異常。,Medication: omeprazole, methotrexate, prednisone, folic acid, gab

23、apentin, and duloxetine. The patient had recently stopped taking etanercept, because she thought her progressive symptoms could be related to that medication. Medical history: gastroesophageal reflux disease, uterine f

24、ibroids, and β-thalassemia minor.Personal history: She was a current smoker, and did not drink alcohol or use illicit drugs. Family history: Her sister had multiple sclerosis; there was no family history of cancer.,,

25、,Admission,,,入院情況,服用藥物：奧美拉唑、甲氨蝶呤、強的松、葉酸、加巴噴丁、和度洛西汀?；颊哒J為疾病進展與藥物相關(guān)，自行停用依那西普。既往史：反流性食管炎、子宮肌瘤、地中海貧血。個人史：吸煙，無飲酒及違禁藥品應用史。家族史：患者姐姐患有多發(fā)性硬化，家族中無腫瘤病史。,,,On examination,T 36.3°C, BP168/78 mm/Hg, P 90 beats per minute, R

26、18 breaths per minute, SPO2 100% while the patient was breathing ambient air.Motor strength was 4 out of 5 in both legs and 4+ out of 5 on both sides during hip flexion; the remainder of the motor examination was norma

27、l. Perception of vibration and temperature was markedly diminished in both legs from the toes to above the knees. Deep-tendon reflexes were 1+ and symmetric at the patellae and were absent at the soleus. The plantar r

28、eflex was absent on both sides.Two firm, nontender subcutaneous nodules (approximately 1 cm in diameter) with overlying excoriations were present in the left submandibular area.,,,入院查體,T36.3°C, BP168/78 mm/Hg, P90

29、次/分, R18次/分，SPO2 100%。雙下肢肌力4級，雙側(cè)髖關(guān)節(jié)屈曲肌力4+級，余未見明顯異常。雙下肢從足趾到膝關(guān)節(jié)震動覺、溫度覺明顯減低。雙側(cè)膝腱反射減弱（+）對稱，雙側(cè)跟膝脛反射消失。雙側(cè)足跖反射消失。左下頜抓痕處可見兩個無痛性硬性結(jié)節(jié)（小于1cm）。,Urinary retention, absence of rectal tone, and saddle anesthesia (loss of sens

30、ation in the area of the buttocks and perineum) developed.The patient was unable to stand without assistance.,,,On examination,,,入院查體,患者存在尿潴留、腸鳴音消失、鞍區(qū)麻痹（臀部和會陰區(qū)域的感覺喪失）?；颊邿o輔助工具不能站立。,,,On examination,Blood levels of ele

31、ctrolytes, glucose, CRP, and angiotensin-converting enzyme and results of kidney- and liver-function tests were normal. With the exception of the presence of a stable microcytic anemia, the complete blood count and whi

32、te-cell differential count were normal. Blood tests for HIV type 1 p24 antigen, HIV type 1 and type 2 antibodies, and Treponema pallidum were negative.,,,檢查,血電解質(zhì)、血糖、C反應蛋白、血管緊張素轉(zhuǎn)換酶、肝腎功能示正常。存在穩(wěn)定小細胞低色素貧血，血液細胞計數(shù)及白細胞分類計數(shù)示

33、正常。血HIV 1型p24抗原、HIV 1型2型抗體、梅毒螺旋體檢測陰性。,Fine-needle aspiration of one of the submandibular nodules was performed but yielded insufficient material for pathological evaluation. Three induced-sputum samples were negative

34、 for acid-fast bacteria. CT of the chest revealed no clinically significant change in the previously identified pulmonary nodules and no lymphadenopathy.,,,On examination,,,檢查,左下頜結(jié)節(jié)處針刺活檢，但病理檢測材料不足。三次誘導痰標本抗酸染色陰性。肺CT

35、示雙肺小結(jié)節(jié)較前無明顯改變，未見淋巴結(jié)腫大。,,Imaging,Sagittal and axial contrast-enhanced, T1-weighted, fat-saturated images of the lumbar spine (Panels A and B, respectively) show gradual progression of the clumping, thickening, and enhance

36、ment of the cauda equina nerve roots (arrows), along with complete obliteration of the thecal sac and mass effect on the lower thoracic spinal cord and conus (Panel A, arrowhead).,,,影像,腰椎MRI+強化：病變發(fā)展到T10水平，椎管內(nèi)可見脊髓彌漫異常強化

37、，考慮存在輕度脊髓腫脹，馬尾顯示不清。脊髓神經(jīng)根強化明顯。箭頭所指處可見占位效應明顯，硬膜囊消失。,,Imaging,An axial, T2-weighted fluid-attenuated inversion recovery image of the head obtained at the level of the frontoparietal convexities (Panel C) shows hyperinte

38、nsity in the cerebral sulci (arrow). An axial contrast-enhanced, T1-weighted image of the head (Panel D) shows patchy, illdefined enhancement in the periventricular white matter along the lateral ventricles (arrow) that

39、is greater on the right side than on the left.,,,影像,頭MRI+強化：腦溝可見彌漫的異常高信號，但軟腦膜未見強化。雙側(cè)側(cè)腦室旁可見片狀異常強化，右側(cè)較左側(cè)明顯。,Nerve-conduction studies revealed asymmetric attenuation in the amplitudes of sensory and motor responses (whi

40、ch was worse on the left side than on the right) and no evidence of primary demyelination. Electro-myography showed abnormal spontaneous activity in the bilateral thoracic paraspinal muscles at the level of T8 and in t

41、he bilateral gluteus maximus, tensor fasciae latae, lateral gastrocnemius, and right tibialis anterior muscles. Diffusely diminished recruitment of normal-appearing motor-unit potentials was observed in all the muscles

42、 tested in both legs.,,Nerve-conduction studies,,,肌電圖及神經(jīng)傳導速度,神經(jīng)傳導速度：感覺和運動神經(jīng)反應振幅不對稱性衰減（左側(cè)較右側(cè)明顯），未發(fā)現(xiàn)原發(fā)性脫髓鞘的證據(jù)。肌電圖：T8水平的雙側(cè)棘旁肌、雙側(cè)臀大肌、闊筋膜張肌、腓腸肌、右側(cè)脛前肌可見異常的自發(fā)性肌電活動。雙下肢所檢測肌肉均可見正常運動電位的減少。,,CSF analysis,Immuno-phenotypic evalu

43、ation of the CSF revealed B cells with indeterminate surface and cytoplasmic expression of kappa and lambda immunoglobulin light chains.,,,,腦脊液分析,淋巴細胞增多，體積增大，但沒有確定的臨床意義。免疫表型評價顯示B細胞表面不穩(wěn)定，可見胞漿k和λ免疫球蛋白輕鏈表達。葡萄糖明顯減低為2mg/d

44、l（正常值 50-75mg/dl），蛋白顯著升高為4620mg/dl（正常值 5-55mg/dl）。,,Differential diagnosis,SarcoidosisTuberculosisCancer,,鑒別診斷,結(jié)節(jié)病肺結(jié)核腫瘤,SarcoidosisSarcoidosis is an important consideration in this patient with pulmonary nodule

45、s.The blood test for angiotensin-converting enzyme was negative.The increased cellularity and elevated protein level in the CSF were more severe than would typically be expected in a patient with sarcoidosis.This p

46、atient presented with marked hypoesthesia and no pain. Involvement of the peripheral nervous system is rare in sarcoidosis, but when it is present, it is typically painful, and the pain is more pronounced than weakness a

47、nd sensory loss.,結(jié)節(jié)病與結(jié)節(jié)病鑒別的一個重要考慮因素：肺結(jié)節(jié)。排除因素：血液檢測血管緊張素轉(zhuǎn)換酶為陰性。CSF分析細胞數(shù)和蛋白水平的增高，比典型結(jié)節(jié)病嚴重?；颊叽嬖诿黠@的感覺減退但是不伴有疼痛。結(jié)節(jié)病中周圍神經(jīng)系統(tǒng)受累罕見，但出現(xiàn)時，伴隨典型疼痛，且疼痛比無力和感覺減退更為明顯。,TuberculosisTuberculosis is an important consideration in thi

48、s immunosuppressed patient with pulmonary nodules. She does not live in an area in which the disease is endemic.An interferon-γ release assay was negative before the initiation of etanercept, and three induced-sputum

49、 specimens were negative for acid-fast bacteria. The increased cellularity, elevated protein level, and diminished glucose level in the CSF were more severe than would typically be expected in a patient with tuberculou

50、s meningitis.The absence of constitutional symptoms and headache would also be unusual.,肺結(jié)核與肺結(jié)核鑒別的重要考慮因素：應用免疫抑制劑、肺結(jié)節(jié)。排除因素：患者未在流行區(qū)域內(nèi)。在應用依那西普開始之前干擾素-γ釋放試驗檢測陰性，痰標本抗酸染色陰性。雖然均缺乏敏感性，但聯(lián)合陰性結(jié)果不支持結(jié)核病的診斷。腦脊液分析中細胞數(shù)升高、蛋白升高、糖

51、降低水平均較典型結(jié)核性腦膜炎患者嚴重。結(jié)核性腦膜炎患者通常有全身癥狀及頭痛。,CancerOf the possible diagnoses in this case, meningitis related to a cancer is the most likely. The rapid extension of disease into the thoracic nerve roots and dorsal-root ga

52、nglia suggests an aggressive, infiltrative process, such as carcinomatous meningitis due to metastasis from a remote solid tumor, leukemic meningitis, or lymphomatous meningitis.,癌癥對于這個病例，最可能的診斷為腫瘤。疾病在胸神經(jīng)到背根神經(jīng)的快速進展，顯

53、示疾病侵襲浸潤，例如癌組織轉(zhuǎn)移的腦膜炎、白血病或淋巴瘤性腦膜炎。,On serial imaging studies of the chest, pulmonary nodules had been stable over a 4-year period; this finding argues against a primary lung cancer or metastasis to the lung. Although an o

54、ccult solid tumor is a possibility, imaging studies of the abdomen and pelvis did not reveal any suspicious lesions, and results of recent screening mammography were normal. The unremarkable peripheral-blood counts make

55、 leukemia unlikely. The most likely diagnosis in this case is isolated lymphomatous meningitis.Most patients with lymphomatous meningitis present with features of systemic disease,such as fever, weight loss, and night s

56、weats. This patient did not have these features, which suggests that she has highly compartmentalized disease.,Cancer,癌癥肺CT的連續(xù)檢查，顯示肺結(jié)節(jié)4年內(nèi)未見明顯改變，故除外肺癌及肺癌轉(zhuǎn)移。雖然隱匿性實體腫瘤是可能的，但腹部和骨盆的影像學檢查并沒有發(fā)現(xiàn)任何可疑的病灶，最近的乳房X光檢查結(jié)果正常。外周血計數(shù)排

57、除白血病可能。目前最可能的診斷是孤立的淋巴瘤性腦膜炎。大多數(shù)淋巴瘤性腦膜炎的患者伴隨全身癥狀，例如發(fā)熱、體重減輕、盜汗。但本例患者未伴隨這些癥狀，故考慮特殊類型的腫瘤疾病。,Myeloradiculoneuropathy due to cancer.,Clinical Diagnosis,Lymphomatous meningitis, most likely due to primary leptomeningeal lympho

58、ma.,臨床診斷：腫瘤相關(guān)的脊髓神經(jīng)根型神經(jīng)病淋巴瘤性腦膜炎，最有可能是原發(fā)性腦膜淋巴瘤病,,Pathological Discussion,,病理活檢,A圖HE染色顯示淋巴細胞浸潤神經(jīng)根。箭頭所指可見有絲分離的體積較大的腫瘤淋巴細胞。B圖免疫組化染色神經(jīng)：顯示腫瘤細胞的浸潤性。C圖CD20染色：棕染為B淋巴細胞，強調(diào)非典型的淋巴細胞增多。Ki-67染色是一種在分裂細胞中特異表達的蛋白，顯示了癌細胞的高度增殖性，并

59、支持病變?yōu)閻盒缘睦碚摗?馬尾神經(jīng)根病理活檢,散瞳檢查及全身PET，這些檢查沒有發(fā)現(xiàn)其他疾病的證據(jù)。,Diffuse large B-cell lymphoma consistent with neurolymphomatosis.,診斷：彌漫性大B細胞淋巴瘤符合神經(jīng)淋巴瘤病,,Treatment,She received chemotherapy with high-dose methotrexate, rituximab, and

60、 temozolomide. After she had received 10 doses of methotrexate, MRI showed clinically significant improvement, which indicated that she had achieved a complete response (i.e., complete resolution of all enhancing disea

61、se).In addition, the strength and sensation in her legs improved.After the patient had achieved a complete response, she underwent autologous stem-cell trans-plantation.The patient’s condition continues to improve, a

62、nd MRI showed no evidence of recurrent disease 1 year after transplantation.,患者接受了原發(fā)性中樞神經(jīng)系統(tǒng)淋巴瘤的治療。,給予患者大劑量的氨甲喋呤、利妥昔單抗、替莫唑胺聯(lián)合治療?；颊呓邮?0次甲氨蝶呤治療后，頭MRI臨床表現(xiàn)明顯改善（如強化明顯緩解），且雙下肢運動及感覺癥狀逐漸改善。在患者藥物治療完成后，接受了自體干細胞移植治療?；颊叩陌Y狀逐漸改善，

63、移植后1年MRI沒有顯示疾病復發(fā)。,,治療,PCNSL, accounting for 3.3% of intracranial tumors, is a highly aggressive non-Hodgkin‘s lymphoma arising in the CNS. DLBCL accounts for about 90% of PCNSL. Unlike other brain tumors, it often ha

64、s a favorable response to both chemotherapy and radiation therapy, but compared with lymphomas outside the CNS, survival is usually inferior.,Primary CNS Lymphoma,原發(fā)性中樞神經(jīng)系統(tǒng)淋巴瘤,原發(fā)性中樞神經(jīng)系統(tǒng)淋巴瘤（PCNSL），占顱內(nèi)腫瘤的3.3%，是一種發(fā)生在中樞神經(jīng)系統(tǒng)高

65、度侵襲性的非霍奇金淋巴瘤，其中彌漫的大B細胞淋巴瘤（DLBCL）約占PCNSL的90%。與其他腦腫瘤不同，PCNSL對化療和放療有良好的療效，但與中樞神經(jīng)系統(tǒng)以外的淋巴瘤相比，生存率通常較低。,Patients with PCNSL develop neurologic signs over weeks, depending on the site of CNS involvement. Imaging usually reve

66、als a homogenously enhancing mass lesion, most often a single brain lesion (66%), with a supratentorial location (87%) and involvement of the frontoparietal lobes (39%). Less frequently, eyes (15% to 25%), CSF (7% to 42%

67、), and only in rare cases, the spinal cord are involved.,Primary CNS Lymphoma,原發(fā)性中樞神經(jīng)系統(tǒng)淋巴瘤,PCNSL患者的神經(jīng)癥狀通常在幾周內(nèi)發(fā)展，癥狀取決于中樞神經(jīng)系統(tǒng)受累的部位。影像學檢查通常表現(xiàn)為均勻強化的腫塊，最常見的一個單一的腦損傷（66%），常見的受累位置，幕上（87%）、額頂葉（39%）。較少受累部位可見眼睛（15%到25%），腦脊液（7%到4