1、Case Report,病例：53岁女性伴下肢麻木无力2017年06月发表于新英格兰杂志资料来源于麻省总医院,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 lateral aspect of the left foot.,Presentation of Case,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
2、史4个月。,病例介绍,During the following 2 daysThe hypoesthesia spread to involve the toes and midfoot; chronic low-back pain, which radiated 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
3、 and pinprick was absent on the left toes and left forefoot; the remainder of the examination was normal.Lab: ESR, VB12, glycated hemoglobin, thyrotropin were normal.,Presentation of Case,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
4、查化验：血沉、维生素B12、糖化血红蛋白、促甲状腺素未见异常。,During the next 5 dayshypoesthesia progressed to involve the proximal portion of the left foot, as well as the ankle and the lateral lower leg, but no pain or bowel or bladder incontinence.Examination: cranial-nerve examinations were normal. Strength was 4+ out of 5 d
5、uring flexion and extension of the toes on the left foot, dorsiflexion and plantar flexion 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 decrease
6、d on the 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。
7、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。,7 days later (3 months before this admission)The sensory and motor responses were 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 electromyogr
8、aphy of the left leg showed diminished recruitment 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。
9、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, show clumped, thickened, and enhancing cauda equina nerve roots in the lumbar spinal canal,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。,CSF analysis,Oligoclonal banding was no
10、t. Cytologic studies showed increased lymphocytes that were polymorphous and occasionally reactive and appeared to be benign. Immunophenotypic evaluation did not reveal evidence of a monoclonal B-cell or unusual T-cell population.,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
11、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,Provisional diagnosis,Intravenous immune globulin was administered 4 weeks and 1 week before the patient was admitted to this hospital.,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,Despite the administration of intravenous imm
12、une globulin, symptoms in the left leg did not improve, and hypoesthesia and weakness developed in the right leg and progressed 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
13、 incontinence that she attributed to leg weakness interfering with her ability to walk to the bathroom quickly.,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。,She reported no fevers, weight loss, or n
14、ight sweats. Rheumatoid arthritis had been diagnosed 18 months before this admission, and therapy with methotrexate and prednisone had been initiated. Because of persistent disease activity, therapy with etanercept was initiated 7 months before this admission, after an interferon- release assay for
15、Mycobacterium tuberculosis had been negative.,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。,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
16、 of routine screening mammography performed 1 month before this admission were normal.,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, folic acid, gabapentin, and duloxetine. The patient had recently stopped taking etanercept, because
17、 she thought her progressive symptoms could be related to that medication. Medical history: gastroesophageal reflux disease, uterine fibroids, and -thalassemia minor.Personal history: She was a current smoker, and did not drink alcohol or use illicit drugs. Family history: Her sister had multiple sc
18、lerosis; there was no family history of cancer.,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。,On examination,T 36.3C, BP168/78 mm/Hg, P 90 beats per minute, R 18 breaths per minute, SPO2 100% while the patien
19、t 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 normal. Perception of vibration and temperature was markedly diminished in both legs from the toes to above the knees. Deep-tendon refle
20、xes were 1+ and symmetric at the patellae and were absent at the soleus. The plantar reflex 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.,入院查体,T36.3C, BP168/78 mm/Hg, P90次/分,
21、 R18次/分，SPO2 100%。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）。,Urinary retention, absence of rectal tone, and saddle anesthesia (loss of sensation in the area of the buttocks and perineum) developed.The patient was unable to stand with
22、out assistance.,On examination,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。,On examination,Blood levels of electrolytes, 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
23、, the complete blood count and white-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.,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HIV 1型p24抗原、HIV 1型2型抗体、梅毒螺旋体检测阴性。,Fine-needle as
24、piration of one of the submandibular nodules was performed but yielded insufficient material for pathological evaluation. Three induced-sputum samples were negative for acid-fast bacteria. CT of the chest revealed no clinically significant change in the previously identified pulmonary nodules and no
25、 lymphadenopathy.,On examination,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,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 enhancement of
26、 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+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,An axial, T2-weighted fluid-atten
27、uated inversion recovery image of the head obtained at the level of the frontoparietal convexities (Panel C) shows hyperintensity 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 matte
28、r along the lateral ventricles (arrow) that is greater on the right side than on the left.,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-conduction studies revealed asymmetric attenuation in the amplitudes of sensory and motor responses (which was worse on the left side than on the
29、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 the bilateral gluteus maximus, tensor fasciae latae, lateral gastrocnemius, and right tibialis anterior muscles. Diffusely di
30、minished recruitment of normal-appearing motor-unit potentials was observed in all the muscles tested in both legs.,Nerve-conduction studies,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。,CSF analysis,Immuno-phenotypic
31、 evaluation of the CSF revealed B cells with indeterminate surface and cytoplasmic expression of kappa and lambda immunoglobulin light chains.,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）。,Differential diagnosis,Sarcoido
32、sisTuberculosisCancer,鉴别诊断,结节病肺结核肿瘤,SarcoidosisSarcoidosis is an important consideration in this patient with pulmonary nodules.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 expec
33、ted in a patient with sarcoidosis.This patient 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 and sensory loss.,结节病与结节病鉴别的一个重要考虑因素：肺结节。
34、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。,TuberculosisTuberculosis is an important consideration in this immunosuppressed patient with pulmonary nodules. She does not live in an area in which the disease is endemic.An interferon- re
35、lease assay was negative before the initiation of etanercept, and three induced-sputum 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 tuberc
36、ulous meningitis.The absence of constitutional symptoms and headache would also be unusual.,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。,CancerOf the possible diagnoses in this case, m
37、eningitis related to a cancer is the most likely. The rapid extension of disease into the thoracic nerve roots and dorsal-root ganglia suggests an aggressive, infiltrative process, such as carcinomatous meningitis due to metastasis from a remote solid tumor, leukemic meningitis, or lymphomatous meni
38、ngitis.,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。,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 occult solid tumor is a possibility,
39、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 leukemia unlikely. The most likely diagnosis in this case is isolated lymphomatous meningitis.Most patients with lym
40、phomatous meningitis present with features of systemic disease,such as fever, weight loss, and night sweats. This patient did not have these features, which suggests that she has highly compartmentalized disease.,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
41、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。,Myeloradiculoneuropathy due to cancer.,Clinical Diagnosis,Lymphomatous meningitis, most likely due to primary leptomeningeal lymphoma.,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,Pathological Discuss
42、ion,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。,Diffuse large B-cell lymphoma consistent with neurolymphomatosis.,诊断：弥漫性大B细胞淋巴瘤符合神经淋巴瘤病,Treatment,She receive
43、d chemotherapy with high-dose methotrexate, rituximab, and 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 disease).In addition, the str
44、ength and sensation in her legs improved.After the patient had achieved a complete response, she underwent autologous stem-cell trans-plantation.The patients condition continues to improve, and MRI showed no evidence of recurrent disease 1 year after transplantation.,患者接受了原发性中枢神经系统淋巴瘤的治疗。,给予患者大剂量的氨甲
45、喋呤、利妥昔单抗、替莫唑胺联合治疗。患者接受10次甲氨蝶呤治疗后，头MRI临床表现明显改善（如强化明显缓解），且双下肢运动及感觉症状逐渐改善。在患者药物治疗完成后，接受了自体干细胞移植治疗。患者的症状逐渐改善，移植后1年MRI没有显示疾病复发。,治疗,PCNSL, accounting for 3.3% of intracranial tumors, is a highly aggressive non-Hodgkins lymphoma arising in the CNS. DLBCL accounts for about 90% of PCNSL. Unlike other brain
46、tumors, it often has a favorable response to both chemotherapy and radiation therapy, but compared with lymphomas outside the CNS, survival is usually inferior.,Primary CNS Lymphoma,原发性中枢神经系统淋巴瘤,原发性中枢神经系统淋巴瘤（PCNSL），占颅内肿瘤的3.3%，是一种发生在中枢神经系统高度侵袭性的非霍奇金淋巴瘤，其中弥漫的大B细胞淋巴瘤（DLBCL）约占PCNSL的90%。与其他脑肿瘤不同，PCNSL对化疗
47、和放疗有良好的疗效，但与中枢神经系统以外的淋巴瘤相比，生存率通常较低。,Patients with PCNSL develop neurologic signs over weeks, depending on the site of CNS involvement. Imaging usually reveals a homogenously enhancing mass lesion, most often a single brain lesion (66%), with a supratentorial location (87%) and involvement of the fro
48、ntoparietal lobes (39%). Less frequently, eyes (15% to 25%), CSF (7% to 42%), and only in rare cases, the spinal cord are involved.,Primary CNS Lymphoma,原发性中枢神经系统淋巴瘤,PCNSL患者的神经症状通常在几周内发展，症状取决于中枢神经系统受累的部位。影像学检查通常表现为均匀强化的肿块，最常见的一个单一的脑损伤（66%），常见的受累位置，幕上（87%）、额顶叶（39%）。较少受累部位可见眼睛（15%到25%），脑脊液（7%到42%），极少情况可见脊髓受累。,Primary CNS Lymphoma,感 谢,
