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A 71-year-old woman presented with a 1-week history of progressive weakness involving her lower extremities, leading to an inability to walk. She also noticed diminished sensation in her lower extremities. She did not complain of bowel or bladder dysfunction. She did not have any neurologic symptoms in her upper extremities. She experienced an upper respiratory tract infection 5 days prior to the start of these symptoms and was treated with antibiotics. There was no history of headache, impaired cognition, or speech impairment.
71岁女性以双下肢进行性无力1周为主诉入院，现患者无法行走，同时伴有双下肢感觉减退。患者无尿便障碍（肠道或膀胱功能障碍）。患者双上肢无任何神经系统症状。患者起病前5天有上呼吸道感染史，应用抗生素治疗。否认有头痛、认知减退或言语障碍等病史。
Her examination revealed normal higher mental functions and intact cranial nerve function bilaterally. She had increased tone in both lower extremities, and muscle strength was 3/5 at the hips and 2/5 at the knees and ankles. The weakness was in a pyramidal distribution with the flexors more affected than extensors. Sensory examination revealed diminished vibration and joint position sense up to her knees; a sensory level for fine touch and pinprick was detected at approximately the T6 level. She had exaggerated reflexes in her lower extremities with no clonus and had extensor plantar responses bilaterally.
体检示高级神经功能正常，双侧颅神经检查正常。患者双下肢肌张力增高，髋部肌力3/5级，膝和踝部肌力2/5级。屈肌无力重于伸肌，呈锥体束分布。感觉检查示双膝关节以下震动觉和关节位置觉减退，大约在T6水平检测到精细触觉和针刺觉感觉障碍平面。患者双下肢腱反射亢进，无肌阵挛，双侧伸性跖反射阳性。 Questions to consider 1. What is the localization of the problem? 2. What are the likely etiologies? 3. What would you do next?
需要考虑的问题 1. 病变的定位？ 2. 可能的病因？ 3. 下一步需要完成的检查？ The involvement of multiple long tracts, increased tone, hyperreflexia, sensory level at T6, and no symptoms or signs in the upper extremities point to a lesion in the thoracic spinal cord.
患者存在双侧锥体束征（多发长束受累）、肌张力增高、腱反射亢进、T6感觉平面，不伴有上肢症状或体征，提示胸髓病变。
The evolution of these complaints over a week would make a vascular etiology unlikely, and the differential for this patient includes demyelinating, inflammatory, infectious, neoplastic, compressive, and metabolic causes.1 In a patient presenting with an acute onset of clinical features consistent with a myelopathy, an urgent MRI of the spine with contrast should be obtained to rule out compressive causes that would require urgent surgical intervention.2
患者症状进展持续1周，不支持血管性病因，需要鉴别的疾病有脱髓鞘性、炎症性、感染性、肿瘤性、压迫性及代谢性疾病。患者以急性脊髓病临床表现起病，急需脊髓MRI平扫+增强除外压迫性病变，后者可能需要急诊手术治疗。
An MRI of the spine was obtained, which demonstrated a longitudinally extensive intramedullary spinal cord lesion extending from T6 to T12 (figure). Due to her compromised renal function, gadolinium contrast could not be administered. A diagnosis of transverse myelitis, possibly postinfectious, was made, and she was started on IV methylprednisolone 1 g daily for 5 days.
脊髓MRI检查示长节段脊髓内病变累及T6-T12（图）。由于患者存在肾功能减退，未接受钆增强扫描。患者诊断为横贯性脊髓炎（感染后可能），予甲强龙1g QD 静滴5天。
Question to consider 1. Given the MRI findings, what would the differential diagnosis be?
需要考虑的问题 1. 基于MRI检查结果，可能的鉴别诊断？ Longitudinally extensive transverse myelitis (LETM) is a term used to describe confluent lesions extending more than 3 spinal cord segments. The differential diagnosis for LETM is fairly broad and a detailed list of causes is given in the table. LETM has gained recognition recently as being suspicious for neuromyelitis optica (NMO) and is part of the diagnostic criteria for this condition.3 Due to concern for this diagnosis, imaging of the brain was obtained.
长节段横断性脊髓炎（LETM）用于描述超过3个脊髓节段的融合病变。LETM的鉴别诊断很多，详见下表。近年来，很多人认识到LETM可能提示视神经脊髓炎（NMO），并作为NMO的诊断标准之一。因为考虑到这一诊断，进行了头影像学检查。
MRI of the brain revealed multiple T2 hyperintense lesions bilaterally both infratentorially and supratentorially, as demonstrated in the figure, B and C.
颅脑MRI示颅内双侧多发幕上及幕下T2高信号病灶，如图B及图C所示。
Imaging features on spinal MRI can help refine the differential diagnosis of LETM. Multiple sclerosis (MS) cord lesions are usually peripheral, involve part of the cord, and have short longitudinal extent. NMO lesions are typically central, T1 hypointense, and cause cord expansion. Acuted isseminated encephalomyelitis spinal cord lesions are similar to MS lesions, but MRI brain usually shows large confluent lesions with basal ganglia involvement. Spinal cord infarcts involve anterior cord with sparing of the dorsal columns, while dural arteriovenous fistulas usually show T2 hyperintensity in the midthoracic cord with flow voids seen in the thecal sac.1
脊髓MRI特征有助于LETM的鉴别诊断。多发性硬化（MS）病灶通常位于脊髓外周，呈短节段病灶。NMO病灶通常位于脊髓中心，T1呈低信号，并造成脊髓肿胀。急性播散性脑脊髓炎的脊髓病灶特点类似MS病灶，颅脑病灶通常表现为多个大片融合病灶，并累及基底节区。脊髓梗死累及前索，而背柱不受累。硬膜动静脉瘘通常表现为胸髓中段T2高信号伴有硬膜囊流空信号。
The patient also underwent a lumbar puncture, which revealed leukocyte count 1 cell/mm3, erythrocyte count 2 cells/mm3, protein 47mg/dL, glucose 57mg/dL (serum glucose 104 mg/dL), immunoglobulin G index 0.6, negative cytology, and no oligoclonal bands. CSF varicella-zoster virus serology, herpes simplex virus PCR, Venereal Disease Research Laboratory, and Lyme serology were negative. Paraneoplastic panel, serum B12, folate, thyroid-stimulating hormone, copper, zinc, antinuclear antibodies, rheumatoid factor, SS-A, SS-B, and NMO antibody were within normal limits.
患者行腰椎穿刺术检查示脑脊液白细胞计数为1个/mm3,红细胞计数为1个/mm3,蛋白为47mg/dl，葡萄糖为57mg/dl（血糖为104mg/dl），免疫球蛋白G指数为0.6，细胞学检查阴性，没有寡克隆带。CSF水痘带状疱疹病毒血清学、单纯疱疹病毒PCR、VDRL检查、莱姆病血清学检查均阴性。副肿瘤筛查（Paraneoplastic panel）、血清维生素B12、叶酸、TSH、铜、锌、ANA、RF、SS-A、SS-B和NMO抗体均在正常范围。
The patient did not improve with IV steroids and continued to worsen in terms of her lower extremity strength and sensation. A course of plasma exchange was initiated for the possibility of a steroid-resistant demyelinating disease. Multiple studies have shown benefit from plasma exchange in fulminant CNS inflammatory demyelinating diseases.4,5 Nevertheless, over the next 2 weeks, she did not respond to plasma exchange and had no benefit from physical therapy.
接受激素治疗后，患者双下肢无力和感觉减退症状并未改善，反倒继续加重。考虑可能存在激素抵抗的脱髓鞘疾病，患者开始接受血浆置换治疗。多个研究表明，对于暴发性CNS炎性脱髓鞘性疾病，血浆置换治疗可以获益。但患者对随后2周的血浆置换治疗无反应，物理治疗也没有效果。 Question to consider 1. How would you further refine the diagnosis?
需要考虑的问题 1. 如何进一步明确诊断？ Repeat imaging showed some progression of the longitudinal extent of the spinal cord lesion and stable brain lesions. At this point, a brain biopsy was considered, given the lack of response to therapy directed at inflammatory and demyelinating disease. 反复影像学检查发现脊髓长节段病灶有所进展，而颅内病灶稳定。这时，由于针对炎性脱髓鞘性疾病的治疗反应不佳，所以考虑进行脑活检。
Brain biopsy of a frontal lobe lesion was performed and revealed metastatic small-cell carcinoma. CT chest was then done and revealed a left hilar mass suggestive of a neoplasm. The hilar mass was not biopsied due to the positive brain biopsy and radiologic appearance of the mass. A diagnosis of longitudinally extensive spinal cord lesion secondary to intramedullary metastasis from stage IV small-cell lung cancer was made. She was seen by the oncology service and chemotherapy was initiated. However, she continued to worsen and was ultimately transferred to hospice.
额叶病灶脑活检提示转移性小细胞癌。胸部CT提示左侧肺门肿块，肿瘤可能。由于脑活检结果及肿块影像学表现，未对肺门肿块进行活检。长节段脊髓病变考虑为继发于IV期小细胞肺癌的脊髓内转移。请肿瘤科会诊后，患者接受化疗。然而，患者症状持续恶化，最终转院至临终关怀医院。
LETM has abroad differential diagnosis. However, the most common causes of LETM are inflammatory demyelinating diseases such as NMO and postinfectious encephalomyelitis. The presence of numerous brain lesions makes NMO less likely, though brain lesions may occur in patients withNMO, producing the so-called NMO spectrum disorder (NMOSD).6 NMOSD brain lesions are usually asymptomatic and may consist of periependymal lesions around the ventricular system, extensive hemispheric lesions, and lesions in the internal capsule and cerebral peduncles.7 NMO immunoglobulin G or aquaporin-4 antibody positivity was included in the diagnostic criteria for NMO in 2006 and improved recognition of the disease. It should be noted that the sensitivity of NMO IgG varies in different series from 51% to 90%, while its specificity lies between 91% and 100%.
LETM需要鉴别诊断的疾病很多。然而，LETM最常见的病因是炎性脱髓鞘性疾病，诸如NMO和感染后脑脊髓炎。颅内存在多发病灶不支持NMO，不过，NMO患者也可有颅内病灶，就是所谓NMO谱系病（NMOSD）。NMOSD患者颅内病灶通常是无症状性，包括围绕脑室系统的室管膜周病变、广泛的半球病变以及位于内囊、大脑脚的病变。2006年，NMO免疫球蛋白G和AQP-4抗体阳性被纳入NMO的诊断标准，改善了对本病的认识。应该注意的是，NMO IgG的敏感性在各个研究中不同，从51%到90%，而特异性为91%-100%。
Postinfectious encephalomyelitis can cause LETM and brain lesions, similar to those of our patient. A recent prospective study described the clinical features and course of postinfectious neurologic syndromes.8 These ranged from isolated encephalitis or myelitis to more diffuse encephalomyeloradiculoneuritis. Patients with postinfectious neurologic syndromes were older, had more severe neurologic disability at onset and poorer outcomes, and were more resistant to steroid treatment than patients with MS.8 In contrast to our patient, almost 90% of patients with postinfectious neurologic syndromes had elevated CSF counts suggesting inflammation, in addition to elevated CSF protein levels.
感染后脑脊髓炎可引起LETM和颅内病变，表现可类似我们的患者。最近一项前瞻性研究对感染后神经综合征的临床特征及病程进行研究。研究涵盖了孤立的脑炎或脊髓炎到弥散性脑脊髓脊神经根神经炎。感染后神经综合征的患者年龄更大，起病时神经功能障碍更严重，预后更差，比MS患者对激素治疗反应更差。与我们的患者不同，将近90%的感染后神经综合征患者CSF细胞计数升高（提示有炎症），此外蛋白水平也升高。
Intramedullary spinal cord metastases presenting as LETM are rarely encountered.9 Intramedullary spinal cord metastases are seen in only 0.1%–0.4% of cancer patients.10 In a recent retrospective review of intramedullary spinal cord metastases, they were the presenting feature in 20% of patients.11 The underlying malignancy was lung cancer in 50%, followed by renal carcinoma, breast cancer, and melanoma. Almost all intramedullary spinal cord metastases in this review exhibited enhancement with gadolinium and had extensive edema on T2-weighted sequences above and below the metastasis.11 In our patient, the diagnosis might have been facilitated if gadolinium contrast had been administered, as this could have revealed an enhancing nodule within the longitudinally extensive spinal cord lesion.
以LETM为表现的脊髓内转移很罕见，仅见于0.1-0.4%癌症患者。最近一项脊髓内转移的回顾性研究表明，只有20%的患者有一定的表现特征（临床或影像学表现，译者注）。50%的患者潜在的恶性肿瘤是肺癌，其次分别是肾癌、乳腺癌和黑色素瘤。在这份文献综述中，几乎所有脊髓内转移病灶钆增强扫描均有强化，T2序列上转移病灶周围有广泛的水肿。我们的患者如果可以进行钆增强扫描的话，可能有助于诊断，因为增强扫描可能会提示长节段脊髓病变内可见强化的结节。
Some of the clues pointing us away from an inflammatory cause in our patient were the patient’s advanced age, lack of pleocytosis in the CSF, and lack of response to steroids and plasma exchange. It should also be noted that in our case the term “myelitis” is a misnomer, since there is no inflammatory lesion of the cord. This case highlights the importance of recognizing the broad differential diagnosis of LETM and appropriately utilizing invasive tests such as brain biopsy when patients do not have the expected response to therapy, especially when imaging and laboratory studies do not fully support the working diagnosis.
提示我们的患者不是炎性疾病的线索是患者年龄较大，CSF没有细胞数异常增多，对激素和血浆置换没有明显的反应。应该注意的是，对于我们的患者，脊髓炎是一个误称，因为患者脊髓不存在炎性病变。该病例不仅突出了认识LETM鉴别诊断的重要性，也强调了在患者对治疗反应差时运用诸如脑活检等有创性操作的重要性，尤其是当影像学和实验室检查结果不能支持目前诊断时。 （全文终） 诗 句 赏 析  海内存知己，天涯若比邻。 A bosom friend afar brings distance near.  编辑：李会琪 ：李神经群招贤榜--招募病历讨论总结员，公众号编辑的通知【公告】 |
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