副肿瘤性脊髓病12例

目的副肿瘤性脊髓病临床及影像学表现多样,本文对副肿瘤性脊髓病的临床、实验室检查、神经影像学特点及治疗反应进行总结分析。方法采集2010年1月1日—2017年12月31日期间首都医科大学宣武医院住院的临床表现为脊髓病,伴有恶性肿瘤和/或与恶性肿瘤具有密切相关性的神经元特异性抗体,符合诊断标准的副肿瘤性脊髓病患者的临床、血清神经元特异性抗体、脑脊液指标及神经影像学、治疗反应进行总结分析。结果 12例副肿瘤性脊髓病患者起病年龄为47～70岁,主要临床表现为进行性脊髓病,其中亚急性起病患者5例(41.7%),隐袭起病患者7例(58.3%)。8例患者确诊恶性肿瘤(66.7%),3例患者在出现脊髓病前诊断,5例患者在出现脊髓病后诊断。7例患者发现抗神经元抗体(58.3%)。脑脊液异常包括淋巴细胞增多5例(41.7%),蛋白升高9例(75.0%),寡克隆区带阳性4例(33.3%)。9例患者发现脊髓T2异常信号(75.0%)。其中3例(25.0%)患者表现为纵向广泛信号异常(3个椎体节段),6例(50.0%)表现为脊髓局灶性信号异常,5例(41.7%)脊髓病变强化。8例患者接受肿瘤治疗,5例患者针对脊髓病接受免疫治疗,仅有2例患者轻度临床改善。结论副肿瘤性脊髓病临床及影像学表现多样,无特异性,治疗反应差。中老年患者亚急性或慢性进行性脊髓病应警惕副肿瘤性脊髓病,肿瘤筛查和恶性肿瘤密切相关性神经元特异性抗体的检测在早期诊断中起重要作用。     

抗SOX-1抗体阳性副肿瘤性脊髓病一例

目的探讨副肿瘤性脊髓病(PM)的临床特点,以提高对该病的诊断水平。方法分析1例PM患者的病历资料。结果 62岁男性患者以双下肢麻木无力起病,呈亚急性进展,脑脊液副肿瘤综合征抗体示:抗SOX-1抗体IgG阳性(+),结合CT及增强磁共振(MRI)等检查,诊断为PM。结论 副肿瘤性脊髓病是由于全身性或潜在的恶性肿瘤的远隔效应从而造成脊髓损伤的一种神经系统副肿瘤综合征,提高对该病的认识,有助于早期诊断,通过检测相关特异性抗体指导疾病的早期治疗。     

不同类型副肿瘤性小脑变性的免疫学研究

报告６例副肿瘤性小脑变性，其中单纯型和复合型各３例。复合型中合并副肿瘤性脑脊髓炎，炎重症肌无力综合征及副肿瘤性眼阵挛－肌阵挛综合征各１例。免疫组化和免疫印迹技术显示全部患者血清和脑脊液中存在特异性抗小脑浦肯野细胞抗体和神经元抗核抗体，其中抗－Ｙｏ     

血清抗recoverin抗体阳性的副肿瘤性脊髓病(附1例报告及文献复习)

目的 神经系统副肿瘤综合征是由肿瘤远隔效应造成神经系统损害的一组综合征,累及脊髓时称为副肿瘤性脊髓病(PM).拟对PM的临床特征及预后进行总结,以期提高PM的诊疗水平.方法 收集神经内科经治的1例恶性胸腺瘤术后放疗和化疗后合并PM患者的临床表现、血清及脑脊液特异性神经抗体及影像学检查、诊疗过程等资料,结合文献复习进行总...     

抗Hu抗体检测在神经系统副肿瘤综合征诊断中的临床意义

目的 探讨抗Hu抗体检测在神经系统副肿瘤综合征诊断中的临床意义.方法 采用间接免疫荧光方法和蛋白免疫印迹法对送检至北京协和医院神经病理实验室的1500余例患者的血清和脑脊液进行抗Hu抗体检测,回顾性分析抗Hu抗体阳性患者的临床资料及诊断.神经系统副肿瘤综合征的诊断标准参照Graus等的诊断标准.结果 共有27例患者抗体阳性,其中血清抗Hu抗体阳性25例,脑脊液抗Hu抗体阳性8例.临床主要表现为感觉神经元神经病、亚急性小脑变性、Lambert-Eaton综合征和抗利尿激素分泌不当综合征引起的脑病等,其中20例(74.1%)患有肿瘤,包括肺癌17例,胃癌2例,不明性质腹部肿瘤1例.7例患者未发现恶性肿瘤,包括多发性肌炎和系统性红斑狼疮(SLE)合并神经肌肉病各1例.根据Graus等神经系统副肿瘤综合征的诊断标准,27例中22例可确诊神经系统副肿瘤综合征或相关的肿瘤,抗Hu抗体的阳性预测值为81.5%.结论 抗Hu抗体阳性对神经系统副肿瘤综合征的诊断具有一定意义;其相关肿瘤以肺癌,特别是小细胞肺癌最常见.其他自身免疫性疾病偶可见抗Hu抗体阳性,需要全面检查和密切随访以排除恶性肿瘤的可能.     

抗SOX-1,GABABR和VGCC抗体阳性的副肿瘤综合征：病例报告与文献回顾

目的 神经系统副肿瘤综合征是罕见的由潜在肿瘤诱发的免疫介导的疾病。早期识别特殊的副肿瘤综合征亚型和特异性的自身抗体可以指导高效的肿瘤筛查,进而促进及时的抗肿瘤治疗并延长生存期。方法回顾潍坊市人民医院神经内科收治的1例合并多个临床表型及多种抗体的副肿瘤综合征患者的诊治过程,同时对相关文献进行系统性综述。结果 患者以行走不稳和精神行为异常为早期突出表现,最初诊断为伴抗SOX-1及GABABR抗体阳性的副肿瘤性小脑变性和副肿瘤性边缘性脑炎,因电生理检查的异常发现和P/Q型VGCC抗体阳性,考虑合并存在Lambert-Eaton肌无力综合征,所有证据均指向该患者存在隐匿的小细胞肺癌。最终胸腔镜活检证实PET-CT上显示的肿大淋巴结符合小细胞肺癌的病理改变。该患者同时接受了抗肿瘤治疗和免疫治疗,生存期为19个月。结论 检测发现抗SOX1抗体阳性应强化对SCLC的筛查。细胞表面抗体介导的副肿瘤性边缘性脑炎和副肿瘤性神经肌肉接头病变患者在抗肿瘤治疗的同时应立即启动免疫治疗,预后相对较好。     

抗Hu抗体阳性副肿瘤性边缘叶脑炎1例报告及文献复习

正神经系统副肿瘤综合征(paraneoplastic neurologic syndromes,PNS)是指肿瘤在中枢神经系统和周围神经、肌肉系统出现的远隔效应,是一组针对神经系统某些靶抗原的自身免疫性疾病,如累及大脑边缘叶系统即表现为副肿瘤性边缘叶脑炎~([1])。在一些PNS患者血清和(或)脑脊液中可发现肿瘤神经抗体,特异性抗神经元抗体有抗Hu、抗Yo、抗CV2、抗Ri、抗Ma2等抗体,现将我院收治的1例抗Hu抗体阳性的副肿瘤性边缘叶脑炎患者病例报道如下,并结合相关文献进行     

中枢神经系统神经元表面抗体综合征5例并文献回顾

目的探讨5例神经元表面抗体综合征的临床特点及诊治。方法总结患者的临床表现、脑脊液检查、影像学检查等并进行相关文献回顾。结果 3例脑脊液+血抗NMDAR抗体阳性或强阳性;1例脑脊液抗NMDAR抗体阳性,血NMDAR抗体阴性;1例脑脊液+血抗GABABR抗体阳性。给予丙种球蛋白或糖皮质激素免疫抑制治疗有效。结论加强对该病的认识,尽早诊断及治疗有利于改善患者的预后。     

抗HU抗体阳性副肿瘤性小脑变性1例及文献复习

副肿瘤性小脑变性(paraneoplastic cerebellar degenertion,PCD)又称亚急性小脑变性(subacute cerebellar degeneration,SCD),是神经系统副肿瘤综合征(praneoplastic neurological syndrome,PNS)引起神经系统的典型损害之一,神经系统副肿瘤综合征(PNS)是一种罕见的副肿瘤综合征,并不是由肿瘤转移或直接浸润到神经系统引起,是由免疫反应的改变引起。是一种与恶性肿瘤相关但原因不明的小脑非转移性病变。本文报道1例以副肿瘤性小脑变性为首发症状的肺癌病例,加强临床医生对该病的认识。该患者即以双下肢行走不稳收入院,表现为小脑受损的症状与体征,脑干受损症状与体征未表现。检查脑脊液生化示,葡萄糖4.73 mmol/L,微量总蛋白548.00 mg/L;脑脊液抗酸、墨汁染色阴性。脑脊液常规示,红细胞数0,白细胞26个/mm~3;副肿瘤相关抗体抗Hu抗体阳性。行胸部增强CT示,左肺上叶前段占位病变,考虑新生物;左肺上叶尖后段纤维条灶索;纵隔内及左肺门区多发淋巴结肿大。结合患者临床表现和辅助检查,临床诊断为副肿瘤性小脑变性。早期诊断副肿瘤性小脑变性对于及时发现和根除宿主体内的肿瘤至关重要,尤其小细胞肺癌、乳腺癌、卵巢癌等。有条件可在血液和脑脊液中检测特定的抗神经元抗体,目前发现许多抗神经元抗体与PCD有关,并且对特定的肿瘤类型的早期诊断提供依据,如抗Hu抗体提示小细胞肺癌,抗Yo抗体提示乳腺、卵巢等肿瘤。该病总体预后不良,应积极采取综合治疗手段,控制肿瘤的转移及复发,以提高患者生存质量,延长生存时间,改善生存率。     

12例抗amphiphysin抗体阳性的副肿瘤神经综合征患者临床分析

目的总结抗amphiphysin抗体阳性副肿瘤神经综合征(PNS)的临床特点和预后,以提高临床对此病的认识。方法回顾性分析2015年04月至2018年11月安徽医科大学第一附属医院收治12例抗amphiphysin抗体阳性的PNS患者临床资料。结果 12例患者中,主要表现为肌无力或共济失调6例,肢体麻木为主2例,癫痫为主2例,认知障碍为主2例;10例患者肿瘤指标异常;2例患者影像学筛查提示肿瘤明确阳性,5例患者影像学筛查提示疑似肿瘤;病理检查明确肿瘤2例;5例患者经糖皮质激素治疗,2例经丙种球蛋白治疗,2例患者选择外科治疗。随访显示病情好转7例,死亡3例,失随访2例。结论抗amphiphysin抗体阳性相关的PNS临床症状多样,免疫治疗能使部分患者获益,及时诊断治疗利于恢复,预后一般。     

Progressive necrotic myelopathy: clinical course in 9 patients

OBJECTIVE: To review the clinical, laboratory, and radiological findings of 9 patients who had progressive idiopathic myelopathy with evidence of spinal cord necrosis. DESIGN AND METHODS: We reviewed personally examined cases of myelopathy that fulfilled the following criteria: (1) regional loss of reflexes, flaccidity, and muscle atrophy; (2) magnetic resonance imaging showing a shrunken or cavitated cord without evidence of arteriovenous malformation; (3) electromyogram showing denervation over several contiguous spinal cord sgements with preservation of sensory potentials in some cases; and (4) the absence of evidence of systemic disease or neoplasm. RESULTS: The illness began in these patients after the age of 40 years, with prominent burning or tingling limb pain, occasionally with radicular features or with less well-defined back, neck, or abdominal pain. Leg or infrequently arm weakness appeared concurrently or soon after the onset of pain. The most distinctive feature was a saltatory progression of symptoms, punctuated by both acute and subacute worsenings approximately every 3 to 9 months, culminating in paraplegia or tetraplegia. The distinguishing clinical findings, together indicative of destruction of gray matter elements of the cord, were limb atrophy, persistent areflexia, and flaccidity. The concentration of cerebrospinal fluid protein was typically elevated between 500 g/L and 1000 g/L, without oligoclonal bands, accompanied infrequently by pleocytosis. Magnetic resonance imaging showed features suggesting cord necrosis, specifically swelling, T2-weighted hyperintensity, and gadolinium enhancement over several spinal cord segments, succeeded months later by atrophy in the same regions. Necrosis of the cord was found in biopsy material from one patient and postmortem pathology in another case, but inflammation and blood vessel abnormalities were absent. Only 2 patients had prolonged visual evoked responses. The disease progressed despite immune-modulating treatments although several patients had brief epochs of limited improvement. CONCLUSIONS: The saltatory course, prolonged visual evoked responses in 2 patients, and a cranial abnormality on magnetic resonance imaging in another, raised the possibility of a link to multiple sclerosis. However, the normal cranial magnetic resonance imaging scans in 6 other patients, uniformly absent oligoclonal bands, and poor response to treatment were atypical for multiple sclerosis. On the basis of shared clinical and laboratory features, idiopathic progressive necrotic myelopathy is indistinguishable from a limited form of Devic disease.     

Progressive necrotizing myelopathy: part of the spectrum of neuromyelitis optica?

This case series reviews the clinical, radiographic and laboratory findings of five patients with progressive idiopathic myelopathy with evidence of cord necrosis who presented in our institution over a 5 year period ending in May 2005. Patients fulfilling the following criteria were included: (1) presentation with myelopathy without overt visual involvement at initial presentation; (2) demonstration with magnetic resonance imaging (MRI) of contiguously abnormal signal in the spinal cord spanning at least three vertebral segments without evidence of arteriovenous malformation or significant disk disease; (3) absence of systemic disease or neoplasm. All patients were women, identified themselves as African American and were older than 35 years. Pain was reported at initial presentation in four cases. The distinctive feature was a relapsing course with intervening variable improvement of function and progression to quadriplegia in less than 4 years. An increased IgG index and/or oligoclonal banding was detected in two patients. The leukocyte count in the cerebrospinal fluid (CSF) was elevated in all cases but in only one specimen did the count exceed 50 cells. None of the patients initially had clinical signs of an optic neuropathy but unilaterally prolonged visual evoked potentials were present in one individual who went on to developed optic neuritis 19 months after the first clinical presentation. Another patient developed optic neuritis 45 months after disease onset. Immunomodulatory and plasma exchange therapy were of some benefit at least early in the course but the disease progressed despite these interventions. Neuromyelitis optica (NMO)-IgG antibody, a serum or CSF marker described in individuals with classic NMO and optico-spinal multiple sclerosis (MS), was present in all cases. On the basis of shared clinical and imaging features in the cord, progressive necrotizing myelopathy observed in this case series exhibits key features of a limited form of NMO (Devic's disease) and opticospinal MS. The presence of NMO-IgG antibody marker suggests that progressive necrotizing myelopathy is part of a disease spectrum of which traditional NMO is a select presentation.     

Diagnosis and treatment of CNS parasite infection with special reference to parasitic myelitis]

The occurrence of visceral larva migrans due to Ascaris suum (A. suum) and Toxocara canis (T. canis) has occasionally been reported in Japan, although parenchymatous involvement of the CNS is extremely rare in A. suum/T. canis visceral larvae migrans. Recently we experienced 7 cases with myelitis caused by visceral larva migrans due to A. suum/T. canis (parasite myelitis). The characteristics of this myelitis are: (1) sensory disturbances (Lhermitte's sign, paresthesia, and hypesthesia) are predominant symptoms, while severe motor weakness is rare, (2) spinal cord lesions on T2-weighted MRI show more extensive lesions compared with mild symptoms, (3) Gadolinium enhancement of spinal cord lesions are limited as compared with spinal cord lesions on T2-weighted MRI lesions, (4) Some cases show the presence of eosinophils in CSF, while others show Th2 deviation in CSF supernatant, and (5) Tests for anti-A. suum/T. canis IgG antibody are strongly positive in serum and CSF. Moreover, 6 percent of 108 consecutive cases with non-compression myelopathy presenting at the Department of Neurology at Kyushu University Hospital from January, 1998 to December, 2002 had parasitic myelitis. Myelitis from visceral larva migrans due to A. suum/T. canis might be overlooked because of its mild neurologic impairment without systemic symptoms, but should be considered as one of the differential diagnoses in non-compression myelopathy.     

Myelopathy patients studied with magnetic resonance for multiple sclerosis plaques

Seven patients with isolated spinal cord symptoms, and with evoked potential (EP) recordings and/or cerebrospinal fluid (CSF) findings supporting a demyelinating cause for their myelopathy, were examined with cervical and cranial magnetic resonance imaging (MRI). Lesions in the cervical spinal cord were detected in 6 of the patients, including 2 who also had disseminated lesions in the brain compatible with multiple sclerosis (MS). In one patient MRI of the cervical spinal cord was normal, while plaques were seen in the periventricular region of the brain and in the brain stem. Thus, in the 3 patients with cerebral plaques, MRI supported the diagnosis of MS by showing dissemination in space. In the remaining 4 patients MRI provided support for the diagnosis of MS by demonstrating the cervical spinal cord plaques while excluding other potential causes of myelopathy, such as spinal cord compression and intramedullary tumor.     

Detection of the 14-3-3 protein in the cerebrospinal fluid of Japanese multiple sclerosis patients presenting with severe myelitis

Recent studies showed that the 14-3-3 protein is detectable in the cerebrospinal fluid (CSF) of prion-unrelated neurological diseases, such as meningoencephalitis and myelitis. To investigate the possible association between the amounts of the 14-3-3 protein in the CSF and the clinical severity of multiple sclerosis (MS), its levels were determined by Western blot in the CSF of the patients with relapsing-remitting MS (RRMS) (n=10), secondary progressive MS (SPMS) (n=7), primary progressive MS (PPMS) (n=2), and non-MS inflammatory diseases of the CNS (n=5). The 14-3-3 protein was identified in seven CSF samples, including four patients with SPMS in acute relapse, one with SPMS in remission accompanied by fresh cerebral infarction, one with RRMS in acute relapse, and one with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy. The patients positive for the CSF 14-3-3 protein immunoreactivity showed more severe disability and higher levels of pleocytosis, protein, IgG, beta2-microglobulin, and neuron-specific enolase in the CSF, compared with those negative for its immunoreactivity. Four of these patients exhibited extensive lesions distributed along multiple vertebral segments in the spinal cord on MRI. In contrast, none of the MS patients without an extensive involvement of the spinal cord showed the CSF 14-3-3 protein immunoreactivity. These results suggest that detection of the 14-3-3 protein in the CSF provides a marker for severe inflammation-induced extensive damage of the central nervous system tissues responsible for poor therapeutic responses and irreversible neurological deficits in MS.     

Over-shunting associated myelopathy

Intracranial hypotension typically presents following cerebrospinal fluid (CSF) leak, but can be induced by CSF diversion. Classically, patients present with positional headache, but less common symptoms include neck pain and cranial nerve palsies. To our knowledge, the neurosurgical literature contains six reports of patients with symptomatic cervical, epidural venous plexus engorgement as the result of CSF shunting. The patient presented herein is a 26-year-old woman with shunt-dependent, congenital hydrocephalus. She presented with rapidly progressive cervical myelopathy following ventriculoperitoneal shunt revision. Imaging revealed engorgement of the cervical epidural venous plexus and mass effect on the cervical spinal cord. “Over-shunting associated myelopathy” is a rare complication of CSF diversion that should be familiar to physicians who routinely evaluate patients with intracranial shunts.     

Lupus-related myelopathy: report of three cases and review of the literature.

Transverse myelopathy is an uncommon complication of systemic lupus erythematosus (SLE). Three patients with SLE are reported who developed transverse myelopathy, including the neuropathological findings in one patient on whom necropsy was performed. Paraparesis was present in all three cases, but definite sensory changes were present in only one patient. In two patients, the CSF findings were remarkable for elevated protein and depressed glucose concentrations. Microscopic examination of the brain demonstrated small, scattered foci of recent necrosis consistent with microinfarctions. Striking abnormalities were found in the spinal cord at all levels, including multiple foci of vacuolar spongy degeneration in the peripheral white matter, as well as ballooning of myelin sheaths, swollen axons, myelin pallor, and loss of glial nuclei. The pathological findings in previously reported cases of SLE-related transverse myelopathy are reviewed, and the possible pathogenesis of the findings in our case are discussed.     

Myelopathy in patients with antiphospholipid antibodies: clinical features, pathogenesis, and review of literature]

We report 5 patients with anti-cardiolipin IgM-positive myelopathy. The lengths of spinal lesions were over two vertebral segments in 4 patients. Four cases showed subacute onset, and 2 out of these 4 cases had inflammatory changes in cerebrospinal fluid (CSF), and all of their symptoms improved. However, in one patient who showed an acute onset and normal findings of CSF, neurological symptoms did not improve. Three patients fulfilled the diagnostic criteria of primary antiphospholipid antibody syndrome. As for the pathophysiology of myelitis associated with antiphospholipid antibodies (aPL), it is suggested that vascular thrombosis affecting the blood cord barrier promotes an inflammatory changes. The heterogeneous CFS findings seem to reflect the difference in the intensity of inflammation. Both vascular thrombosis and inflammatory process should be considered as pathogenesis of these patients. Alone or combination therapy of steroids and anticoagulants might be effective in patients of myelopathy associated with APS.     

Spontaneous spinal cord herniation

Spontaneous spinal cord herniation through a dural defect is an unusual condition. This entity has been probably underestimated before the introduction of MRI. We report a case of a 49-year-old man with a progressive Brown-Sequard syndrome. MRI and CT myelogram showed a ventrally displaced spinal cord at level T6-T7 and expansion of the posterior subarachnoid space. Through a laminectomy, a spinal cord herniation was identified and reduced. The anterior dural defect was repaired with a patch of lyophilized dura. The patient recovered muscle power but there was no improvement of the sensory disturbance. The diagnosis of spontaneous spinal cord herniation must be considered when progressive myelopathy occurs in middle-aged patients, without signs of spinal cord compression and typical radiological findings. Surgical treatment may halt the progressive deficits and even yield improvement in many cases.     

A case of HTLV-I associated myelopathy with abnormal patchy MRI lesions in the spinal cord]

We report a case of HTLV-I associated myelopathy (HAM) with a spinal cord MRI showing abnormal multifocal and patchy lesions. A 50-year-old woman suffering from progressive paraparesis was admitted to our hospital. HTLV-I antibodies in the serum and CSF were positive, and a diagnosis of HAM was made. Her T2 weighted spinal cord MRI showed scattered areas of high signal intensity from the cervical to the thoracic cord. The lesions were enhanced with gadolinium-DTPA on T1 weighted imaging. Atrophy of the thoracic cord has been reported in many patients with HAM. In rare cases, T2 weighed thoracic cord MRI showed diffuse high signal intensity. The pattern of high signal intensity in our case, however, was multifocal and patchy, thus differing from the findings of previous reports. And we believe this is the first such report. This case suggests that the MRI of HAM patient may show multifocal and scattered lesions in the spinal cord.