A case of primary Sj?gren's syndrome with acute transverse myelopathy and polyneuropathy as the initial manifestations]

We report a case of primary Sj?gren's syndrome with acute transverse myelopathy and polyneuropathy as the initial manifestations. A 72-year-old man developed acute right hemiparesis and his symptoms deteriorated to quadriparesis in four days. A cervical spinal MRI showed an extensive intraparenchymal lesion with high T2-weighted signal intensity, gadolinium enhancement, and cord swelling. An electromyographic study and a sural nerve biopsy showed severe axonal degeneration. The patient complained of thirst and a salivary gland biopsy revealed inflammatory changes, while salivary gland scintigraphy showed diminished secretion. These findings led to a diagnosis of Sj?gren's syndrome. Only one case of Sj?gren's syndrome with acute transverse myelopathy as the initial manifestation has been reported. In our case, however, polyneuropathy was observed in addition to transverse myelopathy as the initial manifestation. Even if prominent sicca symptoms are absent, all patients with acute transverse myelopathy and polyneuropathy should be carefully examined with considerations of possible presence of Sj?gren's syndrome.     

Transverse myelopathy in a patient with systemic lupus erythematosus associated with positive anticardiolipin antibody--a case report]

A 52-year-old woman who developed acute transverse myelopathy following systemic lupus erythematosus (SLE) was reported. At the age of 46, she was diagnosed as having atypical psychosis. Neurological examination revealed mild depressive state, paraparesis, diffuse hyperreflexia, hypesthesia below the breasts, and urinary disturbance. Gait was slightly ataxic and Romberg sign was positive. Laboratory study disclosed lymphocytopenia, positive antinuclear antigen, false positive Venereal Disease Research Laboratories flocculation test and prolonged activated partial thromboplastin time. IgG anticardiolipin antibody (aCLA) was positive, whereas IgM aCLA was negative. Cerebrospinal fluid was normal except the elevation of %IgG. Nerve conduction studies were normal and no abnormality was detected in the brain and spinal cord by MRI and CT. We treated her by two series of steroid pulse therapy, which resulted in marked improvement of symptoms and disappearance of aCLA. Before and after the pulse therapy, symptoms were fluctuated in parallel with the levels of aCLA. These findings suggest the relation of aCLA to the transverse myelopathy in SLE. This is the first case report of a good prognosis of myelopathy in a SLE patient who was treated by steroid pulse therapy with the aim of disappearance of aCLA.     

A case of Sj?gren's syndrome with subacute transverse myelitis as the initial manifestation]

We report a case of subacute transverse myelitis associated with Sj?gren's syndrome free of xerosis. A 62-year-old man was admitted due to dysesthesia of both lower extremities and the left trunk, weakness of the left leg, and urinary disturbance. Neurological examination showed myelopathy at the Th7 level. CSF had increased protein (82 mg/dl) and IgG (23.4 mg/dl) and IgG index (1.03) but an almost normal cell count (7/mm3). T2-weighted MRI showed a high signal intensity lesion at the sixth and seventh thoracic levels. Although he was free of xerosis, typical sialographic findings, as well as the presence of anti-SSA antibody, are consistent with the diagnostic criteria for Sj?gren's syndrome decided by the Japanese research group on Sj?gren's syndrome. The patient was treated with prednisolone, 60 mg/day, which completely cured his muscle weakness and difficulty in walking, and sensory disturbance was gradually alleviated. Spinal MRI detected a marked reduction in the size of T2-weighted high signal intensity lesion during prednisolone treatment. In Western countries, central nervous system complications are reported in up to 20% of Sj?gren's syndrome patients, but myelopathy is a very rare condition. Only 12 cases, including ours, have been reported. The clinical manifestations of myelopathy in Sj?gren's syndrome include acute or subacute transverse myelitis (6 cases, including ours), chronic progressive myelopathies (2 cases.), relapsing and remitting cord syndromes (4 cases) and Brown-Séquard syndrome (none). Ten patients were women. In 9 of 12 cases there were sicca symptoms. The level of the myelopathies in 6 of 10 cases was between the third to eighth thoracic level, consistent with the region vulnerable to ischemia. Eight patients were treated successfully with steroids. We speculate that ischemia due to vasculitis is important in the genesis of myelopathy associated with Sj?gren's syndrome. In the case of myelopathy, especially in the thoracic cord, it is necessary to look for evidence of Sj?gren's syndrome even when xerosis is unremarkable.     

The 677C --> T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in epileptic patients affected by systemic lupus erythematosus.

Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is considered as one of the major manifestations of the disease. Epilepsy has been documented in about 10% of patients with systemic lupus erythematosus (SLE). It is well known that vascular damage in SLE occurs because of multiple mechanisms including hypercoagulation. It has been recently reported that in SLE patients raised levels of homocysteine are associated with arterial thrombosis. Hyperhomocysteinaemia is a condition due to both genetic and non-genetic factors. The most common genetic defect in homocysteine metabolism is a decreased activity of a common 5,10-methylenetetrahydrofolate reductase (MTHFR) variant (677C -->T, a thermolabile form).In this paper we describe the epileptic manifestations in six out of 55 SLE patients. Seizures were the SLE onset symptom for three patients, appeared during the active disease in two cases, and occurred during a period of clinical remission in one patient. In all cases we documented the association of epilepsy with the MTHFR mutation: the homozygosity form was present in one case (16.7%), and heterozygosity in five cases (83.3%). Nevertheless, levels of homocysteine in plasma were in the normal range. Moreover, we found a decrease in the level of S protein values in one case, a high titre positivity of anticardiolipin antibodies (aCL) (IgG and IgM) in three patients and low titre positivity (IgG) in one patient, and lupus anticoagulant (LAC) positivity in four cases.In conclusion, we believe that the abnormalities of coagulation present in our patients could be related to epileptogenesis or to an alteration of the seizure threshold.     

A clinically isolated syndrome: A challenging entity

Abstract   Acute isolated neurological syndromes, such as optic neuropathy or transverse myelopathy, may cause diagnostic problems since they can be the first presentations of a number of diseases such as multiple sclerosis (MS) and collageneous tissue disorders. In the present study, particular systemic lupus erythematosus (SLE) and primary Sjogren syndrome (pSS) patients, who were followed up with the initial diagnosis of possible MS with no evidence of collagen tissue disorders for several years, are described. Five patients with the final diagnosis of SLE and five pSS patients are evaluated with their neurologic, systemic and radiologic findings. Over several years, all developed some systemic symptoms like arthritis, arthralgia, headache, dry mouth and eyes unexpected in MS. During the regular and close follow-up laboratory evaluations of vasculitic markers revealed positivity, leading to the final definite diagnosis of SLE or pSS. Patients with atypical neurological presentation of MS, a relapsing remitting clinical profile, or lack of response to the regular MS treatment should be evaluated for the presence of a connective tissue disease. Various laboratory tests, such as cerebrospinal fluid findings, autoantibodies profile, markers, cranial and spinal magnetic resonance imaging, can be helpful for the differential diagnosis. Lack of response to the regular multiple sclerosis treatment, even increasing rate of relapses can force the clinician for the differential diagnosis. In particular cases an accurate diagnosis can only be made after close follow-up.     

Disseminated perivenous necrotizing encephalomyelitis in systemic lupus erythematosus: report of an autopsy case

The patient, a 22-year-old woman who had been treated for systemic lupus erythematosus (SLE) for 10 years, was hospitalized for arthralgia, melena, and difficulty in walking. CT examination of the brain showed grain-like high-density lesions scattered throughout the cerebral white matter and basal ganglia. At autopsy, multiple perivenous, well-demarcated foci of brownish discoloration were seen scattered throughout the cerebral white matter and basal ganglia. Histopathologically these lesions consisted of foci of coagulation necrosis surrounding the veins. The veins in the foci showed fibrous thickening of the walls, but there were no indications of vasculitis. At the periphery of the lesions, the axons were better preserved than their myelin sheaths. The neuropathological findings in the present case closely resemble those of acute disseminated (perivenous) encephalomyelitis, although an inflammatory cell infiltration had apparently already subsided. Although its pathogenesis remains unclear, this finding should not be regarded as an incidental complication but rather as a rare subtype of central nervous system lesion occurring with SLE. Received: 18 July 1997 / Revised: 26 September 1997 / Accepted: 1 October 1997     

Nationwide survey of necrotizing myelopathy associated with malignancy in Japan

Twenty-two cases of transverse myelopathy associated with malignancy were collected in nationwide survey in Japan. Paraneoplastic necrotizing myelopathy (PNM) was suspected in 9 of them and 8 cases were diagnosed as radiation myelopathy (RM), clinically and pathologically. Other 5 cases had different causes of transverse myelopathy. In comparison with PNM and RM, malignant lymphoma, flaccid paraplegia and sphincter dysfunction were highly associated in the patients with PNM. On the other hand, lung cancer, spastic paraplegia, abnormality in spinal MRI and dysesthesia in legs as an initial symptom were prevalent in the cases of RM. Six cases of them were compared pathologically. Although all cases had no metastasis of malignant cells, five cases of PMN showed acute and chronic necrosis and rarefaction of spinal cord with or without perivascular cuffing. One case of RM had focal spinal cord atrophy and no lymphocytes infiltration. Immunohistochemically, herpes simplex virus type 2 (HSV2) infection in spinal cord was shown in the 2 cases of the necrotizing myelopathy. Virus infection such as HSV2 could be one of causes of PNM and virological study must be done in the cases of necrotizing myelopathy associated with malignancy.     

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.     

Neuropathological studies of the spinal cord in early stage HTLV-I-associated myelopathy (HAM).

Necropsy findings for a patient with HTLV-I-associated myelopathy (HAM) of 9 months clinical duration are reported. Loss of myelin sheaths and axons together with perivascular lymphocytic infiltration was seen in the lateral and posterior columns of the spinal cord from the cervical to the lumbar region where vacuolar changes caused by the splitting of myelin sheaths were prominent. Immunohistochemical analyses revealed CD8+ cytotoxic T cell infiltration predominated in the absence of HTLV-I core protein antigen bearing-cells in the brain and spinal cord. Myelin sheath damage and predominant CD8+ cytotoxic T cell infiltration are thought to be the main neuropathological findings in the spinal cord in early stage HAM.     

系统性红斑狼疮神经系统病变的临床及病理特征

目的探讨系统性红斑狼疮（SLE）神经系统病变的临床及病理特征。方法回顾性分析6例SLE神经系统病变患者的临床及病理资料。结果本组患者累及中枢神经系统4例,其中癫痫1例、脑梗死2例、白质脑病1例;多发性单神经病3例,腓肠神经活检示1例有典型血管炎改变,2例无血管炎改变,腓肠神经内可见有髓纤维丢失、轴索和髓鞘断裂呈块状深染及髓磷脂小球形成。肌活检1例示肌纤维轻度变性坏死。皮肤活检3例示胶原变性,小静脉周围可见炎性细胞浸润。结论SLE可导致神经系统广泛病变,故其临床表现和病理改变复杂多样。     

Clinicopathological study on multiple spongy necrosis of the pontine base

Eleven cases with multiple spongy necrosis of the pontine base are reported and their clinicopathologic characteristics discussed. Seven of the cases occurred in men and four in women; age ranged from 42 to 90 years old. Eight patients had various types of cancer as background disease. Three patients received central nervous system (CNS) radiotherapy and six received chemotherapy. No consistent clinical factor (e.g., malignancy, radiotherapy, chemotherapy, severe immunosuppressive state, specific laboratory data and infection) could be found among the cases. Neuropathological findings were characterized as multiple patchy spongy areas of the pontine base with loss of myelin and axons. There were few reactive gliosis or inflammatory changes. Many axonal swellings and a small number of macrophages were scattered in the lesions. Neurons and glial cells adjacent to these lesions were not affected, and calcification was not found. Almost all of the lesions existed in the transverse fibers of the basis pontis. In the literature, malignancy or toxicity due to CNS radiotherapy or chemotherapy was suspected to be the causative factor of these lesions. In our 11 cases, however, the lesions were also found in patients who had not received radiotherapy or chemotherapy. In contrast, the neuropathological findings of the lesions in our patients were similar in each case. Electronmicroscopically, the myelin sheath was seen to be swollen in the early stage of the lesion. Excluding malignancy, radiotherapy and chemotherapy, there may be an additional unknown causative factor. Metabolic disturbances or toxic agents for myelin were suspected as causative factors.     

Sjögren's syndrome with acute transverse myelopathy as the initial manifestation

This is the first report of a patient with acute transverse myelopathy as the initial manifestation of primary Sj?gren's syndrome (SS). The patient developed tetraparesis and sensory disturbance within 6 days of onset. Spinal MRI showed an extensive intraparenchymal lesion with high T2-weighted signal intensity, gadolinium enhancement, and cord swelling. Although the patient did not show clinical sicca symptoms, primary SS was diagnosed on the basis of clinical tests on lacrimal and salivary glands which showed high levels of autoantibodies. Treatment with prednisone improved motor and sensory symptoms and resulted in improvement of MRI findings. The present case suggests that acute transverse myelopathy can occur as an initial symptom of SS.     

Multiple specificities of antibrain antibodies in multiple sclerosis and chronic myelopathy

The presence of complement-fixing antibodies against brain antigens was tested in paired serum and cerebrospinal fluid (CSF) samples from 60 multiple sclerosis (MS) patients, 15 patients with chronic myelopathy of undetermined cause (CM) and 60 control patients. Six MS sera, 34 MS CSF, 4 CM sera, 3 CM CSF, 4 control sera and 1 control CSF gave positive reactions either with a lipid extract or a saline extract of normal human brain. The proportion of anticomplementary CSF was significantly higher in the MS group than in the control group (15% vs 0%, P < 0.01). The reactivity of a large number of individual positive samples was further investigated. Seven antibody specificities were discerned in the MS samples. Most samples reacted with nonlipid antigens, the dominating being a heat-labile, nonlipid component associated with CNS myelin. Antibodies to cerebroside and sulfatide were detected in a few patients. A number of samples reacted with cholesterol in combination with a variety of lipids. Positive samples from the CM patients exhibited a similar heterogeneity. In the control group positive reactions were seen in one patient with systemic lupus erythematosus (SLE), two patients with rheumatoid arthritis (RA), and one with a spinal meningioma. The reaction patterns of these patients were different from those commonly seen in MS patients. The complement-fixing antibrain antibodies in MS CSF are usually of IgG class (Ryberg 1976). This applies also to the positive MS sera in this study. The distribution of the antibodies between serum and CSF indicated, in several cases, an intrathecal synthesis. All of a number of human brains, including one MS brain, contained all 6 antigens (haptens) reactive in saline extracts. Antibodies to tissues outside the CNS were rarely detected in MS patients. The varied humoral autoimmune response in MS might reflect a heterogeneity in the MS patients, the disease itself or its causative agent.     

Humoral antibodies in immune mediated neuropathy

Immune mediated neuropathy includes acute inflammatory demyelinating polyneuropathy (AIDP), chronic inflammatory demyelinating neuropathy (CIDN), paraproteinemic polyneuropathy (PPN) and Crow-Fukase syndrome (CFS). Serum antibodies as humoral immunity in patients with immune mediated neuropathy were measured by the method of immunoblots and ELISA. P0 protein, P2 protein, 170K-Mr glycoprotein and ganglioside (GGD) of human peripheral nerve myelin and MBP, myelin associated glycoprotein (MAG) of human central nerve myelin were used as antigens. In AIDP anti P2 antibodies were elevated significantly. However, anti MBP antibodies were also elevated in parallel. In PPN anti MAG antibodies were detected in 4 patients with IgM-M proteinemia and demyelinating neuropathy. High titers of anti MAG antibodies were also detected in the same 4 patients. Characteristic pathological findings of biopsied sural nerve were segmental demyelination with widening of the intraperiod line of the outer myelin lamella in all 4 patients. Positive rate of anti myelin antibodies were 23% in 23 cases with PPN. Anti 170K-Mr glycoprotein was detected only in one patient with IgM-M proteinemia, polyneuropathy and incurable dermatitis. Anti GGD antibodies were not detected in PPN or CFS. A few patients with GBS or CIDN have anti GGD antibodies in ELISA. It is well known that various antibodies to peripheral nerve myelin are detected in neuropathy, especially demyelinating state. The most important antigen established in this study in the pathogenesis of neuropathy is MAG. IgM monoclonal protein including anti MAG antibodies was absorbed by purified MAG completely. Anti 170K Mr glycoprotein was also absorbed by purified 170K-Mr glycoprotein. Role of humoral antibody to peripheral nerve myelin specific 170K-Mr glycoprotein remains to be solved.     

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.     

Lupus transverse myelopathy: better outcome with early recognition and aggressive high-dose intravenous corticosteroid pulse treatment

Seven patients with transverse myelopathy (TM) were found to have systemic lupus erythematosus (SLE). Four patients had no prior diagnosis of SLE. All patients had positive antinuclear antibody (ANA). All patients had a spinal syndrome which progressed to TM with cervical or thoracic levels. The diagnosis of TM was confirmed with neurological tests and neuro-radiographic studies. Delay in diagnosis and treatment resulted in a poor outcome. Four patients died and one remained wheelchair-bound. Only two patients who received high-dose IV pulse steroid within 1 week of onset of TM had a good outcome, with full ability to ambulate without assistance. Our experience suggest that early diagnosis with early treatment using high-dose IV steroid affects the mortality and improves the outcome.     

A case of transverse myelopathy caused by acupuncture]

A 54-year-old man received insertion of an acupuncture needle into the region extending from the posterior neck to the back on two occasions for the treatment of shoulder stiffness. Two weeks after the second acupuncture, he developed fever, dysarthria and mictionary disturbance, finally reaching the condition of tetraplegia. He was immediately admitted to an emergency room in our hospital, and was diagnosed as sepsis with DIC, ARDS, heart failure, renal failure, liver failure, and myelitis. After one month, he recovered with transverse myelopathy as a residual deficit. Neurological findings showed transverse myelopathy below the level of Th2 at that time. Cervical CT revealed an irregular low density at the periphery of the cervical vertebra from the C2 to C4 level. Cervical MRI revealed an irregular swelling of his spinal cord from the C2 to C7 level. We explained the mechanism of transverse myelopathy in this case as follows. After the acupuncture, he suffered a focal infection of the region of needle insertion, and then the infection expanded to the cervical vertebra, thus causing osteomyelitis, sepsis, and finally cervical myelitis. Direct injury of the spinal cord and nerve roots as a complication of acupuncture was previously reported, but indirect injury of the spinal cord due to myelitis had not been reported except our present case. Careful attentions should be paid to the complications of acupuncture.     

Recurrent myelitis.

Three patients presented with acute complete transverse myelopathy which relapsed several times at the same site. These patients, two women and one man, had two to five attacks spanning three to seven years. All patients underwent detailed investigations including a complete myelogram and serial evoked potential studies. Oligoclonal bands were present in the CSF in one patient. Brain MRI was normal in two patients; MRI of the spinal cord was abnormal and showed cord oedema with multiple areas of hyperintense signals on T2 and proton density weighted scans and hypointense signals on T1 weighted images in areas corresponding to the clinical level, suggesting an inflammatory/demyelinating disorder. These patients may represent a relapsing demyelinating disorder restricted to the spinal cord, distinct from multiple sclerosis.     

Cerebral Venous Sinus Thrombosis as a Rare Complication of Systemic Lupus Erythematosus: Subgroup Analysis of the VENOST Study

AimSystemic lupus erythematosus (SLE) is an unusual risk factor for cerebral venous sinus thrombosis (CVST). As few CVST patients with SLE have been reported, little is known regarding its frequency as an underlying etiology, clinical characteristics, or long-term outcome. We evaluated a large cohort of CVST patients with SLE in a multicenter study of cerebral venous thrombosis, the VENOST study, and their clinical characteristics.Material and MethodAmong the 1144 CVST patients in the VENOST cohort, patients diagnosed with SLE were studied. Their demographic and clinical characteristics, etiological risk factors, venous involvement status, and outcomes were recorded.ResultsIn total, 15 (1.31%) of 1144 CVST patients had SLE. The mean age of these patients was 39.9 ± 12.1 years and 13 (86.7%) were female. Presenting symptoms included headache (73.3%), visual field defects (40.0%), and altered consciousness (26.7%). The main sinuses involved were the transverse (60.0%), sagittal (40.0%), and sigmoid (20.0%) sinuses. Parenchymal involvement was not seen in 73.3% of the patients. On the modified Rankin scale, 92.9% of the patients scored 0-1 at the 1-month follow-up and 90.9% scored 0-1 at the 1-year follow-up.ConclusionsSLE was found in 1.31% of the CVST patients, most frequently in young women. Headache was the most common symptom and the CVST onset was chronic in the majority of cases. The patient outcomes were favorable. CVST should be suspected in SLE patients, even in those with isolated chronic headache symptoms with or without other neurological findings.     

Acute transverse myelopathy in children

Twenty-three children with acute transverse myelopathy (ATM) are reviewed. Antecedent minor trauma or exercise was reported in 10 patients. Despite a positive history in 7 patients no preceding infection was documented. Two patients had a history of less severe ATM followed by recovery prior to a second more severe episode. The most common initial symptom was back pain and the most prominent clinical signs were weakness, sensory level and sphincter disturbances. Myelography and CT myelography at presentation was performed to exclude a compressive lesion. Spinal cord enlargement was demonstrated in 6 of 21 cases. Magnetic resonance imaging (MRI) of the spinal cord, performed in one patient, showed enlargement of the cord. Poor prognostic features were severity of weakness at the time of maximum deficit and a delayed onset of recovery. Maximum motor recovery occurred at a mean of 6 1/2 months but did not occur in one patient until 1 1/2 years. Normal or good outcome was obtained in 64%.