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Objective: To analyze the clinical manifestations, imaging, electroencephalography, treatment, and prognosis of 35 cases of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) in children., Methods: Children hospitalized in the Department of Neurology, Hunan Children's Hospital, China, between January 2015 and June 2021, owing to autoimmune diseases of the central nervous system were subjected to a cell-based assay (CBA). The assay identified 40 children positive for GFAP-immunoglobulin (Ig)G antibodies in the serum and/or the cerebrospinal fluid. Based on clinical manifestations and imaging characteristics, five children who were only positive for GFAP-IgG antibodies in serum were excluded, and the remaining 35 children were diagnosed with autoimmune GFAP-A. The clinical data derived from the 35 children were retrospectively analyzed., Results: A total of 35 children, including 23 males and 12 females with a mean age of 6.3 ± 0.6 years, manifested clinical symptoms of fever (62.9%), headache (42.9%), convulsions (42.9%), abnormal mental behavior (51.4%), disorders of consciousness (54.3%), visual disturbance (22.9%), ataxia (11.4%), paralysis (40%), and autonomic dysfunction (25.7%). One child exhibited only the clinical symptom of peripheral facial nerve palsy. Eleven out of 35 children were also positive for other antibodies. In addition to the common overlapping autoimmune syndromes, one case of autoimmune GFAP-A also manifested as Bickerstaff's brainstem encephalitis. Linear periventricular enhancement upon MRI was significantly less frequent in children (8.5%) than in adults. In pediatric patients, MRI contrast enhancement was principally seen in the meninges and brain lobes. Although repeated relapse (17.1%) and sequelae symptoms (20%) occurred in some cases, most children showed a favorable prognosis. Spearman's rank correlation showed that the antibody titer was not significantly associated with the severity of the initial disease conditions., Conclusions: The disease diagnosis in children seropositive for GFAP antibodies only should receive a comprehensive diagnosis based on their clinical symptoms, imaging, electroencephalographic characteristics, and treatment responses. Some patients with relapses should receive repeated gamma globulin and corticosteroid therapy or the addition of immunosuppressants to their therapeutic regimen, and slow-dose tapering of corticosteroids and extended treatment are recommended for patients with overlapping autoimmune syndromes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fang, Hu, Jiang, Yang, Liao, Yang and Wu.)

Acute flaccid myelitis (AFM) is a serious neurological illness first recognized in the United States in 2014, with subsequent outbreaks every two years. Following extensive etiologic testing by multiple laboratories of hundreds of specimens collected from patients diagnosed with AFM, no consistent cause of AFM has been identified. However, viruses, including enteroviruses, have been implicated through detection in non-sterile site specimens and antibody studies. Cytokines and chemokines play important roles in the modulation of the innate and adaptive immune response to pathogens. In the current study, we measured levels of cytokines and chemokines in serum and CSF collected from confirmed AFM patients and non-AFM control patients, to identify unique biomarkers as potential hallmarks of AFM pathogenesis. Analysis of ratios of cytokines and chemokines in the CSF compared to the serum indicate that the pro-inflammatory cytokines/chemokines IP-10 and IL-6 were significantly elevated in AFM patients compared to non-AFM patients. These results may provide additional insight into potential etiologies, pathogenic mechanisms, and treatments for AFM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Enteroviruses (EVs) can cause infections and outbreaks of mild to severe diseases, such as central nervous system (CNS) and systemic infections. The contribution of EVs to acute CNS/systemic infections requiring hospitalization was assessed by analysing data extracted from virology laboratory database., Methods: Real-life data obtained from two molecular virology laboratories located in Northern Italy were retrieved from databases and analysed retrospectively. The queries used to extract the data were (i) requests for EV-RNA detection in clear cerebrospinal fluid (CSF) specimens collected from hospitalized patients with suspected acute CNS (including aseptic meningitis, encephalitis, and acute flaccid myelitis/paralysis) or systemic infections (sepsis-like illness or fever (≥ 38°C) of unknown origin), (ii) CSF samples collected from January 1st, 2015, to December 31st, 2017., Results: 582 requests of EV-RNA detection in CSF samples collected from as many patients of any age were recorded. EV-RNA was detected in 4.5% of the CSF samples; 92.3% of EV-positive cases were patients < 15 years, 58.3% of whom were < 3 months. EVs circulated all-year-round, and the highest EV-positive rates were observed from May to August. The risk of EV infection and the relative illness ratio value among children < 1 - year - old were significantly higher than those observed for older patients., Conclusions: EV surveillance should be carried out for all pediatric patients < 15 years and especially children less than 1 year of age with clinically suspected CNS infection/systemic infections. The implementation of a laboratory-based surveillance established for analysing the virological data provided by laboratories that routinely perform EV molecular testing may enable us to determine the impact of EVs that can cause infections requiring hospitalization., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Antonio Piralla et al.)

Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) ( P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively). IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease., (Copyright © 2019 Mishra et al.)

Objective: To analyze whether myelin oligodendrocyte glycoprotein antibody (MOG-Ab) titres at onset of the disease were different according to the clinical phenotype at presentation, and to investigate whether the titres were associated with risk of further relapses or predicted clinical outcome in adult patients. Finally, we assessed an alternative method to the classical measurement of MOG-Ab levels by serial dilutions., Methods: This is a retrospective study including 79 MOG-Ab-positive adult patients, whose samples were obtained at first episode. MOG-Ab were tested by cell-based assay. HEK293 cells were transfected (tHEK293) with human-MOG plasmid. Non-tHEK293 cells were used as negative controls. Assessment of antibody titres was performed by serial dilution, and delta mean fluorescence intensity ratio signal (MOG-ratio ΔMFI) by flow cytometry. MOG-ratio ΔMFI was calculated as follows: (MFI tHEK293cells- MFI non-tHEK293cells)/MFI non-tHEK293cells. MOG-ratio ΔMFI was calculated from the first serum dilution at 1:320. The association between MOG-Ab titres and risk of relapse was analyzed by Cox regression. The association between MOG-Ab titres and visual or motor disability at last follow-up was performed by binary logistic regression. Poor visual outcome was defined when patients displayed some degree of visual disability (visual acuity [VA] < 20/20) and poor motor outcome when patients displayed some degree of motor disability (Disability Status Scale [DSS] > 1). We also investigated correlations between MOG-Ab titres and MOG-ratio ΔMFI., Results: MOG-Ab titres were higher in Caucasians than in those with other ethnicities, and in patients with a more severe VA (VA ≤ 20/100) or motor disability (DSS ≥ 3.0) at onset (p = 0.006, 0.034, and 0.058, respectively). MOG-Ab titres were not associated with risk of relapses or with the final clinical outcome. MOG-ratio ΔMFI correlated with MOG-Ab titres in the whole cohort (ρ = 0.90; p < 0.001), and when stratified by initial clinical phenotype., Conclusion: High MOG-Ab titres at onset are associated with a more severe presentation, but do not predict the future disease course. MOG-ratio ΔMFI is an alternative and straightforward method to determine MOG-Ab levels.

Glial fibrillary acidic protein antibody-positive meningoencephalomyelitis is a newly described, possibly under-recognised, severe inflammatory condition of the nervous system. The clinical presentation is variable but most commonly is a combination of meningitis, encephalitis and myelitis; other manifestations may include seizures, psychiatric symptoms and tremor. There is a significant association with malignancies, often occult, and with other autoimmune conditions. Although the disease responds well to corticosteroids acutely, it typically relapses when these are tapered, and so patients need long-term immunosuppression. We report a young man presenting with subacute meningoencephalitis and subsequent myelitis, and discuss the typical presentation and management of this severe but treatable condition., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: The aim of this study was to evaluate the positive rate of serum glutamic acid decarboxylase (GAD) autoantibody in patients with myelitis and to describe the clinical findings in patients with positive GAD antibody., Methods: Serum samples were collected from 390 patients with myelitis, including 210 patients positive for aquaporin 4 (AQP4) antibody and 180 patients negative for AQP4. GAD65 antibody was measured by an indirect immunofluorescence assay., Results: Only 1 serum and cerebral spinal fluid sample from 390 patients (0.26%) was positive for anti-GAD antibodies. The patient was a female with relapsing myelitis and a thymic mass. Thymic resection was undertaken, and pathological examination revealed a benign thymic cyst. Extensive infiltration of lymphocytes positive for CD3, CD4, CD8 and CD20 was found. Immunohistochemistry showed positive expression of GAD65 in the cyst., Conclusions: Although serum GAD65 antibodies were present in a patient, it is not recommended to routinely screen for GAD65 antibodies in patients with myelitis because of their rare occurrence. However, screening for GAD65 antibodies should be considered in patients who have been diagnosed with cancer or a thymic abnormality., (© 2018 S. Karger AG, Basel.)

Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) are present in a subset of aquaporin-4 (AQP4)-IgG-negative patients with optic neuritis (ON) and/or myelitis. Little is known so far about brainstem involvement in MOG-IgG-positive patients., Objective: To investigate the frequency, clinical and paraclinical features, course, outcome, and prognostic implications of brainstem involvement in MOG-IgG-positive ON and/or myelitis., Methods: Retrospective case study., Results: Among 50 patients with MOG-IgG-positive ON and/or myelitis, 15 (30 %) with a history of brainstem encephalitis were identified. All were negative for AQP4-IgG. Symptoms included respiratory insufficiency, intractable nausea and vomiting (INV), dysarthria, dysphagia, impaired cough reflex, oculomotor nerve palsy and diplopia, nystagmus, internuclear ophthalmoplegia (INO), facial nerve paresis, trigeminal hypesthesia/dysesthesia, vertigo, hearing loss, balance difficulties, and gait and limb ataxia; brainstem involvement was asymptomatic in three cases. Brainstem inflammation was already present at or very shortly after disease onset in 7/15 (47 %) patients. 16/21 (76.2 %) brainstem attacks were accompanied by acute myelitis and/or ON. Lesions were located in the pons (11/13), medulla oblongata (8/14), mesencephalon (cerebral peduncles; 2/14), and cerebellar peduncles (5/14), were adjacent to the fourth ventricle in 2/12, and periaqueductal in 1/12; some had concomitant diencephalic (2/13) or cerebellar lesions (1/14). MRI or laboratory signs of blood-brain barrier damage were present in 5/12. Cerebrospinal fluid pleocytosis was found in 11/14 cases, with neutrophils in 7/11 (3-34 % of all CSF white blood cells), and oligoclonal bands in 4/14. Attacks were preceded by acute infection or vaccination in 5/15 (33.3 %). A history of teratoma was noted in one case. The disease followed a relapsing course in 13/15 (87 %); the brainstem was involved more than once in 6. Immunosuppression was not always effective in preventing relapses. Interferon-beta was followed by new attacks in two patients. While one patient died from central hypoventilation, partial or complete recovery was achieved in the remainder following treatment with high-dose steroids and/or plasma exchange. Brainstem involvement was associated with a more aggressive general disease course (higher relapse rate, more myelitis attacks, more frequently supratentorial brain lesions, worse EDSS at last follow-up)., Conclusions: Brainstem involvement is present in around one third of MOG-IgG-positive patients with ON and/or myelitis. Clinical manifestations are diverse and may include symptoms typically seen in AQP4-IgG-positive neuromyelitis optica, such as INV and respiratory insufficiency, or in multiple sclerosis, such as INO. As MOG-IgG-positive brainstem encephalitis may take a serious or even fatal course, particular attention should be paid to signs or symptoms of additional brainstem involvement in patients presenting with MOG-IgG-positive ON and/or myelitis.

Importance: A novel astrocytic autoantibody has been identified as a biomarker of a relapsing autoimmune meningoencephalomyelitis that is immunotherapy responsive. Seropositivity distinguishes autoimmune glial fibrillary acidic protein (GFAP) meningoencephalomyelitis from disorders commonly considered in the differential diagnosis., Objective: To describe a novel IgG autoantibody found in serum or cerebrospinal fluid that is specific for a cytosolic intermediate filament protein of astrocytes., Design, Setting, and Participants: Retrospective review of the medical records of seropositive patients identified in the Mayo Clinic Neuroimmunology Laboratory from October 15, 1998, to April 1, 2016, in blinded comprehensive serologic evaluation for autoantibody profiles to aid the diagnosis of neurologic autoimmunity (and predict cancer likelihood)., Main Outcomes and Measures: Frequency and definition of novel autoantibody, the autoantigen's immunochemical identification, clinical and magnetic resonance imaging correlations of the autoantibody, and immunotherapy responsiveness., Results: Of 103 patients whose medical records were available for review, the 16 initial patients identified as seropositive were the subject of this study. Median age at neurologic symptom onset was 42 years (range, 21-73 years); there was no sex predominance. The novel neural autoantibody, which we discovered to be GFAP-specific, is disease spectrum restricted but not rare (frequency equivalent to Purkinje cell antibody type 1 [anti-Yo]). Its filamentous pial, subventricular, and perivascular immunostaining pattern on mouse tissue resembles the characteristic magnetic resonance imaging findings of linear perivascular enhancement in patients. Prominent clinical manifestations are headache, subacute encephalopathy, optic papillitis, inflammatory myelitis, postural tremor, and cerebellar ataxia. Cerebrospinal fluid was inflammatory in 13 of 14 patients (93%) with data available. Neoplasia was diagnosed within 3 years of neurologic onset in 6 of 16 patients (38%): prostate and gastroesophageal adenocarcinomas, myeloma, melanoma, colonic carcinoid, parotid pleomorphic adenoma, and teratoma. Neurologic improvement followed treatment with high-dose corticosteroids, with a tendency of patients to relapse without long-term immunosuppression., Conclusions and Relevance: Glial fibrillary acidic protein-specific IgG identifies a distinctive, corticosteroid-responsive, sometimes paraneoplastic autoimmune meningoencephalomyelitis. It has a lethal canine equivalent: necrotizing meningoencephalitis. Expression of GFAP has been reported in some of the tumor types identified in paraneoplastic cases. Glial fibrillary acidic protein peptide-specific cytotoxic CD8+ T cells are implicated as effectors in a transgenic mouse model of autoimmune GFAP meningoencephalitis.

Purpose: Comorbidity of celiac disease with demyelinating diseases of the central nervous system has been reported since the 1960s. The objective of this study was to determine the serological prevalence of celiac disease in the largest series of patients diagnosed with multiple sclerosis, neuromyelitis optica, or myelitis., Methods: A prevalence study was conducted with patients evaluated at Sarah Network of Rehabilitation Hospitals between March 2012 and September 2013. They were previously diagnosed with multiple sclerosis, neuromyelitis optica, or idiopathic myelitis. The serum levels of antibodies against tissue transglutaminase and endomysium were assessed., Results: Of the 379 patients evaluated, 249 (65.70%) were diagnosed with multiple sclerosis, 37 (9.56%) with neuromyelitis optica, and 96 (24.54%) with idiopathic myelitis. Two patients (0.53%), one with multiple sclerosis and other with myelitis, tested positive for both antibodies., Conclusion: Our study do not confirm the relationship between celiac serological antibodies with multiple sclerosis, neuromyelitis optica and inflammatory myelitis of an unknown etiology., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Encephalitis with anti-N-methyl-D-aspartate receptor antibodies (anti-NMDAR-Ab) is a rapid-onset encephalitis including psychosis, seizures, various movement disorders and autonomic system disturbances., Case Presentation: We report a very unusual case of extensive myelitis associated with anti-NMDAR-Ab. MRI also revealed a hyperintense T2 lesion, non-suggestive of MS, which progressively extended, associated with periventricular gadolinium enhancement visualized on brain MRI. Ophthalmological evaluation showed subclinical right optic neuritis. The absence of anti-AQP4 antibody argued against neuromyelitis optica spectrum disorder. A slight psychomotor slowing prompted us to search for various causes of autoimmune encephalitis. Anti-NMDAR-Ab was found in cerebrospinal fluid., Conclusion: In patients with extensive myelitis who are seronegative for anti-AQP4 antibodies, and after other classical causes have been excluded, the hypothesis of atypical anti-NMDAR-Ab encephalitis should also be considered.

Objective: High-mobility group box 1 (HMGB1) acts as a proinflammatory mediator when released by cells. Recent studies implicate extracellular HMGB1 in the pathogenesis of various autoimmune diseases. Our main aim of this study is to determine whether HMGB1 is involved in the neuromyelitis optica (NMO) inflammatory process., Methods: Cerebrospinal fluid (CSF) and serum HMGB1 levels in 42 NMO patients were compared with those in 30 multiple sclerosis (MS) patients, and 30 patients with other noninflammatory neurological disorders (ONNDs). We also tested the possible correlation between CSF HMGB1 levels and the clinical and laboratory variables in NMO patients., Results: CSF HMGB1 levels in NMO patients were higher than those in MS and ONNDs patients (p<0.001), and these levels in MS patients were higher than those in ONNDs patients (p<0.001). After treatment, the CSF HMGB1 levels in NMO patients decreased to normal. In addition, CSF HMGB1 levels correlated with CSF cell counts, CSF protein levels, CSF interleukin-6 levels, CSF glial fibrillary acidic protein levels, and CSF/serum albumin ratio (p≤0.001). Serum HMGB1 levels in MS patients were significantly higher than those in ONNDs patients (p=0.002)., Conclusions: HMGB1 could play a key role in central nervous system inflammation in NMO patients.

Background: Low 25-hydroxyvitamin D levels have been associated with a higher risk of developing multiple sclerosis and increased relapse rates in patients with multiple sclerosis. As a sterol hormone involved in multiple immunologic pathways, vitamin D may play a role in preventing monophasic immune-mediated central nervous system attacks from developing into recurrent disease., Objective: To investigate the association between low serum vitamin D levels and recurrent spinal cord disease., Design, Setting, and Patients: We performed a retrospective analysis at Johns Hopkins Transverse Myelitis Center, Baltimore, Maryland, evaluating 25-hydroxyvitamin D levels in 77 patients with monophasic and recurrent inflammatory diseases of the spinal cord., Main Outcome Measure: Levels of 25-hydroxyvitamin D., Results: Vitamin D levels are significantly lower in patients who developed recurrent spinal cord disease, adjusting for season, age, sex, and race., Conclusions: This study provides a basis for a prospective trial of measuring 25-hydroxyvitamin D levels in these patient populations and assessing the influence of vitamin D supplementation on the frequency of relapses in those with recurrent inflammatory spinal cord disease.

Since the description of the association between neuromyelitis optica (Devic's disease) and aquaporin 4 IgG antibody (NMO-IgG), the search for this antibody has been considered a highly recommended laboratory test when centromedullary multisegmental lesions are observed by magnetic resonance imaging (MRI). Such MRI lesions have not been confined to acute NMO myelitis because other infectious and post-infectious disorders may display a similar lesional pattern. However, NMO-IgG has not been currently searched and associated with these myelitides. The objective of this study is to report an infectious myelitis that tested positive for NMO-IgG and comment on the implications of this finding. We report the presence of NMO-IgG in one patient exhibiting centromedullary multisegmental lesions who presented Paracoccidioides brasiliensis myelitis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Dengue infection is caused by a flavivirus, with 4 virus serotypes (types 1 to 4). The serotypes 2 and 3 represent the principal agents related to nervous system involvement. Neurologic involvement occurs in 4%-5% of dengue infection cases. The major mechanisms of the disease may be related to direct viral infection or postinfectious autoimmune process. The detection of intrathecal synthesis of specific antibodies has been used to support neurologic diagnosis as a proof of local reaction. It may be quantitatively calculated by the specific antibody index., Objectives: To determine if patients with neurologic manifestations associated with dengue produce specific antibodies in the CNS and to determine the antibodies' clinical and pathophysiologic relevance., Methods: CSF and serum were evaluated for dengue immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by ELISA and for intrathecal synthesis of IgG antibodies to the dengue virus. Subjects included 10 patients IgM seropositive for dengue virus diagnosed with myelitis, encephalitis, optic neuromyelitis, or Guillain-Barré syndrome., Results: All patients had IgG and IgM antibodies to dengue virus in their sera; 7 were IgM positive and 9 were IgG positive for dengue virus in CSF. Only the 3 patients with myelitis had intrathecal synthesis of specific IgG antibodies., Conclusions: Intrathecal synthesis of antibodies to dengue virus occurs in the CNS. It may be used as a marker of myelitis associated with dengue, and it seems to be related to the pathogenesis of spinal cord disease due to direct viral invasion.

We describe the pathological features of a spinal cord biopsy from a 69-year-old woman with anti-aquaporin-4 antibody-negative recurrent longitudinal myelitis. Spinal cord MRI showed T2 high-intensity lesions with strong gadolinium enhancement, when episodes of sensory-motor impairment were repeated. The radiological abnormality was corrected by corticosteroid administration, but improvement of the symptoms was minimal. Although the patient had sicca symptoms and fulfilled four of the diagnostic criteria for Sjögren syndrome, the diagnosis was excluded, because of infection with hepatitis C virus, an exclusion criterion of Sjögren syndrome. In the spinal cord lesions, necrotic changes affected both myelin and axons. Infiltrating lymphocytes were predominantly T-cells. The proliferation of small vessels with hyalinization and concomitant occlusive change was remarkable. These pathological findings resembled those previously reported in Sjögren syndrome. Ultrastructurally, the endothelial cells of the small vessels showed features of activated cells and contained vesiculo-tubular structures in the cytoplasm, indicating that increased blood-brain barrier (BBB) permeability might contribute to pathogenesis. We speculated that increased BBB permeability and T-cell entry in the spinal parenchyma triggered pathological reactions resulting in necrotic changes in the spinal cord. Obstruction of small vessels might add ischemic damage to the lesions. The clinical course and pathological findings indicated that damage progressed rapidly in the spinal cord and was irreversible. The lesions apparently differed from typical demyelination plaques. Faced with such spinal cord lesions, a preventive therapeutic approach is necessary to avoid attack-associated disability.

The present study evaluated the in vitro response to different mitogens and a candidin antigen (CMA) in Human T-cell lymphotropic virus type 1 (HTLV-1) and co-infected HIV-1/HTLV-1 patients, to identify if this co-infection may modify the spontaneous lymph proliferative response. Peripheral blood mononuclear cells from 72 healthy seronegative controls, 75 asymptomatic HTLV-1-infected carriers, 42 HAM/TSP cases, 33 solely HIV-1-infected subjects and 24 HIV-1/HTLV-1 patients were assayed in the presence and absence of mitogens (PHA, PWM and OKT3) and CMA. The HAM/TSP group had the highest proliferation rate at 3 and 6 days after culture. HAM/TSP cases showed decreased response to PHA, compared with asymptomatic HTLV-1 subjects, and most important, the co-infected HIV-1/HTLV-1 cases presented a similar response to HTLV-1-infected subjects after 3 days of culture. The singles HIV-1-infected group had decreased in vitro response. It appears that during co-infection, the HTLV-1 regulatory proteins overwhelm the action of HIV-1 regulatory proteins.

Background: A sensitive method to detect intrathecal IgG production is important in diagnosing inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS)., Objective: To compare cerebrospinal fluid (CSF) electrophoresis with isoelectric focusing (IEF), immunofixation-peroxidase electrophoresis (IFPE) and high-resolution agarose electrophoresis with protein-staining (HRAGE)., Methods: Paired serum and CSF samples from 307 consecutive patients attending a general neurology clinic were examined with IEF, IFPE and HRAGE. Clinical diagnosis was based on review of the patients' medical records after an average of 4 years., Results: The sensitivity for detecting any inflammatory (autoimmune or infectious) CNS disease (52 patients) was 67% for IEF, 50% for IFPE and 29% for HRAGE. The sensitivity for detecting MS (14 patients) was 93%, 86% and 29% respectively. The sensitivity for detecting clinically isolated syndrome (eight patients) was 75%, 25% and 13% respectively. The number of oligoclonal bands in IEF was higher in inflammatory than in non-inflammatory neurological diseases or symptoms, but similar in MS and other inflammatory diseases., Conclusion: IEF is the method of choice in diagnosing intrathecal IgG synthesis.

Objective: A recent nationwide survey of myelitis with atopic diathesis in Japan disclosed that the disease frequently shows a chronic persistent course. A neuropathological study of the spinal cord also revealed chronic active inflammation. Since the effects of various immunotherapies have not been studied extensively in this condition, we evaluated the efficacies of various immunotherapies in patients with myelitis with atopic diathesis., Patients and Methods: Forty-two treatments in 26 patients with myelitis with atopic diathesis were retrospectively analyzed. One of the following therapies was administered: (1) corticosteroids (CS) (pulse therapy followed by oral administration with gradual tapering); (2) intravenous immunoglobulin (IVIG) (400 mg/kg/day for 5 consecutive days); (3) plasma exchanges (PE); or (4) PE followed by IVIG or CS (PE+IVIG/CS). The therapeutic efficacies were evaluated by thorough neurological examination and laboratory tests including MRI, somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs)., Results: Objective neurological findings improved in 89% of the PE group and 90% of the PE+IVIG/CS group, compared with only 72% of the CS and 60% of the IVIG groups. Improvement determined by laboratory tests was seen in 57% of the PE and 57% of the PE+IVIG/CS groups, compared with only 15% of the CS and none of the IVIG groups. Thus, the improvement rate determined by laboratory tests was significantly greater for therapies including PE than for those without PE (p=0.0187)., Conclusions: These data suggest that immunotherapy is effective in myelitis with atopic diathesis despite a chronic persistent course, and that PE is the most beneficial immunotherapy.

Introduction: Serological confirmation of an infectious acute myelitis injury is difficult to confirm as it is sometimes due to a post-infectious etiology., Objectives: The aim of this study was to define the clinical, biological and prognostic patterns of infectious myelitis., Patients and Methods: This retrospective study included 153 subjects hospitalized in the department of neurology between 1993 and 2002 for treatment of a noncompressive acute myelopathy. Biological confirmation of recent infection was obtained in 12 patients (8 p. 100)., Results: An infectious syndrome, beginning prior to the neurological symptoms, was found in 67 percent of patients. The clinical symptoms were severe with loss of sensoromotor and sphincter functions and ascending spinal cord dysfunction (acute transverse myelopathy). Spinal cord MRI showed extended centromedullar high intensity signals with rapid and complete regression. CSF analysis cell count was above 30/mm3 with hyperproteinorachia, in 75 percent and 58 percent of patients respectively. CSF electrophoresis did not detect oligoclonal bands. Clinical outcome was good in all patients except one, however sphincter disorders recovered slowly., Discussion: Our study illustrates a stereotypical clinical, biological and prognostic pattern for infectious acute myelitis. These findings contribute significantly to therapeutic decision making and establishing prognosis at the initial phase of acute myelopathy.

We report a rare case of mumps myelitis in which parotid swelling appeared 3 days after the symptoms of myelitis. A 10-year-old boy presented with acute paraplegia of grade I-II on MRC (Medical Research Council) scale and retention of urine with normal sensations. Central motor conduction to tibialis anterior (CMCT-TA) on the right side was 32 ms and 24 ms on the left side. Spinal MRI revealed hyperintense signal changes extending from C3 to T12. After 5 days of methylprednisolone therapy, there was marked improvement in weakness, micturition normalized and CMCT-TA also returned to normal. MRI repeated after 1 month was also normal. This response seems to be due to antiedema and to the antiinflammatory effect of methylprednisolone, because of a temporal relationship between MPS and clinical improvement. However, the possibility of natural recovery cannot be ruled out.

Morphometric evaluation was performed on semi-thin sections of core biopsies of the bone marrow and included 20 cases of each group of diseases besides control specimens. (i) Hyperergic myelitis of rheumatic origin. (ii) Chronic granulocytic leukaemia (CGL). (iii) Polycythaemia vera (P. vera). (iv) Chronic megakaryocytic-granulocytic myelosis (CMGM). (v) Myelofibrosis or osteomyelosclerosis (MF/OMS). The following classification of megakaryopoiesis was applied: normal megakaryocytes; giant forms; microforms; intussusceptions; cytoplasmic fragments; naked nuclei. The density distribution shows an increase of megakaryocyte number in those 5 different marrow disorders, ranging from about 13/mm2 in the normal sample up to 65 cells/mm2 in MF/OMS. Microforms are most frequently encountered in CGL, whereas giant megakaryocytes, intussusceptions and many cytoplasmic fragments characterize P. vera, CMGM and MF/OMS. Our measurements suggests 3 distinct categories of bone marrow lesions with corresponding alterations of the megakaryopoiesis: (i) myelitis and CGL; (ii) P. vera; (iii) CMGM and MF/OMS.

The adoption of a six-fraction regime of radiotherapy for patients with locally advanced carcinoma of the bronchus was followed by the appearance of radiation myelitis in eight cases. These were among a group of 130 patients given radiotherapy with anterior and posterior treatment fields, without shielding of the spinal cord. Radiation myelitis was found only in those where the calculated spinal-cord dose exceeded 3350 cGy (rad). The possible precipitating factors in the eight patients who suffered myelopathy were compared with those in the remaining 62 patients who also received spinal-cord doses calculated to be greater than 3350 cGy (rad). Only one difference was found--the haemoglobin concentration was significantly higher in those who suffered neuropathy compared with those who did not (P = 0.05).