Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy in Children: A Retrospective Analysis of 35 Cases.

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.

The increased intrathecal expression of the monocyte-attracting chemokines CCL7 and CXCL12 in tick-borne encephalitis.

Tick-borne encephalitis (TBE) is a relatively severe and clinically variable central nervous system (CNS) disease with a significant contribution of a secondary immunopathology. Monocytes/macrophages play an important role in the CNS inflammation, but their pathogenetic role and migration mechanisms in flavivirus encephalitis in humans are not well known. We have retrospectively analyzed blood and cerebrospinal fluid (CSF) monocyte counts in 240 patients with TBE presenting as meningitis (n = 110), meningoencephalitis (n = 114), or meningoencephalomyelitis (n = 16), searching for associations with other laboratory parameters, clinical presentation, and severity. We have measured concentrations of selected monocytes-attracting chemokines (CCL7, CXCL12, CCL20) in serum and CSF of the prospectively recruited patients with TBE (n = 15), with non-TBE aseptic meningitis (n = 6) and in non-infected controls (n = 8). The data were analyzed with non-parametric tests, p < 0.05 considered significant. Monocyte CSF count correlated with other CSF inflammatory parameters, but not with the peripheral monocytosis, consistent with an active recruitment into CNS. The monocyte count did not correlate with a clinical presentation. The median CSF concentration of CCL7 and CXCL12 was increased in TBE, and that of CCL7 was higher in TBE than in non-TBE meningitis. The comparison of serum and CSF concentrations pointed to the intrathecal synthesis of CCL7 and CXCL12, but with no evident concentration gradients toward CSF. In conclusion, the monocytes are recruited into the intrathecal compartment in concert with other leukocyte populations in TBE. CCL7 and CXCL12 have been found upregulated intrathecally but are not likely to be the main monocyte chemoattractants.

Antiviral Cytokine Response in Neuroinvasive and Non-Neuroinvasive West Nile Virus Infection.

Data on the immune response to West Nile virus (WNV) are limited. We analyzed the antiviral cytokine response in serum and cerebrospinal fluid (CSF) samples of patients with WNV fever and WNV neuroinvasive disease using a multiplex bead-based assay for the simultaneous quantification of 13 human cytokines. The panel included cytokines associated with innate and early pro-inflammatory immune responses (TNF-α/IL-6), Th1 (IL-2/IFN-γ), Th2 (IL-4/IL-5/IL-9/IL-13), Th17 immune response (IL-17A/IL-17F/IL-21/IL-22) and the key anti-inflammatory cytokine IL-10. Elevated levels of IFN-γ were detected in 71.7% of CSF and 22.7% of serum samples (p = 0.003). Expression of IL-2/IL-4/TNF-α and Th1 17 cytokines (IL-17A/IL-17F/IL-21) was detected in the serum but not in the CSF (except one positive CSF sample for IL-17F/IL-4). While IL-6 levels were markedly higher in the CSF compared to serum (CSF median 2036.71, IQR 213.82-6190.50; serum median 24.48, IQR 11.93-49.81; p < 0.001), no difference in the IL-13/IL-9/IL-10/IFN-γ/IL-22 levels in serum/CSF was found. In conclusion, increased concentrations of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-γ) were found in the CNS of patients with WNV infection. In contrast, expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-α appear to be concentrated mainly in the periphery.

Anti-Sjögren's-syndrome-related antigen A autoantibodies (Anti-SSA antibody) and meningoencephalitis: Sjögren's syndrome waiting to be unveiled? A case series and review of literature.

Aseptic meningoencephalitis (AME) constitutes a variable proportion of meningoencephalitis. Patients with AME are not routinely evaluated for autoimmune disorders. Primary Sjögren's syndrome (pSS) is a prevalent, but under suspected systemic autoimmune disease characterised by exocrinopathy, though sicca symptoms may not be the dominant or presenting feature. This study was undertaken to enumerate the clinical, radiological and laboratory features of meningoencephalitis related to pSS among the total cohort of meningoencephalitis admitted in our hospital. Retrospective patient records were screened for diagnosis of meningoencephalitis from April 2016 to March 2020. Those patients with anti-SSA positivity and clinical diagnosis of pSS were included. We have reviewed all cases of Sjögren's syndrome with meningoencephalitis available in literature. Four patients with meningoencephalitis with pSS were identified. Their clinical presentations, investigations, and good response to steroids have been described with special emphasis on evolving clinical features. In all patients, sicca features were absent. Anti-SSA was positive in all. The diagnosis of pSS was considered after ruling out all infectious and other autoimmune aetiologies. Two had extra-neurological organ manifestations and required addition of second line immunosuppressive agents for optimum disease control. Consistent with this case series, absent sicca symptoms have been described in pSS patients presenting with meningoencephalitis in literature. This case series is of special interest as it describes the initial presentation of pSS as meningoencephalitis with sicca features in absentia, thereby highlighting the need for a high index of suspicion and the need for workup for pSS in AME.

Prediction Rule for Scrub Typhus Meningoencephalitis in Children: Emerging Disease in North India.

OBJECTIVES: To evaluate the proportion of scrub typhus meningoencephalitis among children with acute encephalitis syndrome and to outline its differentiating features. To develop a prediction rule for scrub typhus meningoencephalitis. METHODS: A prospective cohort study was conducted at a tertiary care public hospital in Northern India. Consecutive patients of acute encephalitis syndrome who met our inclusion criteria were enrolled over 2 years. Standardized workup including serum IgM against Orientia tsutsugamushi was performed. Clinical and laboratory features were compared between IgM-positive and IgM-negative patients. The area under the receiver operating characteristic curve of the score derived from "independent predictors" was measured. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated at different cut-offs of the score. RESULTS: Scrub typhus IgM enzyme-linked immunosorbent assay was positive in 66/352 patients (18.8%). Longer duration of fever and prodromal stage along with eschar, hepatomegaly, lymphadenopathy, and pneumonia were significantly more prevalent in scrub typhus meningoencephalitis. However, petechiae were frequent in non-scrub typhus patients. Leucocytosis, lymphocytosis, thrombocytopenia, hypoalbuminemia, and elevated levels of serum bilirubin, serum transaminases, and cerebrospinal fluid protein were associated with scrub typhus meningoencephalitis. Logistic regression revealed fever for >8 days, pneumonia, absence of petechiae, cerebrospinal fluid protein >1000 mg/L, and serum glutamic oxaloacetic transaminase >100 IU/L as independent "predictors" of scrub typhus meningoencephalitis. The area under the receiver operating characteristic curve (95% confidence interval) of the prediction score was 0.832 (0.78-0.89). Score at cutoff ≥1 had 91% sensitivity, 96.1% negative predictive value, and at cutoff ≥4 had 99.7% specificity, 88.9% positive predictive value, 83.1% negative predictive value, 40.3 positive likelihood ratio, 0.88 negative likelihood ratio for identifying scrub typhus meningoencephalitis. CONCLUSION: Prediction score may help physicians in peripheral areas to identify and treat scrub typhus meningoencephalitis, an emerging cause of acute encephalitis syndrome in India.

Magnitude of Cryptococcosis among HIV patients in sub-Saharan Africa countries: a systematic review and meta-analysis.

BACKGROUND: Cryptococcus is encapsulated opportunistic yeast that causes life threatening meningoencephalitis of patients with human immunodeficiency virus (HIV). The magnitude of Cryptococcosis among HIV patients varies from 1-10% in Western countries as opposed to almost a one third of HIV-infected individuals in sub-Saharan Africa where it is associated with high mortality. METHODOLOGY: By using key terms "Cryptococcosis among HIV patients in sub-saharan Africa countries", articles that published in different journals from 2010-2017 searched on Pub-Med and Google scholar database. Those freely accessible and included the prevalence of Cryptococcosis in the result section, their PDF file was downloaded and the result extracted manually and presented in table. Articles that did not report the prevalence of Cryptococcosis, with a study design otherthan cross sectional, or a sample size less than 100, and those duplicated in the same study area and period by the same authors were excluded. The article selection followed the PRISMA guidelines and meta- analysis was performed using OpenMeta(analyst). RESULTS: The overall pooled magnitude of Cryptococcosis among HIV patients in sub saharan African countries was 8.3% (95%CI 6.1-10.5%). The highest prevalence was from Uganda (19%) and the least was from Ethiopia at 1.6%. There was 87.2 % of substantial heterogeneity among the studies with p-value<0.001. The symmetry ofthe forest plot showed that there was little publication bias. The most commonly used method for diagnosis of Cryptococcosis was lateral flow assay and latex agglutination test and culture was the least method employed. CONCLUSION: The overall pooled magnitude of Cryptococcosisis high among HIV patients in sub-Saharan African countries. The studies showed substantial heterogeneity, and little publication bias. Most of the studies relied on LFA & LA that showed the scarcity of facilities for fungal culture. Therefore, paying attention to screening HIV patients; those with signs and symptoms of meningitis may help to reduce the loss of HIV patients.

Cerebrospinal fluid and blood lactate concentrations as prognostic biomarkers in dogs with meningoencephalitis of unknown origin.

Meningoencephalitis of unknown origin (MUO) is a common inflammatory disease of the central nervous system. Several studies investigated finding prognostic factors, but results are contradictory. The aim of this study was to determine the concentrations of blood lactate (Blood-L) and cerebrospinal fluid lactate (CSF-L) in dogs with MUO for prognostic purposes. A total of 45 dogs with MUO (MUO group) and 11 with idiopathic epilepsy (IE group) were included. In the MUO group, 22 dogs were treated with prednisolone + cytosine arabinoside, 17 with prednisolone ± cyclosporine, and six received no treatment. In the MUO group, there was a strong-moderate positive correlation between Blood-L and CSF-L (ρ = 0.63557; P < 0.0001), a strong-moderate negative correlation between survival and CSF-L (ρ= -0.50210; P < 0.0004), and a weak negative correlation between survival and Blood-L (ρ= -0.35685; P < 0.0220). Dogs with a favourable response to treatment at 1 month had lower initial concentrations of Blood-L and CSF-L (P < 0.0010; P < 0.0037), and those with a worse response had higher values (P < 0.0497; P < 0.0004). Dogs that remained stable with treatment showed lower CSF-L concentrations (P < 0.0013). Dogs with Blood-L>4 mmol/L (P < 0.03) and/or CSF-L> 4 mmol/L (P < 0.009) had lower survival rates with the latter also showing more severe signs, probably indicating severe neuronal damage. These findings suggest that concentrations of CSF-L and Blood-L in dogs with MUO could be used as prognostic indicators.

A case of anti-MOG antibody-positive unilaterally dominant meningoencephalitis followed by longitudinally extensive transverse myelitis.

BACKGROUND: There are few reports of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive, unilaterally dominant cerebral cortical encephalitis onset with epilepsy. We present such a case in a young female patient with myelitis. CASE PRESENTATION: A 19-year-old female developed generalized tonic seizures lasting several minutes. She had a low-grade fever and headache without other clinical neurological abnormalities while at our hospital. Cerebrospinal fluid (CSF) showed mononuclear pleocytosis. Other laboratory tests indicated no apparent abnormalities. Unilateral meningeal hyperintensity was seen on T2 fluid-attenuated inversion recovery MRI with associated cortical swelling and gadolinium enhancement of the cortical layer. One thousand mg/day of levetiracetam and a 3-day course of intravenous methylprednisolone at 1000 mg/day were administered. Dysuria appeared on the twentieth day of illness, and spinal MRI revealed a longitudinally extensive cord lesion from C5 to L1 consistent with myelitis. Two cycles of a 3-day course of intravenous methylprednisolone at 1000 mg/day were administered, and all symptoms disappeared. We found the patient to be anti-MOG antibody-positive using serum and CSF (titer: serum 1:256; CSF 1:128). CONCLUSION: Our report illustrates a unique case of anti-MOG presenting as new onset epilepsy secondary to unilaterally dominant meningoencephalitis preceding the onset of longitudinally extensive transverse myelitis.

Comparison between cerebrospinal fluid and serum lactate concentrations in neurologic dogs with and without structural intracranial disease.

The objectives of this study were to investigate the relationship between cerebrospinal fluid lactate and serum concentrations in dogs with clinical signs of central nervous system disease and to establish if cerebrospinal fluid lactate (CSF) concentrations are higher in dogs with structural intracranial disease (Group Pos-MRI) compared to dogs that have clinical signs of intracranial disease but no structural brain disease (Group Neg-MRI) based on magnetic resonance imaging (MRI) findings. Using a prospective study canine blood and cerebrospinal fluid were collected in 24 dogs with neurological signs after undergoing brain MRI. Dogs were divided in 2 groups. No significant difference between serum lactate (1.57 ± 0.9 mmol/L) and CSF lactate concentration (1.34 ± 0.3 mmol/L) was detected. There was a direct correlation between CSF and serum lactate concentration (R = 0.731; P = 0.01). No significant difference was found in CSF lactate concentration between the 2 groups of dogs (P = 0.13).

Les objectifs de la présente étude étaient d'examiner la relation entre les concentrations de lactate du liquide céphalo-rachidien (LCR) et du sérum chez des chiens présentant des signes cliniques de pathologie du système nerveux central et établir si les concentrations de lactate du LCR sont plus élevées chez les chiens avec une maladie intracrânienne structurale (Groupe Pos-IRM) comparativement à des chiens avec des signes cliniques de maladie intracrânienne mais sans maladie structurale du cerveau (Groupe Nég-IRM) sur la base des trouvailles en imagerie par résonnance magnétique (IRM). Utilisant une étude prospective, du sang canin et du LCR ont été prélevés chez 24 chiens avec des signes neurologiques après un examen par IRM du cerveau. Les chiens ont été séparés en deux groupes. Aucune différence significative ne fut détectée entre les concentrations de lactate sérique (1,57 ± 0,9 mmol/L) et de lactate du LCR (1,34 ± 0,3 mmol/L). Il y avait une corrélation directe entre les concentrations de lactate du LCR et du sérum (R = 0,731; P = 0,01). Aucune différence significative dans la concentration de lactate du LCR ne fut trouvée entre les deux groupes de chiens (P = 0,13).(Traduit par Docteur Serge Messier).

Autoimmune GFAP astrocytopathy: Prospective evaluation of 90 patients in 1 year.

In this prospective evaluation of serum and CSF samples, all but two CSF GFAPα-IgG positive patients had autoimmune meningoencephalomyelitis while serum GFAPα-IgG positivity alone was less specific. Phenotypes were diverse among patients that were serum positive only. Adult and pediatric clinical presentations were similar. Most patients were immunotherapy responsive. Co-existing NMDA-R-IgG and cancer were associated with lack of response to first-line immunotherapy. Among patients with follow-up information, 18% had relapses. This study demonstrates CSF GFAPα-IgG is a specific autoimmune meningoencephalomyelitis biomarker, with favorable corticosteroid response. Lack of response should prompt evaluation for co-existing NMDA-R-IgG or malignancy.

A four-year survey (2011-2014) of West Nile virus infection in humans, mosquitoes and birds, including the 2012 meningoencephalitis outbreak in Tunisia.

A West Nile virus (WNV) outbreak occurred in Tunisia between mid-July and December 2012. To assess the epidemiological features of the WNV transmission cycle, human cerebrospinal fluid samples from patients with suspected cases (n = 79), Culex pipiens mosquitoes (n = 583) and serum specimens from domestic and migratory birds (n = 70) were collected for 4 years (2011-2014) in the Tunisian Sahel region. Viral testing was performed by polymerase chain reaction (PCR). The WNV genome was detected in 7 patients (8.8%), 4 Culex pipiens pools, and a domestic mallard (Anas platyrhynchos). All PCR-positive samples were from the Monastir region. Phylogenetic analysis revealed that two different WNV strain groups circulated, and isolates from the reservoir (bird), vector (Culex pipiens), and dead-end hosts (humans) were closely related. The Monastir region is a hot-spot for WNV infection, and the reiterative presence of WNV over the years has increased the risk of viral reemergence in Tunisia, which highlights the need for more enhanced and effective WNV surveillance in humans with public awareness campaigns strengthened by monitoring mosquitoes and maintaining avian surveillance for early detection of WNV circulation.

Glial fibrillary acidic protein antibody-positive meningoencephalomyelitis.

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.

Blood-Brain Barrier and Intrathecal Immune Response in patients with neuroinfections.

Cerebrospinal fluid/serum albumin ratio is one of the most informative parameters for blood-brain barrier (BBB) integrity in cases of central nervous system (CNS) infectious diseases. Normally, CNS albumin concentration is a function of diffusion processes along with CSF drainage and resorption. In pathological processes CSF albumin levels are dependent only on the rate of CSF drainage resulting in non-linear reciprocal changes of albumin quotient (Qalb). IgG, IgA and IgM concentrations both in CSF and serum can be compared to Qalb, thus determining the intrathecal immune response. The aim of the study was to detect BBB permeability impairment and the intrathecal immune response in patients with CNS infections with various etiologies. CSF/serum ratios were calculated and related to IgG IgA and IgM concentrations in CSF and blood serum. The results were integrated and presented by Reibergrams. The results demonstrated typical patterns which prove albumin to be the main modulator of protein dynamics and at the same time explicates the complex pathophysiological mechanisms involved in BBB disruption and intrathecal immune response in CNS infections. The diagnostic model presented in our study seeks to explain the observations of meningitis and meningoencephalitis pathophysiology and points out the mandatory cooperation between clinicians and laboratory for accurate diagnosis and proper treatment.

Cross-reactivity of the 31 kDa antigen of Angiostrongylus cantonensis - Dealing with the immunodiagnosis of meningoencephalitis.

The primary causative agent of eosinophilic meningoencephalitis (EoM) in endemic regions is the nematode Angiostrongylus cantonensis. The occurrence of EoM was previously restricted to countries in Southeast Asia and the Pacific Islands; however, more recently, it has been reported from other regions, including Brazil. The commonly used diagnosis is detection of specific antibody reactivity to the 31 kDa antigen, which is derived from female worm somatic extracts. Here we report the occurrence of cross-reactivity to this antigen in sera from other parasitic infections, especially those that may cause EoM, such as gnathostomiasis, toxocariasis, hydatidosis and strongyloidiasis. We also demonstrated that the cross-reactivity, in part, is dependent of the concentration of antigen used in Western blot assays. We discuss the importance of these findings on the interpretation of this test.

Blood-CSF-barrier dysfunction is a marker for encephalitic involvement in patients with aseptic meningitis/meningoencephalitis.

BACKGROUND: The term "aseptic meningitis" encompasses cases of meningitis with negative bacterial CSF culture, which predominantly are of viral etiology. While the clinical course is usually benign, complications such as encephalitic involvement resulting in a more severe clinical course may occur. Dysfunction of the blood-brain-barrier (BBB), which is a prerequisite for viral entry into the brain parenchyma, can be approximated using the CSF/serum albumin ratio, readily obtainable in routine CSF analysis. OBJECITVES: Analysis of CSF patterns in patients with aseptic meningitis/meningoencephalitis with a focus on BBB dysfunction as a marker for encephalitic involvement. STUDY DESIGN: Retrospective chart review of patients admitted to our hospital between 2004 and 2016 with a diagnosis of aseptic meningitis/meningoencephalitis. RESULTS: Patients with aseptic meningitis displaying clinical, MR-tomographic or electroencephalographic signs of encephalitic involvement were significantly older than patients without these features (47.4 vs. 35.5 yrs., p=0.002). In patients with meningoencephalitis, CSF analysis revealed a more severe disruption of BBB, approximated by the CSF/serum albumin ratio (p=0.002). Compromised BBB function correlated positively with length of hospitalization (p=0.007), indicative of a more severe clinical course. The number of CSF lymphocytes was found to predict the severity of the BBB disruption, which additionally was more frequently observed when herpesviridae were identified as infectious agents. CONCLUSIONS: We suggest that the CSF/serum albumin ratio as an estimate for BBB function should be attended to in the evaluation of patients with aseptic meningitis. Severe BBB dysfunction, older age and infection with herpesviridae appear to raise the risk for encephalitic involvement.

Expression of microRNAs miR-21 and miR-181c in cerebrospinal fluid and serum in canine meningoencephalomyelitis of unknown origin.

The potential of microRNAs (miRNAs) as biomarkers for canine meningoencephalomyelitis of unknown origin (MUO) was investigated by using quantitative real-time (qRT)-PCR to determine the expression of microRNA-21 (miR-21) and microRNA-181c (miR-181c) in the cerebrospinal fluid (CSF) of dogs. Dogs with MUO (n = 10) had higher levels of expression of miR-21 and miR-181c in the CSF than dogs with non-inflammatory neurological diseases (n = 8). There was a positive correlation between CSF cellularity and expression of miRNAs in the CSF, particularly for miR-21 in the MUO group.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Novel Meningoencephalomyelitis.

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.