Autoimmune astrocytopathy double negative for AQP4-IgG and GFAP-IgG: Retrospective research of clinical practice, biomarkers, and pathology.

OBJECTIVE: The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies. METHODS: Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA). RESULTS: 116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient. DISCUSSION: There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.

[Autoimmune glial fibrillary acidic protein astrocytopathy]. / Astrocitopatía autoinmune asociada a proteína ácida fibrilar glial.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy was described for the first time in 2016. The most common clinical manifestation is meningoencephalomyelitis associated with a characteristic imaging pattern that allows diagnostic suspicion and its confirmation through determination of antibodies in serum and cerebrospinal fluid (CSF). We present a case of a 35-year-old patient with involvement of the central and peripheral nervous system and a recent diagnosis of thyroid cancer, which compared to the compatible clinical picture of meningoencephalomyelitis, characteristic findings on MRI and after the exclusion of alternative pathologies, we finally arrived at the diagnosis by the positive determination of anti-GFAP in CSF. The patient underwent surgical treatment and radioactive iodine for the diagnosed thyroid tumor and she subsequently received treatment with corticosteroids with partial improvement of the neurological symptomatology. We emphasize that in this pathology the MRI images usually depict a characteristic pattern, although not pathognomonic, it is necessary to consider other causes. Before a high suspicion of this entity due to the clinical and imaging picture, it is convenient to measure the antibody in CSF, given the greater sensitivity and specificity compared to its serum screening, in order to arrive to the definitive etiological diagnosis as it was done in the clinical case that is presented.

La astrocitopatía autoinmune asociada a proteína ácida fibrilar glial (GFAP) fue descripta por primera vez en el año 2016. La manifestación clínica más frecuente es la meningoencefalomielitis asociado a un patrón imagenológico característico que permite la sospecha diagnóstica y su confirmación mediante la determinación de los anticuerpos en suero y en líquido cefalorraquídeo (LCR). Presentamos el caso de una paciente de 35 años con compromiso del sistema nervioso a nivel central y periférico y un reciente diagnóstico de cáncer de tiroides, que frente al cuadro clínico compatible de meningoencefalomielitis, los hallazgos característicos en resonancia magnética y luego de la exclusión de enfermedades alternativas, finalmente se arribó al diagnóstico por la determinación positiva de anti GFAP en LCR. Realizó tratamiento quirúrgico y con iodo radioactivo por su tumor hallado y posteriormente recibió tratamiento con corticoides con mejoría parcial de la signo-sintomatología neurológica. Destacamos que en esta enfermedad las imágenes por resonancia magnética presentan un patrón característico, aunque no patognomónico, siendo necesario considerar otras causas. Ante una alta sospecha de esta entidad por el cuadro clínico e imagenológico, es conveniente realizar dosaje del anticuerpo en LCR, dada la mayor sensibilidad y especificidad en comparación con su pesquisa en suero, con el fin de arribar al diagnóstico etiológico definitivo como en el caso clínico presentado.

A case of chronic progressive autoimmune GFAP astrocytopathy with extensive meningoencephalomyelitis and contrast enhancement on MRI.

•We herein present a case of chronic progressive autoimmune GFAP astrocytopathy.•Symmetrical high-intensity signals on FLAIR were observed in the white matter of the temporal and occipital lobes, lateral cerebral ventricle walls, hippocampus, amygdala, and occipital cortex, with extensive Gd enhancement in radial perivascular lesions and the ependyma in the choroid plexus.•Improvements were achieved by 4 courses of IVMP and one of IVIg.

Co-occurrence of glial fibrillary acidic protein astrocytopathy in a patient with Leber's hereditary optic neuropathy due to DNAJC30 mutations.

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by visual loss, and rarely associated with extraocular manifestations including multiple sclerosis-like lesions. The association of LHON and neuromyelitis optica spectrum disorders has rarely been reported. Here is reported a case of glial fibrillary acidic protein astrocytopathy presenting with area postrema syndrome in a patient with previously diagnosed recessive LHON due to mutations in the nuclear gene DNAJC30. This case emphasizes the necessity of extensive investigations for other treatable conditions in patients with LHON and otherwise unexplained extraocular involvement and the possibility that also visual symptoms can respond to immune therapy.

Case report: Headache as the sole neurological symptom in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently emerging autoimmune disease of the central nervous system (CNS); GFAP astrocytopathy is characterized by optic neuritis and meningoencephalomyelitis. We report the case of a 55-year-old man, otherwise healthy, who presented with isolated headaches for three months, without other features of meningoencephalitis or myelitis. His neurological examination and fundoscopy were unremarkable. Gadolinium-enhanced brain MRI demonstrated increased T2 hyperintensity within the right sub-lenticular basal ganglia, with additional leptomeningeal enhancement along the bilateral perisylvian regions and mesial temporal lobes. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein, matching oligoclonal bands, and a negative infectious and cytological workup. Cell-based assays for anti-aquaporin-4, anti-myelin oligodendrocyte glycoprotein, autoimmune encephalitis panel, and vasculitis workup were all negative, except for CSF positivity for GFAP α antibody. Oncological screening, including CT of the chest, abdomen, pelvis, and scrotal US, was unremarkable. Immunotherapy with high-dose intravenous steroids for five days and subsequent single four-weekly doses resulted in the resolution of both clinical and radiographic features, with a maintained status 24 months after onset. This case highlights isolated headache and basal ganglia, mesial temporal lobe involvement as a rare presentation of autoimmune GFAP astrocytopathy.

[Peripheral neuropathy associated with severe glial fibrillary acidic protein (GFAP) astrocytopathy: a case report].

A 44-year-old man was admitted due to a fever. He developed unconsciousness and respiratory failure, necessitating mechanical ventilation. After the administration of methylprednisolone and intravenous immunoglobulin for suspected autoimmune encephalitis, his consciousness and respiratory state improved. However, he exhibited pronounced tetraparalysis and impaired sensation below the neck. A spinal MRI revealed swelling of the entire spinal cord, indicating myelitis. Deep tendon reflexes were diminished in all extremities, and a nerve conduction study confirmed motor-dominant axonal polyneuropathy. Subsequently, he developed a fever and headache. Brain MRI demonstrated FLAIR hyperintensities in the basal ganglia and brain stem. CSF analysis for anti-glial fibrillary acidic protein (GFAP) antibody turned out positive, leading to the diagnosis of GFAP astrocytopathy. Although the steroid re-administration improved muscle strength in his upper limbs and reduced the range of diminished sensation, severe hemiparalysis remained. Severe GFAP astrocytopathy can be involved with polyneuropathy. Early detection and therapeutic intervention for this condition may lead to a better prognosis.

[A case of autoimmune glial fibrillary acidic protein astrocytopathy with various symptoms such as optic disc edema and cerebellar ataxia].

A 59-year-old man had developed visual abnormality, nausea, headache, and weight loss since three months before. The ophthalmologist found severe optic disc edema in both eyes, and referred him to our hospital. The patient had mild cerebellar ataxia. Increased cerebrospinal fluid pressure, increased protein and cell counts, positive oligoclonal band, and contrast-enhanced head MRI showed multiple linear perivascular radial gadolinium enhancement around bilateral lateral ventricles. His subjective and objective findings significantly improved with steroid treatment. The cerebrospinal fluid was found to be positive for glial fibrillary acidic protein (GFAP) antibodies, and a diagnosis of GFAP astrocytopathy was obtained. When optic edema or radial contrast effects was observed on contrast-enhanced MRI, GFAP astrocytopathy should be considerd. Prompt immunotherapy is required to circumvent the development of permanent visual impairment.

Clinical characteristics and MRI features of autoimmune glial fibrillary acidic protein astrocytopathy: a case series of 34 patients.

Objectives: To analyze the clinical and imaging characteristics of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). Methods: Forty-three patients diagnosed with GFAP-A between March 2017 and July 2023 were retrospectively recruited. The clinical characteristics and magnetic resonance imaging (MRI) features were collected. Results: Twenty-one patients (61.8%) had a fever and 16 (47.1%) had a headache. Five patients (14.7%) had coexisting neural autoantibodies and one patient (2.9%) had a coexisting neoplasm. The most common presentation was meningoencephalomyelitis (13/34, 38.3%), followed by meningoencephalitis (12/34, 35.3%). The other clinical manifestations included blurred visions (5/34, 14.7%) and peripheral nervous system involvement (4/34, 11.8%). Twenty-six patients (76.5%) had elevated nucleated cell count, predominantly lymphocytes (15/15, 100%), and 27 (79.4%) had elevated protein levels of cerebrospinal fluid. One-half (50%) of the patients presented with hyponatremia. A majority of the patients (30/33, 90.9%) exhibited abnormal hyperintense lesions on T2WI, which were often located in juxtacortical white matter (18/33, 54.5%), followed by periventricular white matter (16/33, 48.5%), basal ganglia (15/ 33, 45.5%), brainstem (11/33, 33.3%), and thalamic lesions (9/33, 27.3%). Twenty-four patients (72.7%) had abnormal brain enhancement, with supratentorial leptomeningeal enhancement being the most frequent enhancement pattern (15/33, 45.5%), followed by linear perivascular radial enhancement (14/33, 42.4%). Nineteen patients (70.4%) had hyperintense intramedullary spinal cord lesions, with long segments (15/27, 55.6%) and transverse lesions (14/27, 51.9%) being the most frequent lesions. Most cases were sensitive to immunotherapy, such as glucocorticoids, intravenous immunoglobulin, and tacrolimus, with three patients (8.8%) experiencing relapses. Patients with brainstem lesions had higher onset modified Rankin scale scores and were more prone to intensive care unit admissions. Linear perivascular radial enhancement was positively associated with poor prognosis (p < 0.05). Conclusion: GFAP-A presented with meningoencephalomyelitis and meningoencephalitis. The brain lesions were often located in juxtacortical white matter, periventricular white matter, basal ganglia, brainstem, and thalamus. Long segments and transverse were the most frequent spine lesions. Leptomeningeal enhancement was the most frequent enhancement pattern, followed by linear perivascular radial enhancement, which may provide new insight into the differential diagnosis of GFAP-A.

Case report: Atypical case of autoimmune glial fibrillary acidic protein astrocytopathy following COVID-19 vaccination refractory to immunosuppressive treatments.

A 54-year-old Japanese man presented with headache and fever the day after SARS-CoV-2 vaccination. He became deeply unconscious within a week. Brain MRI showed periventricular linear enhancements and a few spotty lesions in the cerebral white matter. Cerebrospinal fluid (CSF) testing showed mild pleocytosis. He was treated with intravenous methylprednisolone and plasma exchange. However, the white matter lesions enlarged to involve the brainstem and cerebellum, and long cord spinal lesions appeared. Anti-glial fibrillary acidic protein (GFAP) antibody was positive in the CSF and serum, and he was therefore diagnosed as autoimmune GFAP-astrocytopathy (GFAP-A). In addition, high-dose immunoglobulin therapy was administered twice, but his symptoms did not improve; the white matter lesions enlarged further, and modified Rankin Scale score increased to 5. A brain biopsy specimen showed infiltration of macrophages and CD4 + lymphocytes together with neuron and oligodendrocytic injuries and glial scar. Although GFAP-A generally responds well to steroids, the present case developed GFAP-A following SARS-CoV-2 vaccination, with refractory to intensive immunosuppressive therapy and atypical pathologic findings of infiltration of CD4 + lymphocytes and demyelination.

The discrimination between autoimmune glial fibrillary acidic protein astrocytopathy and tuberculous meningitis.

OBJECTIVE: The differential diagnosis between autoimmune glial fibrillary acidic protein astrocytopathy (AGFAPA) mimicking tuberculous meningitis and tuberculous meningitis (TBM) remains challenging in clinical practice. This study aims to identify the clinical, laboratory parameters, and clinical score systems that may be helpful in differentiating AGFAPA from TBM. METHOD: Overall 22 AGFAPA patients who were initially misdiagnosed as TBM (AGFAPA-TBM) and 30 confirmed TBM patients were included. The clinical, laboratory, imaging parameters, Thwaites systems, and Lancet consensus scoring systems (LCSS) of all patients were reviewed. Logistic regression was employed to establish a diagnostic formula to differentiate AGFAPA-TBM from TBM. The receiver operating characteristic (ROC) curve was applied to determine the best diagnostic critical point of the formula. RESULTS: Urinary retention was more frequent in AGFAPA-TBM patients (72.7% vs 33.3%, p = 0.012). A significantly lower ratio of T-SPOT. TB was noted in AGFAPA-TBM patients (9.1% vs 82.1%, p < 0.001). We found the LCSS was able to differentiate AGFAPA-TBM from TBM (AUC value 0.918, 95% CI=0.897-0.924). Furthermore, we set up a new scoring system with three variables: urinary retention, T-SPOT. TB, and cerebral imaging criteria in LCSS. The proposed diagnostic score ranges from -8 to 2, and a score of ≥ 0 was suggestive of AGFAPA-TBM (AUC value 0.938, 95% CI=0.878-0.951). CONCLUSIONS: This study is the first to evaluate the Thwaites system and LCSS in AGFAPA-TBM and TBM. We provide an alternative diagnostic formula to differentiate AGFAPA-TBM from TBM and suggest testing for GFAP antibodies to avoid misdiagnosis when this scoring system meets AGFAPA-TBM.

Glial fibrillary acidic protein astrocytopathy presented as meningitis: A case report.

Introduction: Glial fibrillary acidic protein (GFAP) astrocytopathy is a novel autoimmune neurological disorder and is diagnosed by GFAP-IgG in cerebrospinal fluid (CSF) measurement. Case report: Herein, we described a 10-year-old boy with abnormal neurological symptoms and signs. GFAP-IgG was detected in CSF using cell-based assay (CBA), and his CSF showed an increase in lymphocytes, a slight decrease in glucose and an increase in protein level in the early stage. The cranial MRI showed multiple strips of T2-FLAIR hyperintense signal changes on the surface of medulla oblongata, pons, and gyrus in bilateral cerebral hemispheres. He was treated with immunoglobulin (IVIG) and high-dose methylprednisolone pulse treatment, and his clinical presentations gradually improved. Conclusion: We highlight that patients with normal inflammatory markers in peripheral blood have obvious meningitis-like symptoms, and clinicians need to consider GFAP astrocytopathy. The early diagnosis and treatment of GFAP astrocytopathy are important for improving the prognosis.

Corrigendum: Plasma exchange for two patients with autoimmune GFAP astrocytopathy with rapid progression to respiratory failure: a case report.

[This corrects the article DOI: 10.3389/fimmu.2023.1265609.].

[Clinical features and pathogenesis of Glial fibrillary acidic protein (GFAP) antibody-associated disorders].

Glial fibrillary acidic protein (GFAP) antibody-associated disorders (AD) were recently proposed to be immune-mediated neurological disorders. The pathogenesis of GFAP antibody-AD is poorly understood. Pathologically, there is a marked infiltration of large numbers of lymphocytes, including CD8+ and CD4+ T cells, into the meningeal and brain parenchyma, especially around the perivascular areas. GFAP-specific cytotoxic T cells are considered to be the effector cells of GFAP antibody-AD. The common phenotype of GFAP antibody-AD includes meningoencephalitis with or without myelitis. During the clinical disease course, patients present with consciousness disturbances, urinary dysfunction, movement disorders, meningeal irritation, and cognitive dysfunction. The detection of GFAP antibodies in the cerebrospinal fluid (CSF) by cell-based assay is essential for a diagnosis of GFAP antibody-AD. The CSF can be examined for lymphocyte-predominant pleocytosis and elevated protein levels. Brain linear perivascular radial enhancement patterns are observed in about half of GFAP antibody-AD patients. Spinal cord magnetic resonance imaging is used to detect longitudinal extensive spinal cord lesions. Although corticosteroid therapy is generally effective, some patients have a poor prognosis and relapse.

Prediction of clinical progression in nervous system diseases: plasma glial fibrillary acidic protein (GFAP).

Glial fibrillary acidic protein (GFAP), an intracellular type III intermediate filament protein, provides structural support and maintains the mechanical integrity of astrocytes. It is predominantly found in the astrocytes which are the most abundant subtypes of glial cells in the brain and spinal cord. As a marker protein of astrocytes, GFAP may exert a variety of physiological effects in neurological diseases. For example, previous published literatures showed that autoimmune GFAP astrocytopathy is an inflammatory disease of the central nervous system (CNS). Moreover, the studies of GFAP in brain tumors mainly focus on the predictive value of tumor volume. Furthermore, using biomarkers in the early setting will lead to a simplified and standardized way to estimate the poor outcome in traumatic brain injury (TBI) and ischemic stroke. Recently, observational studies revealed that cerebrospinal fluid (CSF) GFAP, as a valuable potential diagnostic biomarker for neurosyphilis, had a sensitivity of 76.60% and specificity of 85.56%. The reason plasma GFAP could serve as a promising biomarker for diagnosis and prediction of Alzheimer's disease (AD) is that it effectively distinguished AD dementia from multiple neurodegenerative diseases and predicted the individual risk of AD progression. In addition, GFAP can be helpful in differentiating relapsing-remitting multiple sclerosis (RRMS) versus progressive MS (PMS). This review article aims to provide an overview of GFAP in the prediction of clinical progression in neuroinflammation, brain tumors, TBI, ischemic stroke, genetic disorders, neurodegeneration and other diseases in the CNS and to explore the potential therapeutic methods.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Following SARS-CoV-2 Infection.

We herein report the first case of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy after coronavirus disease 2019 (COVID-19). A 23-year-old man experienced fatigue, a fever, and headache 14 days after the resolution of COVID-19. He was severely disoriented and admitted to our hospital. On admission, the patient exhibited disorientation, headache, neck stiffness, myoclonus of both upper limbs, dysuria, and pyramidal signs. A blood examination revealed hyponatremia, and a cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis. The CSF test results were positive for anti-GFAPα antibodies. The patient was treated with methylprednisolone pulse therapy, followed by oral prednisolone, which quickly ameliorated his neurological abnormalities.

Glial Fibrillary Acidic Protein (GFAP) Astrocytopathy: An Emerging Cause of Meningoencephalomyelitis in Children and Adolescents.

Introduction: We describe 5 children with GFAP astrocytopathy with the goal of further characterizing this rare form of meningoencephalomyelitis. Methods: Retrospective chart review of patients diagnosed with GFAP astrocytopathy between 2019 and 2021. Results: Patients were 8-17 years old, and all were male. Fever, headache, and vomiting were common presenting symptoms, and weakness, tremor, and ataxia were common initial examination findings. Initial magnetic resonance imaging (MRI) showed spinal cord abnormalities in 2 patients and leptomeningeal enhancement in 1. Most patients had cerebral spinal fluid pleocytosis, and all screened negative for malignancy. Three patients progressed to coma, and all were treated with immunosuppressant therapy. By discharge, all patients had improved over their clinical nadir, although none had returned to baseline. Discussion: GFAP astrocytopathy is a recently recognized cause of meningoencephalomyelitis in children. Here, we expand our understanding of this entity with the goal of aiding those treating children with GFAP astrocytopathy.

case of autoimmune GFAP astrocytopathy with eosinophils in the cerebrospinal fluid.

Cerebrospinal fluid (CSF) eosinophilia is associated with a narrow differential, primarily including parasitic and fungal infections, neoplasm, and chemical meningitis. It has rarely been reported in neuroinflammatory conditions including as a finding of CSF cytology in two autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy cases. Here we describe a case of autoimmune GFAP astrocytopathy with classic clinical and radiographic features as well as presence of eosinophils in the CSF. This case highlights a potential association of eosinophils in the CSF with autoimmune GFAP astrocytopathy, which may suggest its inclusion in the differential diagnosis of eosinophilic meningitis, encephalitis, or myelitis.

Plasma exchange for two patients with autoimmune GFAP astrocytopathy with rapid progression to respiratory failure: a case report.

Background: Patients with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy can present with early neurological deterioration, but rapidly progressive respiratory failure is rarely reported. We present the cases of two patients with autoimmune GFAP astrocytopathy who experienced rapid progression to respiratory failure and were effectively treated using plasma exchange therapy. Case report: Two patients were diagnosed with autoimmune GFAP astrocytopathy. Their initial symptoms were consistent with those of previously observed cases of autoimmune GFAP astrocytopathy. However, they experienced rapid progression to respiratory failure due to their lesion location. Specifically, case 1 had lesions in the medulla oblongata, and case 2 had lesions in the high cervical spinal cord, which are both common sites of lesions causing respiratory failure. The patients did not respond well to intravenous methylprednisolone and intravenous immunoglobulin initially and could not be withdrawn from ventilator support. Fortunately, subsequent plasma exchange therapy led to significant clinical improvements and successful withdrawal from ventilator support. Discussion: Patients with autoimmune GFAP astrocytopathy can present with rapidly progressive respiratory failure. Early treatment with plasma exchange can be beneficial in withdrawing patients from ventilator support.

Brain radial enhancement pattern in patients with negative glial fibrillary acidic protein-IgG: A cases series study.

BACKGROUND AND OBJECTIVES: Brain radial enhancement pattern on magnetic resonance imaging (MRI) has been identified as typical lesions in autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). However, the authors encountered several patients without GFAP-IgG showing that such specific imaging. In the present study, we reported the clinical pictures of 5 GFAP-IgG-negative patients with GFAP-A specific imaging pattern. METHODS: Data was retrospectively obtained from June 2013 through April 2023, and five GFAP-IgG-negative patients with valid data were recruited. Clinical information was either obtained by the investigators or retrieved from the referring clinicians and included prodromal symptoms, neurologic manifestations, comorbidities, results of ancillary studies. RESULTS: Altogether five GFAP-IgG-negative patients with "meningoencephalitis/encephalitis" manifestations and brain radial perivascular enhancement were confirmed. One patient had peripheral lymphoma. Four patients had other autoimmune antibody in serum and/or cerebrospinal fluid, of which one patient had positive aquaporin IgG. Clinical features of the five patients included headache, fever, epilepsy and abnormal behavioral symptoms. MRI of patients revealed radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter suggestive of autoimmune GFAP-A. CONCLUSION: GFAP-A-like disorders with radial perivascular enhancement could be found in GFAP-IgG-negative patients with or without neoplasm, which could provide new insight into the differential diagnosis of GFAP-A.

Potential Role of Antibodies against Aquaporin-1 in Patients with Central Nervous System Demyelination.

Aquaporins (AQPs; AQP0-AQP12) are water channels expressed in many and diverse cell types, participating in various functions of cells, tissues, and systems, including the central nervous system (CNS). AQP dysfunction and autoimmunity to AQPs are implicated in several diseases. The best-known example of autoimmunity against AQPs concerns the antibodies to AQP4 which are involved in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathy, causing also CNS demyelination. The present review focuses on the discovery and the potential role of antibodies against AQP1 in the CNS, and their potential involvement in the pathophysiology of NMOSD. We describe (a) the several techniques developed for the detection of the AQP1-antibodies, with emphasis on methods that specifically identify antibodies targeting the extracellular domain of AQP1, i.e., those of potential pathogenic role, and (b) the available evidence supporting the pathogenic relevance of AQP1-antibodies in the NMOSD phenotype.