Glial Fibrillary Acidic Protein Astrocytopathy Research Articles

Enlarged perivascular spaces in autoimmune glial fibrillary acidic protein astrocytopathy.

Enlarged perivascular spaces in autoimmune glial fibrillary acidic protein astrocytopathy.

Clinical characteristics and prognostic factors for short-term outcomes of autoimmune glial fibrillary acidic protein astrocytopathy: a retrospective analysis of 33 patients.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a recently discovered inflammatory central nervous system (CNS) disease, whose clinical characteristics and prognostic factors for short-term outcomes have not been defined yet. We aimed to assess the symptoms, laboratory tests, imaging findings, treatment, and short-term prognosis of GFAP-A. A double-center retrospective cohort study was performed between May 2018 and July 2022. The clinical characteristics and prognostic factors for short-term outcomes were determined. We enrolled 33 patients with a median age of 28 years (range: 2-68 years), 15 of whom were children (<18 years). The clinical spectrum is dominated by meningoencephalomyelitis. Besides, we also found nausea, vomiting, poor appetite, and neuropathic pain in some GFAP-A patients, which were not mentioned in previous reports. And adults were more prone to limb numbness than children. Magnetic resonance imaging revealed lesions involving the brain parenchyma, meninges, and spinal cord, exhibiting patchy, linear, punctate, and strip T2 hyperintensities. First-line immunotherapy, including corticosteroid and gamma globulin, was effective in most patients in the acute phase (P = 0.02). However, patients with overlapping AQP4 antibodies did not respond well to first-line immunotherapy and coexisting neural autoantibodies were more common in women. Additionally, the short-term prognosis was significantly better in children than in adults (P = 0.04). Positive non-neural autoantibodies and proven viral infection were independent factors associated with poor outcomes (P = 0.03, 0.02, respectively). We expanded the spectrum of clinical symptoms of autoimmune GFAP-A. The clinical symptoms and short-term prognosis differed between children and adults. Positive non-neural autoantibodies and proven viral infection at admission suggest a poor short-term prognosis.

Isolated optic neuritis with positive glial fibrillary acidic protein antibody

Background and objectivesAutoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) has been reported as a spectrum of autoimmune, inflammatory central nervous system disorders. Linear perivascular radial gadolinium enhancement patterns on brain magnetic resonance imaging (MRI) are a hallmark of these disorders. GFAP-A is associated with cerebrospinal fluid (CSF) GFAP antibody (GFAP-Ab), while the association with serum GFAP-Ab is less clear. This study aimed to observe the clinical characteristic and MRI changes of GFAP-Ab-positive optic neuritis (ON).MethodsWe performed a retrospective, observational case study at the department of neurology, Beijing Tongren Hospital, from December 2020 to December 2021. The serum of 43 patients and CSF samples of 38 patients with ON were tested for GFAP-Ab by cell-based indirect immune-fluorescence test.ResultsFour patients (9.3%) were detected GFAP-Ab positive, and in three out of the four patients, GFAP-Abs were detected only in serum. All of them demonstrated unilateral optic neuritis. Three patients (1, 2, and 4) experienced severe visual loss (best corrected visual acuity ≤ 0.1). Two patients (2 and 4) had experienced more than one episode of ON at the time of sampling. MRI showed optic nerve hyperintensity on T2 FLAIR images in all GFAP-Ab positive patients, and orbital section involvement was the most common. During follow-up (mean 4.5 ± 1 months), only Patient 1 had a recurrent ON, and no patient developed new other neurological events or systemic symptoms.ConclusionGFAP-Ab is rare in patients with ON and may manifest as isolated, relapsing ON. This supports the notion that the GFAP-A spectrum should comprise isolated ON.

GFAP astrocytopathy presenting after COVID-19 infection with meningoencephalomyelitis and good recovery with immunotherapy (P14-4.001)

<h3>Objective:</h3> To describe a case of post-COVID-19 GFAP astrocytopathy presenting with meningoencephalomyelitis. <h3>Background:</h3> Glial fibrillary acidic protein (GFAP) astrocytopathy is a newly described autoimmune disorder that presents with meningoencephalitis, myelitis and cerebellar dysfunction. Differential diagnosis includes inflammatory, neoplastic and infectious etiologies. GFAP astrocytopathy associated meningoencephalomyelitis is a rare, but treatable neurologic sequela of COVID-19. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 62-year-old man presented with progressive confusion, recurrent falls, and weight loss with initial symptom onset during COVID-19 infection 6 weeks prior. MRI showed patchy parenchymal and ependymal enhancement in the brainstem and temporal lobe as well as T2 hyperintensity throughout the cervical and thoracic cord consistent with transverse myelitis. Four lumbar punctures demonstrated elevated protein between 100–200 mg/dl and significant lymphocytic pleocytosis with 300–600 nucleated cells. Extensive infectious work-up was negative. Malignancy work-up showed PET-CT avidity in the spinal cord and positive MYD88 mutation in the CSF, possibly indicating a lymphoproliferative condition. However, CSF cytology, CSF flow cytometry and a bone marrow biopsy showed no evidence of malignancy on repeated testing. CSF autoimmune encephalopathy panel demonstrated high titers of GFAP antibodies. Initial treatment included pulse-dose steroids and IVIG with minimal improvement in cognition. He was then treated with pulse-dose steroids and rituximab with markedly improved cognition, motor function and appetite. Subsequent 2-month MRI demonstrated partial resolution of his cerebral and spinal lesions. <h3>Conclusions:</h3> Subacute meningoencephalitis, with or without myelitis, is a typical presentation of GFAP astrocytopathy. Other symptoms include ataxia, blurred vision with optic disc edema, dysautonomia, seizures, area postrema syndrome and psychiatric symptoms. Most patients have a steroid responsive monophasic course, but approximately 20% of patients have relapsing disease. GFAP astrocytopathy should be on the differential for meningoencephalomyelitis, especially with infectious prodrome, such as COVID-19 infection. Early recognition and treatment can lead to improvement of neurologic deficits and a good outcome. <b>Disclosure:</b> Dr. Song has nothing to disclose. Dr. Oetjen has nothing to disclose. Dr. Harrold has nothing to disclose. Dr. Dietrich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Dietrich has received publishing royalties from a publication relating to health care. Kien-Ninh Ly has nothing to disclose. Dr. Venna has nothing to disclose.

Clinical Manifestation, Auxiliary Examination Features and Prognosis of GFAP Autoimmunity: a Chinese Cohort Study (P5-5.029)

<h3>Objective:</h3> To report the clinical manifestation and auxiliary examination features of 15 Chinese patients with glial fibrillary acidic protein (GFAP) autoimmunity. <h3>Background:</h3> GFAP astrocytopathy is a corticosteroid responsive inflammatory central nervous system (CNS) disorder spectrum predominantly affecting meninges, brain, spinal cord, and optic nerve mimics infectious meningoencephalitis. IgG antibodies binding to GFAP are specific biomarkers with diagnostic significance. <h3>Design/Methods:</h3> From June 2016 to December 2019, patients with suspected neurological autoimmune disease were scanned for autoantibodies by immunohistochemistry. Samples showed a characteristic immunoreactive pattern reminiscent of GFAP of astrocytes were selected and confirmed by cell-based assay. <h3>Results:</h3> Fifteen patients (8 male, 7 female) with a median age at onset of 53 years were identified as GFAP-IgG positive. Eleven of 15 patients presented with an acute monophasic course, of which 10 had antecedent flu-like symptoms. The predominant phenotype was meningoencephalitis (46.7%), followed by meningoencephalomyelitis in 40% of cases. Magnetic resonance imaging revealed enhancement in 10 of 13 patients. Inflammatory CSF showed mild lymphocyte-predominant pleocytosis with a median of 51/μl, elevated protein with a median of 87.5mg/dl. Five of six patients tested for CSF specific oligoclonal bands were positive. Five patients had coexisting antibodies, including NMDAR-IgG in 3 patients, Yo and MOG-IgG in one each patient. One patient underwent stereotactic brain biopsy and neuropathology diagnosis was diffuse large B-cell lymphoma with normal reactive fibrillary astrocytes. One patient had ovarian teratoma. Eleven of 15 patients received both intravenous immunoglobulin and steroids. Among them, 3 patients also received immunosuppressive agents later. During 2-year follow-up, nine of 15 patients achieved complete clinical remission. <h3>Conclusions:</h3> The clinical presentation of GFAP astrocytopathy is heterogeneous, including acute monophasic course or chronic relapsing courses. Patients with an acute monophasic course with antecedent infection symptoms responded well to immunotherapy. In case of primary central nervous system lymphoma, GFAP autoimmunity doesn’t equal to autoimmune GFAP astrocytopathy. <b>Disclosure:</b> Dr. Liu has nothing to disclose. Dr. Zhang has nothing to disclose.

Clinical features and biomarkers of acute encephalitis with claustrum sign (P5-5.027)

<h3>Objective:</h3> To determine clinical features and biomarkers of acute encephalitis with claustrum sign on brain MRI and to clarify the pathogenetic mechanism. <h3>Background:</h3> The claustrum sign has been described as reversible bilateral claustrum MRI hyperintensity on a T2-weighted MRI image. This finding has been reported in acute encephalitis, including acute necrotizing encephalopathy, febrile infection–related epilepsy syndrome, a subcategory of new-onset refractory status epilepticus. <h3>Design/Methods:</h3> We retrospectively analyzed the clinical features and cerebrospinal fluid (CSF) findings of three patients with acute encephalitis with claustrum sign. <h3>Results:</h3> All patients had prior symptoms suspected of infection, including fever, cough, and general fatigue. Two patients had meningeal signs and refractory status epilepticus. One patient had pyramidal signs and tremor. Claustrum sign was noted at 8, 28, and 52 days after the onset. In CSF, a glial fibrillary acidic protein (GFAP) antibody was detected in one patient with pyramidal signs and tremor. The other two patients had no antineuronal antibodies detected by tissue-based immunofluorescence assay using frozen rat brain sections. Compared with GFAP antibody-negative patients, GFAP antibody-positive patients had increased levels of CSF cell counts (antibody-positive vs antibody-negative; 127/μL vs 13 and 32/μL), protein concentrations (157 mg/dL vs 39 and 58 mg/dL), and tumor necrosis factor α (25.3 pg/mL vs 2.82 and 2.95 pg/mL). Interleukin 6 (IL-6) in CSF with GFAP antibody-negative patients was significantly higher than those with antibody-positive patients (195 and 609 pg/mL vs. 19.2 pg/mL). All patients required ventilator management and received immunotherapies. Two GFAP antibody-negative patients had improved, but a GFAP antibody-positive patient had died due to pneumonia. <h3>Conclusions:</h3> Acute encephalitis with claustrum sign is associated with at least increased levels of IL6 and GFAP antibody (i.e., GFAP astrocytopathy). In addition to CSF cytokine measurements, it is considered that GFAP antibody measurements should be performed in this disorder. <b>Disclosure:</b> Dr. Shimohata has nothing to disclose. Akira Takekoshi has nothing to disclose. Kimihiko Kaneko has nothing to disclose. Juichi Fujimori has nothing to disclose. Dr. Ioku has nothing to disclose. Keisuke Imai has nothing to disclose. Dr. Kimura has nothing to disclose.

Sudden Death in Autoimmune GFAP Astrocytopathy (P5-5.020)

<h3>Objective:</h3> To describe a rare fatal outcome in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. <h3>Background:</h3> Our patient was a 42 year old healthy woman who presented with 3 months of low back pain, bilateral upper extremity postural tremor, neck pain which progressed to 1 week of confusion and memory impairment. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> Neurologic exam revealed impaired attention, 3+ deep tendon reflexes throughout, bilateral upper extremity postural tremor and narrow based gait. MRI Brain showed abnormal, diffuse and relatively symmetric periventricular linear enhancement with associated subependymal enhancement. MRI C-spine demonstrated longitudinally extensive T2 FLAIR hyperintensity extending from C2–T2. Lumbar puncture showed opening pressure of 19 cm H2O with lymphocytic pleocytosis. She was treated with 5 days of pulse-dose corticosteroids with significant neurologic improvement and was discharged on prednisone taper. She was at her neurological baseline at Neuroimmunology clinic a week after the discharge. In the interim, CSF studies returned positive for GFAP antibody. Two weeks after the visit, she had new-onset word-finding difficulties, forgetfulness and intermittent staring spells. She was started on prednisone 60 mg daily and had repeat lumbar puncture at the office. Four to five hours after the lumbar puncture, she developed worsening confusion and bilateral upper extremity shaking. She was brought to our ED where her exam revealed dilated pupils with minimal reaction to light. CT head and CTA of the head and neck showed diffuse cerebral edema with absent cortical blood flow. Death by neurologic criteria was met the next day. <h3>Conclusions:</h3> Autoimmune GFAP astrocytopathy has an overall favorable prognosis. Our patient had a fatal outcome secondary to cerebral herniation following lumbar puncture, similar to the first reported fatal case. These two cases suggest that autoimmune GFAP astrocytopathy may present with diffuse cerebral edema and caution should be taken when performing lumbar punctures when this disease is suspected or diagnosed. <b>Disclosure:</b> Dr. Mahat has nothing to disclose. Dr. Dermigny has nothing to disclose. Dr. Alzyoud has nothing to disclose. Dr. Pilato has nothing to disclose.

Pseudo-bulbar affect and Tremors in GFAP Astrocytopathy: A Case Report (P4-5.005)

Pseudo-bulbar affect and Tremors in GFAP Astrocytopathy: A Case Report (P4-5.005)

Autoimmune glial fibrillary acidic protein astrocytopathy: clinical analysis and review of 15 cases

BackgroundTo review clinical characteristics, auxiliary examination results, treatment effects, and outcomes of patients with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).MethodsWe collated and retrospectively analyzed clinical data of 15 patients admitted with clinical characteristics of an autoimmune GFAP-A acute encephalitis or meningitis phenotype.ResultsAll patients were diagnosed with acute-onset meningoencephalitis and meningoencephalomyelitis. Initial presentations included pyrexia and headache at onset; dual symptoms of prominent tremor with urinary and bowel dysfunction; ataxia, psychiatric and behavioral abnormalities, and impaired consciousness; neck resistance; reduced extremity muscle strength; blurred vision; epileptic seizures; and reduced basic blood pressure. Cerebrospinal fluid (CSF) examination showed that the degree of protein elevation was significantly higher than the degree of increase in white blood cells. Moreover, in the absence of obvious low chloride and glucose levels, CSF chloride levels decreased in 13 patients, accompanied by a CSF glucose level decrease in four. Brain abnormalities were found in magnetic resonance imaging of ten patients, with a linear radial perivascular enhancement present in the lateral ventricles of two patients and symmetric abnormalities in the splenium of the corpus callosum in three patients.ConclusionsAutoimmune GFAP-A may be a spectrum disorder, with acute- or subacute-onset meningitis, encephalitis, and myelitis being the main phenotypes. When used for acute stage treatment, combined hormone and immunoglobulin therapy was superior to hormone pulse therapy or immunoglobulin pulse therapy alone. However, hormone pulse therapy alone without immunoglobulin pulse therapy was associated with a greater number of remaining neurological deficits.

Teaching NeuroImages: Linear Radial Periventricular Enhancement in Glial Fibrillary Acidic Protein Astrocytopathy

A 48-year-old woman presented with asymptomatic painless optic disc swelling, seizures, cognitive decline, and weakness over 3 months. She had an upper motor neuron pattern of grade 4/5 weakness in all 4 limbs. Brain MRI revealed striking linear radial perivascular enhancement in the deep white matter1,2 (figure, A and B); MRI spine revealed longitudinally extensive C3-to-conus cord T2 hyperintensity and T1 enhancement2 (figure, C and D). CSF demonstrated glial fibrillary acidic protein (GFAP) pattern by indirect immunofluorescence with GFAPα specificity confirmed by cell-based assay. The patient improved clinically (figure, E and F) with steroid treatment. Linear/radial perivascular enhancement in the deep white matter prompts consideration of a corticosteroid-responsive meningoencephalomyelitis termed autoimmune GFAP astrocytopathy.1

Autoimmune Glial Fibrillary Acidic Protein (Gfap) Astrocytopa-Thy Accompanied with Reversible Splenial Lesion Syndrome (RESLES): A Case Report and Literature Review

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy usually presents as meningoencephalomyelitis. Many patients developed flu-like symptoms preceding the neurologic symptoms. Reversible lesion in the splenium of the corpus callosum (SCC) is a clinical and radiological syndrome secondary to many kinds of etiologies, including infections, which is termed RESLES. we reported a case developing irregularly high fever, both temporal pain, low limbs fatigue with frequent urination admitted to our neurology department. CSF test showed GFAP-IgG positive, elevated WBC counts and protein, with low glucose and chlorine, while MRI showed a reversible lesion on SCC, leading us to diagnose autoimmune GFAP autocytopathy accompanied with RESLES. The boy had significantly improved after anti-virus and steroids therapy. Autoimmune GFAP autocytopathy accompanied with RESLES is rarely seen, and pathogenesis for the co-existence has not been clarified. Autoimmune GFAP autocytopathy and RESLES are both related to viral infection. Our case covered infectious symptoms and improved after antiviral treatment, suggesting virus infection may perform a key role in pathogenesis.

Autoimmune glial fibrillary acidic protein astrocytopathy associated with breast cancer: a case report

BackgroundAutoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is an autoimmune inflammatory central nervous system disorder characterized by the detection of autoantibodies that recognize GFAP in CSF. The pathogenesis of GFAP-A is poorly understood. Some patients had a neoplasm detected and GFAP expressed by neoplasms is plausible as immunogen triggering paraneoplastic neurological autoimmunity.Case presentationWe report a case of 76-year-old female patient with GFAP-A complicated with breast cancer. She presented with altered consciousness, nuchal rigidity, speech disturbances, and weakness. Her clinical symptoms were improved by immunotherapy and cancer treatments. Immunohistochemical analysis showed that the restricted tumor expressed GFAP. The infiltration of CD3 + T cells were observed in the peritumoral and intratumoral areas. The most common infiltrating lymphocytes were CD8 + T cells. CD4 + T cells and CD20 + B cells were also observed in the predominant peritumoral area.ConclusionsThese results suggest that GFAP-A may occur in a paraneoplastic neurological syndrome associated with breast cancer.

Detection and significance of glial fibrillary acidic protein antibody in autoimmune astocytopathy and related diseases

: Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is an antibody-related astrocytic disease for which a specific GFAP antibody serves as a biological marker. Indeed, cerebral spinal fluid positive and/or seropositivity for GFAP is an important basis for its diagnosis. However, because patients with autoimmune encephalitis or demyelinating diseases can have a similar antibody profile, termed overlapping autoimmune syndrome, it remains a challenge for clinicians to diagnose and suitably classify autoimmune GFAP-A. To further understand the significance of GFAP antibody detection in neuroimmune diseases, this article discusses GFAP antibodies in autoimmune GFAP-A, progress for detection of GFAP antibodies, diagnostic significance of GFAP antibodies in prototypical disease, as well as overlapping syndrome.

Detection and significance of glial fibrillary acidic protein antibody in autoimmune astocytopathy and related diseases.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is an antibody-related astrocytic disease for which a specific GFAP antibody serves as a biological marker. Indeed, cerebral spinal fluid positive and/or seropositivity for GFAP is an important basis for its diagnosis. However, because patients with autoimmune encephalitis or demyelinating diseases can have a similar antibody profile, termed overlapping autoimmune syndrome, it remains a challenge for clinicians to diagnose and suitably classify autoimmune GFAP-A. To further understand the significance of GFAP antibody detection in neuroimmune diseases, this article discusses GFAP antibodies in autoimmune GFAP-A, progress for detection of GFAP antibodies, diagnostic significance of GFAP antibodies in prototypical disease, as well as overlapping syndrome.

A case of glial fibrillary acidotic protein (GFAP) meningoencephalitis with rheumatoid arthritis

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an inflammatory disease of the central nervous system (CNS), which affects various regions in the CNS, presenting by variable clinical manifestations. Meningoencephalitis is the most common clinical presentation and association with autoimmune disorders has been reported in about 20% of these patients. Diagnosis is confirmed by the presence of CSF or serum immunoglobulin-G (IgG) against GFAP. The reported case is a 53-year-old woman with the history of long-standing rheumatoid arthritis who first presented with acute-onset dizziness and gait disturbance, periventricular linear and radial enhancement pattern on MRI, and normal CSF analysis, successfully treated with an increase in the dose of oral steroids. After a year she had a subacute-onset, moderate to severe holocephalic headache, normal neurologic examination and CSF analysis, and bilateral diffuse, pachymeningeal, and leptomeningeal enhancement on MRI. According to her Brain MRI imaging with relapsing remitting course steroid responsive ataxia and aseptic meningitis, her serum was tested for GFAP IgG antibodies which was positive. The reported patient is the first in the literature reported pachymeningitis in GFAP astrocytopathy. This case highlights the co-occurrence of rheumatoid arthritis with GFAP-associated astrocytopathy, and expands on the previously reported cases with similar association. This might also suggest a common immune pathogenesis.

Area postrema syndrome with linear enhancement along the surface of the brainstem and fourth ventricle in autoimmune GFAP astrocytopathy

BackgroundGlial fibrillary acidic protein (GFAP) astrocytopathy, a novel autoimmune disease of the nervous system, was first defined in 2016. To our knowledge, area postrema syndrome (APS) with linear enhancement along the surface of the brainstem and fourth ventricle is extremely rare in this disorder.Case presentationA Chinese woman presented with intractable nausea and vomiting after onset of flu-like symptoms. Brain magnetic resonance imaging (MRI) disclosed abnormal signal intensities in the dorsal medulla oblongata including area postrema. Besides, linear enhancement surrounding the surface of the brainstem and fourth ventricle was visualized after gadolinium injection. Cerebrospinal fluid (CSF) analysis showed increased cell count and protein. A cell-based assay was positive for anti-GFAP IgG in CSF. She was diagnosed with autoimmune GFAP astrocytopathy and treated with high-dose glucocorticoid. The patient received a quick recovery with entire resolution of the initial abnormalities.ConclusionsIsolated APS can be the initial manifestation of autoimmune GFAP astrocytopathy. Linear enhancement surrounding the surface of the brainstem and fourth ventricle is another neuroradiological hallmark.

Glial fibrillary acidic protein astrocytopathy and tuberculous meningoencephalitis occurring in a patient with Legionella pneumonia: a case report

BackgroundAutoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently identified recurrent meningoencephalomyelitis with GFAP immunoglobulin G presence in the serum or cerebrospinal fluid (CSF) as a specific biomarker. GFAP astrocytopathy is closely associated with the occurrence of some tumors and often coexists with other antibodies, such as the N-methyl-D-aspartate receptor and aquaporin-4 antibodies. However, GFAP astrocytopathy complicated by central nervous system infection is rare.Case presentationHere, we present the case of a patient admitted to a local hospital due to a prominent fever and cough. The patient had a 1-month history of headaches before admission that were not considered serious at the time. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid revealed a high sequence number of Legionella pneumophila and a few mycobacteria. His cough and fever improved significantly after antibiotic treatment. Still, a slight headache remained. Subsequently, his condition worsened, and he visited our hospital with a disturbance of consciousness. Mycobacterium tuberculosis was detected with mNGS of the CSF, while the CSF and serum were also positive for GFAP antibodies. Following anti-tuberculosis and steroid therapy, the patient’s symptoms improved, and he tested negative for the GFAP antibody.ConclusionThis is the first reported case of GFAP astrocytopathy complicated by tuberculous meningoencephalitis. Due to overlaps in the clinical manifestations of the two diseases, GFAP astrocytopathy is sometimes misdiagnosed as tuberculous meningoencephalitis. Therefore, in addition to ensuring careful identification of the two diseases, clinicians need to be aware of their possible co-existence.

Delayed Appearance of Brain Magnetic Resonance Imaging Abnormalities in a Patient with Glial Fibrillary Acidic Protein Astrocytopathy.

Recent studies have reported that autoantibodies against glial fibrillary acidic protein (GFAP), a major cytoskeletal protein expressed in astrocytes, can lead to GFAP astrocytopathy, an autoimmune central nervous system inflammatory disease. We herein report the unique case of a 59-year-old Japanese woman with GFAP astrocytopathy who presented with characteristic symptoms, including signs of meningeal irritation, cerebellar ataxia, and bladder/rectal dysfunction, in the absence of specific findings on initial brain magnetic resonance imaging (MRI). The patient exhibited new abnormal changes mainly in the brainstem on follow-up MRI, illustrating the need to recognize that MRI abnormalities may appear later in GFAP astrocytopathy.

A case report of autoimmune GFAP astrocytopathy presenting with abnormal heart rate variability and blood pressure variability

BackgroundAutonomic dysfunctions including bladder dysfunction, gastrointestinal dysfunction and orthostasis are common symptoms of autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A); however, cardiac autonomic dysfunction and abnormal circadian rhythm of blood pressure, which can lead to poor prognosis and even sudden cardiac death, has never been reported in A-GFAP-A patient.Case presentationA 68-year-old male Chinese patient presented to our hospital with headache, fever, progressive disturbance of consciousness, dysuria, and limb weakness. Abnormal heart rate variability and non-dipper circadian rhythm of blood pressure gradually developed during hospitalization, which is rare in A-GFAP-A. He had positive GFAP IgG in cerebrospinal fluid (CSF). Enhanced brian MRI showed uneven enhancement and T2 hyperintense lesions of medulla oblongata; Cervical spine MRI showed T2 hyperintense lesions in medulla oblongata and upper margin of the T2 vertebral body. A contrast-enhanced thoracic spine MRI showed uneven enhancement and T2 hyperintense lesions of T1 to T6 vertebral segments. After treatment with intravenous immunoglobulin and corticosteroids, the patient’s symptoms, including autonomic dysfunction, alleviated dramatically. Finally, his heart rate variability and blood pressure variability became normal.ConclusionsOur case broadens the spectrum of expected symptoms in A-GFAP- A syndromes as it presented with heart rate variability and blood pressure variability.

Clinical features of autoimmune glial fibrillary acidic protein astrocytopathy in children: an analysis of 34 cases

To study the clinical features of children with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). A retrospective analysis was performed on the medical data of 34 children with GFAP-A who attended the Department of Neurology, Children's Hospital of Chongqing Medical University, from January 2020 to February 2022. The medical data included clinical manifestations, cerebrospinal fluid features, imaging examination results, treatment, and prognosis. The median age of onset was 8.4 (range 1.9-14.9) years for the 34 children with GFAP-A. The main clinical manifestations included headache (50%, 17/34), fever (47%, 16/34), visual impairment (47%, 16/34), and disturbance of consciousness (44%, 15/34). Abnormal cerebrospinal fluid results were observed in 19 children (56%, 19/34), among whom 8 children had positive autoantibody. The children with overlap syndrome had significantly higher recurrence rate and rate of use of immunosuppressant than those without overlap syndrome (P<0.05). About 77% (24/31) of the children had good response to immunotherapy, and only 1 child had poor prognosis. Children with GFAP-A often have non-specific clinical symptoms and show good response to immunotherapy. Children with overlap syndrome have a high recurrence rate, and early application of immunosuppressants may help to prevent recurrence and alleviate symptoms.