Clinical analysis of pediatric recurrent autoimmune glial fibrillary acidic protein astrocytopathy

Clinical analysis of pediatric recurrent autoimmune glial fibrillary acidic protein astrocytopathy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical analysis of pediatric recurrent autoimmune glial fibrillary acidic protein astrocytopathy Hongjun Fang, Wenjing Hu, Xiao Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4537423/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective To examine the clinical characteristics, treatment, and prognosis of recurrent autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). Methods The data of 17 pediatric patients with recurrent autoimmune GFAP-A who were treated in the neurology department of Hunan Children’s Hospital from January 2015 to January 2024 were collected, and the clinical presentation, laboratory tests, neuroradiology results, electroencephalograms, treatment regimens, and prognosis of these patients were retrospectively analyzed and summarized. Results These 17 patients included 6 males and 11 females. A total of 28 recurrences occurred, with a median of 1 (1, 2) recurrence per patient. Patients experienced 1–5 symptoms on recurrence, with 3 recurrences exhibiting new symptoms. The median number of symptoms at recurrence was 1 (1, 2), with a median mRS score at recurrence of 3 (2, 4) and a median length of hospitalization of 10 (8, 16) days per recurrence episode. The mean number of symptoms, mRS, and length of hospitalization at recurrence were all lower than at initial disease onset (P < 0.05). The serum GFAP antibody positivity rate was 50% and the cerebrospinal fluid GFAP antibody positivity rate was 14.3% at recurrence. The cerebrospinal fluid abnormality rate was 28.6% at recurrence. Abnormal electroencephalograms were observed in 14 (50%) recurrences. There were 16 (57.1%) recurrences with an increased number of lesions visible on head MRI compared with pre-recurrence levels, while there were 8 (66.7%) recurrences with an increased number of lesions visible on spinal cord MRI compared with pre-recurrence levels. First-line immunotherapy was used at initial disease onset with second-line immunotherapy used only in 1 patient. Second-line immunotherapy was used in 11 recurrences. Conclusion Pediatric GFAP-A tends to recur. The condition at recurrence is milder than at initial disease onset. In most cases, the symptoms seen at recurrence are among those that occurred at initial onset, while new symptoms may occur on recurrence in a small number of patients. In addition to new symptoms and disease worsening during recurrence, abnormal antibody levels, cerebrospinal fluid routine biochemistry test results, electroencephalography results, and radiology findings may also be observed. First-line immunotherapy or long-term combined second-line immunotherapy can be used during recurrence. recurrence autoimmune glial fibrillary acidic protein astrocytopathy immunotherapy GFAP-A pediatrics Figures Figure 1 1. INTRODUCTION Glial fibrillary acidic protein astrocytopathy (GFAP-A) is an autoimmune disease of the central nervous system that was first proposed by Fang et al. [ 1 ] from the Mayo Clinic in 2016. GFAP-A lesions can involve the meninges, brain, spinal cord, and optic nerve, and the main clinical presentation is meningoencephalomyelitis. Currently, GFAP-IgG is regarded as a specific biomarker for this disease. The localization characteristics of intracellular antigens in astrocytes suggest that the pathogenesis may be due to a GFAP-specific cytotoxic T-cell-centered immune response and not due to the direct effects of GFAP-IgG [ 2 ]. Most patients are sensitive to glucocorticoids, and rapid improvements in clinical symptoms and radiologic presentation can be achieved after glucocorticoid treatment [ 3 ]. Studies have shown that this disease can recur in at least 20% of patients, and these individuals require long-term immunotherapy. A minority of patients also have poor outcomes [ 4 ]. Currently, only the proportion of recurrence or simple descriptions of recurrence have been seen in the literature when discussing the clinical presentation of patients with recurrent autoimmune GFAP-A, and there have not been any studies focused on the clinical characteristics of recurrent GFAP-A. This study summarizes the clinical characteristics of 17 pediatric patients experiencing recurrent autoimmune GFAP-A to provide guidance for active recognition of recurrent GFAP-A and its clinical treatment. 2 MATERIALS AND METHODS 2.1 Study participants In patients with autoimmune GFAP-A who were treated in the neurology department of Hunan Children’s Hospital from January 2015 to January 2024, 17 experienced recurrent autoimmune GFAP-A. Inclusion criteria were as follows: ① Age at diagnosis ≤ 18 years; ② Positive cerebrospinal fluid or serum GFAP-IgG results in a cell-based assay (CBA); ③ Patients who were diagnosed with autoimmune encephalitis, central nervous system demyelinating disease, or other central nervous system autoimmune diseases on screening; ④ Patients with recurrence as defined by new symptoms or worsening at least 2 months after improvement or stabilization; and ⑤ The pediatric patient and his/her family members provided informed consent for this study. Exclusion criteria were as follows: ① Cerebrospinal fluid and serum GFAP-IgG were both negative; ② Comorbid central nervous system space-occupying lesions, hypoxic-ischemic encephalopathy, psychiatric disorders, or stroke; or ③ Insufficient data to meet the needs of the study. 2.2 Data collection The clinical data of the 17 pediatric patients was retrospectively collected, including demographic characteristics, clinical symptoms, magnetic resonance imaging (MRI) results, electroencephalography results, cerebrospinal fluid (CSF), serum, and CSF antibody test results, chest, abdominal, and pelvic computed tomography (CT) or ultrasound results, treatment regimens, and prognosis. The modified Rankin scale (mRS) was used for evaluation when the condition of the patient was serious, during discharge, and at the last follow-up. An mRS score ≥ 4 at symptom peak was considered indicative of critical illness, an mRS score ≤ 2 at discharge was indicative of a good prognosis, and an mRS score > 2 was indicative of a poor prognosis [ 5 ]. This study was approved by the ethics committee of Hunan Children’s Hospital. 2.3 Experimental methods A highly specific and sensitive CBA method was used to measure GFAP, MOG, AQP4, NMDAR, AMPA1, AMPA2, LGI1, GABAB, CASPR2, Hu, Yo, Ri, CV2, Recoverin, Gt1a, Gt1b, GQ1b, GM1, GM2, GM3, GD2, and GD3 levels in the serum and/or CSF of pediatric patients. 2.4 Statistical Analysis We used SPSS 24.0 for all analyses. Quantitative data that were normally distributed are presented as the mean ± standard deviation, while those that were non-normally distributed are presented as the median. Nonparametric test for two correlated samples were used to compare the differences in the number of symptoms, mRS, and length of hospitalization between at recurrence and initial diagnosis. In addition, qualitative data are presented as the number of patients (percentage). 3 Results 3.1 General condition Out of 60 pediatric patients with autoimmune GFAP-A, 17 (28.3%, 17/60) experienced recurrence, of whom 6 were male and 11 were female. The mean age of onset was 6.1 ± 3.7 years (range: 2 years to 13 years and 2 months). Of these patients, 9 had meningoencephalitis, 5 had encephalomyelitis, 2 had optic neuritis, and 1 had encephalitis and Guillain-Barré syndrome. The follow-up time ranged from 1.1 to 5.8 years, with a mean follow-up duration of 3.4 ± 1.4 years. Five patients had a history of respiratory tract infection 1–2 weeks before disease onset, and herpes simplex virus type I was detected in 2 patients. See Table 1 . Table 1 Summary of the general conditions in patients with GFAP Astrocytopathy. Feature incidence Males: females 6:11 Age at onset (years) 6.1 ± 3.7 Age at follow-up (years) 3.4 ± 1.4 Meningoencephalitis 9/17(52.45) Encephalomyelitis 5/17(29.4%) Optic neuritis 2/17(11.8%) Encephalitis and Guillain-Barré syndrome 1/17(5.9%) 3.2 Clinical presentation and treatment 3.2.1 Clinical presentation and treatment at initial onset Presenting symptoms at initial onset were as follows: 7 patients had fevers, 5 had epileptic seizures, 4 had headaches, 4 had decreased consciousness, 3 had visual impairment, 3 had psychiatric and behavioral abnormalities, 2 had ophthalmalgia, 2 exhibited paralysis, 1 exhibited memory decline, 1 was affected by vomiting, and 1 presented with ataxia. Patients exhibited 1–8 main symptoms (mean: 4.5 ± 2.5), including psychiatric and behavioral symptoms in 13 patients, paralysis in 12 patients, epileptic seizures in 12 patients, fevers in 10 patients, headaches in 10 patients, decreased consciousness in 10 patients, visual impairment in 5 patients, ophthalmalgia in 3 patients, bulbar paralysis in 3 patients, peripheral facial palsy in 2 patients, autonomic impairment in 2 patients, urinary retention in 2 patients, involuntary movements in 2 patients, ataxia in 1 patient, cognitive decline in 1 patient, memory decline in 1 patient, respiratory failure in 1 patient, and vomiting in 1 patient. Of these patients, 5 were admitted to the ICU for treatment. There were 11 patients with mRS scores of 4–5 and 6 patients with mRS scores of 2–3, for a mean mRS score of 3.9 ± 0.9. For treatment, 11 patients received pulse steroid therapy + intravenous gamma globulin treatment, of whom 3 received additional anticonvulsant treatment; 4 received pulse steroid therapy alone, of whom 1 received additional anticonvulsant treatment; 1 received intravenous gamma globulin treatment alone; 1 received pulse steroid therapy + gamma globulin + rituximab treatment. The length of hospitalization was 9–47 days and the median length of hospitalization was 19 (13, 25) days. The prognosis of 10 pediatric patients was good on discharge, with mRS scores of 0–2, whereas 7 patients exhibited a poor prognosis, with sequelae and mRS scores of 3–5. The median mRS score at discharge was 1.9 ± 1.5. See Table 2 . Table 2 Summary of the clinical presentation and treatment at initial onset in patients with GFAP astrocytopathy. Feature Incidence First symptoms Fevers 7/17(41.2%) Epileptic seizures 5/17(29.4%) Headaches 4/17(23.5%) Decreased consciousness 4/17(23.5%) Visual impairment 3/17(17.6%) psychiatric and behavioral abnormalities 3/17(17.6%) Ophthalmalgia 2/17(11.8%) Paralysis 2/17(11.8%) Memory decline 1/17(5.9%) Vomiting 1/17(5.9%) Ataxia 1/17(5.9%) Main symptoms Psychiatric and behavioral symptoms 13/17(76.5%) Paralysis 12/17(70.6%) Epileptic seizures 12/17(70.6%) Fevers 10/17(58.8%) Headaches 10/17(58.8%) Decreased consciousness 10/17(58.8%) Visual impairment 5/17(29.4%) Ophthalmalgia 3/17(17.6%) Bulbar paralysis 3/17(17.6%) Peripheral facial palsy 2/17(11.8%) Autonomic impairment 2/17(11.8%) Urinary retention 2/17(11.8%) Involuntary movements 2/17(11.8%) Ataxia 1/17(5.9%) Cognitive decline 1/17(5.9%) Memory decline 1/17(5.9%) Respiratory failure 1/17(5.9%) Vomiting 1/17(5.9%) Admitted to ICU 5/17(29.4%) Therapy Pulse steroids + gamma globulin 11/17(64.7%) Pulse steroids 4/17(23.5%) Gamma globulin 1/17(5.9%) Pulse steroids + gamma globulin + rituximab 1/17(5.9%) 3.2.2 Clinical presentation and treatment of recurrence (1) Recurrence frequency and pre-recurrence immunotherapy were as follows: 17 patients experienced 28 episodes of recurrence. The number of recurrences per patient ranged from 1–7, with a median of 1 (1, 2). Of these patients, 12 experienced a single recurrence, while 5 (29.4%) experienced multiple (2 or more) recurrences. The interval to recurrence ranged from 2 months to 3 years, with a median of 7 (3, 13) months. Pre-recurrence immunotherapy was as follows: 12 recurrences occurred after immunotherapy was discontinued, 13 occurred during dose reduction of steroid therapy alone, and oral methotrexate and azathioprine were used before recurrence for 1 recurrence each. (2) Symptomatology of recurrence was as follows: 4 recurrences exhibited symptoms of respiratory tract infections before recurrence, with influenza A virus having been detected in 1 recurrence. With respect to the initial symptoms at recurrence, 9 recurrences showed visual impairment, 8 showed epileptic seizures, 8 showed paralysis, 5 showed urinary retention, 3 showed fevers, 3 showed ataxia, 2 showed involuntary movements, 1 showed paresthesia, 1 showed peripheral facial palsy, 1 showed ophthalmalgia, and 1 showed a headache. Patients presented with 1–5 main symptoms at recurrence, with a single symptom in 4 recurrences and multiple (2 or more) symptoms in 24 recurrence episodes. In addition, 3 recurrencess exhibited new symptoms, while in the remaining recurrences the symptoms at recurrence were generally in line with the symptoms at the first occurrence. The median number of symptoms at recurrence was 1 (1, 2) and mRS score ranged from 1 to 5 with a median of 3 (2, 4). These were lower than the mean number of symptoms (P < 0.05, Z = 2.794) and mRS scores (P < 0.05, Z = 2.946) at initial disease onset. No patients were admitted to the ICU during recurrence. The condition at recurrence was less severe than at initial onset in 12 recurrences and the severity of recurrence was the same as at initial onset in 16 recurrences. (3) Treatment at recurrence were as follows: patients received pulse steroid therapy + intravenous gamma globulin in 16 recurrences, plus rituximab in 5 recurrences and azathioprine in 1. Pulse steroid therapy was given in 9 recurrences, plus methotrexate in 1, mycophenolate mofetil in 1, rituximab in 1, and surgical tumor resection in 1. Rituximab alone (single or multiple doses) was given in 2 recurrences, gamma globulin alone was given in 1, and oral steroids + anticonvulsants therapy was administered in 2 cases. Among these 28 recurrences, anticonvulsants were also administered due to epileptic seizures in 7 recurrences. The length of hospitalization for these recurrences ranged from 4 to 45 days with a median of 10 (8, 16) days, which was lower than the mean length of hospitalization at initial onset (P < 0.05, Z = 3.508). Out of 17 patients, the condition of 12 patients improved after immunotherapy, with mRS scores of 0–2, while 5 patients exhibited mRS scores of 3. These patients had sequelae such as intermittent convulsions, visual impairment, or cognitive decline. See Tables 3 and 4 for further details. Table 3 Summary of the clinical presentation and treatment of recurrence in patients with GFAP astrocytopathy. Feature incidence Recurrence frequency/median 28/1(1,2) Single recurrence 12/17(70.6%) Multiple (2 or more) recurrences 5/17(29.4%) Interval to recurrence/median 2 months to 3 years/7 (3, 13) months First symptoms Visual impairment 9/28(32.1%) Epileptic seizures 8/28(28.6%) Paralysis 8/28(28.6%) Urinary retention 5/28(17.9%) Fevers 3/28(10.7%) Ataxia 3/28(10.7%) Involuntary movements 2/28(7.1%) Paresthesia 1/28(3.6%) Peripheral facial palsy 1/28(3.6%) Ophthalmalgia 1/28(3.6%) Headache 1/28(3.6%) Therapy Pulse steroids + gamma globulin 10/28(35.7%) Pulse steroids + gamma globulin + rituximab 5/28(17.9%) Pulse steroids + gamma globulin + azathioprine 1/28(3.6%) Pulse steroids 3/28(10.7%) Pulse steroids + methotrexate 1/28(3.6%) Pulse steroids + mycophenolate mofetil 1/28(3.6%) Pulse steroids + rituximab 1/28(3.6%) Pulse steroids + surgical tumor resection 1/28(3.6%) Rituximab 2/28(7.1%) Gamma globulin 1/28(3.6%) Oral steroids + anticonvulsants 2/28(7.1%) Table 4 Comparison of the number of main symptoms, length of hospitalization, and mRS between initial disease onset and recurrent onset in patients with GFAP astrocytopathy. Initial onset (n = 17) recurrent onset (n = 28) Z P The number of main symptoms 4.47 ± 2.53 1(1,2) 2.794 0.005 Length of hospitalization 19(13,25) 10(8,16) 3.508 0.000 mRS 3.88 ± 0.93 3(2,4) 2.946 0.003 3.3 Serum/CSF test results The serum GFAP antibodies of 17 patients were all positive (100%) at initial onset, with 11 also being positive for CSF antibodies (64.7%). Seven patients had other overlapping antibodies, such as MOG antibodies in 4 patients, GM1 IgM and GM2 IgM antibodies in 1 patient, AQP4 antibodies in 1 patient, and NMDA antibodies in 1 patient. Of the 28 recurrences, serum antibodies were tested in 22 and CSF antibodies were tested in 7. In these tests, positive serum GFAP antibody results were observed in 11 (50%) recurrences, including 9 recurrences with higher antibody titers than when these patients were first discharged, and 1 recurrence with serum positivity for anti-recoverin antibody. One recurrence had positive CSF GFAP antibody results (14.3%), with the antibody levels higher than the level at discharge. The serum and CSF antibody positivity rates at recurrence were all lower than at initial onset. CSF tests were completed in all patients at initial onset, with 13 having abnormal CSF test results that presented as elevated white blood cell counts or protein levels. These included 12 patients with elevated white blood cell counts in the range of 14–360*10 6 /L and a median white blood cell count of 35*10 6 /L (2*10 6 /L, 72*10 6 /L), with mononuclear cell elevation being the predominant form. Only 3 patients had elevated CSF protein levels of 1.56, 0.595, and 0.94 g/L. CSF tests were performed only for 7 recurrences, of which 2 had abnormal CSF test results, which presented as elevated white blood cell counts of 28*10 6 /L and 40*10 6 /L. See Table 5 for further details. Table 5 Summary of auxiliary examination results at initial onset and recurrence in patients with GFAP astrocytopathy. Initial onset (n = 17) Recurrent onset (n = 28) Serum GFAP antibodies 17/17(100%) 11/22(50%) CSF GFAP antibodies 11/17(64.7%) 1/7(14.3%) Abnormal CSF tests 13/17(76.5%) 2/7(28.6%) EEG findings Abnormal 10/17(58.8%) 14/28(50%) Slow wave background 10/17(58.8%) 13/28(46.4%) Epileptiform waves 5/17(29.4%) 5/28(17.9%) Focal seizures 2/17(11.8%) 1/28(3.6%) NCSE 1/17(5.9%) 0 Electrographic seizures 2/17(11.8%) 1/28(3.6%) Spasms, tonic seizures, and myoclonic seizures 0 1/28(3.6%) Neuroimaging Abnormal brain 12/17(70.6%) 22/28(78.6%) Abnormal spinal cord 6/16(37.5%) 9/12(75%) Abnormal optic nerve 6/17(35.3%) 4/28(14.3%) Enhancement 8/17(47.1%) 4/28(14.3%) 3.4 Electroencephalography results Electroencephalography was completed in 17 patients at initial onset, of whom 7 had normal electroencephalograms and 10 had abnormal electroencephalograms (58.8%). Among patients with abnormal electroencephalograms, 10 had background slowing, with slow waves mainly being located in the parietal, occipital, and temporal lobes or were diffuse. Five had epileptiform waves, with focal seizures having been detected in 2 patients, while nonconvulsive status epilepticus (NCSE) was detected in 1 patient, and electrographic seizures (Fig. 1 ) were detected in 2 patients. Electroencephalography was completed in all 28 recurrences, with 14 normal electroencephalograms and 14 abnormal electroencephalograms (50%). Among the abnormal electroencephalograms, 13 had background slowing, 5 had epileptiform waves, 1 had focal seizures, 1 had electrographic seizures, and 1 had spasms, reflex tonic seizures, and reflex myoclonic seizures. The magnitude of electroencephalography slowing in the 13 recurrences was lower than at the initial onset. See Table 5 for further details. 3.5 Radiologic results Head MRI scans were completed in 17 patients and spinal cord MRI scans were completed in 16 patients at initial onset. Among these patients, 6 exhibited head MRI abnormalities, 2 exhibited head + spinal cord MRI abnormalities, 4 exhibited head + spinal cord + optic nerve MRI abnormalities, and 2 exhibited optic nerve MRI abnormalities only. Lesions detected via head MRI included 1–10 involvement sites principally located in the frontal (7 cases), parietal (7 cases), occipital (5 cases), and temporal (5 cases) areas, but also in the brain stem (5 cases), thalamus (4 cases), periventricular area (4 cases), basal ganglia (3 cases), corpus callosum (2 cases), and cerebellum (2 cases). Lesions detected by spinal MRI included 1–13 spinal cord segments, involving the thoracic spinal cord (2 cases), cervical spinal cord (2 cases), thoracolumbar spinal cord (1 case), cervical thoracic spinal cord (1 case), and anterior root of spinal cord nerve (1 case). Among these 17 pediatric patients, 8 exhibited image enhancement, including 3 cases of sulcus enhancement, 3 of intracranial lesion enhancement, 2 of brain meningeal enhancement, 2 of spinal cord lesion enhancement, 1 of spinal meningeal enhancement, 2 of spinal cord anterior root enhancement, and 1 of optic nerve enhancement. The enhanced lesions were cord-like, gyrus-like, patchy, annular, and diffuse. Head MRI scans were completed in all 28 recurrences, with 10 having exhibited normal head MRI scans before recurrence and 18 exhibiting fewer lesions on head MRI scans. In six recurrences the patients presented with normal head MRIs. There were no significant changes in lesions compared with pre-recurrence findings in 6 recurrences, while in 16 (57.1%, 16/28) recurrences there were more lesions relative to pre-recurrence levels, including 7 (43.5%, 7/16) with the reappearance of some of the original lesions that had disappeared following treatment and 9 (56.2%, 9/16) with new lesions. Spinal cord MRI examinations were conducted for 12 of the 28 recurrences. Three showed normal spinal cord MRIs. There were no significant changes in lesions compared with pre-recurrence findings in 1 recurrence, while 8 (66.7%, 8/12) exhibited an increased number of lesions compared with pre-recurrence findings, including 6 (75%, 6/8) with the reappearance of some original lesions that had disappeared following treatment and 2 (25%, 2/8) with new lesions. Among the 28 recurrences, 4 had abnormal optic nerve images, with new optic nerve lesions having been observed in 1 recurrence. Four out of the 28 recurrences exhibited enhancement, including 2 with lesion enhancement, 1 with cord-like enhancement in the cerebral fissure, and 1 with optic nerve enhancement. See Table 5 for further details. 4 Discussion GFAP-A is an autoimmune disease of the nervous system that was first defined in 2016 [ 1 , 6 ]. Currently, there is a lack of epidemiological study data related to this conduction. A study in Minnesota calculated that the overall incidence is 0.6/100,000, which is similar to that of autoimmune NMDAR encephalitis [ 7 ]. Iorio et al. [ 8 ] found that this disease accounts for 5% of immune diseases of the nervous system, indicating that it is not rare. The number of cases of GFAP-A recurrence has been increasing due to a rise in the overall number of confirmed GFAP-A cases and longer follow-up duration. Currently, only the proportion of recurrence has been reported when describing the clinical presentation of relapsed autoimmune GFAP-A and there have not been any studies focused on the clinical characteristics of recurrent GFAP-A. Liu et al. reported that recurrence occurred in 21% (5/24) of patients [ 9 ]. Li et al. [ 10 ] reported that 2 out of 15 pediatric GFAP-A patients developed recurrences at 8 months and 7 months after discharge. In the present study, a total of 17 patients experienced recurrence with a recurrence rate of 28.3%. There were 5 patients with multiple recurrences, accounting for 29.4% of all patients with recurrence. The interval to recurrence was 2 months to 3 years, with a median of 7 (3, 13) months. The initiating factors for recurrence are still unknown. Two Mayo Clinic studies found that 29–39% of autoimmune GFAP-A patients have flu-like symptoms before disease onset [ 2 , 6 ]. A case report described a patient who had a herpes simplex infection 5 months before the onset of symptoms [ 8 ], suggesting that viral infection may be a cause that triggers autoimmune responses. In this study, 5 patients had a history of respiratory tract infections 1–2 weeks before disease onset and herpes simplex virus type I was detected in 2 patients. In 4 recurrences, the patients had symptoms of respiratory tract infections before disease onset, with influenza A virus having been detected in 1 patient. At present, the relationship between viral infection and initial disease onset and recurrence cannot be determined as there are very few cases. Additionally, most pediatric patients do not have a definite history of past infectious disease before disease onset. With respect to risk factors associated with recurrence, one study found that a rapid decrease in steroid dose was associated with recurrence in some patients [ 9 ]. In this study, 12 recurrences were after immunotherapy and steroid treatment were discontinued, 13 recurrences were during dose reduction of steroid therapy alone, and only in 2 episodes the patients took oral methotrexate or azathioprine before recurrence. This suggests that GFAP-A recurrence tends to occur during dose reduction or discontinuation of steroids and other immunotherapies. Further research is required to determine whether appropriate extension of steroid and immunotherapy treatment duration or decreasing the speed of dose reduction can decrease the recurrence rate. One study also found that patients with overlap syndrome are prone to recurrence [ 10 ]. In this study, 47.1% (8/17) of the patients had overlapping antibodies, which were detected at initial onset and during recurrence. Out of 17 patients, 4 had MOG antibodies, 1 had GM1 IgM and GM2 IgM antibodies, 1 had AQP4 antibodies, and 1 had NMDA antibodies. The patient with overlapping AQP4 antibodies experienced 7 episodes of recurrence. This suggests that patients with overlap syndrome are prone to recurrence, with those with overlapping MOG antibodies being more prone to recurrence, while patients with overlapping AQP4 antibodies are prone to more instances of recurrence. Determination of GFAP-A recurrence is dependent on symptomology observations. In our study, the main symptoms of initial GFAP-A onset included psychiatric and behavioral abnormalities, epileptic seizures, impaired consciousness, fevers, headaches, and visual impairment. The main symptoms of recurrence included visual impairment, epilepsy, paralysis, urinary retention, and fevers. In most recurrences the patients had some of the same symptoms as experienced at initial onset while a few patients (10.7%, 3/28) developed new symptoms that were different from those at initial onset. The number of symptoms at recurrence was significantly lower than that at initial onset and severity was milder than that at initial onset. The reason for these milder symptoms at recurrence compared with initial onset is still unknown. One study reported that GFAP-specific T cells participate in the pathogenesis of GFAP-A. Memory CD8 + T cells are critical participants in the adaptive immune response and provide rapid protection against previously encountered pathogens during recurrence [ 11 ], which may explain why symptoms are milder during recurrence than at initial onset. In addition to the observation of clinical symptoms, antibody testing and other auxiliary examinations are helpful for diagnosing GFAP-A recurrence. In this study, the serum GFAP antibody positivity rate was 50% and the CSF GFAP antibody positivity rate was 14.3% at recurrence. The reason for the lower CSF positivity rate relative to the serum positivity rate may be related to the fact that most family members refuse lumbar puncture during recurrence and there were fewer CSF test samples. At initial onset, 76.5% of patients had CSF abnormalities, which primarily consisted of elevated white blood cell counts with a median count of 35*10 6 /L (2*10 6 /L, 72*10 6 /L). During recurrence, 28.6% had CSF abnormalities and only 2 out of 7 patients presented with elevated white blood cell counts of 28*10 6 /L and 40*10 6 /L. There have been few studies reporting on the electroencephalogram findings from GFAP-A patients. Theroux et al. [ 12 ] previously reported extreme delta brush (EDB) in the electroencephalogram of a pediatric GFAP-A patient and this patient was positive for anti-NMDA receptor antibody. EDB and other specific abnormal electroencephalography changes were not observed in this study. Instead, most of the present electroencephalograms showed non-specific changes at initial onset or recurrence, with diffuse or focal slow wave activity in various leads. Some patients had focal epileptiform discharge or normal electroencephalograms and epileptic seizures, NCSE, and electrographic seizures were even monitored in a few patients. We found that the magnitude of electroencephalography slowing was lower at recurrence than at initial onset, suggesting that although there was slowing of the background electroencephalography rhythm at recurrence, it was not as slow as that at initial onset. This is consistent with the fact that symptoms at recurrence are milder than at initial onset. Therefore, antibody, CSF routine biochemical, and electroencephalography examinations are important for evaluating recurrence during follow-up. Oncological evaluation is an important aspect of recurrent GFAP-A management and comprehensive tumor screening is required in patients in whom tumors are not found at initial onset. Attention should still be paid to the possibility of tumor recurrence even in patients with past tumors that have been resected. Flanagan et al. [ 6 ] mentioned that around 34% of patients may have comorbid tumors and 66% of patients develop new tumors within 2 years of the occurrence of related neurological symptoms. Dalmau et al. [ 13 ] pointed out that these tumors may contain nervous tissues or express neuronal proteins that are targeted by antibodies. Apoptotic tumor cells release these ectopically expressed neuronal proteins, which undergo uptake and processing as antigens by antigen-presenting cells in regional lymph nodes and are then presented to the immune system to induce anti-tumor immune responses. In this study, retroperitoneal ganglioneuroma was found after the second recurrence in only 1 patient at 1 year and 4 months after initial onset. Symptoms did not recur within 4 years of follow-up after tumor resection. In this study, the incidence of tumors in recurrent GFAP-A was 5.9%. With respect to radiology, studies have shown that MRI analyses of GFAP-A patients show multiple lesions involving sites such as the cerebral white matter, basal ganglia, hypothalamus, brain stem, and cerebellum [ 6 ]. Around 50% of patients present with vascular, radiating linear enhancement extending from the lateral ventricles [ 14 ]. Of our patients, 8 patients with enhanced lesions showed enhancement in the sulcus, intracranial lesions, brain meninges, spinal cord lesions, spinal cord meninges, anterior root of the spinal cord, and optic nerve. These enhanced lesions were cord-like, gyrus-like, patchy, annular, and diffuse. This was different from radiating linear enhancement beside the lateral ventricles mentioned in previous studies of adult GFAP-A. Two patients had meningeal enhancement, which is rare in autoimmune encephalitis. As GFAP participates in the formation of the blood-brain barrier, abnormal leptomeningeal enhancement may be caused by disruption of the blood-brain barrier and vascular wall injury, leading to contrast agent exudation [ 15 , 16 ]. In this study, lesions were increased in head MRI scans from 57.1% of the recurrences compared with pre-recurrence levels, of which 43.8% of the recurrences exhibited the enlargement of the original lesions while 56.2% presented with new lesions. In spinal cord MRI, 66.7% of the recurrences presented with increased lesions compared with pre-recurrence levels, of which 75% exhibited the enlargement of the original lesions while 25% developed new lesions. This demonstrates that active radiologic evaluation is important in diagnosing recurrence patients. Currently, there is no unified treatment standard for autoimmune GFAP-A. Existing related studies have indicated that the treatment methods for this disease include glucocorticoids, IVIG, plasmapheresis, and immunosuppressants [ 17 ]. Most patients showed improvements in clinical symptoms after undergoing corticosteroid and IVIG treatment. In this study, first-line immunotherapy was used at initial onset and second-line immunotherapy was only used in one patient due to disease exacerbation. Overall, 92.9% of the recurrences in this study occurred during steroid discontinuation or dose reduction. This shows that the steroid treatment course should not be too short and that dose reduction should not be too rapid. However, there is no unified standard for the specific treatment course. One study found that the recurrence rate among overlap syndrome patients was higher than among non-overlap syndrome patients. This indicates that glucocorticoid dose reduction in overlap autoimmune syndrome patients should be slower than non-autoimmune overlap syndrome patients and that second-line immunosuppressants should be aggressively used in patients experiencing recurrence [ 18 ]. In this study, repeated use of first-line immunotherapy and aggressive use of long-term second-line immunotherapy were sufficient to control and alleviate the symptoms in most instances of recurrence. In summary, GFAP-A has the potential to recur, and patients in the remission stage should be closely followed up. Clinical symptoms, antibody tests, CSF biochemical markers, electroencephalography, and radiologic examinations are important methods for recurrence evaluation. There should be an emphasis on tumor screening during recurrence and aggressive first-line immunotherapy should be administered. When necessary, additional second-line immunotherapy can be used. Further research on recurrence cases can help reveal the clinical patterns of this disease and improve diagnosis and treatment levels. Declarations Acknowledgements Not applicable. Authors’ contributions F wrote the main manuscipt text and H prepared figures 1 ,Z prepared table 1-5. All authors reviewed the manuscript. Ethical Approval and Consent to participate All experiments were approved by the medical ethics committee of the Hunan Children’s hospital. This retrospective study was approved by the institutional review board. Informed consent was waived due to the retrospective analysis of anonymized data. Consent for publication Not applicable. Availability of data and materials All data generated or analysed during this study are included in this published article. Competing interests The authors declare that they have no competing interests. Funding This work was supported by grants from Natural Science Foundation of Hunan Province (No. 2022JJ70087). References Boyan Fang, Andrew McKeon, Shannon R Hinson, Thomas J Kryzer, Sean J Pittock, Allen J Aksamit, et al. Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA neurology 2016;73(11):1297–1307 doi: 10.1001/jamaneurol.2016.2549 Divyanshu Dubey, Shannon R Hinson, Evan A Jolliffe, Anastasia Zekeridou, Eoin P Flanagan, Sean J Pittock, et al. Autoimmune gfap astrocytopathy: prospective evaluation of 90 patients in 1 year.Journal of neuroimmunology 2018 08 15;321:157–163 doi: 10.1016/j.jneuroim.2018.04.016 Jun Xiao, Xin Chen, Ke Shang, Yue Tang, Man Chen, Gang Deng, et al. Clinical, neuroradiological, diagnostic and prognostic profile of autoimmune glial fibrillary acidic protein astrocytopathy: A pooled analysis of 324 cases from published data and a single-center retrospective study. Journal of neuroimmunology 2021 11 15;360:577718 doi: 10.1016/j.jneuroim.2021.577718 Amy Kunchok, Anastasia Zekeridou, Andrew McKeonl. Autoimmune glial fibrillary acidic protein astrocytopathy. Current opinion in neurology 2019 06;32(3):452–458 doi: 10.1097/WCO.0000000000000676 Qingmei Huang, Huacai Yang, Tianni Liu, Huiming Xu, Baikeng Chen, Si Liu, et al. Patients with suspected benign tumors and glial fibrillary acidic protein autoantibody: an analysis of five cases. The International journal of neuroscience 2019;129(12):1183–1188 doi: 10.1080/00207454.2019.1645140 Eoin P Flanagan, Shannon R Hinson, Vanda A Lennon, Boyan Fang, Allen J Aksamit, P Pearse Morris,, et al.Glial fibrillary acid-ic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients.Annals of neurology 2017;81(2):298–309 doi:10.1002/ana.24881[14]Dalmau J, Graus F. Antibody-Mediated Encephalitis [J]. N Engl J Med, 2018, 378(9): 840–851. Divyanshu Dubey, Sean J Pittock,Cecilia R Kelly, Andrew McKeon, Alfonso Sebastian Lopez-Chiriboga, Vanda A Lennon, et al.Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis.Annals of neurology 2018 01;83(1):166–177 doi: 10.1002/ana.25131 Raffaele Iorio, Valentina Damato, Amelia Evoli, Marco Gessi, Simona Gaudino, Vincenzo Di Lazzaro, et al. Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients.Journal of neurology, neurosurgery, and psychiatry 2018 02;89(2):138–146 doi: 10.1136/jnnp-2017-316583 Qiang Liu, Xiao Yang, Jingzi Zhang Bao, Boya Ma, Xiaoyan Niu, Xu Wang, et al. Clinical characteristics of patient with GFAP-IgG: a review of 31 patients from two tertiary referral centers in China.The International journal of neuroscience 2023;:1–12 doi: 10.1080/00207454.2023.2277664 Tianyi Li, Xiujuan Li, Siqi Hong, Li Jiang, Jiannan Ma. Clinical characteristics of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children: A case series of 16 patients.Journal of neuroimmunology 2023 09 15;382:578176 doi: 10.1016/j.jneuroim.2023.578176 Scott J Schatzberg. Idiopathic granulomatous and necrotizing inflammatory disorders of the canine system. The Veterinary clinics of North America. Small animal practice 2010;40(1):101–20 doi: 10.1016/j.cvsm.2009.09.003 Liana M Theroux, Howard P Goodkin, Kristen C Heinan, Mark Quigg, J Nicholas Brenton.Extreme delta brush and distinctive imaging in a pediatric patient with autoimmune GFAP astrocytopathy.Multiple sclerosis and related disorders 2018;26:121–123 doi: 10.1016/j.msard.2018.09.015 Josep Dalmau, Francesc Graus. Antibody-Mediated Encephalitis. Francesc Graus The New England journal of medicine 2018 03 01;378(9):840–851 doi: 10.1056/NEJMra1708712 Grace Tewkesbury, Jae W Song, Christopher M Perrone. Magnetic Resonance Imaging of Autoimmune GFAP Astrocytopathy. Annals of neurology 2021 10;90(4):691–692 doi: 10.1002/ana.26195 Akio Kimura, Akira Takekoshi, Nobuaki Yoshikura, Yuichi Hayashi, Takayoshi Shimohata. Clinical characteristics of autoimmune GFAP astrocytopathy. Journal of neuroimmunology 2019 07 15;332:91–98 doi: 10.1016/j.jneuroim.2019.04.004 Maija Saraste, Svetlana Bezukladova, Markus Matilainen, Marcus Sucksdorff, Jens Kuhle, David Leppert, et al. Increased serum glial fibrillary acidic protein associates with microstructural white matter damage in multiple sclerosis: GFAP and DTI. Multiple sclerosis and related disorders 2021;50:102810 doi: 10.1016/j.msard.2021.102810 Xinguang Yang, Junyan Liang, Qingmei Huang, Huiming Xu, Cong Gao, Youming Long,, et al. Treatment of autoimmune glial fibrillary acidic protein astrocytopathy: follow-up in 7 cases. Neuroimmunomodulation 2017;24(2):113–119 doi: 10.1159/000479948 Jiaqi Ding, Kaixi Ren, Jun Wu, Hongzeng Li, Tangna Sun, Yaping Yan, et al. Overlapping syndrome of MOG-IgGassociated disease and autoimmune GFAP astrocytopathy. Journal of neurology 2020;267(9):2589–2593 doi: 10.1007/s00415-020-09869-2 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4537423","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":317557484,"identity":"587e2d81-de4e-4c50-8530-ad80fe7b21b4","order_by":0,"name":"Hongjun Fang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYBAC9gYEm/FBQkUNYS08BxBsZoMHZ46RpoVN8mELMxFa2M8efvGjxsaeX7r9WkViAxsDf3t3An4tPHlplj3H0pgl55wpu5G4Q4ZB4szZDXi12DPkmBkzsB1mM7iRk3Yj8Qwbg4FELn4tPPxvgFr+HeaxB2opSGxjJkKLRI7xY8a2wxIGEunHGIjU8saMsbcvzUDiRg6zRMKZYzwE/cLDn2P84cc3YIjNSH/48UdFjRx/ey9+LUDAJgHVbQAmCSkHAeYPEJr9ATGqR8EoGAWjYAQCALp3RmMNSaOXAAAAAElFTkSuQmCC","orcid":"","institution":"The Affiliated Children's Hospital of Xiangya School of Medicine ,Central South University（Hunan children’s hospital)","correspondingAuthor":true,"prefix":"","firstName":"Hongjun","middleName":"","lastName":"Fang","suffix":""},{"id":317557486,"identity":"5d620176-4a1e-496c-870c-4cf4ae09c537","order_by":1,"name":"Wenjing Hu","email":"","orcid":"","institution":"The Affiliated Children's Hospital of Xiangya School of Medicine ,Central South University（Hunan children’s hospital)","correspondingAuthor":false,"prefix":"","firstName":"Wenjing","middleName":"","lastName":"Hu","suffix":""},{"id":317557487,"identity":"84c4c812-a47c-4c32-b9fb-8df61915bdb2","order_by":2,"name":"Xiao Zhang","email":"","orcid":"","institution":"The Affiliated Children's Hospital of Xiangya School of Medicine ,Central South University（Hunan children’s hospital)","correspondingAuthor":false,"prefix":"","firstName":"Xiao","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-06-06 05:21:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4537423/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4537423/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59292165,"identity":"973fe66c-ba18-40a6-923c-67ca8b1f3c19","added_by":"auto","created_at":"2024-06-28 18:51:39","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3221039,"visible":true,"origin":"","legend":"\u003cp\u003eA male pediatric patient with an age of onset at 6 years and 6 months. His symptoms at onset were fever and status epilepticus, his blood GFAP antibody titer was 1:32, his cerebrospinal fluid GFAP antibody titer was 1:32, and his cerebrospinal fluid white blood cell count was 26*10\u003csup\u003e6\u003c/sup\u003e/L. Electroencephalography revealed the following: A: background rhythm slowing, 5–6 Hz θ rhythm, and a lot of δ activity in various regions (pronounced in the right temporal region); B, C，D: spike wave, and slow spike-wave rhythmic discharges in various regions on the right (pronounced in the right temporal region) that persisted for 40 s, corresponding to electrographic seizures; E: Persistent discharge for 8 s, corresponding to brief potentially ictal rhythmic discharges (BIRDs); F: Electroencephalography findings were normal after pulse steroid therapy. G: After 2 months and 11 days, the patient developed a fever and repeated convulsions after infection with influenza A virus. Retest results revealed a blood GFAP antibody titer of 1:320 and a negative cerebrospinal fluid GFAP antibody titer. Cerebrospinal fluid routine biochemical test results were normal. Electroencephalography retesting revealed background rhythm slowing and 6–8 Hz θ and α rhythms, interspersed with many 3–5 Hz δ waves. H: Electroencephalography was normal after pulse steroid therapy.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4537423/v1/920f788de55950625a6316eb.jpg"},{"id":75606042,"identity":"6401c9a8-4f00-488a-8ed9-9c344b11d662","added_by":"auto","created_at":"2025-02-06 09:32:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4732157,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4537423/v1/92f00207-ec75-47db-96ae-b86a685530c9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical analysis of pediatric recurrent autoimmune glial fibrillary acidic protein astrocytopathy","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eGlial fibrillary acidic protein astrocytopathy (GFAP-A) is an autoimmune disease of the central nervous system that was first proposed by Fang et al. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] from the Mayo Clinic in 2016. GFAP-A lesions can involve the meninges, brain, spinal cord, and optic nerve, and the main clinical presentation is meningoencephalomyelitis. Currently, GFAP-IgG is regarded as a specific biomarker for this disease. The localization characteristics of intracellular antigens in astrocytes suggest that the pathogenesis may be due to a GFAP-specific cytotoxic T-cell-centered immune response and not due to the direct effects of GFAP-IgG [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Most patients are sensitive to glucocorticoids, and rapid improvements in clinical symptoms and radiologic presentation can be achieved after glucocorticoid treatment [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Studies have shown that this disease can recur in at least 20% of patients, and these individuals require long-term immunotherapy. A minority of patients also have poor outcomes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Currently, only the proportion of recurrence or simple descriptions of recurrence have been seen in the literature when discussing the clinical presentation of patients with recurrent autoimmune GFAP-A, and there have not been any studies focused on the clinical characteristics of recurrent GFAP-A. This study summarizes the clinical characteristics of 17 pediatric patients experiencing recurrent autoimmune GFAP-A to provide guidance for active recognition of recurrent GFAP-A and its clinical treatment.\u003c/p\u003e"},{"header":"2 MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study participants\u003c/h2\u003e \u003cp\u003eIn patients with autoimmune GFAP-A who were treated in the neurology department of Hunan Children\u0026rsquo;s Hospital from January 2015 to January 2024, 17 experienced recurrent autoimmune GFAP-A. Inclusion criteria were as follows: ① Age at diagnosis\u0026thinsp;\u0026le;\u0026thinsp;18 years; ② Positive cerebrospinal fluid or serum GFAP-IgG results in a cell-based assay (CBA); ③ Patients who were diagnosed with autoimmune encephalitis, central nervous system demyelinating disease, or other central nervous system autoimmune diseases on screening; ④ Patients with recurrence as defined by new symptoms or worsening at least 2 months after improvement or stabilization; and ⑤ The pediatric patient and his/her family members provided informed consent for this study. Exclusion criteria were as follows: ① Cerebrospinal fluid and serum GFAP-IgG were both negative; ② Comorbid central nervous system space-occupying lesions, hypoxic-ischemic encephalopathy, psychiatric disorders, or stroke; or ③ Insufficient data to meet the needs of the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data collection\u003c/h2\u003e \u003cp\u003eThe clinical data of the 17 pediatric patients was retrospectively collected, including demographic characteristics, clinical symptoms, magnetic resonance imaging (MRI) results, electroencephalography results, cerebrospinal fluid (CSF), serum, and CSF antibody test results, chest, abdominal, and pelvic computed tomography (CT) or ultrasound results, treatment regimens, and prognosis. The modified Rankin scale (mRS) was used for evaluation when the condition of the patient was serious, during discharge, and at the last follow-up. An mRS score\u0026thinsp;\u0026ge;\u0026thinsp;4 at symptom peak was considered indicative of critical illness, an mRS score\u0026thinsp;\u0026le;\u0026thinsp;2 at discharge was indicative of a good prognosis, and an mRS score\u0026thinsp;\u0026gt;\u0026thinsp;2 was indicative of a poor prognosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This study was approved by the ethics committee of Hunan Children\u0026rsquo;s Hospital.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Experimental methods\u003c/h2\u003e \u003cp\u003eA highly specific and sensitive CBA method was used to measure GFAP, MOG, AQP4, NMDAR, AMPA1, AMPA2, LGI1, GABAB, CASPR2, Hu, Yo, Ri, CV2, Recoverin, Gt1a, Gt1b, GQ1b, GM1, GM2, GM3, GD2, and GD3 levels in the serum and/or CSF of pediatric patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical Analysis\u003c/h2\u003e \u003cp\u003eWe used SPSS 24.0 for all analyses. Quantitative data that were normally distributed are presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, while those that were non-normally distributed are presented as the median. Nonparametric test for two correlated samples were used to compare the differences in the number of symptoms, mRS, and length of hospitalization between at recurrence and initial diagnosis. In addition, qualitative data are presented as the number of patients (percentage).\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 General condition\u003c/h2\u003e \u003cp\u003eOut of 60 pediatric patients with autoimmune GFAP-A, 17 (28.3%, 17/60) experienced recurrence, of whom 6 were male and 11 were female. The mean age of onset was 6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7 years (range: 2 years to 13 years and 2 months). Of these patients, 9 had meningoencephalitis, 5 had encephalomyelitis, 2 had optic neuritis, and 1 had encephalitis and Guillain-Barr\u0026eacute; syndrome. The follow-up time ranged from 1.1 to 5.8 years, with a mean follow-up duration of 3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 years. Five patients had a history of respiratory tract infection 1\u0026ndash;2 weeks before disease onset, and herpes simplex virus type I was detected in 2 patients. See Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of the general conditions in patients with GFAP Astrocytopathy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeature\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eincidence\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMales: females\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6:11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at onset (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at follow-up (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeningoencephalitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9/17(52.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEncephalomyelitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/17(29.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptic neuritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/17(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEncephalitis and Guillain-Barr\u0026eacute; syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Clinical presentation and treatment\u003c/h2\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e3.2.1 Clinical presentation and treatment at initial onset\u003c/h2\u003e \u003cp\u003ePresenting symptoms at initial onset were as follows: 7 patients had fevers, 5 had epileptic seizures, 4 had headaches, 4 had decreased consciousness, 3 had visual impairment, 3 had psychiatric and behavioral abnormalities, 2 had ophthalmalgia, 2 exhibited paralysis, 1 exhibited memory decline, 1 was affected by vomiting, and 1 presented with ataxia. Patients exhibited 1\u0026ndash;8 main symptoms (mean: 4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5), including psychiatric and behavioral symptoms in 13 patients, paralysis in 12 patients, epileptic seizures in 12 patients, fevers in 10 patients, headaches in 10 patients, decreased consciousness in 10 patients, visual impairment in 5 patients, ophthalmalgia in 3 patients, bulbar paralysis in 3 patients, peripheral facial palsy in 2 patients, autonomic impairment in 2 patients, urinary retention in 2 patients, involuntary movements in 2 patients, ataxia in 1 patient, cognitive decline in 1 patient, memory decline in 1 patient, respiratory failure in 1 patient, and vomiting in 1 patient. Of these patients, 5 were admitted to the ICU for treatment. There were 11 patients with mRS scores of 4\u0026ndash;5 and 6 patients with mRS scores of 2\u0026ndash;3, for a mean mRS score of 3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9. For treatment, 11 patients received pulse steroid therapy\u0026thinsp;+\u0026thinsp;intravenous gamma globulin treatment, of whom 3 received additional anticonvulsant treatment; 4 received pulse steroid therapy alone, of whom 1 received additional anticonvulsant treatment; 1 received intravenous gamma globulin treatment alone; 1 received pulse steroid therapy\u0026thinsp;+\u0026thinsp;gamma globulin\u0026thinsp;+\u0026thinsp;rituximab treatment. The length of hospitalization was 9\u0026ndash;47 days and the median length of hospitalization was 19 (13, 25) days. The prognosis of 10 pediatric patients was good on discharge, with mRS scores of 0\u0026ndash;2, whereas 7 patients exhibited a poor prognosis, with sequelae and mRS scores of 3\u0026ndash;5. The median mRS score at discharge was 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5. See Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of the clinical presentation and treatment at initial onset in patients with GFAP astrocytopathy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeature\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncidence\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFevers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7/17(41.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpileptic seizures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5/17(29.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadaches\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4/17(23.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecreased consciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4/17(23.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3/17(17.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epsychiatric and behavioral abnormalities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3/17(17.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOphthalmalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2/17(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParalysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2/17(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMemory decline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtaxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMain symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychiatric and behavioral symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13/17(76.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParalysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12/17(70.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpileptic seizures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12/17(70.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFevers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10/17(58.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadaches\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10/17(58.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDecreased consciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10/17(58.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5/17(29.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOphthalmalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3/17(17.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBulbar paralysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3/17(17.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral facial palsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2/17(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutonomic impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2/17(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary retention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2/17(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvoluntary movements\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2/17(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtaxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive decline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMemory decline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdmitted to ICU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5/17(29.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u0026thinsp;+\u0026thinsp;gamma globulin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11/17(64.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4/17(23.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGamma globulin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u0026thinsp;+\u0026thinsp;gamma globulin\u0026thinsp;+\u0026thinsp;rituximab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003ch2\u003e3.2.2 Clinical presentation and treatment of recurrence\u003c/h2\u003e \u003cp\u003e(1) Recurrence frequency and pre-recurrence immunotherapy were as follows: 17 patients experienced 28 episodes of recurrence. The number of recurrences per patient ranged from 1\u0026ndash;7, with a median of 1 (1, 2). Of these patients, 12 experienced a single recurrence, while 5 (29.4%) experienced multiple (2 or more) recurrences. The interval to recurrence ranged from 2 months to 3 years, with a median of 7 (3, 13) months. Pre-recurrence immunotherapy was as follows: 12 recurrences occurred after immunotherapy was discontinued, 13 occurred during dose reduction of steroid therapy alone, and oral methotrexate and azathioprine were used before recurrence for 1 recurrence each. (2) Symptomatology of recurrence was as follows: 4 recurrences exhibited symptoms of respiratory tract infections before recurrence, with influenza A virus having been detected in 1 recurrence. With respect to the initial symptoms at recurrence, 9 recurrences showed visual impairment, 8 showed epileptic seizures, 8 showed paralysis, 5 showed urinary retention, 3 showed fevers, 3 showed ataxia, 2 showed involuntary movements, 1 showed paresthesia, 1 showed peripheral facial palsy, 1 showed ophthalmalgia, and 1 showed a headache. Patients presented with 1\u0026ndash;5 main symptoms at recurrence, with a single symptom in 4 recurrences and multiple (2 or more) symptoms in 24 recurrence episodes. In addition, 3 recurrencess exhibited new symptoms, while in the remaining recurrences the symptoms at recurrence were generally in line with the symptoms at the first occurrence. The median number of symptoms at recurrence was 1 (1, 2) and mRS score ranged from 1 to 5 with a median of 3 (2, 4). These were lower than the mean number of symptoms (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Z\u0026thinsp;=\u0026thinsp;2.794) and mRS scores (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Z\u0026thinsp;=\u0026thinsp;2.946) at initial disease onset. No patients were admitted to the ICU during recurrence. The condition at recurrence was less severe than at initial onset in 12 recurrences and the severity of recurrence was the same as at initial onset in 16 recurrences. (3) Treatment at recurrence were as follows: patients received pulse steroid therapy\u0026thinsp;+\u0026thinsp;intravenous gamma globulin in 16 recurrences, plus rituximab in 5 recurrences and azathioprine in 1. Pulse steroid therapy was given in 9 recurrences, plus methotrexate in 1, mycophenolate mofetil in 1, rituximab in 1, and surgical tumor resection in 1. Rituximab alone (single or multiple doses) was given in 2 recurrences, gamma globulin alone was given in 1, and oral steroids\u0026thinsp;+\u0026thinsp;anticonvulsants therapy was administered in 2 cases. Among these 28 recurrences, anticonvulsants were also administered due to epileptic seizures in 7 recurrences. The length of hospitalization for these recurrences ranged from 4 to 45 days with a median of 10 (8, 16) days, which was lower than the mean length of hospitalization at initial onset (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Z\u0026thinsp;=\u0026thinsp;3.508). Out of 17 patients, the condition of 12 patients improved after immunotherapy, with mRS scores of 0\u0026ndash;2, while 5 patients exhibited mRS scores of 3. These patients had sequelae such as intermittent convulsions, visual impairment, or cognitive decline. See Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e for further details.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of the clinical presentation and treatment of recurrence in patients with GFAP astrocytopathy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeature\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eincidence\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrence frequency/median\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28/1(1,2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle recurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/17(70.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple (2 or more) recurrences\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/17(29.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterval to recurrence/median\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 months to 3 years/7 (3, 13) months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9/28(32.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpileptic seizures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/28(28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParalysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/28(28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary retention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/28(17.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFevers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/28(10.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtaxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/28(10.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvoluntary movements\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/28(7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParesthesia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral facial palsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOphthalmalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u0026thinsp;+\u0026thinsp;gamma globulin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/28(35.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u0026thinsp;+\u0026thinsp;gamma globulin\u0026thinsp;+\u0026thinsp;rituximab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/28(17.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u0026thinsp;+\u0026thinsp;gamma globulin\u0026thinsp;+\u0026thinsp;azathioprine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/28(10.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u0026thinsp;+\u0026thinsp;methotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u0026thinsp;+\u0026thinsp;mycophenolate mofetil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u0026thinsp;+\u0026thinsp;rituximab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulse steroids\u0026thinsp;+\u0026thinsp;surgical tumor resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRituximab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/28(7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGamma globulin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral steroids\u0026thinsp;+\u0026thinsp;anticonvulsants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/28(7.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the number of main symptoms, length of hospitalization, and mRS between initial disease onset and recurrent onset in patients with GFAP astrocytopathy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInitial onset (n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003erecurrent onset (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eZ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe number of main symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.794\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospitalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(13,25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(8,16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.508\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(2,4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.946\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Serum/CSF test results\u003c/h2\u003e \u003cp\u003eThe serum GFAP antibodies of 17 patients were all positive (100%) at initial onset, with 11 also being positive for CSF antibodies (64.7%). Seven patients had other overlapping antibodies, such as MOG antibodies in 4 patients, GM1 IgM and GM2 IgM antibodies in 1 patient, AQP4 antibodies in 1 patient, and NMDA antibodies in 1 patient. Of the 28 recurrences, serum antibodies were tested in 22 and CSF antibodies were tested in 7. In these tests, positive serum GFAP antibody results were observed in 11 (50%) recurrences, including 9 recurrences with higher antibody titers than when these patients were first discharged, and 1 recurrence with serum positivity for anti-recoverin antibody. One recurrence had positive CSF GFAP antibody results (14.3%), with the antibody levels higher than the level at discharge. The serum and CSF antibody positivity rates at recurrence were all lower than at initial onset. CSF tests were completed in all patients at initial onset, with 13 having abnormal CSF test results that presented as elevated white blood cell counts or protein levels. These included 12 patients with elevated white blood cell counts in the range of 14\u0026ndash;360*10\u003csup\u003e6\u003c/sup\u003e/L and a median white blood cell count of 35*10\u003csup\u003e6\u003c/sup\u003e/L (2*10\u003csup\u003e6\u003c/sup\u003e/L, 72*10\u003csup\u003e6\u003c/sup\u003e/L), with mononuclear cell elevation being the predominant form. Only 3 patients had elevated CSF protein levels of 1.56, 0.595, and 0.94 g/L. CSF tests were performed only for 7 recurrences, of which 2 had abnormal CSF test results, which presented as elevated white blood cell counts of 28*10\u003csup\u003e6\u003c/sup\u003e/L and 40*10\u003csup\u003e6\u003c/sup\u003e/L. See Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e for further details.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of auxiliary examination results at initial onset and recurrence in patients with GFAP astrocytopathy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInitial onset (n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRecurrent onset (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum GFAP antibodies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17/17(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11/22(50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSF GFAP antibodies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11/17(64.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/7(14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal CSF tests\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/17(76.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/7(28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEEG findings\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/17(58.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14/28(50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSlow wave background\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/17(58.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13/28(46.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpileptiform waves\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/17(29.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5/28(17.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFocal seizures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/17(11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCSE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/17(5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElectrographic seizures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/17(11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpasms, tonic seizures, and myoclonic seizures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/28(3.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeuroimaging\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal brain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/17(70.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22/28(78.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal spinal cord\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/16(37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9/12(75%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal optic nerve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/17(35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/28(14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnhancement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/17(47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/28(14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Electroencephalography results\u003c/h2\u003e \u003cp\u003eElectroencephalography was completed in 17 patients at initial onset, of whom 7 had normal electroencephalograms and 10 had abnormal electroencephalograms (58.8%). Among patients with abnormal electroencephalograms, 10 had background slowing, with slow waves mainly being located in the parietal, occipital, and temporal lobes or were diffuse. Five had epileptiform waves, with focal seizures having been detected in 2 patients, while nonconvulsive status epilepticus (NCSE) was detected in 1 patient, and electrographic seizures (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) were detected in 2 patients. Electroencephalography was completed in all 28 recurrences, with 14 normal electroencephalograms and 14 abnormal electroencephalograms (50%). Among the abnormal electroencephalograms, 13 had background slowing, 5 had epileptiform waves, 1 had focal seizures, 1 had electrographic seizures, and 1 had spasms, reflex tonic seizures, and reflex myoclonic seizures. The magnitude of electroencephalography slowing in the 13 recurrences was lower than at the initial onset. See Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e for further details.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Radiologic results\u003c/h2\u003e \u003cp\u003eHead MRI scans were completed in 17 patients and spinal cord MRI scans were completed in 16 patients at initial onset. Among these patients, 6 exhibited head MRI abnormalities, 2 exhibited head\u0026thinsp;+\u0026thinsp;spinal cord MRI abnormalities, 4 exhibited head\u0026thinsp;+\u0026thinsp;spinal cord\u0026thinsp;+\u0026thinsp;optic nerve MRI abnormalities, and 2 exhibited optic nerve MRI abnormalities only. Lesions detected via head MRI included 1\u0026ndash;10 involvement sites principally located in the frontal (7 cases), parietal (7 cases), occipital (5 cases), and temporal (5 cases) areas, but also in the brain stem (5 cases), thalamus (4 cases), periventricular area (4 cases), basal ganglia (3 cases), corpus callosum (2 cases), and cerebellum (2 cases). Lesions detected by spinal MRI included 1\u0026ndash;13 spinal cord segments, involving the thoracic spinal cord (2 cases), cervical spinal cord (2 cases), thoracolumbar spinal cord (1 case), cervical thoracic spinal cord (1 case), and anterior root of spinal cord nerve (1 case). Among these 17 pediatric patients, 8 exhibited image enhancement, including 3 cases of sulcus enhancement, 3 of intracranial lesion enhancement, 2 of brain meningeal enhancement, 2 of spinal cord lesion enhancement, 1 of spinal meningeal enhancement, 2 of spinal cord anterior root enhancement, and 1 of optic nerve enhancement. The enhanced lesions were cord-like, gyrus-like, patchy, annular, and diffuse. Head MRI scans were completed in all 28 recurrences, with 10 having exhibited normal head MRI scans before recurrence and 18 exhibiting fewer lesions on head MRI scans. In six recurrences the patients presented with normal head MRIs. There were no significant changes in lesions compared with pre-recurrence findings in 6 recurrences, while in 16 (57.1%, 16/28) recurrences there were more lesions relative to pre-recurrence levels, including 7 (43.5%, 7/16) with the reappearance of some of the original lesions that had disappeared following treatment and 9 (56.2%, 9/16) with new lesions. Spinal cord MRI examinations were conducted for 12 of the 28 recurrences. Three showed normal spinal cord MRIs. There were no significant changes in lesions compared with pre-recurrence findings in 1 recurrence, while 8 (66.7%, 8/12) exhibited an increased number of lesions compared with pre-recurrence findings, including 6 (75%, 6/8) with the reappearance of some original lesions that had disappeared following treatment and 2 (25%, 2/8) with new lesions. Among the 28 recurrences, 4 had abnormal optic nerve images, with new optic nerve lesions having been observed in 1 recurrence. Four out of the 28 recurrences exhibited enhancement, including 2 with lesion enhancement, 1 with cord-like enhancement in the cerebral fissure, and 1 with optic nerve enhancement. See Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e for further details.\u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eGFAP-A is an autoimmune disease of the nervous system that was first defined in 2016 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Currently, there is a lack of epidemiological study data related to this conduction. A study in Minnesota calculated that the overall incidence is 0.6/100,000, which is similar to that of autoimmune NMDAR encephalitis [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Iorio et al. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] found that this disease accounts for 5% of immune diseases of the nervous system, indicating that it is not rare. The number of cases of GFAP-A recurrence has been increasing due to a rise in the overall number of confirmed GFAP-A cases and longer follow-up duration. Currently, only the proportion of recurrence has been reported when describing the clinical presentation of relapsed autoimmune GFAP-A and there have not been any studies focused on the clinical characteristics of recurrent GFAP-A. Liu et al. reported that recurrence occurred in 21% (5/24) of patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Li et al. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] reported that 2 out of 15 pediatric GFAP-A patients developed recurrences at 8 months and 7 months after discharge. In the present study, a total of 17 patients experienced recurrence with a recurrence rate of 28.3%. There were 5 patients with multiple recurrences, accounting for 29.4% of all patients with recurrence. The interval to recurrence was 2 months to 3 years, with a median of 7 (3, 13) months.\u003c/p\u003e \u003cp\u003eThe initiating factors for recurrence are still unknown. Two Mayo Clinic studies found that 29\u0026ndash;39% of autoimmune GFAP-A patients have flu-like symptoms before disease onset [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A case report described a patient who had a herpes simplex infection 5 months before the onset of symptoms [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], suggesting that viral infection may be a cause that triggers autoimmune responses. In this study, 5 patients had a history of respiratory tract infections 1\u0026ndash;2 weeks before disease onset and herpes simplex virus type I was detected in 2 patients. In 4 recurrences, the patients had symptoms of respiratory tract infections before disease onset, with influenza A virus having been detected in 1 patient. At present, the relationship between viral infection and initial disease onset and recurrence cannot be determined as there are very few cases. Additionally, most pediatric patients do not have a definite history of past infectious disease before disease onset.\u003c/p\u003e \u003cp\u003eWith respect to risk factors associated with recurrence, one study found that a rapid decrease in steroid dose was associated with recurrence in some patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In this study, 12 recurrences were after immunotherapy and steroid treatment were discontinued, 13 recurrences were during dose reduction of steroid therapy alone, and only in 2 episodes the patients took oral methotrexate or azathioprine before recurrence. This suggests that GFAP-A recurrence tends to occur during dose reduction or discontinuation of steroids and other immunotherapies. Further research is required to determine whether appropriate extension of steroid and immunotherapy treatment duration or decreasing the speed of dose reduction can decrease the recurrence rate. One study also found that patients with overlap syndrome are prone to recurrence [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In this study, 47.1% (8/17) of the patients had overlapping antibodies, which were detected at initial onset and during recurrence. Out of 17 patients, 4 had MOG antibodies, 1 had GM1 IgM and GM2 IgM antibodies, 1 had AQP4 antibodies, and 1 had NMDA antibodies. The patient with overlapping AQP4 antibodies experienced 7 episodes of recurrence. This suggests that patients with overlap syndrome are prone to recurrence, with those with overlapping MOG antibodies being more prone to recurrence, while patients with overlapping AQP4 antibodies are prone to more instances of recurrence.\u003c/p\u003e \u003cp\u003eDetermination of GFAP-A recurrence is dependent on symptomology observations. In our study, the main symptoms of initial GFAP-A onset included psychiatric and behavioral abnormalities, epileptic seizures, impaired consciousness, fevers, headaches, and visual impairment. The main symptoms of recurrence included visual impairment, epilepsy, paralysis, urinary retention, and fevers. In most recurrences the patients had some of the same symptoms as experienced at initial onset while a few patients (10.7%, 3/28) developed new symptoms that were different from those at initial onset. The number of symptoms at recurrence was significantly lower than that at initial onset and severity was milder than that at initial onset. The reason for these milder symptoms at recurrence compared with initial onset is still unknown. One study reported that GFAP-specific T cells participate in the pathogenesis of GFAP-A. Memory CD8\u0026thinsp;+\u0026thinsp;T cells are critical participants in the adaptive immune response and provide rapid protection against previously encountered pathogens during recurrence [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], which may explain why symptoms are milder during recurrence than at initial onset.\u003c/p\u003e \u003cp\u003eIn addition to the observation of clinical symptoms, antibody testing and other auxiliary examinations are helpful for diagnosing GFAP-A recurrence. In this study, the serum GFAP antibody positivity rate was 50% and the CSF GFAP antibody positivity rate was 14.3% at recurrence. The reason for the lower CSF positivity rate relative to the serum positivity rate may be related to the fact that most family members refuse lumbar puncture during recurrence and there were fewer CSF test samples. At initial onset, 76.5% of patients had CSF abnormalities, which primarily consisted of elevated white blood cell counts with a median count of 35*10\u003csup\u003e6\u003c/sup\u003e/L (2*10\u003csup\u003e6\u003c/sup\u003e/L, 72*10\u003csup\u003e6\u003c/sup\u003e/L). During recurrence, 28.6% had CSF abnormalities and only 2 out of 7 patients presented with elevated white blood cell counts of 28*10\u003csup\u003e6\u003c/sup\u003e/L and 40*10\u003csup\u003e6\u003c/sup\u003e/L. There have been few studies reporting on the electroencephalogram findings from GFAP-A patients. Theroux et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] previously reported extreme delta brush (EDB) in the electroencephalogram of a pediatric GFAP-A patient and this patient was positive for anti-NMDA receptor antibody. EDB and other specific abnormal electroencephalography changes were not observed in this study. Instead, most of the present electroencephalograms showed non-specific changes at initial onset or recurrence, with diffuse or focal slow wave activity in various leads. Some patients had focal epileptiform discharge or normal electroencephalograms and epileptic seizures, NCSE, and electrographic seizures were even monitored in a few patients. We found that the magnitude of electroencephalography slowing was lower at recurrence than at initial onset, suggesting that although there was slowing of the background electroencephalography rhythm at recurrence, it was not as slow as that at initial onset. This is consistent with the fact that symptoms at recurrence are milder than at initial onset. Therefore, antibody, CSF routine biochemical, and electroencephalography examinations are important for evaluating recurrence during follow-up.\u003c/p\u003e \u003cp\u003eOncological evaluation is an important aspect of recurrent GFAP-A management and comprehensive tumor screening is required in patients in whom tumors are not found at initial onset. Attention should still be paid to the possibility of tumor recurrence even in patients with past tumors that have been resected. Flanagan et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] mentioned that around 34% of patients may have comorbid tumors and 66% of patients develop new tumors within 2 years of the occurrence of related neurological symptoms. Dalmau et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] pointed out that these tumors may contain nervous tissues or express neuronal proteins that are targeted by antibodies. Apoptotic tumor cells release these ectopically expressed neuronal proteins, which undergo uptake and processing as antigens by antigen-presenting cells in regional lymph nodes and are then presented to the immune system to induce anti-tumor immune responses. In this study, retroperitoneal ganglioneuroma was found after the second recurrence in only 1 patient at 1 year and 4 months after initial onset. Symptoms did not recur within 4 years of follow-up after tumor resection. In this study, the incidence of tumors in recurrent GFAP-A was 5.9%.\u003c/p\u003e \u003cp\u003eWith respect to radiology, studies have shown that MRI analyses of GFAP-A patients show multiple lesions involving sites such as the cerebral white matter, basal ganglia, hypothalamus, brain stem, and cerebellum [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Around 50% of patients present with vascular, radiating linear enhancement extending from the lateral ventricles [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Of our patients, 8 patients with enhanced lesions showed enhancement in the sulcus, intracranial lesions, brain meninges, spinal cord lesions, spinal cord meninges, anterior root of the spinal cord, and optic nerve. These enhanced lesions were cord-like, gyrus-like, patchy, annular, and diffuse. This was different from radiating linear enhancement beside the lateral ventricles mentioned in previous studies of adult GFAP-A. Two patients had meningeal enhancement, which is rare in autoimmune encephalitis. As GFAP participates in the formation of the blood-brain barrier, abnormal leptomeningeal enhancement may be caused by disruption of the blood-brain barrier and vascular wall injury, leading to contrast agent exudation [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In this study, lesions were increased in head MRI scans from 57.1% of the recurrences compared with pre-recurrence levels, of which 43.8% of the recurrences exhibited the enlargement of the original lesions while 56.2% presented with new lesions. In spinal cord MRI, 66.7% of the recurrences presented with increased lesions compared with pre-recurrence levels, of which 75% exhibited the enlargement of the original lesions while 25% developed new lesions. This demonstrates that active radiologic evaluation is important in diagnosing recurrence patients.\u003c/p\u003e \u003cp\u003eCurrently, there is no unified treatment standard for autoimmune GFAP-A. Existing related studies have indicated that the treatment methods for this disease include glucocorticoids, IVIG, plasmapheresis, and immunosuppressants [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Most patients showed improvements in clinical symptoms after undergoing corticosteroid and IVIG treatment. In this study, first-line immunotherapy was used at initial onset and second-line immunotherapy was only used in one patient due to disease exacerbation. Overall, 92.9% of the recurrences in this study occurred during steroid discontinuation or dose reduction. This shows that the steroid treatment course should not be too short and that dose reduction should not be too rapid. However, there is no unified standard for the specific treatment course. One study found that the recurrence rate among overlap syndrome patients was higher than among non-overlap syndrome patients. This indicates that glucocorticoid dose reduction in overlap autoimmune syndrome patients should be slower than non-autoimmune overlap syndrome patients and that second-line immunosuppressants should be aggressively used in patients experiencing recurrence [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In this study, repeated use of first-line immunotherapy and aggressive use of long-term second-line immunotherapy were sufficient to control and alleviate the symptoms in most instances of recurrence.\u003c/p\u003e \u003cp\u003eIn summary, GFAP-A has the potential to recur, and patients in the remission stage should be closely followed up. Clinical symptoms, antibody tests, CSF biochemical markers, electroencephalography, and radiologic examinations are important methods for recurrence evaluation. There should be an emphasis on tumor screening during recurrence and aggressive first-line immunotherapy should be administered. When necessary, additional second-line immunotherapy can be used. Further research on recurrence cases can help reveal the clinical patterns of this disease and improve diagnosis and treatment levels.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eF wrote the main manuscipt text and H prepared figures 1 ,Z prepared table 1-5. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval and Consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll experiments were approved by the medical ethics committee of the Hunan Children\u0026rsquo;s hospital. This retrospective study was approved by the institutional review board. Informed consent was waived due to the retrospective analysis of anonymized data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from Natural Science Foundation of Hunan Province (No. 2022JJ70087).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBoyan Fang, Andrew McKeon, Shannon R Hinson, Thomas J Kryzer, Sean J Pittock, Allen J Aksamit, et al. Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA neurology 2016;73(11):1297\u0026ndash;1307 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaneurol.2016.2549\u003c/span\u003e\u003cspan address=\"10.1001/jamaneurol.2016.2549\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDivyanshu Dubey, Shannon R Hinson, Evan A Jolliffe, Anastasia Zekeridou, Eoin P Flanagan, Sean J Pittock, et al. Autoimmune gfap astrocytopathy: prospective evaluation of 90 patients in 1 year.Journal of neuroimmunology 2018 08 15;321:157\u0026ndash;163 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jneuroim.2018.04.016\u003c/span\u003e\u003cspan address=\"10.1016/j.jneuroim.2018.04.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJun Xiao, Xin Chen, Ke Shang, Yue Tang, Man Chen, Gang Deng, et al. Clinical, neuroradiological, diagnostic and prognostic profile of autoimmune glial fibrillary acidic protein astrocytopathy: A pooled analysis of 324 cases from published data and a single-center retrospective study. Journal of neuroimmunology 2021 11 15;360:577718 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jneuroim.2021.577718\u003c/span\u003e\u003cspan address=\"10.1016/j.jneuroim.2021.577718\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmy Kunchok, Anastasia Zekeridou, Andrew McKeonl. Autoimmune glial fibrillary acidic protein astrocytopathy. Current opinion in neurology 2019 06;32(3):452\u0026ndash;458 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/WCO.0000000000000676\u003c/span\u003e\u003cspan address=\"10.1097/WCO.0000000000000676\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQingmei Huang, Huacai Yang, Tianni Liu, Huiming Xu, Baikeng Chen, Si Liu, et al. Patients with suspected benign tumors and glial fibrillary acidic protein autoantibody: an analysis of five cases. The International journal of neuroscience 2019;129(12):1183\u0026ndash;1188 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/00207454.2019.1645140\u003c/span\u003e\u003cspan address=\"10.1080/00207454.2019.1645140\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEoin P Flanagan, Shannon R Hinson, Vanda A Lennon, Boyan Fang, Allen J Aksamit, P Pearse Morris,, et al.Glial fibrillary acid-ic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients.Annals of neurology 2017;81(2):298\u0026ndash;309 doi:10.1002/ana.24881[14]Dalmau J, Graus F. Antibody-Mediated Encephalitis [J]. N Engl J Med, 2018, 378(9): 840\u0026ndash;851.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDivyanshu Dubey, Sean J Pittock,Cecilia R Kelly, Andrew McKeon, Alfonso Sebastian Lopez-Chiriboga, Vanda A Lennon, et al.Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis.Annals of neurology 2018 01;83(1):166\u0026ndash;177 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ana.25131\u003c/span\u003e\u003cspan address=\"10.1002/ana.25131\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaffaele Iorio, Valentina Damato, Amelia Evoli, Marco Gessi, Simona Gaudino, Vincenzo Di Lazzaro, et al. Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients.Journal of neurology, neurosurgery, and psychiatry 2018 02;89(2):138\u0026ndash;146 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/jnnp-2017-316583\u003c/span\u003e\u003cspan address=\"10.1136/jnnp-2017-316583\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQiang Liu, Xiao Yang, Jingzi Zhang Bao, Boya Ma, Xiaoyan Niu, Xu Wang, et al. Clinical characteristics of patient with GFAP-IgG: a review of 31 patients from two tertiary referral centers in China.The International journal of neuroscience 2023;:1\u0026ndash;12 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/00207454.2023.2277664\u003c/span\u003e\u003cspan address=\"10.1080/00207454.2023.2277664\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTianyi Li, Xiujuan Li, Siqi Hong, Li Jiang, Jiannan Ma. Clinical characteristics of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children: A case series of 16 patients.Journal of neuroimmunology 2023 09 15;382:578176 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jneuroim.2023.578176\u003c/span\u003e\u003cspan address=\"10.1016/j.jneuroim.2023.578176\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScott J Schatzberg. Idiopathic granulomatous and necrotizing inflammatory disorders of the canine system. The Veterinary clinics of North America. Small animal practice 2010;40(1):101\u0026ndash;20 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cvsm.2009.09.003\u003c/span\u003e\u003cspan address=\"10.1016/j.cvsm.2009.09.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiana M Theroux, Howard P Goodkin, Kristen C Heinan, Mark Quigg, J Nicholas Brenton.Extreme delta brush and distinctive imaging in a pediatric patient with autoimmune GFAP astrocytopathy.Multiple sclerosis and related disorders 2018;26:121\u0026ndash;123 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.msard.2018.09.015\u003c/span\u003e\u003cspan address=\"10.1016/j.msard.2018.09.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJosep Dalmau, Francesc Graus. Antibody-Mediated Encephalitis. Francesc Graus The New England journal of medicine 2018 03 01;378(9):840\u0026ndash;851 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMra1708712\u003c/span\u003e\u003cspan address=\"10.1056/NEJMra1708712\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrace Tewkesbury, Jae W Song, Christopher M Perrone. Magnetic Resonance Imaging of Autoimmune GFAP Astrocytopathy. Annals of neurology 2021 10;90(4):691\u0026ndash;692 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ana.26195\u003c/span\u003e\u003cspan address=\"10.1002/ana.26195\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkio Kimura, Akira Takekoshi, Nobuaki Yoshikura, Yuichi Hayashi, Takayoshi Shimohata. Clinical characteristics of autoimmune GFAP astrocytopathy. Journal of neuroimmunology 2019 07 15;332:91\u0026ndash;98 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jneuroim.2019.04.004\u003c/span\u003e\u003cspan address=\"10.1016/j.jneuroim.2019.04.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaija Saraste, Svetlana Bezukladova, Markus Matilainen, Marcus Sucksdorff, Jens Kuhle, David Leppert, et al. Increased serum glial fibrillary acidic protein associates with microstructural white matter damage in multiple sclerosis: GFAP and DTI. Multiple sclerosis and related disorders 2021;50:102810 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.msard.2021.102810\u003c/span\u003e\u003cspan address=\"10.1016/j.msard.2021.102810\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXinguang Yang, Junyan Liang, Qingmei Huang, Huiming Xu, Cong Gao, Youming Long,, et al. Treatment of autoimmune glial fibrillary acidic protein astrocytopathy: follow-up in 7 cases. Neuroimmunomodulation 2017;24(2):113\u0026ndash;119 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000479948\u003c/span\u003e\u003cspan address=\"10.1159/000479948\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiaqi Ding, Kaixi Ren, Jun Wu, Hongzeng Li, Tangna Sun, Yaping Yan, et al. Overlapping syndrome of MOG-IgGassociated disease and autoimmune GFAP astrocytopathy. Journal of neurology 2020;267(9):2589\u0026ndash;2593 doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00415-020-09869-2\u003c/span\u003e\u003cspan address=\"10.1007/s00415-020-09869-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"recurrence, autoimmune glial fibrillary acidic protein astrocytopathy, immunotherapy, GFAP-A, pediatrics","lastPublishedDoi":"10.21203/rs.3.rs-4537423/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4537423/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo examine the clinical characteristics, treatment, and prognosis of recurrent autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe data of 17 pediatric patients with recurrent autoimmune GFAP-A who were treated in the neurology department of Hunan Children\u0026rsquo;s Hospital from January 2015 to January 2024 were collected, and the clinical presentation, laboratory tests, neuroradiology results, electroencephalograms, treatment regimens, and prognosis of these patients were retrospectively analyzed and summarized.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThese 17 patients included 6 males and 11 females. A total of 28 recurrences occurred, with a median of 1 (1, 2) recurrence per patient. Patients experienced 1\u0026ndash;5 symptoms on recurrence, with 3 recurrences exhibiting new symptoms. The median number of symptoms at recurrence was 1 (1, 2), with a median mRS score at recurrence of 3 (2, 4) and a median length of hospitalization of 10 (8, 16) days per recurrence episode. The mean number of symptoms, mRS, and length of hospitalization at recurrence were all lower than at initial disease onset (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The serum GFAP antibody positivity rate was 50% and the cerebrospinal fluid GFAP antibody positivity rate was 14.3% at recurrence. The cerebrospinal fluid abnormality rate was 28.6% at recurrence. Abnormal electroencephalograms were observed in 14 (50%) recurrences. There were 16 (57.1%) recurrences with an increased number of lesions visible on head MRI compared with pre-recurrence levels, while there were 8 (66.7%) recurrences with an increased number of lesions visible on spinal cord MRI compared with pre-recurrence levels. First-line immunotherapy was used at initial disease onset with second-line immunotherapy used only in 1 patient. Second-line immunotherapy was used in 11 recurrences.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePediatric GFAP-A tends to recur. The condition at recurrence is milder than at initial disease onset. In most cases, the symptoms seen at recurrence are among those that occurred at initial onset, while new symptoms may occur on recurrence in a small number of patients. In addition to new symptoms and disease worsening during recurrence, abnormal antibody levels, cerebrospinal fluid routine biochemistry test results, electroencephalography results, and radiology findings may also be observed. First-line immunotherapy or long-term combined second-line immunotherapy can be used during recurrence.\u003c/p\u003e","manuscriptTitle":"Clinical analysis of pediatric recurrent autoimmune glial fibrillary acidic protein astrocytopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-28 18:51:34","doi":"10.21203/rs.3.rs-4537423/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cdf4ea9b-c861-4e3c-b682-22600f89de9c","owner":[],"postedDate":"June 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-06T09:24:02+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-28 18:51:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4537423","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4537423","identity":"rs-4537423","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}