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

Abstract

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

Use of anti-seizure medications in different types of autoimmune encephalitis: A narrative review

“…Antibody (GAD65 and hu)-mediated AE seizures are often poorly responsive to ASMs alone ( 50 ) and only moderately responsive to immunotherapy supplemented with ASMs, narcotics plus a ketogenic diet, or tumor therapy. In anti-GFAP AE with seizures, immunotherapy supplemented with ASMs may provide a good prognosis ( 51 , 52 ). Due to the good responses to treatment both were administered to children ( 51 ); however, these data are not comparable.…”

Autoimmune diseases and cancers overlapping with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): A systematic review

“… 68 , 75 Given the overall rarity of double positive cases based on the results of the larger studies, and considering the superior specificity of the AQP4-IgG test compared to the MOG-IgG test, and that a reliable cell-based-assay (CBA) for detecting MOG-IgG has been available just recently (2017), there is a high possibility that most of the double positive cases may likely be AQP4-IgG + NMOSD with false positive MOG-IgG test results, especially in reports made before this time with using enzyme-linked immunosorbent assay (ELISA). 68 , 75 …”

“…MOGAD was perceived primarily as a monophasic CNS inflammatory disease, but further observations showed that a relapsing course occur in 28–60% of patients, and in up to 83% of cases with long-term observation, especially those with persistent positive MOG-IgG status. 99,143 Some evidence of subclinical disease activity and progression has been shown to be present in some of the patients with MOGAD. 2 Patients with anti-NMDAR-EN tend to have more severe neurologic presentations, and poor long-term functional outcomes, and the mortality rate has been reported between 5% and 7%.…”

A case of GFAP-IgG positivity followed by anti-NMDAR encephalitis

“…The diagnosis of GFAP-A should be based on the clinical symptoms, imaging, EEG characteristics, and treatment response. GFAP antibody is positive in the serum of some patients before positive detection in CSF, which may be due to the occurrence of peripheral nerve injury earlier than injury in the central nervous system [ 9 ]. In this case, the patient started with fever, headache, and seizures.…”

“…Among the 35 children with GFAP-A reported by Fang et al, 11 (31.4%) were positive for other antibodies, and one patient developed autoimmune GFAP-A 1 year after the diagnosis of AQP4 antibody-associated neuromyelitis optica (NMO). One MOGAD patient was found to be positive for antibodies to GFAP several months after treatment [ 9 ]. Of the 30 GFAP IgG-positive patients reported by Yang et al, 10 had overlap syndrome, with one patient developing GFAP-A 10 years after diagnosis of NMO and the other diagnosed GFAP-A 1 year after diagnosis of anti-NMDAR encephalitis [ 10 ], similar to this patient.…”