A pediatric case of autoimmune glial fibrillary acidic protein astrocytopathy with unique brain imaging patterns and increased cytokines/chemokines



      Autoimmune anti-glial fibrillary acidic protein (GFAP) astrocytopathy represents a new spectrum of autoimmune inflammatory central nervous system disorders. In recent years, there have been an increasing number of reports on pediatric patients with this disease other than those in Japan.

      Case Report

      A 6-year-old previously healthy boy presented with fever persisting for approximately 10 days, consciousness disturbance, anorexia, and hyponatremia (Na, 121 mEq/L). Even after appropriate correction of hyponatremia, consciousness disturbance was prolonged and was accompanied by gait disturbance, visual hallucinations, and autonomic dysfunction (bradycardia and urinary dysfunction). On a plain MRI, T2-weighted and fluid-attenuated inversion recovery images showed abnormal hyperintense lesions in the bilateral basal ganglia, thalamus, and periventricular white matter. The cerebrospinal fluid was positive for anti-GFAP antibody before treatment, and cytokines/chemokines were increased. He received three courses of intravenous methylprednisolone, followed by gradually tapered oral prednisolone for 6 months, without relapse after 1 year of observation.


      In cases of autoimmune encephalitis with prolonged consciousness disturbance, hyponatremia, urinary dysfunction, and MRI findings with hyperintensities in the bilateral basal ganglia, thalamus, and periventricular white matter, anti-glial fibrillary acidic protein antibodies should be examined.


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        • Fang B.
        • McKeon A.
        • Hinson S.R.
        • Kryzer T.J.
        • Pittock S.J.
        • Aksamit A.J.
        • et al.
        Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis.
        JAMA Neurol. 2016; 73: 1297-1307
        • Kimura A.
        • Takekoshi A.
        • Yoshikura N.
        • Hayashi Y.
        • Shimohata T.
        Clinical characteristics of autoimmune GFAP astrocytopathy.
        J Neuroimmunol. 2019; 332: 91-98
      1. Flanagan E, Dubey D, Hinson S, Lennon V, Fang B, Aksamit A, et al. Specificity of glial fibrillary acidic protein IgG autoantibody (GFAP-IgG) for autoimmune meningoencephalomyelitis diagnosis (s20. 002). Neurology. 2017;88(16 Supplement).

        • Kunchok A.
        • Zekeridou A.
        • McKeon A.
        Autoimmune glial fibrillary acidic protein astrocytopathy.
        Curr Opin Neurol. 2019; 32: 452-458
        • Yang X.
        • Liang J.
        • Huang Q.
        • Xu H.
        • Gao C.
        • Long Y.
        • et al.
        Treatment of autoimmune glial fibrillary acidic protein astrocytopathy: follow-up in 7 cases.
        NeuroImmunoModulation. 2017; 24: 113-119
        • Fang H.
        • Hu W.
        • Jiang Z.
        • Yang H.
        • Liao H.
        • Yang L.
        • et al.
        Autoimmune glial fibrillary acidic protein astrocytopathy in children: A retrospective analysis of 35 cases.
        Front Immunol. 2021; 12: 761354
        • Huang H.
        • Bai K.
        • Fu Y.
        • Lu S.
        • Ran Y.
        • Dang H.
        • et al.
        Glial fibrillary acidic protein astrocytopathy in pediatric patients: A retrospective study.
        Front Pediatr. 2021; 8: 626564
        • Theroux L.M.
        • Goodkin H.P.
        • Heinan K.C.
        • Quigg M.
        • Brenton J.N.
        Extreme delta brush and distinctive imaging in a pediatric patient with autoimmune GFAP astrocytopathy.
        Mult Scler Relat Disord. 2018; 26: 121-123
        • Dubey D.
        • Hinson S.R.
        • Jolliffe E.A.
        • Zekeridou A.
        • Flanagan E.P.
        • Pittock S.J.
        • et al.
        Autoimmune GFAP astrocytopathy: Prospective evaluation of 90 patients in 1 year.
        J Neuroimmunol. 2018; 321: 157-163
        • Omae T.
        • Saito Y.
        • Tsuchie H.
        • Ohno K.
        • Maegaki Y.
        • Sakuma H.
        Cytokine/chemokine elevation during the transition phase from HSV encephalitis to autoimmune anti-NMDA receptor encephalitis.
        Brain Dev. 2018; 40: 361-365
        • Okada T.
        • Fujita Y.
        • Imataka G.
        • Takase N.
        • Tada H.
        • Sakuma H.
        • et al.
        Increased cytokines/chemokines and hyponatremia as a possible cause of clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with acute focal bacterial nephritis.
        Brain Dev. 2022; 44: 30-35
        • Irani S.R.
        • Vincent A.
        Autoimmune encephalitis—new awareness, challenging questions.
        Discov Med. 2011; 11: 449-458
        • Bakpa O.D.
        • Reuber M.
        • Irani S.R.
        Antibody-associated epilepsies: clinical features, evidence for immunotherapies and future research questions.
        Seizure. 2016; 41: 26-41
      2. Vincent A, Buckley C, Schott JM, Baker I, Dewar BK, Detert N, et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain. 2004;127:701–12.

        • Kothur K.
        • Wienholt L.
        • Brilot F.
        • Dale R.C.
        CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: a systematic review.
        Cytokine. 2016; 77: 227-237
        • Becher B.
        • Spath S.
        • Goverman J.
        Cytokine networks in neuroinflammation.
        Nat Rev Immunol. 2017; 17: 49-59
        • Oh J.-W.
        • Schwiebert L.M.
        • Benveniste E.N.
        Cytokine regulation of CC and CXC chemokine expression by human astrocytes.
        J Neurovirol. 1999; 5: 82-94
        • Kimura A.
        • Takemura M.
        • Yamamoto Y.
        • Hayashi Y.
        • Saito K.
        • Shimohata T.
        Cytokines and biological markers in autoimmune GFAP astrocytopathy: The potential role for pathogenesis and therapeutic implications.
        J Neuroimmunol. 2019; 334: 576999
        • Li J.
        • Wang C.
        • Cao Y.
        • Shi J.
        • Liu H.
        • Zhou M.
        • et al.
        Autoimmune glial fibrillary acidic protein astrocytopathy mimicking acute disseminated encephalomyelitis: A case report.
        Medicine (Baltimore). 2021; 100: e26448
        • Cellucci T.
        • Van Mater H.
        • Graus F.
        • Muscal E.
        • Gallentine W.
        • Klein-Gitelman M.S.
        • et al.
        Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient.
        Neurol Neuroimmunol Neuroinflamm. 2020; 7: e663