Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Presenting with Area Postrema Syndrome-Like Symptoms without Medulla Oblongata Lesions

Abstract

<b><i>Introduction:</i></b> Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently described steroid-responsive meningoencephalomyelitis positive for cerebrospinal fluid (CSF) anti-GFAP antibody. Area postrema syndrome (APS) involves intractable hiccups, nausea, and vomiting, which is caused by medulla oblongata (MO) impairment. APS is a characteristic symptom of aquaporin-4 (AQP4) autoimmunity, and it helps to differentiate between AQP4 and GFAP autoimmunity. Conversely, although 6 cases of autoimmune GFAP astrocytopathy with APS and MO lesions have been reported, the association between GFAP autoimmunity and APS is unclear. We report the case of a patient with autoimmune GFAP astrocytopathy presenting with APS-like symptoms without MO lesions and discuss the mechanisms underlying the symptoms. <b><i>Methods:</i></b> CSF anti-GFAP antibody was detected using cell-based assays and immunohistochemical assays. <b><i>Results:</i></b> A 54-year-old Japanese man developed persistent hiccups, intermittent vomiting, fever, anorexia, and inattention. Brain magnetic resonance imaging (MRI) showed periventricular lesions with radial linear periventricular enhancement, suggesting autoimmune GFAP astrocytopathy. However, no obvious MO lesions were identified on thin-slice images. Spinal cord MRI revealed hazy lesions with patchy enhancement along the cervical and thoracic cord. CSF analysis demonstrated inflammation, with positive results for anti-GFAP antibodies. Anti-AQP4 antibodies in the serum and CSF were negative. Esophagogastroduodenoscopy revealed gastroparesis and gastroesophageal reflux disease, and vonoprazan, mosapride, and rikkunshito were effective only against persistent hiccups. Steroid therapy was initiated, allowing clinical and radiological improvements. Repeated MRIs demonstrated no obvious MO lesions. <b><i>Conclusion:</i></b> This report suggests that autoimmune GFAP astrocytopathy presents with APS-like symptoms without obvious MO lesions. The possible causes of hiccups were gastroparesis and cervical cord lesions. Gastroesophageal reflux disease was not considered a major cause of the hiccups. Intermittent vomiting appeared to be associated with gastroparesis, cervical cord lesions, and viral-like symptoms. Testing for anti-GFAP antibodies should be considered in patients with APS-like symptoms in the context of typical clinical-MRI features of autoimmune GFAP astrocytopathy.

Area Postrema Syndrome in Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy

“…Since 2018, several studies have noticed that APS could be a symptom of autoimmune GFAP astrocytopathy. [10][11][12][13][14][15][16][17][18] However, the incidence of APS in this disorder is unknown. We found that 8 of the 74 patients (11%) with autoimmune GFAP astrocytopathy presented with APS and the frequency of APS as the onset symptom is 4%.…”

“…10 Thereafter, APS was increasingly reported as a noticeable manifestation of this disorder. [11][12][13][14][15][16][17] However, the incidence and phenotypes of APS in autoimmune GFAP astrocytopathy have not been described comprehensively.…”

Paraneoplastic Neurologic Syndromes

“…9, 10 For patients with brainstem syndromes and area postrema symptoms (ie, intractable hiccups, nausea and vomiting, or involvement around the medulla oblongata) anti-aquaporin-4 or anti-GFAP antibody associations should be considered (see Optic Neuropathy section). 50 Isolated cochleovestibulopathy has rarely been reported as a paraneoplastic syndrome related to a variety of tumors, but no characteristic tumor or antibody has been described. 51 CEREBELLAR SYNDROMES Anti-PCA-1 (Yo) antibodies remain the most commonly recognized association with paraneoplastic cerebellar syndromes and predominantly occur in women KEY POINT…”

“…For patients with brainstem syndromes and area postrema symptoms (ie, intractable hiccups, nausea and vomiting, or involvement around the medulla oblongata) anti–aquaporin-4 or anti-GFAP antibody associations should be considered (see Optic Neuropathy section) 50 …”

An elderly female case of AQP4 and GFAP double-positive NMOSD coexisting with ovarian teratoma

“…Transverse myelitis and ON also occur frequently in GFAP-A [ 2 ]. Area postrema syndrome (APS) is considered as one of the symptoms of GFAP astrocytopathy [ 3 ]. We currently report a rare case of AQP4 and GFAP double-positive NMOSD complicated with ovarian teratoma, presenting with APS, long-segment myelitis, and encephalopathy.…”