Autoimmune glial fibrillary acidic protein astrocytopathy: case report of a treatable cause of rapidly progressive dementia

Abstract

Dear Sir or Madam, A 54-year-old white man developed an insidious cognitive decline preceded by a mild upper respiratory infection, which evolved into a stuporous state with headaches, hallucinations, and a remarkable weight loss. Initial brain MRI showed no abnormalities. Full-body CT scan showed no alterations. Brain SPECT scan revealed frontal cortical bilateral hypoperfusion. EEG showed periodic short-interval diffuse discharges. Blood tests for onconeural antibodies were negative. CSF showed increased proteins and lymphocytic pleocytosis, with negative results for 14-3-3 protein. He was diagnosed with a prion disease and was discharged with neuroleptics. Six months after the symptoms started, he was referred to our center. Cognitive evaluation showed severe deficits in memory, attention and executive functions, with an MMSE score of 4/30. Neurological examination revealed bilateral papilledema, frontal release signs, multifocal myoclonus, hyperekplexia, right extremities hyperreflexia, right hand muscle atrophy, and mild ataxic gait. A new brain MRI (Fig. 1a–c) showed multiple T2-hyperintensities in periventricular white matter, thalamus, and right cerebellar peduncle; radial-punctuate enhancement was observed on T1-weighted sequences after gadolinium. Spine MRI (Fig. 1d) showed T2-weighted central cord hyperintensity with longitudinal extension from brainstem to T9 vertebral level. Enhancement was present with a punctate appearance in brainstem. Brain [18F]-FDG PET (Fig. 1e) revealed bilateral areas of hypermetabolism in medial temporal lobes, motor cortex, basal ganglia, and brainstem, while hypometabolic areas were found in dorsolateral frontal and lateral temporal and parietal cortex. High metabolic activity was seen caudally throughout the spine [1]. Whole-body PET scan showed no evidence of neoplasm. New CSF analysis showed increasing lymphocytic predominant pleocytosis with elevated proteins. A brain biopsy was performed before initiating high-dose intravenous methylprednisolone. Infiltration of lymphocytes and plasmatic cells with a patchy pattern around microvessels was encountered (Fig. 1f). Corticosteroid treatment was followed by an outstanding clinical improvement, and antibodies against glial fibrillary acidic protein (GFAP) were reported in the CSF sample using indirect immunofluorescence with human embryonic kidney 293 (HEK-293) cells transfected for the expression of GFAP-α isoform. Cyclophosphamide was initiated. Control brain MRI performed 3 and 6 months later showed normalization, and cognitive evaluation showed marked improvement. No underlying neoplasm was discovered 1 year after symptoms onset. Rapidly progressive dementia often prompts diagnosis of prion diseases; however, an extensive workup is required as some reversible conditions can present similarly [2]. Autoimmune GFAP astrocytopathy is a recently described form of steroid-responsive meningoencephalomyelitis [3]. GFAP is an intracellular protein not accessible to IgG in intact glial cells. Rather than an ultimate cause, autoantibodies are thought to be surrogate markers of an underlying complex autoimmune process that involves cytotoxic T cells [4, 5]. The condition typically develops in middle-age patients, occasionally with a prodrome of respiratory infection followed by headache, fever, ataxia, and motor and sensory deficits. Rapidly progressive dementia can be an infrequent presentation [4, 6] of which neurologists should be aware. Typical CSF findings show lymphocytic pleocytosis and * Carlos Toledano-Illán [email protected]