A Case Report of Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Diagnosed After Long Term Diagnosis of Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids

Abstract

Cases of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy who were initially diagnosed with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) were rarely reported. Herein, we reported a 31-year-old woman who presented with 7 years of recurrent headache. Her clinical history, symptoms, brain MRI enhancement features, and response to treatment during each attack were reviewed. Her brain MRI 7 years ago demonstrated characteristic pepper-like enhancement of pontine and cerebellum and her symptoms resolved completely after taking a high-dose of steroids. She was suspected with the diagnosis of CLIPPERS, and she experienced five relapses once the oral steroid was tapered below 20 mg/day. During her last relapse, she experienced fever and psychosis, and GFAPα-antibodies were detected in her serum and cerebrospinal fluid by antigen-transfected HEK293 cell-based assay (indirect immunofluorescence assay). She obtained relief again after steroid therapy, and her diagnosis converted to autoimmune GFAP astrocytopathy. Autoimmune GFAP astrocytopathy may mimic CLIPPERS, both clinically and radiologically. Long-term follow-up is essential for necessary diagnosis revision at each new attack in patients with a diagnosis of CLIPPERS.

Repeated Brain Magnetic Resonance Imaging Provides Clues for the Diagnosis of Autoimmune Glial Fibrillary Acid Protein Astrocytopathy

“…These patients were similar to our own in that characteristic enhancement was revealed after initially unremarkable MRI findings, but their clinical courses involved relapse and remission or were insidious. Some patients with GFAP-A experience relapses ( 9 ) or chronic progression ( 10 , 11 ), but this is not common for GFAP-A. Our patient showed an acute meningoencephalitis-like disease course, which is representative of GFAP-A, and characteristic enhancement was observed even after intravenous methylprednisolone therapy in the acute phase.…”

“…Since we did not strongly suspect that he had GFAP-A at first, we did not check for antibodies on admission. Previously, a 31-year-old woman who had been receiving oral corticosteroids for 7 years, and initially been diagnosed with chronic lymphocytic inflammation with pontine perivascular enhancement-responsive lesions was reevaluated at the time of the seventh relapse, when haracteristic gadolinium enhancement of GFAP-A was first observed ( 9 ). Furthermore, a rapidly progressive demented 54-year-old man whose symptoms mimicked Creuzfeldt-Jakob disease was confirmed to have GFAP-A at six months from the first brain MRI ( 10 ).…”

CLIPPERS: Multiparametric and quantitative MRI features

“…In this report, we present a unique fatal case of a briefly observed clinical history of a patient as well as repeated MRI with several atypical features fulfilling revised criteria for CLIPPERS [12] . The young woman did not have typical manifestations of subacute pontocerebellar dysfunction, such as gait ataxia and diplopia.…”

“…It has been proposed that a relapse with atypical symptoms or radiological features should be a “red flag” suggestive of a diagnosis of CLIPPERS [12] . Our patient showed an extreme and unusual discrepancy between the clinical and radiological findings, which caused us to revise the diagnosis by additional MRI quantitative techniques.…”

“…Although ideally, neuropathological analysis should be performed in suspected CLIPPERS, this approach will be infeasible in many cases where vital CNS regions are affected primarily, as in our case. A blood or CSF sample of the patient during and after a flareup is not always available for antibody tests to exclude other autoimmune CLIPPERS-like diseases that should be taken into account in the differential diagnosis: autoimmune glial fibrillary acidic protein astrocytopathy [12] and neuromyelitis optica spectrum disorders [2] . Even in cases where a CSF analysis is performed in CLIPPERS, it yields inconsistent patterns, including mild pleocytosis, mildly elevated protein levels, and/or (partially transient) CSF oligoclonal bands, without malignant cells [ 1 , 17 ].…”