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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 GFAP?-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.

SUBMITTER: Yin HX

PROVIDER: S-EPMC7705065 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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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.

Yin He-Xiang HX Zhou Yan Y Xu Yan Y Li Ming-Li ML Zhang Zhe Z Zhou Li-Xin LX Zhang Yao Y Zhu Yi-Cheng YC Peng Bin B Cui Li-Ying LY

Frontiers in neurology 20201117

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 characterist ...[more]

PMID: 33281735

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Project description:Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relatively newly discovered and characterized condition affecting the central nervous system (CNS) that involves the brainstem almost ubiquitously and that focuses primarily on the pons. Characteristically, CLIPPERS represents a combination of clinical symptoms related to the pathology of the brainstem in particular and has a characteristic appearance on magnetic resonance imaging (MRI), with punctate and curvilinear gadolinium enhancement 'peppering' the pons. The lesions can be viewed via neuroimaging with a predominance in the pons and adjacent rhombencephalic structures, such as the cerebellar peduncles, cerebellum, medulla, and middle brain. These lesions may also spread and appear in other areas of the brain such as the thalamus or white matter. As the name suggests, this clinical syndrome responds to immunosuppressive treatment based on glucocorticosteroids (GCSs), expressed as both clinical and radiological improvements. Support for this treatment is required for a long period, since exacerbations may occur without. Thus, the diagnosis of CLIPPERS has garnered increased attention from clinicians and the active exclusion of differential alternative diagnoses is needed. A specific biomarker of serum or cerebrospinal fluid (CSF) for this condition has not been discovered. The pathophysiology of this condition is not fully elucidated, and it is not yet clear whether CLIPPERS is a disease in its own right or is the culmination of several already known syndromes. Clinicians and radiologists should pay close attention to this condition as it is relatively easy to treat and patients can benefit from the early introduction of GCSs, which can produce significant results through long-term immunosuppression. Taking into account previous reports in the literature, which currently include over 50 cases reported as CLIPPERS, this analysis addressed the clinical features, and paraclinical and differential diagnoses of cases described in the literature.

Project description:Objective:Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare syndrome with relapsing brainstem/cerebellar symptoms. To examine the pathogenic processes and investigate potential biomarkers, we analyzed combined materials of brain and cerebrospinal fluid (CSF) by comprehensive methodologies. Materials and methods:To identify major pathways of perivascular inflammation in CLIPPERS, we first compared the CSF proteome (n = 5) to a neurodegenerative condition, Alzheimer's disease (AD, n = 5). Activation of complement was confirmed by immunohistochemistry (IHC) on CLIPPERS brain samples (n = 3) and by ELISA in the CSF. For potential biomarkers, we used biomarker arrays, and compared inflammatory and vessel-associated proteins in the CSF of CLIPPERS (n = 5) with another inflammatory relapsing CNS disease, multiple sclerosis (RMS, n = 9) and healthy subjects (HS, n = 7). Results:Two hundred and seven proteins in the CSF discriminated CLIPPERS from AD. The complement cascade, immunoglobulins, and matrix proteins were among the most frequently represented pathways. Pathway analysis of upstream regulators suggested the importance of vascular cell adhesion protein 1 (VCAM1), IFN-γ, interleukin (IL)-1, and IL-10. Differential regulation of more than 10 complement proteins of the 3 complement pathways in the CSF pointed to the role of complement activation. IHC on brain samples confirmed the perivascular complement activation, i.e., deposition of C3bc, C3d, and the terminal C5b-9 complement complex that partially overlapped with accumulation of IgG in the vessel wall. Besides endothelial cell damage, reactivity to smooth muscle actin was lost in the walls of inflamed vessels, but the glia limitans was preserved. The semi-quantitative array indicated that increased level of IL-8/CXCL8 (p < 0.05), eotaxin/CCL11 (p < 0.01), and granulocyte colony-stimulating factor (p < 0.05) in CSF could distinguish CLIPPERS from HS. The quantitative array confirmed elevated concentration of IL-8/CXCL8 and eotaxin/CCL11 compared to HS (p < 0.05, respectively) besides increased levels of ICAM-1 (p < 0.05) and VCAM-1 (p < 0.001). The increased concentration of VCAM-1 were able to differentiate CLIPPERS from RMS (p < 0.01), and a trend of elevated levels of ICAM-1 and IL-8/CXCL8 compared to RMS was also observed (p = 0.06, respectively). Conclusion:Complement activation, IgG deposition, and alterations of the extracellular matrix may contribute to inflammation in CLIPPERS. VCAM1, ICAM1, and IL-8 in the CSF may differentiate CLIPPERS from RMS.

Project description:Background and objectivesGlial fibrillary acidic protein (GFAP) antibodies can associate with an astrocytopathy often presenting as a meningoencephalitis. Visual involvement has been reported but scarcely defined. We describe 2 cases of GFAP astrocytopathy with predominant visual symptoms and present a systematic review of the literature.MethodsWe describe 2 patients with GFAP astrocytopathy from our neurology department. We performed a systematic review of the literature according to PRISMA guidelines, including all patients with this disease and available clinical data, focusing on visual involvement.ResultsPatient 1 presented with bilateral optic disc edema and severe sudden bilateral loss of vision poorly responsive to therapy. Patient 2 showed bilateral optic disc edema, headache, and mild visual loss with complete recovery after steroids. We screened 275 records and included 84 articles (62 case reports and 22 case series) for a total of 592 patients. Visual involvement was reported in 149/592 (25%), with either clinical symptoms or paraclinical test-restricted abnormalities. Bilateral optic disc edema was found in 80/159 (50%) of patients investigated with fundoscopy, among which 49/80 (61%) were asymptomatic. One hundred (100/592, 17%) reported visual symptoms, often described as blurred vision or transient visual obscurations. Optic neuritis was rare and diagnosed in only 6% of all patients with GFAP astrocytopathy, often without consistent clinical and paraclinical evidence to support the diagnosis. Four patients (including patient 1) manifested a severe, bilateral optic neuritis with poor treatment response. In patients with follow-up information, a relapsing disease course was more frequently observed in those with vs without visual involvement (35% vs 11%, p = 0.0035, OR 3.6 [CI 1.44-8.88]).DiscussionVisual system involvement in GFAP astrocytopathy is common and heterogeneous, ranging from asymptomatic bilateral optic disc edema to severe bilateral loss of vision, but optic neuritis is rare. GFAP CSF antibody testing should be considered in patients with encephalitis/meningoencephalitis or myelitis and bilateral optic disc edema, even without visual symptoms, and in patients with severe bilateral optic neuritis, especially when AQP4 antibodies are negative. Visual symptoms might associate with a higher relapse risk and help to identify patients who may require chronic immunosuppression.

Project description:BackgroundThe phenotype of peripheral neuropathy (PN) associated with glial fibrillary acidic protein-immunoglobulin G (GFAP-IgG) has not been well described.ObjectivesThe aim of this study was to report the frequency, clinical, and electrophysiological characteristics of PN in GFAP-IgG-positive patients.DesignThis study is a single-center retrospective observational study.Data sources and methodsGFAP-IgG-positive patients with PN were retrospectively identified from the Huashan Hospital Autoimmune Encephalitis Cohort between 2017 and 2021. Eight patients who presented with PN from other published studies were also included in the analysis. The clinical and electrophysiological characteristics of GFAP-IgG-related PN were described.ResultsA total of 21 (31%) patients (7 females, 14 males; M age: 42 ± 16 years) from a cohort of 68 GFAP-IgG-positive patients presented with PN. Twenty of 21 patients had symmetrical weakness. Sensory and autonomic symptoms were present in 16 and 15 patients, respectively. Lower extremities were the most frequently involved regions for both motor (20/21) and sensory (15/21) symptoms. Moreover, 13 patients (4 females, 9 males; M age: 43 ± 13 years) had electrodiagnostic study data, and 12 of 13 patients had abnormal findings. Regarding clinical features, motor nerve fibers were predominantly involved (12/13), and symmetric lower extremities (12/13) were the most commonly affected regions. Axonal neuropathy is the typical underlying pathophysiologic process of PN. All 21 patients responded to immunotherapy. However, four patients with tetraplegia had poor outcomes, and PN was the major determinant of their long-term disability. Most cases (6/8) from the literature presented with similar clinical and electrophysiological features to those from our cohort.ConclusionPeripheral nerves could be involved in autoimmune GFAP astrocytopathy. Predominant motor axonal neuropathy mainly involving the lower extremities is the most common PN phenotype in this disorder. GFAP-IgG-related PN is responsive to immunotherapy.RegistrationChinese Clinical Trial Registry: ChiCTR2000029115 (http://www.chictr.org).

Dataset Information

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.

Publications

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.

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