Visual System Involvement in Glial Fibrillary Acidic Protein Astrocytopathy: Two Case Reports and a Systematic Literature Review

Abstract

Background and objectives: Glial 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.

Methods: We 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.

Results: Patient 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]).

Discussion: Visual 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.

Figure 1. GFAP Antibodies Detection in Patient 1

(A, B) Immunohistochemistry on rat brain and (C, D) in-house GFAP cell-based assay for the detection of GFAP antibodies. (A) CSF of patient 1 stains cytoplasm of astrocytes in periventricular areas (arrow). (B) This staining completely disappears after plasma exchange. (C) Cell-based assay for GFAP antibodies. The CSF IgG bind GFAP-transfected HEK293T cells. (D) Negative control (serum from a healthy subject; green: anti-human IgG; blue: 4',6-diamidino-2-phenylindole).

Figure 2. MRI and OCT Features in Patient 2

Postcontrast axial T1 MRI shows a very subtle radial enhancement and a diffuse venular congestion, both supratentorial and infratentorial, indicated by the white arrows (panels A, B).

Figure 3. Flowchart Presenting the Search Process Based on the PRISMA Systematic Review of the Literature

Figure 4. Proportion of Patients With vs Without Visual Symptoms, and Optic Disc Edema

Pie graphs on the left describe all included patients. Graphs on the right indicate the proportion of symptomatic patients with optic disc edema (when assessed; top right) and the proportion of those with optic disc edema who did or did not report visual symptoms (bottom right).