Autopsy Case of Meningoencephalomyelitis Associated With Glial Fibrillary Acidic Protein Antibody

Yamakawa, Mai; Hogan, Keenan O.; Leever, John; Jassam, Yasir

doi:10.1212/nxi.0000000000001081

Cited by 11 publications

(9 citation statements)

References 11 publications

(18 reference statements)

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“…Although GFAP-Ab were identified in 21 of 31 examined patients, GFAP is an intracellular autoantigen, thus the IgG GFAP-Ab is unlikely pathogenic ( 1 ). GFAP-positive meningoencephalitis is currently presumed to be T-cell mediated ( 25 ), and the antibodies can be seen without association of distinct clinical-radiological features ( 3 ), but the presence of IgG GFAP-Ab provides a clue supporting immune-mediated disorder as a biomarker of the disease.…”

Section: Discussionmentioning

confidence: 99%

Neuronal surface antigen-specific immunostaining pattern on a rat brain immunohistochemistry in autoimmune encephalitis

et al. 2023

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A variety of neuronal surface (NS) antibodies (NS-Ab) have been identified in autoimmune encephalitis (AE). Tissue-based assay (TBA) using a rodent brain immunohistochemistry (IHC) is used to screen NS-Ab, while cell-based assay (CBA) to determine NS antigens. Commercial rat brain IHC is currently available but its clinical relevance remains unclear. Immunostaining patterns of NS antigens have not been extensively studied yet. To address these issues, we assessed a predictive value of “neuropil pattern” and “GFAP pattern” on commercial IHC in 261 patients, and characterized an immunostaining pattern of 7 NS antigens (NMDAR, LGI1, GABAaR, GABAbR, AMPAR, Caspr2, GluK2). Sensitivity and specificity of “neuropil pattern” for predicting NS-Ab were 66.0% (95% CI 55.7-75.3), and 98.2% (95% CI 94.8-99.6), respectively. False-positive rate was 1.8% (3/164) while false-negative rate was 34.0% (33/97). In all 3 false-positive patients, neuropil-like staining was attributed to high titers of GAD65-Ab. In 33 false-negative patients, NMDAR was most frequently identified (n=18 [54.5%], 16/18 [88.9%] had low titers [< 1:32]), followed by GABAaR (n=5). Of 261 patients, 25 (9.6%) had either GFAP (n=21) or GFAP-mimicking pattern (n=4). GFAP-Ab were identified in 21 of 31 patients examined with CBA (20 with GFAP pattern, 1 with GFAP-mimicking pattern). Immunostaining pattern of each NS antigen was as follows: 1) NMDAR revealed homogenous reactivity in the dentate gyrus molecular layer (DG-ML) with less intense dot-like reactivity in the cerebellar granular layer (CB-GL); 2) both GABAaR and GluK2 revealed intense dot-like reactivity in the CB-GL, but GABAaR revealed homogenous reactivity in the DG-ML while GluK2 revealed intense reactivity along the inner layer of the DG-ML; and 3) LGI1, Caspr2, GABAbR, and AMPAR revealed intense reactivity in the cerebellar ML (CB-ML) but LGI1 revealed intense reactivity along the middle layer of the DG-ML. Whereas, Caspr2, GABAbR, and AMPAR revealed similar reactivity in the DG-ML but some difference in other regions. TBA is useful not only for screening NS- or GFAP-Ab but also for estimating NS antigens; however, negative results should be interpreted cautiously because “neuropil pattern” may be missed on commercial IHC when antibody titers are low. Antigen-specific immunoreactivity is a useful biomarker of AE.

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Section: Discussionmentioning

confidence: 99%

Neuronal surface antigen-specific immunostaining pattern on a rat brain immunohistochemistry in autoimmune encephalitis

et al. 2023

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“…The role of GFAP antibody as an antibody to intracellular antigen has not been unanimously recognized. It has been reported [ 17 ] that absence of astrocytes involvement was found in autopsies of GFAP-positive patients. GFAP encephalitis is sensitive to hormones, but the effect of human immunoglobulin on GFAP encephalitis is unclear and needs to be further studied in depth.…”

Section: Discussionmentioning

confidence: 99%

A case report of autoimmune GFAP astrocytopathy presenting with abnormal heart rate variability and blood pressure variability

et al. 2023

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Background Autonomic dysfunctions including bladder dysfunction, gastrointestinal dysfunction and orthostasis are common symptoms of autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A); however, cardiac autonomic dysfunction and abnormal circadian rhythm of blood pressure, which can lead to poor prognosis and even sudden cardiac death, has never been reported in A-GFAP-A patient. Case presentation A 68-year-old male Chinese patient presented to our hospital with headache, fever, progressive disturbance of consciousness, dysuria, and limb weakness. Abnormal heart rate variability and non-dipper circadian rhythm of blood pressure gradually developed during hospitalization, which is rare in A-GFAP-A. He had positive GFAP IgG in cerebrospinal fluid (CSF). Enhanced brian MRI showed uneven enhancement and T2 hyperintense lesions of medulla oblongata; Cervical spine MRI showed T2 hyperintense lesions in medulla oblongata and upper margin of the T2 vertebral body. A contrast-enhanced thoracic spine MRI showed uneven enhancement and T2 hyperintense lesions of T1 to T6 vertebral segments. After treatment with intravenous immunoglobulin and corticosteroids, the patient’s symptoms, including autonomic dysfunction, alleviated dramatically. Finally, his heart rate variability and blood pressure variability became normal. Conclusions Our case broadens the spectrum of expected symptoms in A-GFAP- A syndromes as it presented with heart rate variability and blood pressure variability.

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“…There is limited information about the histopathological research of GFAP astrocytopathy. An autopsy case demonstrated diffuse inflammation involving the brain parenchyma, perivascular spaces, and leptomeninges, with prominent T-cells, macrophages, and activated microglia [ 13 ]. Histopathology analysis of a leptomeningeal biopsy specimen illustrated a mononuclear infiltration with macrophages and CD8 + T cells [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Area postrema syndrome with linear enhancement along the surface of the brainstem and fourth ventricle in autoimmune GFAP astrocytopathy

Liang

Shen

2023

BMC Neurol

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Background Glial fibrillary acidic protein (GFAP) astrocytopathy, a novel autoimmune disease of the nervous system, was first defined in 2016. To our knowledge, area postrema syndrome (APS) with linear enhancement along the surface of the brainstem and fourth ventricle is extremely rare in this disorder. Case presentation A Chinese woman presented with intractable nausea and vomiting after onset of flu-like symptoms. Brain magnetic resonance imaging (MRI) disclosed abnormal signal intensities in the dorsal medulla oblongata including area postrema. Besides, linear enhancement surrounding the surface of the brainstem and fourth ventricle was visualized after gadolinium injection. Cerebrospinal fluid (CSF) analysis showed increased cell count and protein. A cell-based assay was positive for anti-GFAP IgG in CSF. She was diagnosed with autoimmune GFAP astrocytopathy and treated with high-dose glucocorticoid. The patient received a quick recovery with entire resolution of the initial abnormalities. Conclusions Isolated APS can be the initial manifestation of autoimmune GFAP astrocytopathy. Linear enhancement surrounding the surface of the brainstem and fourth ventricle is another neuroradiological hallmark.

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Autopsy Case of Meningoencephalomyelitis Associated With Glial Fibrillary Acidic Protein Antibody

Cited by 11 publications

References 11 publications

Neuronal surface antigen-specific immunostaining pattern on a rat brain immunohistochemistry in autoimmune encephalitis

Neuronal surface antigen-specific immunostaining pattern on a rat brain immunohistochemistry in autoimmune encephalitis

A case report of autoimmune GFAP astrocytopathy presenting with abnormal heart rate variability and blood pressure variability

Area postrema syndrome with linear enhancement along the surface of the brainstem and fourth ventricle in autoimmune GFAP astrocytopathy

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