From the Hans Berger Department of Neurology (J.W., H.-Y.C., C.G., A.G.), Section of Translational Neuroimmunology, Jena University Hospital Germany; Department of Neuroradiology (K.K.), Jena University Hospital, Germany; Department of Neurology (D.B.), Sana Hospital Borna, Germany; Department of Neurology (S.M.), Heinrich-Braun Hospital, Zwickau; and Department of Neuropathology (P.K., W.C.M.), Leipzig University Hospital, Germany.
Neurol Neuroimmunol Neuroinflamm. 2020 Feb 4;7(2). doi: 10.1212/NXI.0000000000000670. Print 2020 Mar 5.
Autoimmune steroid-responsive meningoencephalomyelitis with linear perivascular gadolinium enhancement in brain MRI is regarded as glial fibrillary acidic protein (GFAP) astrocytopathy characterized by anti-GFAP antibodies (ABs). We questioned whether anti-GFAP ABs are necessarily associated with this syndrome.
Two patients with a strikingly similar disease course suggestive of autoimmune GFAP astrocytopathy are reported. Clinical examination, MRI, laboratory, and CSF analysis were performed. Neuropathologic examination of brain tissue was obtained from one patient. Serum and CSF were additionally tested using mouse brain slices, microglia-astrocyte cocultures, and a GFAP-specific cell-based assay.
Both patients presented with subacute influenza-like symptoms and developed severe neurocognitive and neurologic deficits and impaired consciousness. MRIs of both patients revealed radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter suggestive of autoimmune GFAP astrocytopathy. Both patients responded well to high doses of methylprednisolone. Only one patient had anti-GFAP ABs with a typical staining pattern of astrocytes, whereas serum and CSF of the other patient were negative and showed neither reactivity to brain tissue nor to vital or permeabilized astrocytes. Neuropathologic examination of the anti-GFAP AB-negative patient revealed infiltration of macrophages and T cells around blood vessels and activation of microglia without obvious features of clasmatodendrosis.
The GFAP-AB negative patient had both a striking (para)clinical similarity and an immediate response to immunotherapy. This supports the hypothesis that the clinical spectrum of steroid-responsive meningoencephalomyelitis suggestive of autoimmune GFAP astrocytopathy may be broader and may comprise also seronegative cases.
脑 MRI 上表现为线性血管周围钆增强的自身免疫性类固醇反应性脑膜脑炎被认为是胶质纤维酸性蛋白（GFAP）星形胶质细胞病，其特征是抗 GFAP 抗体（ABs）。我们质疑抗 GFAP AB 是否必然与该综合征相关。
报告了两例具有明显相似疾病过程的患者，提示自身免疫性 GFAP 星形胶质细胞病。进行了临床检查、MRI、实验室和 CSF 分析。从一名患者获得脑组织的神经病理学检查。使用鼠脑切片、小胶质细胞-星形胶质细胞共培养物和 GFAP 特异性基于细胞的测定法，还对血清和 CSF 进行了测试。
两名患者均表现出亚急性流感样症状，并出现严重的神经认知和神经功能缺陷以及意识障碍。两名患者的 MRI 均显示从侧脑室延伸至白质的放射状血管周围钆增强，提示自身免疫性 GFAP 星形胶质细胞病。两名患者均对大剂量甲基强的松龙反应良好。只有一名患者具有抗 GFAP AB，其具有典型的星形胶质细胞染色模式，而另一名患者的血清和 CSF 均为阴性，既没有对脑组织反应，也没有对活细胞或通透细胞反应。抗 GFAP AB 阴性患者的神经病理学检查显示血管周围巨噬细胞和 T 细胞浸润以及小胶质细胞激活，而没有明显的 clasmatodendrosis 特征。
抗 GFAP AB 阴性患者具有明显的（前）临床相似性和对免疫治疗的即刻反应。这支持了这样的假设，即类固醇反应性脑膜脑炎的临床谱提示自身免疫性 GFAP 星形胶质细胞病可能更广泛，并且可能还包括血清阴性病例。
