Saab Georges, Munoz David G, Rotstein Dalia L
Department of Medicine, University of Toronto, Toronto, ON, Canada.
St. Michael's Hospital, Toronto, ON, Canada.
Front Neurol. 2022 May 13;13:863151. doi: 10.3389/fneur.2022.863151. eCollection 2022.
Cognitive impairment may be associated with aquaporin-4 antibody positive (AQP4+) NMOSD, particularly where there is prominent cerebral, corpus callosum, or thalamic involvement. It is unclear to what extent this phenomenon may be treatable after months to years. We describe two cases of AQP4+ NMOSD with cognitive impairment persisting over more than 6 months, where cognition improved after eculizumab was initiated. In the first case, a 51-year-old woman presented with a 2-month history of cognitive decline and ataxia, and diffuse involvement of the corpus callosum on MRI. AQP4 antibody testing returned positive. Cognitive impairment persisted on therapy with mycophenolate, then rituximab. She was switched to eculizumab from rituximab 18 months after disease onset because of breakthrough optic neuritis; memory and cognitive function improved on eculizumab. In the second case, a 26-year-old woman initially presented with visual, auditory and tactile hallucinations, and impairment in activities of daily living, and was given a diagnosis of schizophrenia. Nine months later she was hospitalized for increasing confusion. MRI showed leukoencephalopathy and diffuse involvement of the corpus callosum with multiple enhancing callosal lesions. AQP4 antibody testing was positive and CSF testing for other antibodies of autoimmune encephalitis was negative. She had some improvement in cognition with high dose corticosteroids but remained significantly impaired. On follow-up, her repeat MRI showed a small new right inferomedial frontal enhancing lesion although she did not complain of any new cognitive issues, her MOCA score was 21/30, and she was started on eculizumab. Two months after eculizumab initiation she and her family reported cognitive improvement and MOCA score was 25/30. Common features of these two cases included extensive callosal involvement and an element of ongoing gadolinium enhancement on MRI. Our experience suggests the possibility that cognitive impairment may be amenable to immunotherapy in certain cases of NMOSD.
认知障碍可能与水通道蛋白4抗体阳性（AQP4+）的视神经脊髓炎谱系障碍（NMOSD）相关，尤其是在存在明显的大脑、胼胝体或丘脑受累的情况下。目前尚不清楚在数月至数年之后，这种现象在何种程度上可以得到治疗。我们描述了两例AQP4+ NMOSD患者，其认知障碍持续超过6个月，在开始使用依库珠单抗后认知功能得到改善。在第一例中，一名51岁女性出现了2个月的认知衰退和共济失调病史，MRI显示胼胝体弥漫性受累。AQP4抗体检测呈阳性。在使用霉酚酸酯，然后是利妥昔单抗治疗期间，认知障碍持续存在。由于出现突破性视神经炎，在疾病发作18个月后，她从利妥昔单抗改用依库珠单抗；使用依库珠单抗后，记忆力和认知功能得到改善。在第二例中，一名26岁女性最初出现视觉、听觉和触觉幻觉以及日常生活活动障碍，并被诊断为精神分裂症。9个月后，她因意识模糊加重而住院。MRI显示白质脑病和胼胝体弥漫性受累，伴有多个胼胝体强化病灶。AQP4抗体检测呈阳性，自身免疫性脑炎其他抗体的脑脊液检测为阴性。她在使用高剂量皮质类固醇后认知功能有一些改善，但仍有明显损害。在随访中，她的重复MRI显示右额下内侧有一个新的小强化病灶，尽管她没有抱怨任何新的认知问题，她的蒙特利尔认知评估量表（MOCA）得分为21/30，于是开始使用依库珠单抗。开始使用依库珠单抗两个月后，她和家人报告认知功能有所改善，MOCA得分为25/30。这两个病例的共同特征包括胼胝体广泛受累以及MRI上持续存在钆增强成分。我们的经验表明，在某些NMOSD病例中，认知障碍可能对免疫治疗有反应。
