From the Department of Neurology (X.A., C.C.-D., P.L.), Montpellier University Hospital, INSERM, Univ Montpellier, Montpellier; Internal Medicine Department (R.G.), Caremeau University Hospital, Nimes; Department of Paediatrics (E.J.), Montpellier University Hospital, INSERM, Univ Montpellier; Médecine interne multi-organes (P.R., P.G.), Montpellier University Hospital, INSERM, Univ Montpellier; Department of Immunology (C.L., P.P., T.V.), Montpellier University Hospital, INSERM, Univ Montpellier; Internal Medicine Department (J.F.V.), Bordeaux University Hospital, Univ Bordeaux; Department of Neuroradiology (N.M.C.), Montpellier University Hospital, INSERM, Univ Montpellier; Université de Paris (F.R.-L., C.B.), Imagine institute, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Paris; and Laboratory of Molecular Genetics (M.K., C.G.), Montpellier University Hospital, INSERM, Univ Montpellier, France.
Neurol Neuroimmunol Neuroinflamm. 2020 Jun 4;7(4). doi: 10.1212/NXI.0000000000000751. Print 2020 Jul.
To describe the clinical and radiologic neurologic characteristics of patients with cytotoxic T-lymphocyte antigen-4 () haploinsufficiency.
Three patients from 2 families had neurologic manifestations in the context of haploinsufficiency. Their clinical and MRI findings are presented.
A 16-year-old boy with a previous diagnosis of combined immunodeficiency presented with severe recurrent episodes of headaches, motor deficit, and seizures associated with waxing and waning gadolinium-enhancing FLAIR cortical/juxtacortical hyperintensities. His sister, who also had combined immunodeficiency, had a brain MRI when she was aged 13 years due to recent headaches and transient right hemianopsia. It revealed a gadolinium-enhancing left occipital white matter hyperintensity. Another 49-year-old woman had progressive visual loss and cerebellar ataxia in the context of recurrent pulmonary infections. All 3 patients were found to have inherited haploinsufficiency. Patient 1's general condition and neurologic manifestations were completely controlled with abatacept (CTLA4-Ig).
These cases suggest that in addition to the variable clinical penetrance and wide spectrum of haploinsufficiency, its neurologic spectrum is broad, ranging from recurrent tumefactive lesions to progressive deficits including cerebellar ataxia and optic atrophy with leukoencephalopathy. These phenotypes must be recognized, and should lead to a complete immunologic workup, because potentially effective targeted immunotherapy exists.
描述细胞毒性 T 淋巴细胞相关抗原 4（）单倍体不足患者的临床和影像学神经学特征。
2 个家族的 3 名患者均存在单倍体不足伴神经表现，介绍其临床和 MRI 发现。
16 岁男孩，先前诊断为联合免疫缺陷，表现为严重复发性头痛、运动功能障碍和癫痫，伴增强钆 FLASH 皮质/皮质下高信号的时消时现。他的妹妹也患有联合免疫缺陷，13 岁时因近期头痛和短暂性右侧偏盲行脑部 MRI 检查，结果显示左侧枕叶白质增强高信号。另一名 49 岁女性因反复肺部感染出现进行性视力丧失和小脑共济失调。这 3 名患者均发现存在遗传的单倍体不足。1 号患者经阿巴西普（CTLA4-Ig）治疗后一般状况和神经表现完全控制。
这些病例提示，除了可变的临床外显率和广泛的单倍体不足外，其神经学表现谱广泛，从复发性肿块样病变到进行性神经功能缺损，包括小脑共济失调和视神经萎缩伴脑白质病。必须认识到这些表型，并应进行全面的免疫检查，因为存在潜在有效的靶向免疫治疗。
