From the Division of Infectious Diseases and Immunology (M.S.W.Q., C.V., A.M.C.R.), Department of Pediatrics, Erasmus MC University Medical Center-Sophia Children's Hospital; Department of Neurology (M.S.J.B., M.J.T., R.F.N.); Department of Clinical Genetics (V.J.M.V.), Erasmus MC University Medical Center, Rotterdam; Pediatric Stem Cell Transplantation Program (E.P.B.), Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center; Division Gastroenterology and Nutrition (M.H., J.N.S.), Department of Pediatrics/Laboratory of Pediatrics, Erasmus MC University Medical Center; and Division of Rheumatology (S.K.), Department of Pediatrics, Erasmus MC University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
Neurol Neuroimmunol Neuroinflamm. 2024 Jul;11(4):e200254. doi: 10.1212/NXI.0000000000200254. Epub 2024 May 10.
We report on the therapeutic management of early-onset severe neurologic symptoms in cytotoxic T lymphocyte antigen-4 haploinsufficiency (CTLA-4h) and the presence of antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) as an important finding.
This is a case report from a Dutch academic hospital. Repeated clinical examinations, repeated brain MRI and extended diagnostics on serum and CSF were performed. We used the CARE checklist.
A 7-year-old boy was diagnosed with CTLA-4h based on family screening. On diagnosis, he had mild chronic diarrhea and autism spectrum disorder, but no abnormalities in extensive laboratory screening. Six months later, he presented with sudden-onset autoimmune encephalitis. Repeated brain MRI revealed no abnormalities, but immunohistochemistry analysis on serum and CSF showed the presence of AMPAR antibodies. Treatment was initially focused on immunomodulation and targeted CTLA-4 replacement therapy. Because of the persistent fluctuating cerebellar and neuropsychiatric symptoms and the potential clinical significance of the AMPAR antibodies, treatment was intensified with repetition of first-line immunomodulation and rituximab. This combined therapy resulted in sustained clinical improvement and served as a bridge to curative hematopoietic stem cell transplantation.
This case illustrates the rare early onset of autoimmune encephalitis and presence of AMPAR antibodies in CTLA-4h. Targeted CTLA-4 replacement therapy resulted in a partial response. However, awaiting its optimal therapeutic effect, refractory CNS symptoms required intensification of immunomodulation. The identification of AMPAR antibodies guided our treatment decisions.
This provides Class IV evidence. It is a single observational study without controls.
我们报告了细胞毒性 T 淋巴细胞相关抗原 4 单倍体不足（CTLA-4h）患者出现早期严重神经症状的治疗管理情况，以及抗α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）抗体的出现是一个重要发现。
这是一家荷兰学术医院的病例报告。对患者进行了反复的临床检查、反复的脑部 MRI 检查以及血清和 CSF 的扩展诊断。我们使用了 CARE 清单。
一名 7 岁男孩通过家族筛查被诊断为 CTLA-4h。确诊时，他有轻度慢性腹泻和自闭症谱系障碍，但广泛的实验室筛查未见异常。6 个月后，他突然出现自身免疫性脑炎。反复的脑部 MRI 未见异常，但血清和 CSF 的免疫组化分析显示存在 AMPAR 抗体。治疗最初侧重于免疫调节和靶向 CTLA-4 替代治疗。由于持续波动的小脑和神经精神症状以及 AMPAR 抗体的潜在临床意义，治疗方案被强化，重复使用一线免疫调节和利妥昔单抗。这种联合治疗导致持续的临床改善，并作为治愈性造血干细胞移植的桥梁。
该病例说明了 CTLA-4h 患者中罕见的自身免疫性脑炎早期发病和 AMPAR 抗体的存在。靶向 CTLA-4 替代治疗导致部分缓解。然而，在等待其最佳治疗效果的同时，中枢神经系统症状的难治性需要强化免疫调节。AMPAR 抗体的鉴定指导了我们的治疗决策。
这提供了 IV 级证据。这是一项没有对照的单中心观察性研究。
