From the Department of Internal Medicine and Multi-Organic Diseases (C.C., P.G., P.R.), Local Referral Center for Rare Autoimmune Diseases, Montpellier University Hospital; University of Montpellier (C.C., R.G., P.L., P.G., E. Jeziorski, X.A.); Internal Medicine Department (R.G.), CHU Nîmes; Department of Neurology (P.L., C.C.-D., X.A.), Montpellier University Hospital; INM (P.L., X.A.), INSERM; Institute of Regenerative Medicine and Biotherapy (P.G.), INSERM U1183, Montpellier; Sorbonne Université (E. Januel); Institut Pierre Louis d'Epidémiologie et de Santé Publique (E. Januel), Département de Santé Publique; Département de Neurologie (E. Januel), Hôpital Pitié Salpêtrière, AP-HP, Paris; Pediatrics Department (E. Jeziorski), Montpellier University Hospital; Department of Internal Medicine (V.S.), Amiens University Medical Center; Internal Medicine Department (J.-F.V.), Bordeaux University Hospital Centre, Hôpital Haut-Lévêque, Pessac; Clinical Immunology Department (D.B., C.F.), National Reference Center for Castleman Disease; UMR 1149 CRI INSERM (D.B.), Hôpital Saint Louis, Assistance Publique Hôpitaux de Paris (APHP); Université Paris Diderot (D.B., C.F.); Inserm U1126 (C.F.), Centre Hayem, Hôpital Saint-Louis; Internal Medicine Department (D.G.), Hôpital Saint Antoine, APHP, Paris; Pediatric Oncology Hematology Unit (N.A.), Bordeaux University Hospital; Plurithématique CIC (CICP) (N.A.), Centre d'Investigation Clinique (CIC) 1401, INSERM; Centre de Référence National des Cytopénies Autoimmunes de l'Enfant (CEREVANCE) (N.A.), Bordeaux; Department of Internal Medicine (J.G.), Saint-Nazaire Hospital; Department of Internal Medicine (M.P.-J.), Purpan University Hospital, Toulouse; Department of Hematology (F.S.), Necker-Enfants Malades University Hospital, AP-HP; INSERM UMR 1163 and CNRS ERL 8254 (F.S.), Imagine Institut; Descartes University (F.S., B.N.); Pediatric Hematology-Immunology and Rheumatology Department (B.N., N.M.), Hôpital Necker-Enfants Malades, AP-HP; Laboratory of Immunogenetics of Pediatric Autoimmunity (B.N.), INSERM UMR 1163, Imagine Institute; and French National Reference Center for Primary Immune Deficiencies (CEREDIH) (N.M.), Necker Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
Neurology. 2023 Oct 10;101(15):e1560-e1566. doi: 10.1212/WNL.0000000000207609. Epub 2023 Jul 24.
CTLA4 deficiency (CTLA4d) is a disease with multisystem autoimmune features, including neurologic manifestations. We aimed to describe neurologic involvement in these patients.
We performed a cross-sectional observational study using the French Reference Centre for Primary Immunodeficiencies (CEREDIH) registry plus a surveillance in national society networks. Participants with confirmed CTLA4d and neurologic involvement were included. Clinical, laboratory, and radiologic features were collected, as well as treatments. Available MRI was double-reviewed.
Among 70 patients with CTLA4d, 13 patients (21%) had neurologic involvement. Neurologic symptoms began at a median age of 18 [15-45] years, mostly occurring after systemic manifestations (median delay: 8.5 [4.5-10.5] years). Main symptoms included headaches, focal deficit (54% each), and seizures (38%). MRI detected at least 1 large contrast-enhancing lesion in 8 patients. Lesions reminiscent of multiple sclerosis lesions were found in 6 patients. Cerebellar (6 patients) and large spinal cord lesions (3 patients) were common. Ten patients were treated with abatacept, of whom 9 (90%) showed good clinical and radiologic response.
Neurologic involvement is common among patients with CTLA4d. Despite its rarity, and considering the suspected efficacy of abatacept, neurologists should be aware of the characteristics of CTLA4d neurologic involvement.
CTLA4 缺陷（CTLA4d）是一种具有多系统自身免疫特征的疾病，包括神经系统表现。我们旨在描述这些患者的神经系统受累情况。
我们使用法国原发性免疫缺陷参考中心（CEREDIH）登记处进行了一项横断面观察性研究，并在国家学会网络中进行了监测。纳入了确诊的 CTLA4d 且有神经系统受累的患者。收集了临床、实验室和影像学特征，以及治疗方法。对现有的 MRI 进行了双盲复查。
在 70 例 CTLA4d 患者中，有 13 例（21%）存在神经系统受累。神经系统症状的发病中位年龄为 18 [15-45] 岁，主要发生在全身表现之后（中位延迟时间：8.5 [4.5-10.5] 年）。主要症状包括头痛、局灶性缺损（各占 54%）和癫痫发作（各占 38%）。8 例患者的 MRI 至少发现了 1 个大的增强病变。6 例患者发现了类似于多发性硬化病变的病变。小脑（6 例）和大脊髓病变（3 例）常见。10 例患者接受了阿巴西普治疗，其中 9 例（90%）表现出良好的临床和影像学反应。
CTLA4d 患者的神经系统受累较为常见。尽管其罕见，但考虑到阿巴西普的疑似疗效，神经科医生应了解 CTLA4d 神经系统受累的特征。
