钙黏蛋白 2 自身免疫性疾病在儿童中扩展为伴有高血压的轻度脑病。
CASPR2 autoimmunity in children expanding to mild encephalopathy with hypertension.
机构信息
From the Division of Pediatric Epileptology (S. Syrbe), Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg, Germany; Division of Pediatric Neurology (G.M.S., R.S.), University Children's Hospital Zurich; Department of Neurology (J.B., R.I.F.), University & University Hospitals of Geneva, Switzerland; Division of Pediatric Neurology (I.B.), Developmental Neurology and Social Pediatrics, Department of Pediatrics and Epilepsy Center for Children, Adolescents and Adults, University Hospital LMU Munich; Laboratory Krone (C.I.B., C.G.B.), Bad Salzuflen; Department of Pediatrics and Pediatric Neurology (P.H.), Faculty of Medicine, Georg August University, Goettingen; Department of Child Neurology (J.K., A.W.), University Children's Hospital, Tuebingen; Epilepsy Center Bethel (T.P., C.G.B.), Krankenhaus Mara, Bielefeld, Germany; Clinic of Immunology (E.P.-M.), University Hospital Zurich; Kantonsspital Graubünden (S. Schmid, S. Strozzi), Chur; Pediatric Nephrology Unit (M.W.), University Children's Hospital Zurich, Switzerland; Division of Child Neurology and Metabolic Medicine (A.Z.), Centre for Paediatrics and Adolescent Medicine, University Hospital Heidelberg; Institute of Clinical Chemistry (K.-P.W., F.L.), Neuroimmunology Section, University Hospital Schleswig-Holstein Kiel/Lübeck; Department of Neurology (K.-P.W.), University of Lübeck; and Department of Neurology (F.L.), Christian-Albrechts-University Kiel, Germany.
出版信息
Neurology. 2020 Jun 2;94(22):e2290-e2301. doi: 10.1212/WNL.0000000000009523. Epub 2020 May 18.
OBJECTIVE
To delineate autoimmune disease in association with contactin-associated protein 2 (CASPR2) antibodies in childhood, we reviewed the clinical phenotype of children with CASPR2 antibodies.
METHODS
Retrospective assessment of patients recruited through laboratories specialized in autoimmune CNS disease.
RESULTS
Ten children with serum CASPR2 antibodies were identified (age at manifestation 18 months to 17 years). Eight children with CASPR2 antibody titers from ≥1:160 to 1:5,120 had complex autoimmune diseases with an age-dependent clinical phenotype. Two children with structural epilepsy due to CNS malformations harbored nonspecific low-titer CASPR2 antibodies (serum titers 1:80). The clinical symptoms of the 8 children with high-titer CASPR2 antibodies were general weakness (8/8), sleep dysregulation (8/8), dysautonomia (8/8) encephalopathy (7/8), neuropathic pain (7/8), neuromyotonia (3/8), and flaccid paresis (3/8). Adolescents (3/8) showed pain, neuromyotonia, and encephalopathy, whereas younger children (5/8) displayed severe hypertension, encephalopathy, and hormonal dysfunction mimicking a systemic disease. No tumors were identified. Motor symptoms remitted with immunotherapy. Mild behavioral changes persisted in 1 child, and autism spectrum disorder was diagnosed during follow-up in a young boy.
CONCLUSION
High-titer CASPR2 antibodies are associated with Morvan syndrome in children as young as 2 years. However, CASPR2 autoimmunity mimics systemic disease and hypertensive encephalopathy in children younger than 7 years. The outcome following immunotherapy was mostly favorable; long-term behavioral impairment may occur in younger children.
目的
为了描绘与接触蛋白相关蛋白 2（CASPR2）抗体相关的自身免疫性疾病，我们回顾了 CASPR2 抗体患儿的临床表型。
方法
通过专门研究自身免疫性中枢神经系统疾病的实验室对患者进行回顾性评估。
结果
鉴定出 10 例血清 CASPR2 抗体阳性患儿（发病年龄为 18 个月至 17 岁）。8 例 CASPR2 抗体滴度为≥1:160 至 1:5,120 的患儿具有年龄依赖性的复杂自身免疫性疾病表现。2 例因中枢神经系统畸形导致结构性癫痫的患儿存在非特异性低滴度 CASPR2 抗体（血清滴度 1:80）。8 例高滴度 CASPR2 抗体患儿的临床症状为全身无力（8/8）、睡眠失调（8/8）、自主神经功能紊乱（8/8）、脑病（7/8）、神经性疼痛（7/8）、肌强直（3/8）和弛缓性瘫痪（3/8）。青少年（3/8）出现疼痛、肌强直和脑病，而年龄较小的儿童（5/8）表现为严重的高血压、脑病和类似全身性疾病的激素功能障碍。未发现肿瘤。免疫治疗后运动症状缓解。1 例患儿仍存在轻度行为改变，1 名小男孩在随访中被诊断为自闭症谱系障碍。
结论
高滴度 CASPR2 抗体与 2 岁以下儿童的莫旺综合征相关。然而，CASPR2 自身免疫在 7 岁以下儿童中表现为类似全身性疾病和高血压性脑病。免疫治疗后的结局大多良好；年龄较小的儿童可能会出现长期的行为障碍。
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