CASPR2 autoimmunity in children expanding to mild encephalopathy with hypertension. (2nd June 2020)

• Record Type: Journal Article
• Authors: Syrbe, Steffen; Stettner, Georg M.; Bally, Julien; Borggraefe, Ingo; Bien, Corinna I.; Ferfoglia, Ruxandra Iancu; Huppke, Peter; Kern, Jan; Polster, Tilman; Probst-Müller, Elisabeth; Schmid, Silvia; Steinfeld, Robert; Strozzi, Susi; Weichselbaum, Annette; Weitz, Marcus; Ziegler, Andreas; Wandinger, Klaus-Peter; Leypoldt, Frank; Bien, Christian G.
• Is Part Of: Neurology. Volume 94:Number 22(2020)
• Publication Date: 2020-06-02
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000009523
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : 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.