Clinical Features and Outcomes in Pediatric Autoimmune Encephalitis Associated With CASPR2 Antibody.

Chengbing Tan,Yue Hu,Yan Jiang,Li Jiang,Min Zhong,Xiujuan Li,Siqi Hong

doi:10.3389/fped.2021.736035

Abstract

Background: Contactin-associated protein-like 2 (CASPR2) neurological autoimmunity has been associated with various clinical syndromes involving central and peripheral nervous system. CASPR2 antibody-associated autoimmune encephalitis is mostly reported in adults. Analysis of the clinical presentation and prognostic data of CASPR2 antibody-associated autoimmune encephalitis in children remains important.Methods: A single-center retrospective review of children diagnosed with CASPR2 antibody-associated autoimmune encephalitis from June 1st, 2018 to October 31st, 2020.Results: Six patients were identified. The median age was 12 years (range 1.8–14), with an overall male predominance of 83% (5/6). Commonest clinical features were psychiatric symptoms (6/6), movement disorders (4/6), altered consciousness (3/6), sleep disorders (3/6), and headache (3/6). Four patients (4/6) received first-line therapy alone (steroids combined with intravenous immunoglobulins), and two patients (2/6) received second-line therapy (rituximab, mycophenolate mofetil, or cyclophosphamide). All patients showed no peripheral nervous system involvement. One patient had comorbidities with systemic lupus erythematosus. No evidence of neoplastic disease was found in the whole cohort. All patients had favorable outcomes (modified Rankin Score 0–2) with recurrence rate at 0%, respectively.Conclusion: CASPR2 antibody-associated autoimmune encephalitis is rare in children. Our findings suggest that this type of encephalitis seems to occur more frequently in older children. Patients respond well to immunotherapy and usually demonstrate a favorable clinical outcome. Associated tumors are extremely rare.

Highlights

Autoimmune encephalitis (AE) refers to a group of antibody-mediated inflammatory diseases of the brain
All the patients included in the study met the pediatric autoimmune encephalitis criteria as follows [5]: [1] Onset of neurologic and/or psychiatric symptoms over ≤3 months in a previously healthy child; [2] Two or more clinical features including altered mental status/level of consciousness or EEG with slowing or epileptiform activity, focal neurologic deficits, cognitive difficulties, acute developmental regression, movement disorder, psychiatric symptoms, seizures not explained by a previously known seizure disorder or other condition; [3] Two or more neuroinflammation features including cerebrospinal fluid (CSF) inflammatory changes, magnetic resonance imaging (MRI) features of encephalitis, brain biopsy showing inflammatory infiltrates and excluding other disorders; [4] Presence in serum and/or CSF of well-characterized autoantibodies associated with AE; [5] Reasonable exclusion of alternative causes
Sera or CSF Caspr2IgG were detected by a cell-based assay (CBA) using human embryonic kidney (HEK293T) cells transiently co-transfected with full-length human Caspr2 and pcDNA3.1-EGFP

Summary

Introduction

Autoimmune encephalitis (AE) refers to a group of antibody-mediated inflammatory diseases of the brain. Voltage-gated potassium channels (VGKCs) are present on the membrane of neurons in both the central and peripheral nervous system which were initially detected in rare patients suffering from neuromyotonia (NMT) in 1995. Mutations in the gene encoding CASPR2 have been reported in patients with autism spectrum disorder, epilepsy and other neuropsychiatric problems. The clinical spectrum of autoimmune diseases associated with antiCASPR2 antibody can manifest as encephalitis, NMT, MoS and painful neuropathy, and are mostly reported in adults [3]. We report 6 pediatric cases of CASPR2 antibody-associated autoimmune encephalitis. Contactin-associated protein-like 2 (CASPR2) neurological autoimmunity has been associated with various clinical syndromes involving central and peripheral nervous system. Analysis of the clinical presentation and prognostic data of CASPR2 antibody-associated autoimmune encephalitis in children remains important

Methods

Results

Discussion

Conclusion