Contactin‐Associated Protein‐Like 2 (CASPR2)–Associated Movement Disorder in a Child

Abstract

A 5-year-old boy with a 1-month history of seizures and abnormal twisting movements and posturing of the left upper and lower limbs presented to us with altered sensorium and involuntary jerks for the past 1 week. The child was born out of a nonconsanguineous marriage with full-term normal vaginal delivery. Antenatal, perinatal, and postnatal periods were uneventful. Developmental milestones including motor and language milestones were achieved appropriate to age. Immunization history was normal as per the schedule. Child's cognition was normal, and there were no other comorbidities before this illness. No history suggestive of autonomic involvement, sleep disturbances, mood/psychiatric issues, or peripheral nerve symptoms was found. Neurological examination revealed altered mental status with dystonic posturing of the bilateral upper limbs and left lower limb and myoclonic jerks noted over the left upper limb and left lower limb (Video 1 ). His routine blood counts, biochemical profile, serum ceruloplasmin, systemic autoimmune markers, cerebrospinal fluid (CSF) immunoglobulin G index for measles, nerve conduction studies (NCS), electromyography, electroencephalogram, and cranial magnetic resonance imaging were normal. CSF analysis revealed 6 cells and 0.25 g/L protein and glucose of 2.6 mmol/L. Contactin-associated protein-like 2 (CASPR2) antibodies assessed by cell-based assay were found to be positive in the serum sample. The patient was initiated on intravenousimmunoglobulin (IVIG) at a dose of 2 g/kg for 5 days followed by oral steroids. The child's altered sensorium improved, and the myoclonic jerks were reduced. The patient was screened for underlying malignancy, which was negative. Autoimmune syndromes are an important cause of treatable movement disorders, and hence early recognition is of prime importance.1 They may mimic metabolic or neurodegenerative diseases. Chorea, dyskinesias, cerebellar ataxia, dystonia, myoclonus, parkinsonism, tics, tremors, and stiff person spectrum disorders are some of the movement disorders with associated autoantibodies.1 The occurrence of some of them gives a strong clue to the underlying antibody because of their high specificity. Anti-N-methyl-d-aspartate receptor-encephalitis, the most common form of autoimmune encephalitis predominantly involving young individuals, is characterized by neuropsychiatric manifestations, speech abnormalities, memory disturbances, autonomic dysfunction, and a wide variety of movement disorders. Antibodies directed to proteins such as Leucine-rich glioma-inactivated 1 (LGI1), CASPR2, and rarely to contactin-2 are most frequently encountered in patients with limbic encephalitis.2 CASPR2, a membrane protein expressed both in the central and peripheral nervous system, is essential for proper localization of voltage-gated potassium channels (VGKC).3 The clinical spectrum of CASPR2 antibodies is broader in comparison with antibodies to LGI1, which is mainly associated with limbic encephalitis and faciobrachial dystonic seizures. Neuromyotonia, neuropathic pain, insomnia, dysautonomia, and weight loss are more common in patients with CASPR2 antibodies compared with patients with LGI1antibody positivity.3 Movement disorders are rarely seen in association with CASPR2 antibodies. Chorea in association with behavioral changes, paroxysmal myoclonus, and parkinsonism are the movement disorders rarely reported in patients with CASPR2 antibodies.1, 3 More than 60% of the patients had 4 or more of the core symptoms: cerebral symptoms (cognition, epilepsy), cerebellar symptoms, weight loss, peripheral nerve hyperexcitability (PNH), autonomic dysfunction, neuropathic pain, and insomnia.3 Idiopathic chorea in an adult with CASPR2 antibodies3 and isolated chorea with and without limbic encephalitis in adults with LGI1 antibodies have been previously described in single case reports.4 A case of CASPR2-mediated autoimmune limbic encephalitis in a 19-month-old toddler in India has been recently described.5 In 1 of the recently reported case series, encephalopathy, seizures, and PNH were the commonly reported symptoms.6 Movement disorders associated with CASPR2 antibodies are rare and underreported. Our patient presented with encephalitis, dystonia, and myoclonus. He responded to immunotherapy thus emphasizing the need for early diagnosis and treatment. With the discovery of an array of antineuronal autoantibodies, there has been an expansion in the phenotypic spectrum of autoimmune movement disorders in children. As early diagnosis and treatment improve the outcomes, prompt recognition by the practicing clinician is of utmost importance. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. R.B.R.N.: 1A, 1B, 1C, 2A, 2B A.K.: 1A, 2B D.J.: 1A, 1B, 2B The authors confirm that the approval of an institutional review board was not required for this work. We also confirm that the written informed consent was obtained from the parents for the publication of the video. We confirm that we have read the Journal's position on issues involved in the ethical publication and affirm that this work is consistent with those guidelines. No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. The authors declare that there are no additional disclosures to report.