Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens

Yael Hacohen, Sukhvir Wright, Patrick Waters, Shakti Agrawal, Lucinda Carr, Helen Cross, Carlos De Sousa, Catherine DeVile, Penny Fallon, Rajat Gupta, Tamasine Hedderly, Elaine Hughes, Tim Kerr, Karine Lascelles, Jean-Pierre Lin, Sunny Philip, Keith Pohl, Prab Prabahkar, Martin Smith, Ruth WilliamsAntonia Clarke, Cheryl Hemingway, Evangeline Wassmer, Angela Vincent, Ming Lim

    Research output: Contribution to journalArticlepeer-review

    198 Citations (Scopus)

    Abstract

    Objective: To report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens.

    Method: Patients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007-2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B) R and glutamic acid decarboxylase.

    Results: Seizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to influence the treatment effect.

    Conclusions: Our study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further antibody targets may be defined in the future.

    Original languageEnglish
    Pages (from-to)748-755
    Number of pages8
    JournalJournal of Neurology, Neurosurgery and Psychiatry
    Volume84
    Issue number7
    DOIs
    Publication statusPublished - Jul 2013

    Keywords

    • ASPARTATE RECEPTOR ENCEPHALITIS
    • VGKC-COMPLEX ANTIBODIES
    • LIMBIC ENCEPHALITIS
    • PROGRESSIVE ENCEPHALOMYELITIS
    • EPILEPTIC ENCEPHALOPATHY
    • NMDAR ENCEPHALITIS
    • CHILDREN
    • ADOLESCENTS
    • ETIOLOGIES
    • CHALLENGES

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