Abstract
Acute autoimmune encephalitis is a severe neurological disorder presenting with altered level of consciousness, confusion, irritability, headache, vomiting, and in some cases seizures. An infective event precedes by 1–2 weeks the onset of the symptoms. Cognitive impairment is considered the cardinal symptom. The autoimmune encephalitis comprises an increasingly group of inflammatory brain disorder caused by an underlying abnormal immune response to the CNS to the infective agent. In children, several antibodies have been recorded as causative agent. Among these, GAD65, MOG, and NMDAR antibodies are more commonly reported and with less frequency, the Dopamine-2 receptor, GABA A receptor, GABA B receptor, and Glycinereceptorandm-GluR5. We report here a 10-year-old male with acute autoimmune encephalitis with altered status of consciousness and severe cerebral involvement at the brain-MRI. Serum and cerebrospinal fluid disclosed the presence of anti-AMPA-GluR3 antibodies suggesting a possible pathogenetic correlation with the disorder presented by the proband. Precocious treatment with intravenous methylprednisolone and immunoglobulin resulted in progressive but constant improvement. At 3-month follow-up, the clinical condition of the child and the neuro-radiological brain anomalies returned to the normal. At the 2-year follow-up, no recurrence or other disturbances were reported.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Said S, Kang M (2021) Viral encephalitis. Stat Pearls [Internet]. Treasure Island (FL): Stat Pearls Publishing
Erickson T, Musca l, Munoz F et al (2020) Infectious and autoimmune causes of encephalitis in children. Pediatrics 145(6)
Dubey D, Pittock S, Krecke K et al (2019) Clinical, radiologic, and prognostic features of myelitis associated with myelin oligodendrocyte glycoprotein autoantibody. JAMA Neurol 76(3):301–309
de Bruijn M, Bruijstens A, Bastiaansen A et al (2020) Pediatric autoimmune encephalitis: recognition and diagnosis. Neurol Neuroimmunol Neuroinflamm 7(3):e682
Cellucci T, Van Mater H, Graus F et al (2020) Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient. Neurol Neuroimmunol Neuroinflamm 7(2):e663
Dutra L, Abrantes F, Toso F et al (2018) Autoimmune encephalitis: a review of diagnosis and treatment. Arq Neuropsiquiatr 76(1):41–49
Abboud H, Probasco J, Irani S et al (2021) Autoimmune Encephalitis Alliance Clinicians Network. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry 92(7):757–768
Hacohen Y, Wright S, Waters P et al (2013) Paediatric autoimmune encephalopathies: clinical features, laboratory investigation sand out comesin patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 84(7):748–55
Levite M (2014) Glutamate receptor antibodies in neurological diseases: anti-AMPA-GluR3antibodies, anti-NMDA-NR1 antibodies, anti-NMDA-NR2A/B antibodies, anti-mGluR1 antibodies oranti-mGluR5 antibodies are present in subpopulations of patients with either: epilepsy, encephalitis, cerebellar ataxia, systemic lupus erythematosus (SLE) and neuropsychiatric SLE, Sjogren’s syndrome, schizophrenia, mania or stroke. These autoimmune anti-glutamate receptor antibodies can bind neurons in few brain regions, activate glutamate receptors, decrease glutamate receptor’s expression, impair glutamate-induced signaling and function, activate blood brain barrier endothelial cells, kill neurons, damage the brain, induce behavioral/psychiatric/cognitive abnormalities and ataxia in animal models, and can be removed or silenced in some patients by immunotherapy. J NeuralTransm 121(8):1029–75
Spatola M, Pedrol M, Maudes E et al (2020) Clinical features, prognostic factors, and antibody effects in anti-mGluR1encephalitis. Neurology 95(22):e3012–e3025
Lancaster E, Martinez-Hernandez E, Titulaer M (2011) Antibodies to metabotropic glutamate receptor 5 in the Ophelia syndrome. Neurology 77(18):1698–1701
Guevara C, Farias G, Silva-Rosas C et al (2018) Encephalitis associated to metabotropic glutamate receptor 5 (mGluR5) antibodies in cerebrospinal fluid. Front Immunol 9:2568
Scherer S, Duvoisin R, Kuhn R et al (1996) Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q. Genomics 31(2):230–233
Saini S, Mancuso S, Mostaid S et al (2017) Meta-analysis supports GWAS-implicated link between GRM3 and schizophrenia risk. Transl Psychiatry7(8)
Fromer M, Pocklington AJ, Kavanagh DH et al (2014) De novo mutations in schizophrenia implicate synaptic networks. Nature 506(7487):179–84
Kandaswamy R, McQuillin A, Sharp SI et al (2013) Genetic association, mutation screening, and functional analysis of a Kozak sequence variant in the metabotropic glutamate receptor 3 gene in bipolar disorder. JAMA Psychiatry 70(6):591–8
Mantegazza R, Bernasconi P, Baggi F et al (2002) Antibodies against GluR3 peptides are not specific for Rasmussen’s encephalitis but are also present in epilepsy patients with severe, early onset disease and intractable seizures. J Neuroimmunol 131(1–2):179–185
Buscarinu M, Fornasiero A, Pellicciari G et al (2019) Autoimmune encephalitis and CSF anti-GluR3 antibodies in an MS patient after alemtuzumab
Acknowledgements
We thank our colleagues from the “Policlinico-Vittorio Emanuele”, “Cannizzaro”, and “Garibaldi” hospitals for providing their cases and contributing to the research. We thank American Journal Experts (AJE) to revise manuscript’s English (code 0A67-727B-905A-21D7-00B5).
Author information
Authors and Affiliations
Contributions
Maria Elena Cucuzza: conception and design, acquisition, analysis and interpretation of data, drafting the article; PieroPavone: analysis and interpretation of data, drafting and revising the article critically for important intellectual content; Angela D’Ambra: acquisition of data and drafting the article; Maria Carla Finocchiaro, FilippoGreco, PierluigiSmilari, Martino Ruggieri, Vita Antonella Di Stefano: formal analysis and investigation. All authors whose names appear on the submission approved the version to be published, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors adhere to the guidelines for authorship that are applicable in their specific research field.
Corresponding author
Ethics declarations
Ethical approval
The study was conducted ethically in accordance with the ethical standards of the Institutional research committee and with the 1964 Helsinki Declaration and its later amendments or Comparable ethical standards and was approved by the ethics committee of the University of Catania, Italy.
Consent to publish
Informed consent was obtained from the parents of the proband regarding publishing.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Cucuzza, M.E., Pavone, P., D’Ambra, A. et al. Autoimmune encephalitis and CSF anti-AMPA GluR3 antibodies in childhood: a case report and literature review. Neurol Sci 43, 5237–5241 (2022). https://doi.org/10.1007/s10072-022-06170-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10072-022-06170-0