Significance of Neuronal Autoantibodies in Comparison to Infectious Etiologies among Patients Presenting with Encephalitis in a Region with a High Prevalence of Infections

Thashi Chang; Teresa Moloney; Leslie Jacobson; Neelika Malavige; Janarthani Lohitharajah; Jithangi Wanigasinghe; Sian Peach; Mark Woodhall; Antonio Berretta; Patrick Waters; Angela Vincent

doi:10.4103/aian.aian_280_21

Significance of Neuronal Autoantibodies in Comparison to Infectious Etiologies among Patients Presenting with Encephalitis in a Region with a High Prevalence of Infections

Ann Indian Acad Neurol. 2022 May-Jun;25(3):473-478. doi: 10.4103/aian.aian_280_21. Epub 2022 Mar 17.

Affiliations

¹ Department of Clinical Medicine, University of Colombo, Sri Lanka.
² Nuffield Department of Clinical Neurosciences, University of Oxford, United Kingdom.
³ Department of Immunology, University of Sri Jayawardenapura, Sri Lanka.
⁴ Department of Pathophysiology, Eastern University, Sri Lanka.
⁵ Department of Paediatrics, University of Colombo, Sri Lanka.

Abstract

Background: Prevalence of antibody-mediated autoimmune encephalitis (AE) is reported to be comparable to infectious encephalitis in Western populations. We evaluated the frequency and significance of AE and neuronal autoantibodies in comparison to infectious etiologies among patients presenting with encephalitis in a South Asian population.

Methods: Ninety-nine consecutive patients with a clinical diagnosis of encephalitis/meningoencephalitis admitted to two of the largest tertiary-care hospitals in Sri Lanka were studied. PCR and ELISA were used to screen viruses while Gram stain and culture were used to screen bacteria. Sera were tested for antibodies binding to primary embryonic rat hippocampal neuronal cultures and cell-based assays for antibodies to NMDAR, LGI1, CASPR2, Contactin2, AMPAR, GABA_AR, GABA_BR, aquaporin-4 and MOG.

Results: Patient ages ranged from 1 month to 73 years (mean = 24.91; SD = 21.33) with a male: female ratio of 1.75:1. A viral etiology was identified in 27.3% and bacterial meningoencephalitis was diagnosed in 17.1%. Sera of nine patients had antibodies binding to live primary neurons, but only five had specific antibodies to CASPR2 (n = 1), NMDAR (n = 2) or GABA_BR-antibodies (n = 2). Moreover, the patients with CASPR2 antibodies and NMDAR-antibodies were also positive for dengue antibodies. Only the two patients with NMDAR-antibodies had features and responses to immunotherapy consistent with AE.

Conclusions: Identified infectious forms of meningoencephalitis (44.4%) greatly exceeded the occurrence of neuronal autoantibodies (9.1%) and AE (2%) in Sri Lanka, and this may be common in those regions where infections are prevalent.

Keywords: Autoimmune encephalitis; NMDAR; Sri Lanka; meningoencephalitis.