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

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 A R, GABA B R, aquaporin-4 and MOG. Results: Patient ages ranged from 1 month to 73 years (mea n = 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 B R-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.

A systematic review of the epidemiology of pediatric autoimmune encephalitis: disease burden and clinical decision-making

“…Ten studies reported data on age of onset and/or presenting symptoms specific to the pediatric population with AIE ( 17–26 ). Age of onset of AIE ranged from 8 to 16 years for AIE overall, whereas age of onset for NMDAR-AIE ranged from 3.5–17 years in the identified studies.…”

“…Age of onset was not reported for other AIE subtypes. The most common presenting symptoms, irrespective of AIE subtype, were seizures and behavioral change in combination with other neuropsychiatric features ( 17–25 ). These findings highlight the heterogenous presentation of AIE with little distinction among the different subtypes in the key presenting features.…”

Navigating the diagnostic and therapeutic complexities of autoimmune encephalitis

“…6 AE has emerged as the third most common cause of encephalitis after infections and acute disseminated encephalomyelitis. 7,8 Thus, AE is increasingly considered in the differential diagnoses of patients presenting with subacute memory loss, cognitive dysfunction, psychiatric symptoms or refractory seizures. Despite diagnostic algorithms for AE being proposed in 2016, 9 misdiagnosis remains a frequent clinical problem leading to morbidity resulting from unnecessary immunotherapies and delayed treatment of the correct diagnosis.…”