Autoimmune encephalitis in a South Asian population

Nilanka Wickramasinghe,Dhanushka Dasanayake,Neelika Malavige,Thashi Chang,Rajiva De Silva

doi:10.1186/s12883-021-02232-6

Nilanka Wickramasinghe, Dhanushka Dasanayake + Show 3 more

Open Access

https://doi.org/10.1186/s12883-021-02232-6

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Abstract

BackgroundAutoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka.MethodsPatients admitting to government hospitals who were clinically suspected of AE by an on-site neurologist were prospectively recruited over a period of 12 months. Sera and cerebrospinal fluid were tested for NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABARB1/B2 antibodies (Ab) using commercial cell-based assays. Demographic, clinical and laboratory data were compiled into an investigator-administered proforma. Patients were reviewed at 1 year follow up either in person or via telephone.ResultsOne-hundred and forty-two patients from 21 of 25 districts in Sri Lanka (median age = 20.5 years; range 1–86 years; females = 61.3%) were recruited. Of them, 65 (45.8%; median age = 19 years; range 1–86 years; females = 64.6%) fulfilled diagnostic criteria for probable NMDAR-antibody encephalitis (NMDARE) and 6 (4.2%; median age = 44 years; range 28–71 years; females = 83.3%) limbic encephalitis (LE). Abnormal behaviour (95.3%), seizures (81.5%) and movement disorders (69.2%) were the most frequent clinical manifestations of probable NMDARE. NMDAR-antibodies were detectable in 29 (44.6%) and not detectable in 36 in CSF of probable-NMDARE patients. Abnormal EEG was more frequent (p = 0.003) while a worse outcome (OR = 2.78; 95% CI = 0.88–9.09) and deaths (OR = 2.38; 95% CI = 0.67–8.33) were more likely in antibody-negative than antibody-positive probable-NMDARE. Most patients with LE had amnesia (50%) and/or confusion (100%) with agitation (83.3%) and seizures (100%) but none had detectable antibodies to any of the antigens tested.ConclusionsNMDARE is the commonest type of AE among South Asians as is the case worldwide. Clinical presentations of NMDARAb-positive and NMDARAb-negative AE patients do not significantly differ but EEG may be a useful marker of an autoimmune basis for psychiatric symptoms.

Highlights

Autoimmune encephalitis (AE) is considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia
Among the antibody mediated encephalitides, N-methyl D-aspartate receptor (NMDAR)-antibody encephalitis (NMDARE) is the most common followed by limbic encephalitis (LE) mediated by antibodies directed against Leucine-rich glioma-inactivated protein 1 (LGI1), Contactin-associated protein-like 2 (CASPR2), α-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid receptor (AMPAR) or GABABR while encephalitis mediated by other antibodies are rare [2]
No ovarian or other tumours were detected in imaging studies

Summary

Introduction

Autoimmune encephalitis (AE) is considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. Among an estimated annual incidence of approximately 5 to 8 cases of encephalitis per 100,000 persons, autoimmune encephalitis (AE) has emerged as the third most common cause after infections, mostly viral, and acute disseminated encephalomyelitis [1]. NMDARE is characterised by a female predominance (4:1), younger onset (median age 21 years), associated tumours (ovarian teratoma) and a multi-phenomenological syndrome that evolves over time with seizures, abnormal movements, insomnia and irritability more frequent in children, and psychosis, abnormal behaviour, dysautonomia and coma more common in adults [3, 4]. LE is characterised by an older age of onset (> 45 years), amnesia, confusion, seizures, hyponatraemia, increased signal of medial temporal lobes on magnetic resonance imaging and variable association with tumours determined by the associated antibody [2, 3]. LGI1 antibodies account for most of the LE and is characterised by faciobrachial dystonic seizures that may predate cognitive impairment [5]

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