Autoimmune encephalitis in a South Asian population

Abstract

Background Autoimmune 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. Methods Patients 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. Results One-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. Conclusions NMDARE 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.

Novel qEEG Biomarker to Distinguish Anti-NMDAR Encephalitis From Other Types of Autoimmune Encephalitis

“…The sensitivity of the proNMDARE criteria ( 4 ) was 0.67 in our cohort, as three of nine patients with NMDARE were false negatives. This value was consistent with that of other cohort studies (approximately 0.70) ( 5 , 12 – 14 ). However, the method using an FSR cutoff value salvaged the three patients who did not meet proNMDARE criteria, thereby achieving a sensitivity of 1.00 ( Table 2 ).…”

“…Antibodies that flock to neuronal surface antigens trigger both paraneoplastic and non-paraneoplastic AE, which includes a variety of inflammatory brain disorders (2), accounting for 21%-39% of acute encephalitis (10)(11)(12). Since Graus et al ( 4) developed an algorithm for the diagnosis of AE, which consisted of syndrome-based approach and antibody testing, several studies have been reported that classified the encephalitis cohort into specific conditions of autoimmune etiology by the criteria (5,(12)(13)(14). Given that the AE defined by the criteria is not a single disease entity, it is no wonder the proportion of each specific condition is varied among the studies.…”

“…Since Graus et al. ( 4 ) developed an algorithm for the diagnosis of AE, which consisted of syndrome-based approach and antibody testing, several studies have been reported that classified the encephalitis cohort into specific conditions of autoimmune etiology by the criteria ( 5 , 12 – 14 ). Given that the AE defined by the criteria is not a single disease entity, it is no wonder the proportion of each specific condition is varied among the studies.…”

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

“…Although in this study AE was diagnosed in only 2% of unselected encephalitis patients, a recent study which selected patients with suspected AE based on established diagnostic criteria[ 11 ] found up to 50% of patients to have AE and 44.6% of them to have detectable pathogenic antibodies to recognized AE in CSF. [ 5 ] The higher yield in the cited study is likely due to exclusion of patients with likely infectious etiologies, which probably accounts for most of the encephalitis in regions with a high prevalence of infections.…”

“…[ 2 3 ] In temperate regions, the incidence and prevalence of AE has been reported to be comparable to viral encephalitis. [ 4 ] However, research on AE from South Asia remains sparse,[ 5 ] but infectious etiologies are assumed to predominate. [ 6 ] Although neuronal autoantibodies can occur as para- or post-infectious epiphenomena, only about one-third would result in AE.…”