Antibody negative autoimmune encephalitis- Does it differ from definite one?

Abstract

Context:Autoimmune encephalitis (AE) is an emerging cause of non-infective encephalitis, presentations of which vary widely. Traditionally the diagnosis of AE is based on detection of antibodies in a patient with clinical picture suggestive of AE.Aim:To evaluate the clinical characteristics and response to immunotherapy in patients with antibody negative autoimmune encephalitis and to compare them with definite cases.Settings and Design:A prospective follow-up study was done in patients presenting with presumptive symptoms of AE from January 2017 to January 2019. The study was done in a tertiary care institute of Northern India.Patients and Methods:Demographic and clinical parameters were noted and relevant investigations for management were done according to well-defined protocol. The patients were treated with immunomodulatory therapy in the form of steroids and/or intravenous immunoglobulins (IVIg). They were followed up for treatment response and relapse at 2 monthly intervals.Statistical Analysis Used:The data was expressed as either proportions or mean/median. Chi-square test/Independent T test was used to compare antibody positive and antibody negative group.Results:Out of 31 patients with presumptive AE, 16 patients tested positive for autoimmune antibodies (definite AE). Incidences of seizure, behavioral abnormalities, dementia and altered sensorium were similar between the 2 groups (p > 0.05). Complete or partial response was seen in all treated patients in both groups with no significant difference (p 0.716). CSF protein concentration and cellularity were higher in the definite group although only high protein concentration could reach statistical significance (p 0.002). Malignancy could be confirmed after extensive search in 2 out of 16 patients with definite AE and in 1 out of 15 antibody negative AE patients.Conclusions:Clinical presentation of antibody negative cases does not differ significantly from definite ones. Since treatment response is also similar in both the groups, starting immunotherapy in a patient presenting with presumptive symptoms of AE, while ruling out other common mimickers, seems to be the need of the hour in the management of this evolving entity.

Autoimmune encephalitis in a South Asian population

“…The inability to detect autoantibodies does not rule out a diagnosis of AE, particularly if consistent with a syndromic diagnosis of AE and logical differential diagnosis to exclude an alternative aetiology. Antibody-negative AE is a recognised entity [ 6 , 13 , 14 ], usually based on response to immunotherapy in clinically suggestive patients and is attributed to lack of sensitivity of the assay used, low titres, timing of the assays and the possibility of unrecognised pathogenic antibodies that are not yet tested. Indeed, more than half of the probable NMDARE patients and all the LE patients in our study were antibody negative.…”

“…However, the excess antibody negativity in our study may have also been contributed by a less stringent clinical ascertainment by the on-site neurologists and a relatively lesser sensitivity of commercial, fixed cell-based assays compared to live cell-based assays [ 15 ]. It is tempting to postulate that the lower assay sensitivity may have been related to lower AE antibody titres among South Asians given similar results in an Indian population [ 14 ], but this has not been verified. Unlike NMDARE with a single antibody target, LE with many antibody targets and more being recognised, is more likely to be diagnosed in the absence of detectable antibodies.…”

Antibody Negative Autoimmune Encephalitis: A Case Report

“…Currently, the guidelines for diagnosis suggest that a complete antibody panel (intracellular, surface antigen and ion channels) should be done if there is a suspicion of AIE. 11 Treatment for probable encephalitis is frequently given empirically prior to the results. In this case, acyclovir was given empirically for presumed HSE.…”

“…6,12 The treatment should not be delayed since the evidence suggests early immunotherapy is associated with favourable outcomes and better prognosis. 1,11,12…”

Diagnostic Value of Structural and Functional Neuroimaging in Autoimmune Epilepsy

“…It should be noted that there was no difference in prevalence or incidence between autoimmune and infectious factors for inflammatory lesions of the central nervous system, and more than 50% of patients do not have specific autoantibodies [ 16 , 17 ]. In patients with presumptive autoimmune encephalitis, there was no significant difference in the clinical manifestations of antibody-negative cases and confirmed cases, and the therapeutic response to immunotherapy was similar [ 18 ]. Therefore, the better application of convenient and fast imaging examination cannot be postponed.…”