Neuropsychological Performance in Autoimmune Limbic Encephalitis: Evidence from an Immunotherapy-Naïve Cohort

Abstract

Objective Autoimmune limbic encephalitis (ALE) is characterized by memory impairment, psychiatric symptoms, and epileptic seizures. Though, the neuropsychological profile of ALE is not yet well defined. However, there is some evidence that neuropsychological impairments might exceed those related to the limbic system and that different autoantibodies (AABs) are associated with distinguishable pattern of neuropsychological impairments. We provide a comprehensive presentation of neuropsychological performance of ALE in an immune therapy-naïve sample. Methods We retrospectively analyzed 69 immunotherapy-naïve ALE-patients (26 seropositive—[8 LGI1-, 4 CASPR2-, 2 GABAB-R-, 3 Hu-, 4 GAD65-, 2 Ma2-, 2 unknown antigen, and 1 Yo-AABs] and 43 seronegative patients, mean age 56.0 years [21.9–78.2], mean disease duration 88 weeks [0–572]). Neuropsychological evaluations comprised of the domains memory, attention, praxis, executive functions, language, social cognition, and psychological symptoms. We compared these functions between seronegative −, seropositive patients with AABs against intracellular neural antigens and seropositive patients with AABs against surface membrane neural antigens. Results No effect of AAB group on neuropsychological performance could be detected. Overall, ALE predominantly presents with deficits in long-term memory and memory recognition, autobiographical-episodic memory loss, impairment of emotion recognition, and depressed mood. Furthermore, deficits in praxis of pantomimes and imitations, visuo-construction, and flexibility may occur. Conclusion ALE shows a wide spectrum of neuropsychological impairments, which might exceed the limbic system, with no evidence of differences between AAB groups. Neuropsychological assessment for diagnosing ALE should include long-term memory, memory recognition, autobiographical-episodic memory, emotion recognition, and a detailed investigation of depression.

Remote digital cognitive assessment reveals cognitive deficits related to hippocampal atrophy in autoimmune limbic encephalitis: a cross-sectional validation study

“…No difference in emotional discrimination was found between the two groups. Previous studies have reported impaired emotion processing at acute phases of the disease, 38 , 39 and the evidence points to recovery after treatment. However, impaired emotion recognition 40 and abnormalities in emotional regulatory processes 41 have been reported in chronic ALE as well.…”

Memory function in autoimmune encephalitis: a cross-sectional prospective study utilising multiple memory paradigms

“…Previous studies have reported variable memory outcomes across different ab-mediated AE subtypes, with reports of both normal and abnormal memory function [2][3][4][5][6][7]. The heterogeneous findings might be due to the different approaches used to detect memory impairment.…”

“…This emphasises the importance of comprehensive assessment approaches in understanding memory deficits, particularly in the context of neuroimmunology populations like AE, where memory deficits may coexist with impairments in attention and executive functions, contributing to functional memory difficulties. This is particularly important as there is evidence of a number of cognitive deficits in AE patients [4,5,7,9,10]. Collectively, these factors limit the ability to draw clear conclusions regarding memory impairments after AE.…”

Language impairments in seropositive and seronegative autoimmune encephalitis

“…letter) and semantic (e.g. animals) lexical retrieval, as well as visual confrontation naming, yielded results that, on average, fell within age-expected ranges, where impairment was defined at one standard deviation below expectations [ 4 ]. However, frequency analysis indicated impairments in 23.5% of the cohort on a naming test, 25.0% on lexical word fluency, and 33.3% on semantic word fluency [ 4 ].…”

“…animals) lexical retrieval, as well as visual confrontation naming, yielded results that, on average, fell within age-expected ranges, where impairment was defined at one standard deviation below expectations [ 4 ]. However, frequency analysis indicated impairments in 23.5% of the cohort on a naming test, 25.0% on lexical word fluency, and 33.3% on semantic word fluency [ 4 ]. A systematic review of anti-NMDAR ab-mediated AE patients in the chronic stage of disease (greater than 12 months after initial administration of immunotherapy) reported language impairments in 28.6% of cases, highlighting that there can be potential persistence of deficits [ 5 ].…”