Determinants of cognition in autoimmune limbic encephalitis-A retrospective cohort study

Autoimmune limbic encephalitis (ALE) is the most common type of autoimmune encephalitis (AIE). Subacute memory disturbance, temporal lobe seizures, and psychiatric symptoms are clinical hallmarks of the disease. However, little is known on the factors contributing to cognitive functioning in ALE. Hence, we here investigate major determinants of cognitive functioning in ALE. In a retrospective analysis of 102 patients with ALE, we first compared verbal learning capacity, nonverbal learning capacity, and attentional and executive functioning by absence or presence of different types of neural autoantibodies (AABs). Subsequently we established three linear regression models including 63, 38, and 61 patients, respectively to investigate how cognitive functioning in these domains may depend on common markers of ALE such as intrathecal inflammation, blood-cerebrospinal fluid (CSF)-barrier function, mesiotemporal epileptiform discharges and slowing, determined by electroencephalography (EEG) and structural mesiotemporal changes, measured with magnetic resonance imaging (MRI). We also accounted for possible effects of cancer- and immunotherapy and other centrally effective medication. There was no effect of AAB status on cognitive functioning. Although the regression models could not predict verbal and nonverbal learning capacity, structural mesiotemporal neural network alterations on T2-/fluid attenuated inversion recovery (FLAIR)-signal-weighted MRI and mesiotemporal epileptiform discharges or slowing on EEG exerted a significant impact on memory functions. In contrast, the regression model significantly predicted attentional and executive functioning with CSF white blood cell count and centrally effective medication being significant determinants. In this cohort, cognitive functioning in ALE does not depend on the AAB status. Common markers of ALE cannot predict memory functioning that only partially depends on structural and functional alterations of mesiotemporal neural networks. Common markers of ALE significantly predict attentional and executive functioning that is significantly related to centrally effective medication and CSF white blood cell count, which may point toward inflammation affecting brain regions beyond the limbic system.