Mesiotemporal Volumetry, Cortical Thickness, and Neuropsychological Deficits in the Long-term Course of Limbic Encephalitis

Abstract

Background and ObjectivesLimbic encephalitis (LE) is an autoimmune disease often associated with temporal lobe epilepsy and subacute memory deficits. It is categorized into serologic subgroups, which differ in clinical progress, therapy response, and prognosis. Using longitudinal MRI analysis, we hypothesized that mesiotemporal and cortical atrophy rates would reveal serotype-specific patterns and reflect disease severity.MethodsIn this longitudinal case-control study, all individuals with antibody-positive (glutamic acid decarboxylase 65 [GAD], leucine-rich glioma-inactivated protein 1 [LGI1], contactin-associated protein 2 [CASPR2], andN-methyl-d-aspartate receptor [NMDAR]) nonparaneoplastic LE according to Graus' diagnostic criteria treated between 2005 and 2019 at the University Hospital Bonn were enrolled. A longitudinal healthy cohort was included as the control group. Subcortical segmentation and cortical reconstruction of T1-weighted MRI were performed using the longitudinal framework in FreeSurfer. We applied linear mixed models to examine mesiotemporal volumes and cortical thickness longitudinally.ResultsTwo hundred fifty-seven MRI scans from 59 individuals with LE (34 female, age at disease onset [mean ± SD] 42.5 ± 20.4 years; GAD: n = 30, 135 scans; LGI1: n = 15, 55 scans; CASPR2: n = 9, 37 scans; and NMDAR: n = 5, 30 scans) were included. The healthy control group consisted of 128 scans from 41 individuals (22 female, age at first scan [mean ± SD] 37.7 ± 14.6 years). The amygdalar volume at disease onset was significantly higher in individuals with LE (p≤0.048 for all antibody subgroups) compared with that in healthy controls and decreased over time in all antibody subgroups, except in the GAD subgroup. We observed a significantly higher hippocampal atrophy rate in all antibody subgroups compared with that in healthy controls (allp≤0.002), except in the GAD subgroup. Cortical atrophy rates exceeded normal aging in individuals with impaired verbal memory, while those who were not impaired did not differ significantly from healthy controls.DiscussionOur data depict higher mesiotemporal volumes in the early disease stage, most likely due to edematous swelling, followed by volume regression and atrophy/hippocampal sclerosis in the late disease stage. Our study reveals a continuous and pathophysiologically meaningful trajectory of mesiotemporal volumetry across all serogroups and provides evidence that LE should be considered a network disorder in which extratemporal involvement is an important determinant of disease severity.

Subcortical grey matter volume and asymmetry in the long-term course of Rasmussen’s encephalitis

“…This sequence of signal increase with accompanying volume increase in the acute stage, followed by atrophy in the chronic stage, is thought to be caused by a cytotoxic oedema, which also occurs in status epilepticus or autoimmune encephalitis. 28 , 29 This aligns with our observation that volume increase of contralesional mesiotemporal structures is found only in type 1 RE, since in these cases contralesional epileptiform EEG findings were more frequent than in type 2 RE. This hints towards ongoing contralesional inflammation and fits in the picture that the contralesional hemisphere in RE is not unaffected, at least when contralesional epileptiform EEG patterns are present.…”

Regional patterns of human cortex development correlate with underlying neurobiology

“…Finally, strong quasi-experimental human evidence for the biological validity of spatial colocalizations between cortical morphology and neurobiological processes would be provided by the study of human subjects involuntarily exposed to development-affecting drugs (e.g., cocaine 18 ) or rare disorders with specific targets such as genetic deletion/duplication syndromes or (pediatric) autoimmune encephalitides. Especially the latter could, due to their rapid onset, clinical course, and known targets (e.g., NMDA, GABA A , or GAD), lead to specific alteration patterns of expected developmental trajectories that might be captured with spatial colocalization approaches 78,79 .…”