Our recent study “Structural Brain Changes Are Linked to Clinical and Cognitive Outcomes in Anti-LGI1 Encephalitis” has been published in Neurology: Neuroimmunology & Neuroinflammation.
Background:
Anti–leucine-rich glioma–inactivated 1 encephalitis (LGI1E) has traditionally been considered a form of limbic encephalitis. However, growing neuroimaging evidence suggests involvement beyond the limbic system. Previous structural MRI studies have focused mainly on cross-sectional volumetric changes, potentially limiting the detection of subtle morphological alterations.
In this study, we investigated brain size and shape using volumetric measures and fractal dimensionality (FD), a geometric measure of structural complexity. We analyzed structural MRI data from 34 patients with LGI1E and 34 age- and sex-matched healthy controls, including up to three study visits per patient to assess both cross-sectional and longitudinal changes.
Key results:
- Structural brain changes in LGI1E extend beyond the limbic system: Cross-sectional analyses revealed widespread morphological alterations involving both limbic and extralimbic brain regions. While volume reductions were primarily found in subcortical structures, FD additionally detected alterations across fronto-temporo-parietal cortical regions (see figure below).
- Brain morphology is linked to clinical recovery and cognitive performance: Lower FD and volume in subcortical regions were associated with less clinical improvement since peak illness, as measured by the modified Rankin Scale and the Clinical Assessment Scale in Autoimmune Encephalitis. Furthermore, reductions in FD and volume across widespread cortical and subcortical regions were associated with poorer overall cognitive performance and deficits in specific domains, including verbal episodic memory, working memory, and executive function.
- Longitudinal brain changes are linked to disease course: Longer disease duration and clinical relapses were associated with reductions in FD and volume, particularly in subcortical regions. Furthermore, older age at disease onset was associated with more widespread morphological reductions across cortical and subcortical regions.
- Fractal analysis provides additional insights beyond conventional volumetry: FD detected morphological alterations not captured by volume across analyses. Furthermore, FD contributed more than volume to explaining disease-related brain changes and brain–cognition associations.
Interpretation:
Our findings support the concept of LGI1E as a whole-brain disorder rather than a purely limbic encephalitis. Importantly, these widespread morphological alterations were associated with clinical recovery, cognitive performance, and the longitudinal disease course. By capturing subtle changes in brain shape that are not detected by conventional volumetry, fractal analysis provides a more comprehensive characterization of structural brain alterations in LGI1E.
Like to know more?
You can find the full open-access paper here (https://doi.org/10.1212/nxi.0000000000200649) (open access).
If you’re interested, do reach out to us; we are always happy to discuss!