Authors :
Presenting Author: Aaron Struck, MD – Washington University School of Medicine in St. Louis
Camille Garcia-Ramos, PhD – University of Wisconsin School of Medicine and Public Health
Vivek Prabhakaran, MD, PhD – University of Wisconsin School of Medicine and Public Health
Veena Nair, MD, PhD – University of Wisconsin School of Medicine and Public Health
Anusha Adluru, MS – University of Wisconsin School of Medicine and Public Health
Santiago Philibert-Rosas, MD – Washington University School of Medicine in St. Louis
Dace Almane, MS – University of Wisconsin-Madison
Nagesh Adluru, PhD – University of Wisconsin School of Medicine and Public Health
Jana Jones, PhD – University of Wisconsin–Madison
Bruce Hermann, PhD – University of Wisconsin School of Medicine and Public Health
Rationale:
To determine the thalamic nuclei that are different between Juvenile Myoclonic Epilepsy (JME) and healthy age-matched control participants obtained from the Juvenile Myoclonic Epilepsy Connectome Project. Then, to determine their relationship with other subcortical gray matter volumes, disease covariates including duration of epilepsy, chronological age, as well as motor performance.
Methods:
62 patients with JME and 41 age matched controls were examined using 3T MRI T1-weighted images. Patients and controls had a mean age of 20 years (range 12 to 25). Thalamic nuclei volumes were compared after normalization to total intracranial volume. Nuclei volumes were measured using Freesurfer pipeline with thalamic segmentation package. The relationship between thalamic nuclei volumes with age, duration of epilepsy, number of anti-seizure medications and age of onset were examined using linear models with relative assessment of regressors. Correlation with other subcortical volumes was undertaken to identify a potential network effect. Nuclei volumes were related to a task of speeded fine motor dexterity (Grooved Pegboard).
Results:
Ventral motor associated thalamic nuclei (Ventral Anterior, Ventral Lateral Anterior, and Ventral Lateral Posterior) as well as one intralaminar nuclei (Parafascicular) volumes were reduced in JME. These thalamic nuclei volumes reductions were correlated with cerebellar and ventral diencephalon volume reductions. The reduction in thalamic volumes were associated with age (that differed from controls) in only the ventral thalamic nuclei. Duration of epilepsy also had an effect. JME was associated with decreased dominant and nondominant hand speeded dexterity with greater deficits relative to reduction of thalamic nuclei volume than in controls, the findings suggest a baseline decreased ventral thalamic volume with an inability to make efficiency gains because of disordered adolescent synaptic pruning.
Conclusions:
Motor-related ventral thalamic nuclei may play a central role in the pathogenesis of JME, contributing to both ictal and interictal motor dysfunction. Their established connections with the pre-motor cortex, basal ganglia, and cerebellum suggest potential network-level dysfunction. A better understanding of this circuitry may guide future neuromodulation strategies beyond current vagal and centromedian thalamic approaches, targeting the motor thalamocortical pathway to improve seizure control and neurocognitive outcomes in JME.
Funding:
This work was supported by NIH NINDS – R01 NS111022. NINDS NIH HHS – R01NS117568, R01NS123378, R01NS105646. NICHD – P50HD105353.