Motor-associated thalamic nuclei are reduced in juvenile myoclonic epilepsy.

Objective: This study was undertaken to determine the thalamic nuclei that are different between juvenile myoclonic epilepsy (JME) and healthy controls from the Juvenile Myoclonic Epilepsy Connectome Project and then to determine their relationship with other subcortical gray matter volumes, disease covariates, and motor performance.

Methods: Sixty-two patients with JME and 41 age-matched controls (mean age = 20 years) were examined using T1-weighted images. Thalamic nuclei volumes were compared after normalization to total intracranial volume. The relationship between thalamic nuclei volumes and age, duration of epilepsy, number of antiseizure medications, and age at 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.

Results: Ventral motor-associated thalamic nuclei (ventral anterior, ventral lateral anterior, and ventral lateral posterior) as well as one intralaminar nucleus (parafascicular) volumes were reduced in JME. These thalamic nuclei volume reductions were correlated with cerebellar and ventral diencephalon volume reductions. The reduction in thalamic volumes was associated with age (which 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 decrease in ventral thalamic volume with an inability to make efficiency gains because of disordered adolescent synaptic pruning.

Significance: Motor-related ventral thalamic nuclei appear to be a core factor in JME pathogenesis. These motor-associated nuclei have known connections with premotor cortex, basal ganglion, and cerebellar pathways that are related to motor control. Their dysregulation may account for the myoclonus seen in JME and interictal motor effects. Further longitudinal investigation and comparison with other cohorts are needed. Targeted neuromodulation of JME may be possible.