Thalamic volume reduction in drug-naive patients with new-onset genetic generalized epilepsy

Abstract

Objective: Patients with genetic generalized epilepsy (GGE) have subtle morphologic abnormalities of the brain revealed with magnetic resonance imaging (MRI), particularly in the thalamus. However, it is unclear whether morphologic abnormalities of the brain in GGE are a consequence of repeated seizures over the duration of the disease, or are a consequence of treatment with antiepileptic drugs (AEDs), or are independent of these factors. Therefore, we measured brain morphometry in a cohort of AED-naive patients with GGE at disease onset. We hypothesize that drug-naive patients at disease onset have gray matter changes compared to age-matched healthy controls.

Methods: We performed quantitative measures of gray matter volume in the thalamus, putamen, caudate, pallidum, hippocampus, precuneus, prefrontal cortex, precentral cortex, and cingulate in 29 AED-naive patients with new-onset GGE and compared them to 32 age-matched healthy controls. We subsequently compared the shape of any brain structures found to differ in gray matter volume between the groups.

Results: The thalamus was the only structure to show reduced gray matter volume in AED-naive patients with new-onset GGE compared to healthy controls. Shape analysis revealed that the thalamus showed deflation, which was not uniformly distributed, but particularly affected a circumferential strip involving anterior, superior, posterior, and inferior regions with sparing of medial and lateral regions.

Significance: Structural abnormalities in the thalamus are present at the initial onset of GGE in AED-naive patients, suggesting that thalamic structural abnormality is an intrinsic feature of GGE and not a consequence of AEDs or disease duration.

Keywords: drug naive; genetic generalized epilepsy; new onset; thalamus; volumetric MRI.

Figure 1

Cortical and subcortical volumetric segmentation. Gray matter masks of the cortical and subcortical areas selected for volumetric analysis between patients and controls. Average volumes and standard deviations for each area in the healthy control and AED‐naive group are reported in mm³

Figure 2

AED‐naive thalamic shape change. Bilateral changes in thalamic shape between healthy controls and AED‐naive patients are in red; the mask of thalamus is in green

Figure 3

Correspondence between thalamic shape change and thalamic nuclei. Overlay of the Morel atlas on regions showing shape change comparing AED‐naive patients with GGE and healthy controls. A list of thalamic nuclei is on the right. Medial group: MV, medioventral nucleus; CL, central lateral nucleus; CeM, central medial nucleus; CM, centromedian nucleus; Pf, parafascicular nucleus; sPf, subparafascicular nucleus. Posterior group: PuM, medial pulvinar; PuL, lateral pulvinar; LP, lateral posterior nucleus; SG, suprageniculate nucleus; Li, limitans nucleus; Po, posterior nucleus. Lateral group: VPM, ventral posterior medial nucleus; VLa, ventral lateral anterior nucleus; VLpd/VLpv, ventral anterior nucleus dorsal and ventral parts; VAmc/VApc, ventral anterior nucleus magnocellular and parvocellular parts; VM, ventral medial nucleus. Anterior group: AM, anterior medial nucleus; AV, anterior ventral nucleus; LD, lateral dorsal nucleus