Thalamofrontal circuitry and executive dysfunction in recent‐onset juvenile myoclonic epilepsy

Abstract

Summary Purpose: Thalamofrontal abnormalities have been identified in chronic primary generalized epilepsy, specifically in juvenile myoclonic epilepsy (JME). These regions also underlie executive functioning, although their relationship has yet to be examined in JME. This study examined the relationship between thalamic and frontal volumes and executive function in recent‐onset JME compared to healthy control subjects and recent‐onset benign childhood epilepsy with centrotemporal spikes (BCECTS), a syndrome not typically associated with thalamocortical or executive dysfunction. Methods: Twenty children with recent‐onset JME were compared to 51 healthy controls and 12 children with BCECTS using quantitative magnetic resonance imaging (MRI) and measures of executive abilities. Quantitative thalamic and frontal volumes were obtained through semi‐automated software. Subtests from the Delis–Kaplan Executive Function System (D‐KEFS) and the Behavior Rating Inventory of Executive Function (BRIEF) were used to measure executive function. Results: Executive functions were impaired in JME subjects compared to control and BCECTS subjects. Subjects with JME had significantly smaller thalamic volumes and more frontal cerebrospinal fluid (CSF) than control and BCECTS subjects. Thalamic and frontal volumes were significantly related to executive functioning in the JME group, but not in the other two groups. Discussion: Children with JME have significant executive dysfunction associated with significantly smaller thalami and more frontal CSF. Children with recent‐onset BCECTS do not display the same pattern. Frontal and thalamic volumes appear to mediate the relationship between executive functioning and brain structure in JME.

Thalamofrontal neurodevelopment in new-onset pediatric idiopathic generalized epilepsy

“…Increased gray matter frontal cortex volume, 21 decreased frontal gray matter, 22 and both regional increased and decreased regional white matter volumes 8 have all been reported. Thalamic findings in IGE include anterior thalamic gray matter volume reductions, 8,21,22 increased anterior thalamic gray matter density, 7,23,24 decreased thalamic volume, 11 and no thalamic volumetric differences. [25][26][27] Although studies reporting thalamic abnormalities conflict, these studies consistently report that differences lie in the anterior and medial thalamus, a region strongly connected to the prefrontal cortex via the anterior thalamic radiation.…”

“…16 A more detailed description of thalamic tracing is available elsewhere. 11 Briefly, images were traced in the coronal plane using a color-enhanced T1 with reference to the segmented image and unenhanced T1. An automated thalamic mask was derived from the BRAINS2 software and manually edited slice by slice, beginning at the rostral portion and proceeding caudally.…”

“…We previously reported thalamic and frontal volumetric changes within 1 year of epilepsy onset in juvenile myo-clonic epilepsy (JME) and found that these abnormalities were related to executive dysfunction. 11 Due to the cross-sectional nature of previous studies, it is unclear whether these changes early in the course of epilepsy are static and unchanging or whether neurodevelopment is negatively impacted. Thus, the present study reports on longitudinal thalamofrontal neurodevelopment in IGE.…”

Besondere bildgebende Befunde bei primär generalisierten Epilepsien

“…Diese Vermutung erhärtet sich durch Untersuchungen an neu diagnostizierten JME-Patienten, die bereits im ersten Erkrankungsjahr in volumetrischen [13] …”

Reduced Cortical Thickness in Children with New-Onset Seizures: Fig 1.

“…Children with idiopathic generalized epilepsies have also shown distributed patterns of abnormality affecting the thalamus and frontal lobe. [17][18][19][20][21] It is not known whether the structural alterations developed during a vulnerable phase of cerebral development or are the cumulative effects of recurrent seizures 22 or are a combination of these factors acting synergistically. 11 To determine whether antecedent neurobiologic alterations are present, assessment could be performed in a population of patients with newonset seizures, which would exclude the confounding effects of recurrent seizures and long-term antiepileptic medications on the brain.…”