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

Abstract

SummaryObjectivePatients 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.MethodsWe 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.ResultsThe 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.SignificanceStructural 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.

Brain morphological abnormalities in genetic generalized epilepsies: The starting point?

“…The award was given to Miss Suejen Perani for the work she developed in pursuit of her Doctor of Philosophy with the supervision of Professors Mark Richardson and David Carmichael, from the King's College London and UCL Great Ormond Street Institute of Child Health, respectively. The authors present a novelty in the study of GGEs, evaluating drug‐naive patients just after the clinical diagnosis . Through a rapid referral from first seizure clinics, Perani et al were able to perform MRI scans in individuals with confirmed GGE within 1 week from the diagnosis and before the start of antiseizure medication.…”

“…Previous publications evaluated mainly individuals after a long period from epilepsy onset, with prolonged use of medication and often pharmacoresistant seizures . Closer to the profile of the study of Perani et al, in 2016, Wang et al detected thalamic atrophy in a group of drug‐naive children with childhood absence epilepsy. Although the study by Wang et al eliminated the influence of the medication in the thalamic abnormality in this specific GGE syndrome, the role of the recurrent seizures could not be excluded, because the majority of the patients in their cohort were >1 year from epilepsy onset …”

“… Is thalamic atrophy specific for a single GGE syndrome or is this present in all GGE syndromes? Are cortical and other subcortical structures normal at epilepsy onset in GGEs? (The number of individuals evaluated in the study by Perani et al could have prevented the detection of more subtle abnormalities. ) Does the brain damage to the thalamus and other brain structures progress over time, and if so, how? Is the thalamic atrophy in GGEs associated with pharmacoresistance or seizure recurrence with medication withdrawal after long‐term control? …”

“…The Epilepsia clinical paper of the year by Perani et al constitutes a significant step toward the understanding of causes and consequences of brain morphological abnormalities in GGEs. It will be interesting to follow up this group of patients to investigate the possible evolution of brain changes and their association with clinical variables in GGEs.…”

“…10 The Epilepsia clinical paper of the year closes at least one of the gaps in the knowledge of brain morphological abnormalities in GGEs. 11 The award was given to Miss Suejen Perani for the work she developed in pursuit of her Doctor of Philosophy with the supervision of Professors Mark Richardson and David Carmichael, from the King's College London and UCL Great Ormond Street Institute of Child Health, respectively. The authors present a novelty in the study of GGEs, evaluating drugnaive patients just after the clinical diagnosis.…”