Sodium Valproate Modulates Cortical Morphology in Juvenile Myoclonic Epilepsy

Abstract

AbstractImportanceIdiopathic generalized epilepsy syndromes in are associated with cortical thinning of the premotor areas. Whether this represents an underlying disease signature, a consequence of seizure activity or is related to anti-seizure medication is unknown.ObjectiveTo investigate valproate-related effects on cortical morphology in people with juvenile myoclonic epilepsy (JME), one of the most common IGE syndromes.DesignRetrospective neuroimaging case-control study.SettingRecruitment took place in epilepsy clinics in two European epilepsy referral centers.ParticipantsWe matched individuals with JME on valproate (n=36) to a group of healthy controls (n=36), as well as individuals with JME not on valproate (n=36) and a group of people with temporal lobe epilepsy (n=19) on valproate using propensity scores for age, sex, occurrence of bilateral tonic-clonic seizures and drug refractoriness.Main outcomes and MeasuresAll participants underwent structural T1-weighted brain imaging and MRI-derived vertex-wise measurements of cortical thickness were calculated. Results were reported in effect-sizes using cohen’sd.ResultsCompared to healthy controls, individuals with JME on valproate demonstrated cortical thinning bilaterally in the precentral gyri (left:d= -1.0,p<.001; right: d = -1.0,p<.001). This effect was localized to the left precentral gyrus when comparing JME on VPA with individuals with JME not on valproate (d= -0.89;p<.01) or with individuals with temporal lobe epilepsy on valproate (d = -0.18, p<.001). No significant differences in cortical thickness were detected between individuals with JME not on valproate and healthy controls. Cortical thinning in precentral gyrus, postcentral gyrus and superior frontal was more marked with increasing valproate dose (left:t= -6,65,p<.0001; right:t= -5,20,p<.0001).Conclusions and RelevanceIn this cross-sectional study of 91 patients with epilepsy, valproate treatment was associated with JME-specific and dose-dependent cortical thinning of the precentral gyri. Our findings suggest a valproate-induced reorganization of disease-specific areas in JME that may not only help explain the high efficacy of this medication in IGEs but also potentially account for previously described changes of cortical thickness in this disease group.