Rationale:
To determine the cognitive burden of anti-seizure medications (ASM) in people with focal epilepsy.
To determine the cognitive burden of anti-seizure medications (ASM) in people with focal epilepsy.
Method:
Retrospective analysis of language functional Magnetic Resonance Imaging (fMRI) data in people with focal epilepsy treated with different combinations of anti-seizure medications (ASM). We done propensity score matching to control for treatment selection bias. Comparison of verbal fluency fMRI patterns between people (i) taking dual therapy of ASMs either considered to be associated with moderate (levetiracetam, lamotrigine, lacosamide, carbamazepine/oxcarbazepine, eslicarbazepine, valproic acid; n=119) or severe (topiramate, zonisamide, phenobarbitone, phenytoin; n=119) side-effects (SE), (ii) taking different moderate SE-ASM in monotherapy, (iii) taking moderate SE-ASM in either mono- (n=60), dual- (n=60) or triple-therapy (n=60), or (iv) taking different dosages of two moderate SE-ASMs. “Drug load” defined as composite value of numbers of ASM and dosages, normalized to account for highest and lowest dose of each specific ASM prescribed.
Retrospective analysis of language functional Magnetic Resonance Imaging (fMRI) data in people with focal epilepsy treated with different combinations of anti-seizure medications (ASM). We done propensity score matching to control for treatment selection bias. Comparison of verbal fluency fMRI patterns between people (i) taking dual therapy of ASMs either considered to be associated with moderate (levetiracetam, lamotrigine, lacosamide, carbamazepine/oxcarbazepine, eslicarbazepine, valproic acid; n=119) or severe (topiramate, zonisamide, phenobarbitone, phenytoin; n=119) side-effects (SE), (ii) taking different moderate SE-ASM in monotherapy, (iii) taking moderate SE-ASM in either mono- (n=60), dual- (n=60) or triple-therapy (n=60), or (iv) taking different dosages of two moderate SE-ASMs. “Drug load” defined as composite value of numbers of ASM and dosages, normalized to account for highest and lowest dose of each specific ASM prescribed. Results
People on levetiracetam monotherapy showed greater frontal activation and parieto-occipital deactivations than those taking other ASMs as monotherapy. Irrespective of the specific ASM, those on monotherapy, showed greater activations in the frontal verbal fluency network than people taking two or three ASMs. People on two ASMs showed less deactivation in the default mode (precuneus) than those on monotherapy. Increased drug load correlated with reduced activation in left inferior frontal gyrus and right piriform cortex.
People on levetiracetam monotherapy showed greater frontal activation and parieto-occipital deactivations than those taking other ASMs as monotherapy. Irrespective of the specific ASM, those on monotherapy, showed greater activations in the frontal verbal fluency network than people taking two or three ASMs. People on two ASMs showed less deactivation in the default mode (precuneus) than those on monotherapy. Increased drug load correlated with reduced activation in left inferior frontal gyrus and right piriform cortex.
People on levetiracetam monotherapy showed greater frontal activation and parieto-occipital deactivations than those taking other ASMs as monotherapy. Irrespective of the specific ASM, those on monotherapy, showed greater activations in the frontal verbal fluency network than people taking two or three ASMs. People on two ASMs showed less deactivation in the default mode (precuneus) than those on monotherapy. Increased drug load correlated with reduced activation in left inferior frontal gyrus and right piriform cortex.
People on levetiracetam monotherapy showed greater frontal activation and parieto-occipital deactivations than those taking other ASMs as monotherapy. Irrespective of the specific ASM, those on monotherapy, showed greater activations in the frontal verbal fluency network than people taking two or three ASMs. People on two ASMs showed less deactivation in the default mode (precuneus) than those on monotherapy. Increased drug load correlated with reduced activation in left inferior frontal gyrus and right piriform cortex.
Conclusion:
Combination therapy and a higher drug load were associated with impairment of cognitive activation patterns. Levetiracetam showed less effect on cognitive activation patterns than were other frequently prescribed ASMs.
Combination therapy and a higher drug load were associated with impairment of cognitive activation patterns. Levetiracetam showed less effect on cognitive activation patterns than were other frequently prescribed ASMs.
Funding:
:This work was supported by Epilepsy Society, UK and undertaken at University College London Hospitals Comprehensive Research Centre, which received a proportion of funding from the NIHR Biomedical Research Centres scheme. Funders did not have any role in the study design. The work was supported by Newton International Fellowship.
FIGURES
Figure 1