Editors' ChoiceEpilepsy

Let’s talk about antiseizure medications and verbal fluency

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Science Translational Medicine  11 Jul 2018:
Vol. 10, Issue 449, eaau1976
DOI: 10.1126/scitranslmed.aau1976

Abstract

Antiseizure drugs modulate functional connectivity in language networks.

The goal of epilepsy treatment is easily stated: no seizures, no side effects. However, this can be difficult to achieve: Any drug that modifies neural electrophysiology enough to prevent seizures also has the potential to alter brain function more broadly, resulting in unwanted secondary effects. Some individuals with epilepsy report that the fatigue, mood changes, and mental slowing caused by their medications—which need to be taken daily, indefinitely—affect their quality of life as much as the seizures themselves. Epilepsy pharmacology research is generally focused upon the development of medications to prevent seizures. The causes and clinical consequences of these medications’ off-target effects remain relatively unexplored.

In this paper, Xiao et al. investigated the impact of antiseizure medications upon language production, which they assess from both mechanistic and pragmatic standpoints. Using functional magnetic resonance imaging (fMRI)–based techniques in combination with standard neuropsychological tests of verbal fluency, the authors compared individuals with epilepsy taking the sodium channel–modulating antiseizure drugs carbamazepine (CBZ) or lamotrigine (LTG) to patients taking the sodium channel–independent antiseizure agent [levetiracetam (LEV)], and to healthy, unmedicated controls. On fMRI, patients taking LEV and healthy controls showed similar patterns of network activation. In contrast, CBZ was associated with reduced brain frontal lobe activation and LTG with fewer task-related deactivations. On standard measures of verbal fluency, patients taking LEV and LTG scored as well as healthy controls; only patients taking CBZ performed worse.

Xiao et al. made use of existing data collected from a large cohort of patients treated at a regional epilepsy center. Patients were not assigned to take specific medications for the purposes of the study; they were already on them as part of their clinical care. Unknown or unquantifiable factors could have influenced both exposures (choice of antiseizure medication) and outcome (verbal fluency), which might have affected results in unpredictable ways. Despite the inherent limitation of its retrospective design, however, Xiao and colleagues’ work shows that fMRI might be useful in determining differential effects of medications upon functional brain connectivity. Moreover, changes in functional brain connectivity do not necessarily correspond to measurable cognitive deficits. The lack of correlation between fMRI data and neuropsychological tests suggests that the link between brain connectivity and cognition is extremely complex and needs deeper investigation.

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