Timing matters: Impact of anticonvulsant drug treatment and spikes on seizure risk in benign epilepsy with centrotemporal spikes

Abstract

SummaryObjectiveBenign epilepsy with centrotemporal spikes (BECTS) is a common, self‐limited epilepsy syndrome affecting school‐age children. Classic interictal epileptiform discharges (IEDs) confirm diagnosis, and BECTS is presumed to be pharmacoresponsive. As seizure risk decreases in time with this disease, we hypothesize that the impact of IEDs and anticonvulsive drug (ACD) treatment on the risk of subsequent seizure will differ based on disease duration.MethodsWe calculate subsequent seizure risk following diagnosis in a large retrospective cohort of children with BECTS (n = 130), evaluating the impact of IEDs and ACD treatment in the first, second, third, and fourth years of disease. We use a Kaplan–Meier survival analysis and logistic regression models. Patients were censored if they were lost to follow‐up or if they changed group status.ResultsTwo‐thirds of children had a subsequent seizure within 2 years of diagnosis. The majority of children had a subsequent seizure within 3 years despite treatment. The presence of IEDs on electroencephalography (EEG) did not impact subsequent seizure risk early in the disease. By the fourth year of disease, all children without IEDs remained seizure free, whereas one‐third of children with IEDs at this stage had a subsequent seizure. Conversely, ACD treatment corresponded with lower risk of seizure early in the disease but did not impact seizure risk in later years.SignificanceIn this cohort, the majority of children with BECTS had a subsequent seizure despite treatment. In addition, ACD treatment and IEDs predicted seizure risk at specific points of disease duration. Future prospective studies are needed to validate these exploratory findings.

Persistent abnormalities in Rolandic thalamocortical white matter circuits in childhood epilepsy with centrotemporal spikes

“…First, spike rate is not a reliable biomarker of disease progression in CECTS. 38,39 This is further supported by previous findings that centrotemporal spikes are not sufficient for the development of CECTS and are associated with a number of other epilepsy and neurocognitive disorders. 40 Other compensatory mechanisms, such as those mentioned above, may contribute to spike rate, requiring a more…”

“…There are a number of potential physiologic explanations for this unexpected finding. First, spike rate is not a reliable biomarker of disease progression in CECTS 38,39 . This is further supported by previous findings that centrotemporal spikes are not sufficient for the development of CECTS and are associated with a number of other epilepsy and neurocognitive disorders 40 .…”

“…We utilized a popular, advanced probabilistic tractography algorithm to compute thalamocortical connectivity in a well‐characterized dataset of children with CECTS. Probabilistic tractography offers a number of advantages over deterministic approaches, including the estimation of the relative strength of connectivity and sensitivity to focal abnormalities along fiber tracts 27,39 . This technique has also been previously validated in the reconstruction of thalamocortical radiations 27,46 .…”

“…Probabilistic tractography offers a number of advantages over deterministic approaches, including the estimation of the relative strength of connectivity and sensitivity to focal abnormalities along fiber tracts. 27,39 This technique has also been previously validated in the reconstruction of thalamocortical radiations. 27,46 Despite these advantages, the largest limitation of our study is the small size, limiting the power to identify small effects.…”

Beta oscillations in the sensorimotor cortex correlate with disease and remission in benign epilepsy with centrotemporal spikes

“…While 15% of children will have only a single seizure, 85% may have recurrent seizures over several years (Bouma, Bovenkerk, Westendorp, & Brouwer, 1997). The perirolandic epileptiform spikes characteristic of this disease have been found to be unreliable indicators of seizure risk or remission (Kobayashi et al 2010;Xie et al, 2018;Kim et al, 2018). Current clinical practice requires a trial-and-error method for administering anti-epileptic drugs with wide variability and controversy over treatment strategy (Shields & Carter Snead III, 2009).…”