ABSTRACT
Background and Purpose: To date, there is no specific treatment guideline for the benign childhood epilepsy with centrotemporal spikes (BECTS). Several countries recommend levetiracetam, carbamazepine, sodium valproate, oxcarbazepine, and lamotrigine as first-line drugs. Nevertheless, some of these drugs are associated with cognitive decline. Available studies that investigated the efficacy of levetiracetam and sodium valproate on BECTS involved small sample sizes. This study aimed to evaluate the efficacy of levetiracetam and sodium valproate on cognition, and to investigate the prognostic factors for BECTS as whole. Methods: Clinical data and treatment status of all patients with BECTS at Xiangya Hospital, Central South University followed from 2008 to 2013 were analyzed retrospectively. Since electrical status epilepticus in sleep (ESES) has been confirmed to play a role in cognitive deterioration, in order to evaluate the response to drugs and their cognitive effects, we created two groups of patients according to the levels of spike wave index (SWI): group 1; 0-50% SWI and group 2; >50% SWI at the last follow up. Results: A total of 195 cases were enrolled: 49.7% received monotherapies, 24.1% duotherapies and 27.2% polytherapies. Medications included; levetiracetam plus other drug (s) (75.9%), levetiracetam alone (32.8%), sodium valproate plus other drug (s) (31.3%), and sodium valproate alone (5.1%). After 2 years of treatment and follow up, 71% of the cases had a good seizure outcome, 15.9% had an improvement of SWI, and 91.7% had a normal DQ/IQ. Sodium valproate combined with levetiracetam, and sodium valproate alone correlated with good improvement of SWI, whereas, focal spikes were linked with poor improvement. For both groups (group 1 and group 2): monotherapy, levetiracetam alone, and a normal DQ/IQ at seizure onset correlated with good cognitive outcomes, in contrast, polytherapy, sodium valproate plus other drug (s), levetiracetam plus sodium valproate, an initial SWI of ≥85%, and multifocal spikes were linked to cognitive deterioration. Conclusions: Monotherapy, particularly levetiracetam seems to be a good first-line therapy which can help in normalizing the electroencephalograph and preventing cognitive decline. Polytherapy, mostly the administration of sodium valproate seems to relate with poor cognition, therefore, it is recommended to avoid it.
ABSTRACT
Intellectual disability (ID) manifests prior to adulthood as severe limitations to intellectual function and adaptive behavior. The role of potassium channelopathies in ID is poorly understood. Therefore, we aimed to evaluate the relationship between ID and potassium channelopathies. We hypothesized that potassium channelopathies are strongly associated with ID initiation, and that both gain- and loss-of-function mutations lead to ID. This systematic review explores the burden of potassium channelopathies, possible mechanisms, advancements using animal models, therapies, and existing gaps. The literature search encompassed both PubMed and Embase up to October 2019. A total of 75 articles describing 338 cases were included in this review. Nineteen channelopathies were identified, affecting the following genes: KCNMA1, KCNN3, KCNT1, KCNT2, KCNJ10, KCNJ6, KCNJ11, KCNA2, KCNA4, KCND3, KCNH1, KCNQ2, KCNAB1, KCNQ3, KCNQ5, KCNC1, KCNB1, KCNC3, and KCTD3. Twelve of these genes presented both gain- and loss-of-function properties, three displayed gain-of-function only, three exhibited loss-of-function only, and one had unknown function. How gain- and loss-of-function mutations can both lead to ID remains largely unknown. We identified only a few animal studies that focused on the mechanisms of ID in relation to potassium channelopathies and some of the few available therapeutic options (channel openers or blockers) appear to offer limited efficacy. In conclusion, potassium channelopathies contribute to the initiation of ID in several instances and this review provides a comprehensive overview of which molecular players are involved in some of the most prominent disease phenotypes.
