Study register · detailSystematic Review · Epilepsy · 2024
Efficacy of anti-seizure medications and alternative therapies (ketogenic diet, CBD, and quinidine) in KCNT1-related epilepsy: A systematic review.
Gras et al.·Epilepsia OpenImpact 3.1
MixedGRADEHigh17 citations
Samplek = 43 Studien n = 197 Pat.
Durationunclear
EndpointSeizure frequency/intensity
Blindingunklar
DesignSystematic Review
Cannabinoidcbd
”Key finding
Ketogenic diet, CBD and quinidine show benefits in subgroups of patients with KCNT1-related epilepsy (KD 44,6–62,5%, CBD 50%, quinidine 44,6%), while conventional antiepileptic drugs are rarely effective (5–25%).
Summary
Systematic review on KCNT1-associated epilepsy; k=43 studies, n=197 patients. CBD (incl. Epidyolex) led to improvement in seizure frequency or intensity in 50% (6/12) of EIMFS patients; in DEE patients in 1/2 cases. Ketogenic diet and CBD are classified as options worth investigating for treatment-resistant KCNT1 epilepsy; conventional antiepileptic drugs showed effect in only 5–25% of cases.
P
PopulationPatients with KCNT1-associated epilepsy (EIMFS, (AD)SHE, DEE), pooled n=197
I
InterventionKetogenic diet, cannabidiol (CBD incl. Epidyolex), quinidine as well as conventional antiepileptic drugs
O
OutcomeKD benefit in 62,5% of EIMFS patients (25/40), CBD in 50% (6/12), quinidine in 44,6% (25/56); for (AD)SHE no benefit for KD or quinidine; for DEE: KD 4/7, CBD 1/2, quinidine 6/9; conventional ASM rarely effective (5–25%)
Confidence in the evidence
Very lowLowModerateHigh
High
The highest of four GRADE levels, the effect estimate is very reliable.
KCNT1-related epilepsies encompass three main phenotypes: (i) epilepsy of infancy with migrating focal seizures (EIMFS), (ii) autosomal dominant or sporadic sleep-related hypermotor epilepsy [(AD)SHE], and (iii) different types of developmental and epileptic encephalopathies (DEE). Many patients present with drug-resistant seizures and global developmental delays. In addition to conventional anti-seizure medications (ASM), multiple alternative therapies have been tested including the ketogenic diet (KD), cannabidiol (CBD-including Epidyolex and other CBD derivatives) and quinidine (QUIN). We aimed to clarify the current state of the art concerning the benefits of those therapies administered to the three groups of patients. We performed a literature review on PubMed and EMBase with the keyword "KCNT1" and selected articles reporting qualitative and/or quantitative information on responses to these treatments. A treatment was considered beneficial if it improved seizure frequency and/or intensity and/or quality of life. Patients were grouped by phenotype. A total of 43 studies including 197 patients were reviewed. For EIMFS patients (32 studies, 135 patients), KD resulted in benefit in 62.5% (25/40), all types of CBD resulted in benefit in 50% (6/12), and QUIN resulted in benefit in 44.6% (25/56). For (AD)SHE patients (10 studies, 32 patients), we found only one report of treatment with KD, with no benefit noted. QUIN was trialed in 8 patients with no reported benefit. For DEE patients (10 studies, 30 patients), KD resulted in benefit for 4/7, CBD for 1/2, and QUIN for 6/9. In all groups, conventional ASM are rarely reported as beneficial (in 5%-25% of patients). Ketogenic diet, CBD, and QUIN treatments appear to be beneficial in a subset of patient with drug-resistant epilepsy. The KD and CBD are reasonable to trial in patients with KCNT1-related epilepsy. Further studies are needed to identify optimal treatment strategies and to establish predictive response factors.