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Published on: May 16, 2019
Potential induction of epileptic spasms by nonselective voltage-gated sodium channel blockade: Interaction with
Shaun A Hussain1, Jaeden Heesch1, Julius Weng1
1Division of Pediatric Neurology, David Geffen School of Medicine and UCLA Mattel Children's Hospital, Los Angeles, CA, United States.
Purpose:
Epileptic spasms are often preceded by focal (or multifocal) seizures. Based on a series of case reports suggesting that carbamazepine and oxcarbazepine may induce epileptic spasms, we set out to rigorously evaluate the potential association between exposure to voltage-gated sodium channel blockade and latency to epileptic spasms.
Methods:
We identified 50 cases (children with focal seizures and evolution to epileptic spasms) and 50 controls (children with focal seizures without evolution to epileptic spasms). For each patient, we reviewed all sequential neurology encounters between onset of epilepsy and emergence of epileptic spasms. For each encounter we recorded seizure-frequency and all anti-seizure therapy exposures. Using multivariable Cox proportional hazards regression, we evaluated the association between voltage-gated sodium channel exposure (carbamazepine, oxcarbazepine, lacosamide, or phenytoin) and latency to epileptic spasms onset, with adjustment for etiology and seizure-frequency.
Results:
Latency to epileptic spasms onset was independently associated with exposure to sodium channel blockade (hazard ratio = 2.4; 95% CI 1.1-5.2; P = 0.03) and high-risk etiology (hazard ratio = 2.8; 95% CI 1.5-5.1; P = 0.001). With assessment for interaction between sodium channel blockade and etiology, we identified an estimated 7-fold increased risk of epileptic spasms with the combination of sodium channel blockade and high-risk etiology (hazard ratio = 7.0, 95% CI 2.5-19.8; P < 0.001).
Conclusion:
This study suggests that voltage-gated sodium channel blockade may induce epileptic spasms among children at risk on the basis of etiology. Further study is warranted to replicate these findings, ascertain possible drug- and dose-specific risks, and identify potential mechanisms of harm.
Insights
Voltage-gated sodium channel blockers may increase the risk of epileptic spasms in children with focal seizures. This risk is significantly higher when combined with a high-risk etiology, suggesting a potential drug-induced effect.
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
- Epileptology
Background:
- Epileptic spasms can follow focal seizures.
- Case reports suggest carbamazepine and oxcarbazepine may trigger epileptic spasms.
- The association between sodium channel blockade and epileptic spasms requires rigorous evaluation.
Purpose of the Study:
- To investigate the association between voltage-gated sodium channel (VGSC) blockade and the latency to epileptic spasms in children.
- To evaluate if specific anti-seizure therapies influence the development of epileptic spasms.
Main Methods:
- A case-control study identified 50 children with focal seizures evolving to epileptic spasms and 50 controls.
- Sequential neurology encounters were reviewed for seizure frequency and anti-seizure therapy exposure.
- Multivariable Cox proportional hazards regression analyzed the association between VGSC exposure and latency to epileptic spasms.
Main Results:
- VGSC blockade (carbamazepine, oxcarbazepine, lacosamide, phenytoin) was independently associated with a 2.4-fold increased risk of epileptic spasms.
- High-risk etiology independently increased the risk of epileptic spasms by 2.8-fold.
- The combination of VGSC blockade and high-risk etiology resulted in an estimated 7-fold increased risk of epileptic spasms.
Conclusions:
- VGSC blockade may induce epileptic spasms in children with a high-risk etiology.
- Further research is needed to confirm these findings and explore drug-specific risks and mechanisms.
- This study highlights potential iatrogenic risks associated with certain anti-epileptic drugs in vulnerable pediatric populations.
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