Below you will find a curated collection of medical literature related to epilepsy summarized in plain English so you can have access to the same information that your doctors have.
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Kwan & Brodie. Early identification of refractory epilepsy. The New England Journal of Medicine. 2000. 342(5):314. This is a critically important paper published in one of the most prestigious medical journals now over 20 years ago characterizing rates of seizure control using medication alone over time at a large hospital treating many patients with epilepsy. The paper highlights the seizure control rates of 525 people with epilepsy cared for during a 13 year time span (1984-1997). People ranged in age from 9-93 years old. Approximately two-thirds of patients (333 people or 63%) achieved and maintained seizure freedom using medication alone. The remaining individuals continued to have seizures despite the use of medication. Of the 525 patients included in the analysis, 470 received medication for seizure control for the first time during the study period. Of these 470 patients who began seizure medication, approximately half (222 people or 47%) became seizure free after starting their first seizure medication. An additional 13% of people achieved and maintained seizure freedom following addition of a second medication. Only 4% of people achieved and maintained seizure freedom using three or more medications. Importantly, there was no difference in seizure control rates with newer age medications compared to older or more historic seizure medications that had been around for many decades although the side effects were improved with the newer medications.
*Takeaway: This paper defines medication-resistant epilepsy to include epilepsy characterized by persistent seizures following the use of two or more seizure medications.
Wiebe, et al., A randomized, controlled trial of surgery for temporal-lobe epilepsy. The New England Journal of Medicine. 2001. 345(5):311. Another critically important paper published in one of the most prestigious medical journals now over 20 years ago characterizing the benefits of surgery in the management of seizures beginning within one of the brain’s temporal lobes (the most common type of medication-resistant epilepsy in adults). This study randomly assigned 80 patients with medication-resistant epilepsy beginning within one temporal lobe (watch my “Neuroanatomy of epilepsy” video in the Knowledge Nuggets archive for more information) to either surgery or medical management for one year. Seizure control rates between the two groups were then compared at one year. 58% of patients undergoing surgery for seizure control were free of seizures that impaired their awareness at one year while only 8% of patients on medication alone achieved the same degree of seizure control. 10% of patients who underwent surgery (four patients) had a surgical complication (one patient had new numbness in their thigh from a small stroke following surgery, one patient had a wound infection, two patients had new or worsened difficulties with word finding and naming). One patient in the medical management group died, presumably following an unwitnessed seizure.
*Takeaway: This paper challenges the notion of reserving surgery for epilepsy as a last resort for medication-resistant epilepsy given the profound advantages surgery can offer compared to continued medical management alone with relatively low risks.
Englot, et al., Epilepsy surgery trends in the United States, 1990-2008. Neurology. 2012. 78(16):1200. This is a follow up paper to the Wiebe paper (see above) evaluating what, if any, impact the previous seminal paper published in 2001 had had on the field of epilepsy care ten years later. Unfortunately, the short answer is not much. This study pulled data from a large national electronic database of anonymous medical records and looked at the frequency of surgery performed for patients with medication-resistant seizures. The findings demonstrate that more patients were admitted with poor seizure control over time but that no significant change in the number of surgeries occurred, resulting in a relative decline in surgery for epilepsy (more patients, the same number of surgeries over time). This trend was attributed to an increase over time in epilepsy care at smaller hospitals rather than larger hospitals where surgery is more likely to be offered to patients.
*Takeaway: This paper demonstrates that no significant changes have resulted from Dr. Wiebe and colleagues’ landmark paper in 2001 (see above) and that more work needs to be done to get the message out about safe surgical options for seizure control. Specifically, there should be a greater effort made to get patients with medication-resistant seizures to large, comprehensive epilepsy centers so that they can be offered the full range of treatment options to maximize seizure control (watch my forthcoming “What is an epilepsy center and how can I find one?” video in the Knowledge Nuggets archive for more information).
von Wrede, et al., Cannabidiol in the treatment of epilepsy. Clinical Drug Investigation. 2021. 41(3):211. This paper is a review article highlighting the findings of other scientific investigations regarding cannabidiol or CBD in the treatment of epilepsy. It begins by providing a historical overview of the field citing the first major paper on the topic in 2016. This first paper followed 214 children and young adults with severe medication-resistant epilepsy (60 or more seizures per month) on CBD for seizure control. This paper found that after 12 weeks, relatively high dose CBD (22.7mg/kg) could achieve a seizure reduction of about one third (so, approximately 40 seizures per month instead of 60) across all patients. It also found that different seizure types responded better than others with focal onset and atonic seizures responded the most while tonic-clonic seizures responded the least. Importantly, 79% of patients had an adverse reaction to this dose of CBD which could range from daytime sleepiness and diarrhea to impaired liver function and low blood cell counts. The review then transitions to discuss five placebo-controlled clinical trials investigating a medical grade CBD product for use in two different severe pediatric epilepsy syndromes, Dravet Syndrome and Lennox-Gastaut Syndrome as well as Tuberous Sclerosis which is a condition frequently associated with medication-resistant epilepsy. These studies demonstrated moderate improvement in seizure control (ranging from 37-49% average reduction of seizure frequency) using this medical grade CBD product at doses ranging from 10mg/kg to 50mg/kg compared to placebo. Side effects remained common and highly variable across patients. These five clinical trials led to the first FDA approved CBD-derived medication for use in epilepsy, Epidiolex, in 2018. Approval of Epidiolex is very narrow and specifically for these syndromes in particular and its effect can not be generalized to all epilepsies although additional studies are currently underway.
*Takeaway: This paper discusses the current scientific understanding of the role of CBD in the treatment of epilepsy. Specifically, high quality, relatively high dose CBD can offer a moderate reduction of seizure frequency to children suffering from frequent seizures due to Dravet Syndrome, Lennox-Gastaut Syndrome or Tuberous Sclerosis. Side effects are common and can be significant so any use of CBD should be discussed with your medical team.
Tomson, et al., Management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epileptic Disorders. 2019. 21(6):497. This paper, written by representatives from the one of the largest international epilepsy organizations, the International League Epilepsy provides a summary of data related to the risk/benefit balance of medication to prevent seizures during pregnancy compared to maternal and fetal risks of poorly controlled seizures during pregnancy. It finds that the likelihood of a healthy, uneventful pregnancy is maximized by multi-disciplinary pre-conception counseling between the women interesting in having children as well as her epilepsy neurologist and obstetrician. The benefits of seizure medication for seizure control during pregnancy outweigh the associated risks to fetal development. Many seizure medications can be taken safely during pregnancy but some carry more risks than others. Specifically, valproate is associated with the highest risks during pregnancy and should be avoided whenever possible. Folate supplementation is important for all women desiring pregnancy, but it is especially important for women on medication to prevent seizures. Many seizure medications require close monitoring of blood levels during pregnancy due to the metabolic changes that occur with pregnancy.
*Takeaway: The vast majority of women with epilepsy will have uneventful pregnancies and give birth to healthy children. Close, multi-disciplinary counseling (starting before conception) maximizes the likelihood of an uneventful, healthy pregnancy.
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