AES 2016: Insight into Seizure Clusters

"Seizures beget seizure." This oft-repeated 19th century adage accurately describes seizure clusters.

These repetitive seizures occur in groups or clusters over a period of time. While optimal treatment is not yet known, clinicians employ a variety of strategies to stop them from escalating, including rescue benzodiazepines, progesterone for catamenial epilepsy, or increases in daily medication.

Lara Marcuse, MD, an associate professor and co-director of the Mt. Sinai Epilepsy Center, shared current insights about seizure clusters, at the 70^th annual meeting of the American Epilepsy Society. They are a problem affecting the quality of life of many epilepsy patients, she said.

To improve understanding, Dr Marcuse called for a unified definition of seizure clusters. She shared examples of significantly different classifications: 3 seizures within 24 hours, 3 seizures within 4 hours, and 2 seizures within 4 hours.

Reports on prevalence also vary widely depending on the definition and the setting-ranging from 3% of people with epilepsy, in a UK cohort study,¹ to 61% of epilepsy patients monitored pre-surgery.² Seizure clusters are estimated to occur in 40% of women with catamenial epilepsy, triggered by the menstrual cycle.

Repetitive seizures can occur with any seizure type and in any electroclinical syndrome. But they commonly occur in patients with catastrophic epilepsies of infancy and childhood, refractory focal epilepsy, benign occipital epilepsy (Gastaut variant), absence epilepsy, sleep-related hypermotor epilepsy, and catamenial epilepsy.

In any patient, the greatest risk that a seizure will occur, is that a seizure has recently occurred.

So what happens after the first seizure that makes the second seizure so likely? Dr Marcuse says one possibility is that inhibitory tone is lost after the first seizure. 

Medication levels, hormone levels, and neurotransmitter tone can offer protection from seizure clusters. Dr Marcuse compares these factors to water topping an underwater mountain range. The mountain range consists of the underlying structural, metabolic, and genetic causes for epilepsy. When the water subsides, the mountain range and the seizure clusters emerge.

While there many treatment practices routinely used for seizure clusters, little formal evidence backs them. At her center, Dr Marcuse treats seizures with intravenous benzodiazepines, typically lorazepam. Examples of other common treatment strategies include:

• Clonazepam, disintegrating wafer after the first seizure

• Adding a second anti-epileptic drug

• IN (intranasal) or buccal midazolam after the first seizure

• Rectal diazepam after the first seizure

In patients with catamenial epilepsy:

• Extended oral contraception to suppress menstruation

• Progesterone 200 mg lozenge given on days 14-28 of the menstrual cycle

• Acetazolamide/clobazam taken perimenstrually

Dr Marcuse also recommended considering if the patient might be a surgical candidate.

Better identification of the pre-ictal state in seizure clusters could open up enormous therapeutic therapies, added Marcuse. The pre-ictal state is the period prior to the seizure when a seizure is inevitable, or the probability of a seizure is greatly increased.

In the meantime, clinicians should devote adequate time to monitoring patients who come to the ER with seizure clusters.

“We really should pay attention to their seizure patterns, and understand that it can give us a window into our patients’ seizures, so we can serve our patients better,” Dr Marcuse said.

The AES 2016 Annual Meeting was held December 2-6 in Houston.

Marcuse L, Seizure clustering: what is it and how do we keep it from escalating?, 2016, American Epilepsy Society Annual Meeting, www.aesnet.org.

References:

1. Martinez C, et al. Prevalence of acute repetitive seizures (ARS) in the United Kingdom. Epilepsy Res. 2009 Dec;87(2-3):137-143.

2. Haut SR, et al. Seizure clustering during epilepsy monitoring. Epilepsia. 2002 Jul;43(7):711-715.