Epilepsy Center | Chronoepileptology

Treating epilepsy by the clock

Nearly one-third of children with epilepsy continue to have seizures even with many new anti-epileptic medications on the market. Tobias Loddenkemper, MD, a neurologist with the Epilepsy Center, has been finding that an approach called chronotherapy can often help. It involves carefully timing treatment to the times when seizures most often happen.

Circadian patterns of seizures

Parents sometimes notice that their children have seizures in patterns: day/night, sleep/wake or even monthly patterns. Some seizure patterns may follow a child’s own circadian rhythms; others may be created by disturbances in sleep, which are common in epilepsy, especially when seizures cluster late at night or early in the morning. Being aware of these patterns can help you and your physician figure out the best timing for anti-seizure medications.

Chronotherapy works by adjusting anti-epileptic drug treatment to correspond with times of greatest seizure severity or susceptibility. In this graph, based on information from 41 children over several days, the blue line shows variations in blood levels of the drug carbamazepine in patients given a higher evening dose, while the white dotted line shows the pattern of frontal lobe seizures.

Research by the Epilepsy Center has shown, for example, that evening treatment can provide better seizure control for many children and reduce nighttime “spiking” in epilepsy activity (see ESES, below). Evening treatment can also help limit the side effects of anti-epileptic medications, allowing children to remain alert during the daytime.

The first step: Tracking seizure activity

If you’re interested in trying chronotherapy, the first step is to keep a careful seizure diary, noting the times when your child has seizures. Based on these observations, we can adjust when your child takes medications to ensure the right levels of medication are “on board” at the right times.

Beyond paper diaries, the Epilepsy Center is testing a number of wearable seizure tracking devices, such as an epilepsy wristband, to help track seizure patterns around the clock, based on sweat secretion and other physiologic markers.

A seizure-detecting wristband being tested at Boston Children’s

Wearable devices make logging automatic and are very helpful in picking up nighttime seizures or “silent” seizures that parents might not always be aware of. To get more detailed information, we may suggest your child stay in the hospital for one or more days for continuous electroencephalography (EEG) recordings.

Electrical status epilepticus during sleep (ESES)

Sometimes children can have nighttime “spikes” in brain electrical activity, even when daytime EEGs are near-normal. This seizure-like activity often goes unnoticed, but it can cause young children to struggle with or lose early milestones like language, walking skills and fine motor abilities.

The good news is that this nighttime spiking, called electrical status epilepticus during sleep (ESES), can be readily detected and suppressed with nighttime anti-seizure drugs—putting learning and development back on track.

This EEG showing constant nighttime spiking is from a child with no apparent seizure disorder. Few such spikes appeared in the daytime EEG.

In a study published in the journal Neurology, Loddenkemper and Iván Sánchez Fernández, MD, of the Epilepsy Center reviewed overnight EEG recordings from children with developmental delay or regression. Of the 147 children, 100 had prominent nighttime spikes—and of these, about one in five were not previously known to have epilepsy, and about half had MRI evidence of an early brain injury such as a stroke. In another study published in the journal Pediatric Neurology, Loddenkemper and Sánchez Fernández showed that ESES can be reduced with high doses of Valium given at bedtime.

Read more about ESES and “taking back the night” in epilepsy.

Fine-tuning treatment

More research is ongoing at Boston Children’s to refine chronotherapy and maximize its benefits. This work is helping us understand some subtleties that are allowing us to fine-tune treatment. For example, anti-epileptic drugs themselves can sometimes alter sleep/wake patterns, and differences in a child’s metabolism over the course of the day may influence how much medication gets to the brain or the severity of side effects.

The Epilepsy Center is developing computer models that interpret a child’s information to predict his or her circadian seizure patterns and calculate the best individualized dosing strategy. We are also investigating other markers to help us understand seizure patterns, like melatonin or cortisol levels in the blood or urine.

For the future

Our ultimate goal is to develop automatic, “closed-loop treatments” that both detect a developing seizure and treat it, using such techniques as an implanted brain stimulator or a pump that provides medication “just in time.” We hope to report back on our progress soon!