2023 Grant Recipient – Aaron Warren

Neurostimulation to Remodel Sleep Architecture in LGS

Dr. Aaron Warren, PhD

Brigham and Women’s Hospital, Harvard Medical School

Highlights:

• Enrolled 20 patients participating in an ongoing clinical trial of dual thalamic and cortical responsive neurostimulation (RNS)
• Determining the correlation between seizure severity during sleep and circadian rhythm in LGS patients during a 12+ months observation period.
• Assesses whether clinical improvements after RNS can be predicted by treatment-related changes in rhythmicity.

Results: Grant In Progress

Results will be shared when the grant is completed.

Lay Abstract:

Families rank sleep disturbances among the most harmful and challenging parts of caring for a loved one with LGS. Seizures tend to increase in the nighttime, suggesting they are intricately linked to the changes in brain activity that occur during sleep. If we can alter this activity, for example, by using brain stimulation treatments, we might be able to reduce seizures whilst promoting better sleep. This would help patients as well as caregivers, who are often awakened multiple times throughout the night to check on and care for patients. In patients with other types of epilepsy, we recently found that the efficacy of brain stimulation treatment was associated with circadian rhythms (i.e., sleep-wake cycles) in daily recordings of brain activity. Specifically, we found that people who had more intact sleep-wake rhythms responded better to treatment.

In this project, we will see if there is a similar relationship in LGS. We will study 20 patients who are participating in a recently commenced clinical trial where a stimulation and recording device is surgically implanted into the brain. We will analyze sleep-wake rhythms in daily recordings of brain activity captured by the device. We will explore how the recordings change when the device delivers stimulation and examine whether these changes can predict whether treatment helps reduce seizures and improve quality of life.

If successful, the findings will have far-reaching benefits for patients and caregivers. They will provide a new target of treatment for existing therapies like brain stimulation and new therapies aimed at improving sleep-wake cycles. Fewer seizures and better sleep will also reduce the risk of secondary health conditions that we know can result from disrupted sleep, including mood disorders, diabetes, and learning difficulties.

Updated February 13, 2024