Title: Exploring potential biomarkers for epilepsy and the effects of physical exercise in children with epilepsy and autism

Main supervisor: Christine Ekdahl Clementson, MD, PhD, Associate Professor

Reviewers: Petrea Frid, MD, PhD and Malin Wennström, PhD, Associate Professor

Abstract

Background

Epilepsy is a common neurological disorder affecting almost 1% of the general population. However, the prevalence of epilepsy is >10% among children with autism spectrum disorder (ASD). Here, we examine potential biomarkers for epilepsy regarding the peripheral immune response, circadian rhythm and sleep characteristics. We also evaluate how physical activity may alter circadian rhythm and cognitive function.

Firstly, we conducted a study in adults with temporal lobe epilepsy(TLE), frontal lobe epilepsy(FLE), and psychogenic non-epileptic seizures (PNES), and measured the levels of immune factors before and after seizures. Secondly, we conducted a prospective study in children with epilepsy and/or autism, where we focused on immune responses, sleep characteristics and circadian rhythm. We also provided an exercise program and measured cognitive function and circadian rhythm before and after enrolment. 

Research questions

1. How does the immune response in blood differ between adults with epileptic vs psychogenic  seizures? 
2. How does the immune response in blood differ between children with ASD +/- epilepsy? 
3. How do sleep patterns and circadian rhythm differ between children with ASD +/- epilepsy and is there a correlation to the expression of immune factors? 
4. How may physical activity alter circadian rhythm and cognitive function in children with ASD and ASD+epilepsy?

Preliminary results

In publication 1 we show increased IL-6 levels in adults with TLE and FLE, compared to PNES and healthy controls. In adults with TLE, IL-6 was increased even further acutely after seizures, suggesting IL-6 as a potential biomarker for epileptic seizures. 

In our study in children, preliminary results suggest no differences in the immune response between children with ASD and ASD+epilepsy. Sleep patterns and circadian rhythm are being analyzed by actigraphy and EEG. Data collection from genetic sampling, cognitive testing and pulse watch data from physical exercise is completed.

Significance

Today, existing knowledge on the correlation of sleep disturbances, EEG patterns and peripheral inflammation in relation to the study population is sparse, and no similar project involving both biomarker research and physical exercise programs has been carried out, to the best of our knowledge. 

Published studies

1. Ahl M, Taylor MK, Avdic U, Lundin A, Andersson M, Amandusson Å, Kumlien E, Compagno Strandberg M, Ekdahl CT. Immune response in blood before and after epileptic and psychogenic non-epileptic seizures. Heliyon. 2023 Feb 21;9(3):e13938. doi: 10.1016/j.heliyon.2023.e13938. PMID: 36895367; PMCID: PMC9988551.
2. Draft: Immune responses and sleep patterns in children with epilepsy and autism (Taylor MK, Fredlund F, Richter, M, Krilh, S, Backman, S, Wickham, J, Rask, O, Ekdahl CT)