Patients with epilepsy often experience interictal dysfunction in brainstem areas, which are used to regulate respiration, according to a study that used functional MRI (fMRI) published in the journal Neurology.
The results showed that brainstem activation was reduced in patients with epilepsy compared to healthy controls during both inspiratory breath-holding (Cohen d=1.31; 95% CI 0.70–1.92; P=0.006) and expiratory breath-holding (Cohen d=1.43; 95% CI 0.81–2.05; P=0.005), reported Carolina Ciumas, Lausanne University Hospital in Switzerland, and colleagues.
“A significant proportion of [patients with epilepsy] seem to suffer from interictal dysfunction of brainstem regions involved in respiratory control. These abnormalities could be detected at the individual level using a simple BH [breath hold] fMRI paradigm, suggesting potential for translation into a clinical biomarker,” the study team wrote.
The existing literature suggests that patients with epilepsy often have peri-ictal apnea, the study team noted. This condition may eventually lead to sudden unexpected death in epilepsy, the authors noted. It is unclear if the response to voluntary apnea is distinct in the brainstem respiratory regions, they added.
Hence, the investigators set out to evaluate how brainstem respiratory regions changed in response to breath holding. They relied on fMRI data to do so.
The research team evaluated 21 controls and 31 patients with epilepsy from an outpatient clinic. For the control group, mean age was 32.8 years, and 52.4% were female. Mean age was 34 years for the patients with epilepsy. Females accounted for 51.6% of the patients with epilepsy.
The researchers also evaluated sex-matched and age-matched healthy controls. They selected controls using advertisements. While conducting voluntary expiratory and inspiratory breath-holding tasks, the entire cohort underwent fMRI.
The investigators documented the patient’s oxygen saturation, respiratory rate, and end-tidal CO2 and O2. Using a standard general linear model, they then assessed functional data. They also looked at seed-to-voxel and region of interest (ROI)-to-ROI connectivity analyses focused on specific predefined brainstem areas.
The researchers also reported that patients with epilepsy had reduced activation in select areas of the brain. Lower activation areas of the brain included those related to the median raphe nucleus during the inspiratory breath-holding and the cuneiform nucleus during expiratory breath-holding.
The researchers also used fMRI to assess the cohort during expiratory breath holding. They found that 90% of controls and 61% of the epilepsy group had substantial brainstem activation based on variations in fMRI data.
The results indicated that although the healthy controls included in the study did not have a noteworthy reduction in brainstem activation, 35% of the epilepsy cohort did.
“Future studies at a larger scale are warranted to test whether BH-fMRI or resting-state functional connectivity could prove clinically relevant, particularly to predict the risk of SUDEP [sudden unexpected death in epilepsy],” the authors concluded.