Exploring Brain Activity in Sudden Unexpected Death in Epilepsy (SUDEP)

Kommajosyula SP, Randall ME, Brozoski TJ, Odintsov BM, Faingold CL. Epilepsy Research, 135 (2017): 87-94.

The article “Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese-enhanced magnetic resonance imaging study” examined the changes of certain brain activities upon sudden unexpected death in epilepsy (SUDEP) in a mouse model. 

Purpose

Understanding cause or changes in a brain with SUDEP is an area of major concern. This study is the first one to use a special type of MRI (called MEMRI) for SUDEP research to look at the activity changes in specific brain structures. 

• Sudden unexpected death in epilepsy (SUDEP) is likely the greatest single cause of death in people with epilepsy. 
  • Each year, about 1 in 1,000 people with epilepsy die from SUDEP. 
  • People with epilepsy have a 24-28 times higher risk of sudden death as compared to the general population.
  • No one knows what causes SUDEP, but many areas are being looked at including problems with breathing, hearth rhythm, and brain function that occur with seizures.
• Imaging studies have found changes in brain activity in specific areas of the brain in people who passed away from SUDEP.
  • The parts of the brain affected in SUDEP are mainly those that regulate the heart and the respiratory or breathing systems (i.e., cardio-respiratory functions). It is thought that the impaired cardio-respiratory functions would then lead to SUDEP.
  • However, the specific structure of the brain where these neutral activity changes occurred is not yet known. 
• A specialized MRI scan that uses a substance called manganese to detect brain activities in mice was used in this study. MEMRI can better track changes in brain activity and give images with higher brightness.
• A mouse model is commonly used to mimic human SUDEP. When given acoustical stimuli, the mice experience seizures, followed by seizure-induced respiratory arrest (S-IRA), which leads to sudden death. Images of brain activity are then done.

Description of Study

• Acoustic stimuli or sounds were used to trigger seizures and respiratory arrest in mice. Results were compared to a control group of mice who were not affected by the stimuli. 
• Manganese-enhanced MRI (MEMRI) was used to measure the brain activity. 

Summary of Study Findings

• A comparison of the patterns of MEMRI activation between DBA/1 mice with respiratory arrest after a seizure and controls showed increased activity levels in areas of the brain involved in controlling breathing.
• Respiratory arrest after a seizure was found to increase the activity in certain brain regions that contain a large number of serotonergic neurons. Loss of serotonergic signaling can predisopse mice to SUDEP. 

What does this mean?

• These findings provide additional evidence that problems in the brain areas critical for regulating breathing through serotonin signaling are involved in SUDEP.
• In this paper, the scientists were able to successfully detect the specific brain structures that showed activity changes related to respiratory arrest after a seizure.
• More research is needed to investigate the electrical and chemical changes in these specific brain areas and if this can point to ways to prevent SUDEP.

Related Links

• #AimForZero: Striving Toward a Future Free from SUDEP
• SUDEP Research Efforts
• Information and Resources for Professionals
• SUDEP Challenge Initiative