Sudden unexpected death in epilepsy (SUDEP)
Sudden Unexpected Death in Epilepsy (SUDEP) refers to the sudden, unexpected, and unexplained death of an otherwise healthy person with epilepsy. SUDEP typically occurs during or immediately after a seizure, and it is one of the most significant risks associated with epilepsy. While SUDEP is rare, it remains a major concern for individuals with epilepsy, their families, and healthcare providers.
Seizure Activity: SUDEP often occurs during or immediately following a seizure. In some cases, seizures may be generalized tonic-clonic (formerly known as grand mal) seizures, which involve loss of consciousness and convulsions.
Respiratory and Cardiac Issues: The exact cause of SUDEP is not fully understood, but it is believed to involve a combination of factors. Seizures can lead to temporary interruptions in breathing (apnea) or irregular heart rhythms, which may contribute to SUDEP.
Prevention: Reducing the risk of SUDEP involves effective management of epilepsy. This includes following treatment plans, taking medications as prescribed, avoiding seizure triggers, and seeking regular medical care. For those with uncontrolled epilepsy, exploring alternative treatment options with a healthcare provider is crucial.
Awareness and Education: It's essential for people with epilepsy and their caregivers to be aware of SUDEP and understand the risk factors. Open communication with healthcare providers can help develop strategies to mitigate these risks.
Research: Ongoing research is focused on understanding the mechanisms underlying SUDEP and developing strategies to reduce its occurrence. Some studies have explored the use of seizure detection devices and alarms to alert caregivers during seizures.
It's important to remember that while SUDEP is a concern, many individuals with epilepsy live full and productive lives. Effective epilepsy management, seizure control, and a strong support system can significantly reduce the risk of SUDEP. If you or someone you know has epilepsy, it's advisable to work closely with a healthcare provider to create a personalized epilepsy management plan.
It is the leading cause of death for patients with refractory epilepsy.
Focal-to-bilateral tonic-clonic seizures (FBTCS) are a major risk factor, and centrally-mediated respiratory depression may increase the risk further.
Several factors may increase the risk of SUDEP, including uncontrolled or poorly managed epilepsy, a history of frequent generalized tonic-clonic seizures, young adulthood, and not taking prescribed antiepileptic medications regularly.
Zeicu et al. determined the volume and microstructure of the amygdala, a key structure that can trigger apnea in people with focal epilepsy, stratified by the presence or absence of FBTCS, ictal central apnea (ICA), and post-convulsive central apnea (PCCA).
73 patients with focal impaired awareness seizures without FBTC seizures (FBTCneg group) and 30 with FBTCS (FBTCpos group) recorded during video EEG (VEEG) with respiratory monitoring were recruited prospectively during presurgical investigations. They acquired high-resolution T1-weighted anatomical and multi-shell diffusion images, and computed neurite orientation dispersion and density imaging (NODDI) metrics in all epilepsy patients and 69 healthy controls. Amygdala volumetric and microstructure alterations were compared between three groups: healthy subjects, FBTCneg, and FBTCpos groups. The FBTCpos group was further subdivided by the presence of ICA and PCCA, verified by VEEG.
Bilateral amygdala volumes were significantly increased in the FBTCpos cohort compared to healthy controls and the FBTCneg group. Patients with recorded PCCA had the highest increase in bilateral amygdala volume of the FBTCpos cohort. Amygdala neurite density index (NDI) values were significantly decreased in both the FBTCneg and FBTCpos groups relative to healthy controls, with values in the FBTCpos group being the lowest of the two. The presence of PCCA was associated with significantly lower NDI values vs the non-apnea FBTCpos group (p=0.004).
Significance: Individuals with FBTCpos and PCCA show significantly increased amygdala volumes and disrupted architecture bilaterally, with greater changes on the left side. The structural alterations reflected by NODDI and volume differences may be associated with inappropriate cardiorespiratory patterns mediated by the amygdala, particularly after FBTCS. Determination of amygdala volumetric and architectural changes may assist identification of individuals at risk 1).
The study involving 73 patients with focal impaired awareness seizures without focal to bilateral tonic-clonic (FBTC) seizures and 30 patients with FBTC seizures (FBTCpos group) provides valuable insights into the structural and volumetric changes in the amygdala, as well as the potential association with inappropriate cardiorespiratory patterns mediated by the amygdala. Below is a critical review of the study: 1. Well-Defined Patient Groups: The study presents well-defined patient groups, including those with FBTC seizures and those without FBTC seizures (FBTCneg group). Further subgrouping within the FBTCpos group based on the presence of ictal central apnea (ICA) and postictal central apnea (PCCA) adds depth to the analysis. This comprehensive categorization allows for a nuanced investigation into the structural and microstructural differences in the amygdala. 2. Neuroimaging Techniques: The use of high-resolution T1-weighted anatomical and multi-shell diffusion images to compute neurite orientation dispersion and density imaging (NODDI) metrics is a strength of the study. These neuroimaging techniques provide detailed information about amygdala microstructure, which can be critical for understanding the neural basis of epilepsy-related phenomena. 3. Amygdala Volumetric Changes: The finding of significantly increased bilateral amygdala volumes in the FBTCpos cohort compared to healthy controls and the FBTCneg group is intriguing. This suggests that FBTC seizures may be associated with structural changes in the amygdala, particularly when central apnea is involved. This finding may help identify structural biomarkers related to epilepsy. 4. Microstructural Alterations: The study reports decreased amygdala neurite density index (NDI) values in both the FBTCneg and FBTCpos groups, with the FBTCpos group showing the lowest values. The decrease in NDI suggests disrupted amygdala microstructure in these patient groups. The association between NDI values and central apnea in the FBTCpos group is particularly noteworthy, indicating that specific seizure characteristics may contribute to microstructural changes. 5. Left Lateralization: The study notes greater changes in the left amygdala, both in terms of volume and microstructure. This lateralization is interesting and warrants further investigation. Understanding why structural and microstructural changes are more pronounced on the left side may provide insights into the lateralization of seizure-related effects on the brain. 6. Clinical Significance: The study's findings have clinical significance as they suggest that amygdala structural and microstructural alterations may be linked to cardiorespiratory patterns, especially following FBTC seizures. Identifying these changes may assist in identifying individuals at risk, potentially allowing for more targeted interventions or monitoring. 7. Limitations: While the study is valuable, it's essential to acknowledge its limitations. The sample size, particularly in the FBTCpos group, is relatively small. Additionally, the study is observational, and causal relationships cannot be determined. Long-term follow-up data on clinical outcomes and further research are needed to confirm the clinical implications of these findings. In conclusion, this study offers important insights into the structural and microstructural changes in the amygdala associated with FBTC seizures, particularly in the presence of central apnea. These findings open avenues for future research on epilepsy-related brain alterations and their clinical implications.
There is increasing evidence for a centrally mediated respiratory depression as a pathophysiological mechanism. The brain regions responsible for a seizure’s inducing respiratory depression are unclear—the respiratory nuclei in the brainstem are thought to be involved, but the involvement of forebrain structures is not yet understood.
The aim of a study by Nobis et al. was to analyze intracranial EEGs in combination with the results of respiratory monitoring to investigate the relationship between seizure spread to specific mesial temporal brain regions and the onset of respiratory dysfunction and apnea.
The authors reviewed all invasive electroencephalographic studies performed at Northwestern Memorial Hospital (Chicago) since 2010 to identify those cases in which 1) multiple mesial temporal electrodes (amygdala and hippocampal) were placed, 2) seizures were captured, and 3) patients’ respiration was monitored. They identified 8 investigations meeting these criteria in patients with temporal lobe epilepsy, and these investigations yielded data on a total of 22 seizures for analysis.
The onset of ictal apnea associated with each seizure was highly correlated with seizure spread to the amygdala. The onset of apnea occurred 2.7 ± 0.4 (mean ± SEM) seconds after the spread of the seizure to the amygdala, which was significantly earlier than after spreading to the hippocampus (10.2 ± 0.7 seconds; p < 0.01).
The findings suggest that the activation of amygdalar networks is correlated with central apnea during seizures. This study builds on the authors’ prior work that demonstrates a role for the amygdala in voluntary respiratory control and suggests a further role in dysfunctional breathing states seen during seizures, with implications for SUDEP pathophysiology 2).