Morse AM, Kothare SV. Pediatric Sudden Unexpected Death in Epilepsy. Pediatr Neurol. 2016 Apr;57:7-16.
Epilepsy is a common neurological disorder among children and adolescents that is associated with increased mortality for numerous reasons. Sudden unexpected death in epilepsy is a critically important entity for physicians who treat patients with epilepsy. Many pediatric neurologists are hesitant to discuss this condition with patients and families because of the lower risk in the pediatric age group.
We searched for studies published between January 2000 and June 2015 by means of a PubMed search and a cumulative review of reference lists of all relevant publications, using the keywords "sudden unexpected death in epilepsy patients," "pediatric SUDEP," "sudden unexpected death in epilepsy patients and children," "sudden unexpected death in children" and "sudden infant death syndrome."
SUDEP is a rare condition in children. Its mechanism is poorly understood and may have a distinct pathogenesis from adult sudden unexpected death in epilepsy. Limited comfort, experience, and knowledge to provide appropriate education about sudden unexpected death in epilepsy leads to fewer physicians discussing this subject leading to less informed and less prepared patients and families.
We provide a detailed review of the literature on pediatric SUDEP, including the definition, classification, and proposed mechanisms of sudden unexpected death in epilepsy in children, as well as discuss the incidence in the pediatric population and risk factors in children, concluding with possible prevention strategies.
From the article:
Many researchers have attempted to identify the underlying pathophysiology for SUDEP but without conclusive success. Most of the proposed mechanisms for SUDEP are based on adult studies. Some studies performed in children demonstrate overlap with adult pathophysiology, but others suggest that it may be a phenomenologically different process. It has been suggested that SUDEP in children may be caused by similar mechanisms as postulated in adult SUDEP, but the pattern of seizure-related cardiopulmonary disturbances differ. Ryvlin et al. performed a retrospective analysis of 133,788 subjects from 147 epilepsy monitoring units: 70% adults and 30% children with video electroencephalography (EEG), evaluating cardiorespiratory deaths encountered during monitoring. They suggested that the main mechanism leading to SUDEP starts with an early, centrally mediated, severe alteration of both respiratory and cardiac functions after generalized tonic-clonic seizures. However, no differences between the adult and pediatric cohorts were addressed in this study. In general, there are several proposed mechanisms of SUDEP that may occur either independently, such as cardiac, pulmonary, or autonomic dysregulation, or in combination.
Cardiac mechanisms are likely related to cardiac dysrhythmia precipitated by seizures. Sevcencu and Struijk outlined the spectrum of cardiac effects in adults related to epilepsy include subtle changes in heart rate variability to ictal sinus arrest, and from QT-interval shortening to atrial fibrillation. Transient bradycardia, sinus tachycardia, various arrhythmias, and prolongation of the QT interval are often seen in children during seizure. Temporal lobe complex partial seizures are more likely to cause cardiovascular dysregulation as compared with seizures from an extratemporal origin.
Respiratory mechanisms suggested to play a role in SUDEP include respiratory arrest, neurogenic pulmonary edema, and asphyxiation. Another possible mechanism is severe postictal laryngospasm. Respiratory dysfunction is likely a result of abnormal neuronal activation and deactivation of the respiratory center in the brainstem during both generalized and focal seizures. Although central apnea and neurogenic pulmonary edema are the two major proposed pathways linking seizures to SUDEP, most studies performed were in adults, with mostly case reports found in children.
Cardiac and respiratory abnormalities commonly overlap, resulting in an exacerbation of the detrimental effects of each. Pavlova et al. evaluated the relationship of cardiorespiratory abnormalities and EEG changes during seizures according to age in patients with epilepsy. The results suggested that there may be an age-related effect on cardiorespiratory changes with EEG abnormalities associated with seizures with higher rates of apnea and bradycardia in children, but a much higher prevalence of postictal generalized EEG suppression (PGES) of longer duration in adults. However, it is important to note that the children in the study more commonly had frontal-onset seizures, whereas the adult patients had a temporal onset. This finding suggests a possible relationship of seizure foci to cardiorespiratory changes. Singh et al. also identified potentially life-threatening cardiopulmonary abnormalities, such as bradycardia, apnea, and hypoxemia, in pediatric epileptic seizures are associated with predictable patient and seizure characteristics, including seizure subtype and duration.
PGES, which is EEG amplitude less than 10 μV at the end of a seizure lasting more than 50 seconds, was identified by Lhatoo et al. in a series of 10 adult patients as a risk factor to development of SUDEP in the future. PGES is an EEG phenomenon linked to the end of a tonic, not clonic, phase of generalized tonic-clonic seizures and observed after the seizure is over. Moseley et al. was the first to identify a relationship between PGES and SUDEP in children. In fact, their study revealed that PGES is not uncommon in children, as it occurred in almost a third of the children evaluated and appeared to have a positive correlation with a higher score on the SUDEP 7 inventory. The magnitude of both sympathetic and parasympathetic changes corresponds to the duration of EEG suppression after tonic-clonic seizures in children (tachycardia/bradycardia, prolonged QTc, heart rate variability). These changes were measured by a special device worn, for 3-7 days, on the wrist by 11 patients utilizing a unique algorithm to calculate these abnormalities. There are age-specific differences for PGES in adults and children. Freitas et al. found that the mean PGES duration was eight times longer in adults and recovery duration twice as long as found in children.
Autonomic alterations during seizures occur independently or secondary to both cardiac and respiratory dysfunction as a cascade of complex, multifactorial, and often bidirectional changes with dominance of one autonomic system over the other in most patients. Autonomic failure has been postulated to be the ultimate driving force toward PGES with cerebral shutdown leading to SUDEP.
Mosely et al. found that SUDEP accounts for 12% of all epilepsy-related deaths in children. It is estimated that the rate of SUDEP in children is approximately two per 10,000 patient-years based on retrospective studies.