Abstract
Summary: There is increasing evidence that periictal respiratory disturbances are an important contributor to the pathophysiological changes leading to sudden unexpected death in epilepsy (SUDEP). In patients with SUDEP occurring in epilepsy monitoring units, respiratory disturbances occurred early in the postictal period and frequently preceded terminal bradycardia and asystole. Periictal hypoxemia and hypercapnia are observed in about one-third of patients undergoing video-EEG telemetry. Pulmonary edema is frequently observed at autopsy in cases of SUDEP and may be relevant as a contributing cause in a subset of SUDEP. Animal studies support the notion that periictal respiratory disturbances are crucial to the pathophysiology of SUDEP. Serotonergic neurons modulate the excitability of the neuronal network generating the respiratory rhythm. Ictal and periictal impairment of serotonergic and glutaminergic neurons involved in the arousal system may also predispose to SUDEP by impeding the patient's ability to reposition the head and facilitate ventilation after a seizure. Periictal functional impairment of serotonergic neurons seems to be important in the pathophysiology of SUDEP and a potential target for pharmacotherapy aimed at SUDEP risk reduction.
Kennedy JD, Seyal M. Respiratory pathophysiology with seizures and
implications for sudden unexpected death in epilepsy. J Clin Neurophysiol. 2015
Feb;32(1):10-3.
The lethal trigger might in some individuals be a life threatening cardiac arrhythmia initiated ictally or via a lockstep interictal epileptiform activity. Yet, in others, it may be ictally induced prolonged hypoxemia and hypercapnia resulting in acidosis that aids in seizure termination but at the same time predisposes to bradycardias or asystole in vulnerable individuals...
ReplyDeleteAs indicated by the published data, global molecular profiling in patients with epilepsy will be invaluable in unraveling the individually unique genomic complexities and interactions that underlie the physiological signature of each patient, thus improving the precision of SUDEP risk assessment in the individual. At the same time, sophisticated model systems will be an indispensable tool in the iterative translation of human genetics and physiology as well as in testing pharmacological interventions and preventive interventions. Many essential components for clinically relevant SUDEP research have recently come together as the Center for SUDEP Research (http://csr.case.edu/), a National Institute for Neurological Disorders and Stroke (NINDS) funded Center Without Walls for Collaborative Research in the Epilepsies. This unique collaborative network of researchers from the United States and Europe is exceptionally poised for making important discoveries related to SUDEP etiology and individually relevant and quantifiable risk factors, and for prompt clinical application of the findings.
http://www.medscape.com/viewarticle/842451?nlid=81945_3001
Massey CA, Sowers LP, Dlouhy BJ, Richerson GB. Mechanisms of sudden unexpected death in epilepsy: the pathway to prevention. Nat Rev Neurol. 2014
ReplyDeleteMay;10(5):271-82.
Abstract
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy, with an estimated 35% lifetime risk in this patient population. There is a surprising lack of awareness among patients and physicians of this increased risk of sudden death: in a recent survey, only 33% of Canadian paediatricians who treated patients with epilepsy knew the term SUDEP. Controversy prevails over whether cardiac arrhythmia or respiratory arrest is more important as the primary cause of death. Effective preventive strategies in high-risk patients will rely on definition of the mechanisms that lead from seizures to death. Here, we summarize evidence for the mechanisms that cause cardiac, respiratory and arousal abnormalities during the ictal and postictal period. We highlight potential cellular mechanisms underlying these abnormalities, such as a defect in the serotonergic system, ictal adenosine release, and changes in autonomic output. We discuss genetic mutations that cause Dravet and long QT syndromes, both of which are linked with increased risk of sudden death. We then highlight possible preventive interventions that are likely to decrease SUDEP incidence, including respiratory monitoring in epilepsy monitoring units and overnight supervision. Finally, we discuss treatments, such as selective serotonin reuptake inhibitors, that might be personalized to a specific genetic or pathological defect.