Affiliation:
1. Department of Pharmacology Southern Illinois University School of Medicine Springfield Illinois USA
2. Department of Neurology Southern Illinois University School of Medicine Springfield Illinois USA
3. Department of Anesthesia, Critical Care, and Pain Medicine Massachusetts General Hospital Boston Massachusetts USA
4. Department of Anesthesia Harvard Medical School Boston Massachusetts USA
Abstract
AbstractIn response to the comments by Singh and colleagues about our recent paper proposing a unified hypothesis of SUDEP, we definitely agree that more research is needed. This research should include studies in other models, including Dravet mice, emphasized by Singh et al. However, we strongly believe the hypothesis is timely, because it is based on the continuing progress on SUDEP‐related research on serotonin (5‐HT) and adenosine as well as neuroanatomical findings.We propose testing of 5‐HT enhancing drugs, neurotoxicity blocking drugs, such as N‐methyl‐D‐aspartate (NMDA) antagonists and periaqueductal gray (PAG) electrical stimulation for SUDEP prevention. There are FDA‐approved drugs that enhance the action of 5‐HT, including fluoxetine and fenfluramine, which is approved for Dravet syndrome. NMDA antagonists, including memantine and ketamine, are also approved for other disorders. PAG electrical stimulation, which is proposed to activate a suffocation alarm, is also approved to treat other conditions and is known to enhance respiration. Experiments using these methods are currently being carried out in animal studies. If these approaches are validated in SUDEP models, treatments could be evaluated relatively quickly in patients with epilepsy (PWE) who exhibit a biomarker for high SUDEP risk, such as peri‐ictal respiratory abnormalities. An example of such a study is the ongoing clinical trial of a selective serotonin reuptake inhibitor in PWE. Although, gene‐based therapies may ultimately become treatments of choice to prevent SUDEP, as Singh et al suggested, one or more of the approaches we proposed could become temporizing treatments before gene‐based therapies can be available. Establishing genetic treatments would require extensive time for each of the genetic abnormalities associated with SUDEP, and too many PWE are likely to die in the meantime.The temporizing treatments may help to reduce the incidence of SUDEP sooner, which is urgently needed.
Funder
National Institute of Neurological Disorders and Stroke
Subject
Neurology (clinical),Neurology