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. 2021 Feb 5:11:632510.
doi: 10.3389/fneur.2020.632510. eCollection 2020.

Autonomic Characteristics of Sudden Unexpected Death in Epilepsy in Children-A Systematic Review of Studies and Their Relevance to the Management of Epilepsy in Rett Syndrome

Jatinder Singh  1   2   3 , Evamaria Lanzarini  4 , Paramala Santosh  1   2   3
Affiliations

Autonomic Characteristics of Sudden Unexpected Death in Epilepsy in Children-A Systematic Review of Studies and Their Relevance to the Management of Epilepsy in Rett Syndrome

Jatinder Singh et al. Front Neurol. .

Abstract

Aim: To systematically identify and critically appraise studies that investigate the autonomic characteristics of Sudden Unexpected Death in Epilepsy (SUDEP) in the pediatric population. We also wanted to explore how this information would be relevant to the management of epilepsy in patients with Rett Syndrome. Method: Using PRISMA guidelines, a systematic review of PubMed, Scopus, Cochrane, PsycINFO, Embase, and Web of Science databases was performed to identify eligible studies. After extracting data from the included studies, a thematic analysis was undertaken to identify emerging themes. A quality appraisal was also done to assess the quality of the included studies. Results: The systematic search revealed 41 records, and 15 full-text articles on the autonomic characteristics of SUDEP in children were included in the final analysis. Following thematic analysis, three themes were identified (I) modulation in sympathovagal tone, (II) pre- and post-ictal autonomic changes, and (III) other markers of autonomic dysregulation in children with epilepsy. Modulation in sympathovagal tone emerged as the theme with the highest frequency followed by pre- and post-ictal autonomic changes. While the themes provide additional insight into the management of epilepsy in the Rett Syndrome population, the quality of evidence concerning the autonomic characteristics of SUDEP in the pediatric population was low and underscores the importance of much needed research in this area. Conclusion: The mechanism of SUDEP in the pediatric population is complex and involves an interplay between several components of the autonomic nervous system. While direct clinical inferences regarding pediatric SUDEP could not be made, the thematic analysis does suggest that in vulnerable populations such as Rett Syndrome, where there is already a pervasive autonomic dysregulation, pro-active surveillance of the autonomic profile in this patient group would be useful to better manage epilepsy and reduce the SUDEP risk.

Keywords: Rett Syndrome; autonomic dysregulation; epilepsy; pediatric; sudden unexpected death in epilepsy.

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Conflict of interest statement

PS was a Principal Investigator (PI) on the Sarizotan (Protocol Number Sarizotan/001/II/2015; ClinicalTrials.gov Identifier: NCT02790034) and is currently the PI for the Anavex Life Sciences Corp. (Protocol Number: ANAVEX2-73-RS-002) clinical trial in Rett Syndrome (RTT). PS is the co-inventor of the HealthTrackerTM and is the Chief Executive Officer and shareholder in HealthTrackerTM. JS was a Trial Research Methodologist on the Sarizotan Clinical Trial (Protocol Number Sarizotan/001/II/2015; ClinicalTrials.gov Identifier: NCT02790034) in patients with RTT and is a Research Manager on the Anavex Life Sciences Corp. (Protocol Number: ANAVEX2-73-RS-002) clinical trial for RTT. JS is also an advisor for Reverse Rett. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow-diagram.
Figure 2
Figure 2
Frequency of identified themes.
Figure 3
Figure 3
Autonomic characteristics of pre-ictal, ictal, post-ictal states, and propensity to SUDEP. ASMs, Anti-Seizure Medications; EDA, Electrodermal Activity; HF, High Frequency; HRV, Heart Rate Variability; LF, Low Frequency; PGES, Post-ictal Generalized Electroencephalographic Suppression; QT, Q and T waves on ECG [electrocardiogram]; RMSSD, Root Mean Square of Successive Differences; R-R, Inter-Beat Interval; SUDEP-7, Sudden Unexpected Death in Epilepsy Risk Inventory.
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