Evidence map›Paper›PMID 33570173›Full record

ArticleEpilepsia2021

Ictal activation of oxygen-conserving reflexes as a mechanism for sudden death in epilepsy.

Ethan N Biggs, Ryan Budde, John G R Jefferys, Pedro P Irazoqui

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Sudden unexpected death in epilepsy.Current opinion in neurology · 2022
    Review
  10. Article
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 2 countries.

Ethan N BiggsWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.ORCID 0000-0001-6120-4718
Ryan BuddeWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.ORCID 0000-0003-4381-8673
John G R JefferysWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.ORCID 0000-0003-0106-4412
Pedro P IrazoquiWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.ORCID 0000-0002-4791-4593
Purdue University West Lafayette · US

Funding

Sequence of physiological events during oxygen conserving reflex activation leading to sudden death in epilepsyR01NS119390 · NINDS · PURDUE UNIVERSITY · PI KOLIATSOS, VASSILIS E · 2021 to 2025
$2.2M
NINDS NIH HHS R01 NS119390
6 · The paper itself

Abstract

objectiveTo test the hypothesis that death with physiological parallels to human cases of sudden unexpected death in epilepsy (SUDEP) can be induced in seizing rats by ictal activation of oxygen-conserving reflexes (OCRs).

methodsUrethane-anesthetized female Long-Evans rats were implanted with electrodes for electrocardiography (ECG), electrocorticography (ECoG), and respiratory thermocouple; venous and arterial cannulas; and a laryngoscope guide and cannula or nasal cannula for activation of the laryngeal chemoreflex (LCR) or mammalian diving reflex (MDR), respectively. Kainic acid injection, either systemic or into the ventral hippocampus, induced prolonged acute seizures.

resultsReflex challenges during seizures caused sudden death in 18 of 20 rats-all MDR rats (10) and all but two LCR rats (8) failed to recover from ictal activation of OCRs and died within minutes of the reflexes. By comparison, 4 of 4 control (ie, nonseizing) rats recovered from 64 induced diving reflexes (16 per rat), and 4 of 4 controls recovered from 64 induced chemoreflexes (16 per rat). Multiple measures were consistent with reports of human SUDEP. Terminal central apnea preceded terminal asystole in all cases. Heart and respiratory rate fluctuations that paralleled those seen in human SUDEP occurred during OCR-induced sudden death, and mean arterial pressure (MAP) was predictive of death, showing a 17 or 15 mm Hg drop (MDR and LCR, respectively) in the 20 s window centered on the time of brain death. OCR activation was never fatal in nonseizing rats. SIGNIFICANCE: These results present a method of inducing sudden death in two seizure models that show pathophysiology consistent with that observed in human cases of SUDEP. This proposed mechanism directly informs previous findings by our group and others in the field; provides a repeatable, inducible animal model for the study of sudden death; and offers a potential explanation for observations made in cases of human SUDEP.

Indexed as

AnimalsDiving ReflexElectrocardiographyElectrodes, ImplantedElectroencephalographyElectrooculographyFemaleHeart RateOxygenOxygen ConsumptionRatsRats, Long-EvansReflexRespiratory RateSeizuresSudden Unexpected Death in EpilepsyOxygenapneadiving reflexlaryngeal chemoreflexseizuressudden unexpected death in epilepsy

Identifiers

PMID33570173
PMCPMC9153691
OpenAlexW3127403343

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.