Obstructive apnea due to laryngospasm links ictal to postictal events in <scp>SUDEP</scp> cases and offers practical biomarkers for review of past cases and prevention of new ones

Stewart, Mark; Kollmar, Richard; Nakase, Ko; Silverman, Joshua B.; Sundaram, Krishnamurthi; Orman, Rena; Lazar, Jason

doi:10.1111/epi.13765

Cited by 46 publications

(53 citation statements)

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“…Thus, the importance of video‐EEG monitoring and additional polygraphy in apparently intractable epilepsy cannot be understated since laryngospasm may be an under‐recognized phenomenon in SUDEP series. A combination of obstructive apnea and bradycardia (typically seen in laryngospasm) have been postulated as a deleterious combination of signs in the SUDEP and near‐SUDEP contexts (Nashef et al, 1996; Stewart et al, 2017). Recent evidence has been put forward to suggest that some MORTEMUS SUDEP cases may have suffered laryngospasm (Stewart et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…A combination of obstructive apnea and bradycardia (typically seen in laryngospasm) have been postulated as a deleterious combination of signs in the SUDEP and near‐SUDEP contexts (Nashef et al, 1996; Stewart et al, 2017). Recent evidence has been put forward to suggest that some MORTEMUS SUDEP cases may have suffered laryngospasm (Stewart et al, 2017). The animal evidence comes from studies in an adult Sprague‐Dawley urethane/kainite rat seizure model, characterized by severe laryngospasm, increasing respiratory effort, ST segment elevation, bradycardia, and death (Nakase et al, 2016; Stewart et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence has been put forward to suggest that some MORTEMUS SUDEP cases may have suffered laryngospasm (Stewart et al, 2017). The animal evidence comes from studies in an adult Sprague‐Dawley urethane/kainite rat seizure model, characterized by severe laryngospasm, increasing respiratory effort, ST segment elevation, bradycardia, and death (Nakase et al, 2016; Stewart et al, 2017). A typically seen EMG artifact representing increased inspiratory effort during endoscopically‐proven laryngospasm in these animals (not seen in normal inspiration) was postulated as a potential SUDEP biomarker, and seen in MORTEMUS SUDEP patients, thereby raising laryngospasm as a significant concern in human seizures too.…”

Section: Discussionmentioning

confidence: 99%

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Ictal laryngospasm monitored by video‐EEG and polygraphy: a potential SUDEP mechanism

Lacuey¹,

Vilella²,

Hampson³

et al. 2018

Epileptic Disorders

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A 56‐year‐old man with refractory bitemporal epilepsy was monitored in the Epilepsy Monitoring Unit (EMU). In a video‐EEG captured seizure, brief oroalimentary automatisms were followed by increased inspiratory effort, accompanied by prominent, visible tracheal movements and audible inspiratory stridor. The patient's oxygen saturation rapidly declined to 62%; persistent severe hypoxemia ended with spontaneous effective respiration commencing at seizure end. Subsequent seizures necessitated intensive care unit admission for respiratory distress, and ventilator support. This case suggests that ictal laryngospasm, a rare seizure manifestation, may represent another potential mechanism of sudden unexpected death in epilepsy (SUDEP). [Published with video sequence on http://www.epilepticdisorders.com].

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ictal laryngospasm monitored by video‐EEG and polygraphy: a potential SUDEP mechanism

Lacuey¹,

Vilella²,

Hampson³

et al. 2018

Epileptic Disorders

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“…To test the hypothesis that reported cardiorespiratory consequences, including deaths, of systemic KA 6,7,11,14 were due to seizures, rather than to its direct actions on brainstem sites, we induced seizures by local microinjection of KA directly into the hippocampus of anesthetized rats. 15 Identical injections of dyes and other toxins show that they are limited to the hippocampus.…”

Section: Introductionmentioning

confidence: 99%

Brainstem activity, apnea, and death during seizures induced by intrahippocampal kainic acid in anaesthetized rats

et al. 2019

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Objective: To investigate how prolonged seizure activity affects cardiorespiratory function and activity of pre-Bötzinger complex, leading to sudden death. Methods: Urethane-anesthetized female Long-Evans rats were implanted with nasal thermocouple; venous and arterial cannulae; and electrodes for electrocardiography (ECG) and hippocampal, cortical, and brainstem recording. Kainic acid injection into the ventral hippocampus induced status epilepticus. Results: Seizures caused hypertension, tachycardia, and tachypnea punctuated by recurrent transient apneas. Salivation increased considerably: in 11 of 12 rats, liquid with alkaline pH consistent with saliva was expelled from the mouth. Most transient apneas were obstructive: nasal airflow ceased, while, in 83%, efforts to breathe persisted as continued rhythmic activity of respiratory pre-Bötzinger neurons, inspiratory electromyography (EMG), and excursions of the chest wall and abdomen. Blood pressure oscillated in time with respiratory efforts. This pattern also occurred in a minority of cases (16%) of incomplete apnea, but not in rare cases (1%) of transient central apneas. During transient obstructive apneas, the frequency of all inspiratory efforts decreased abruptly by ~30%, suggesting a resetting of the central respiratory rhythm generator. Twenty-two of thirty-one rats died, due either to obstructive apnea (12) or central apnea following progressive slowing of respiration (10). Most rats dying of central apnea had experienced several transient obstructive apneas.Negative DC field potential shifts of the brainstem followed the final breath, consistent with previous reports on spreading depolarization in mouse models. Timing suggests that the DC shift is a consequence rather than cause of respiratory collapse.Cardiac activity continued for tens of seconds. Significance: Seizure activity in forebrain induces pronounced autonomic activation and disrupts activity in medullary respiratory centers, resulting in death from either obstructive or central apnea. These results directly inform mechanisms of death in status epilepticus, and indirectly provide clues to mechanisms of sudden unexpected death in epilepsy (SUDEP). K E Y W O R D SHeart rate, obstructive apnea, status epilepticus, SUDEP | 2347 JEFFERYS Et al.

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“…We have demonstrated in a rat model that seizure activity induces laryngospasm and that laryngospasm can be sufficient to cause obstructive apnea, rapid desaturation, and death . The hypoxemia and decreased cardiac output during obstructive apnea cause the seizure to abort, but the laryngospasm can persist beyond the termination of the seizure to the point of respiratory arrest, followed ultimately by cardiac arrest . The profound forces of vocal fold contractions during seizure‐induced laryngospasm were demonstrated by: 1) direct visualization of an active vocal fold crossing the midline when it was unopposed by a paralyzed vocal fold, and 2) the complete absence of their usual abduction during attempts to gasp in the presence of an obstructed airway .…”

Section: Introductionmentioning

confidence: 99%

A Resuscitation Option for Upper Airway Occlusion Based on Bolus Transtracheal Lung Inflation

Villiere

Nakase

Kollmar

et al. 2018

Laryngoscope Investig Oto

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BackgroundAcute laryngospasm sufficient to cause obstructive apnea is a medical emergency that can be difficult to manage within the very short time available for establishing an airway. We have presented substantial evidence that laryngospasm‐based obstructive apnea is the cause of sudden death in epilepsy, and airway management is particularly challenging during seizure activity.ObjectiveWe sought to determine if the transtracheal delivery of a bolus of oxygen or room air below the level of an obstruction to inflate the lungs could be an effective method to prolong the time available for responders seeking to establish a stable airway, and, if so, what could be learned about optimization of delivery parameters from a rat model.MethodsRats were fitted with a t‐shaped tracheal tube for controlling access to air and for measuring airway pressures. After respiratory arrest from simulated laryngospasm, bolus transtracheal lung inflation with a volume of gas equivalent to half the vital capacity was delivered to the closed respiratory system as the only resuscitation step.ResultsBolus lung inflation was sufficient for resuscitation, improving cardiac function and re‐establishing adequate oxygen status to support life. Inflation steps could be repeated and survival times were approximately 3 times that of non‐inflated lungs.ConclusionThe properties and consequences of bolus lung inflation are described as a foundation for procedures or devices that can be useful in cases of severe laryngospasm and other cases of upper airway obstruction.Level of Evidence3

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Obstructive apnea due to laryngospasm links ictal to postictal events in SUDEP cases and offers practical biomarkers for review of past cases and prevention of new ones

Cited by 46 publications

References 9 publications

Ictal laryngospasm monitored by video‐EEG and polygraphy: a potential SUDEP mechanism

Ictal laryngospasm monitored by video‐EEG and polygraphy: a potential SUDEP mechanism

Brainstem activity, apnea, and death during seizures induced by intrahippocampal kainic acid in anaesthetized rats

A Resuscitation Option for Upper Airway Occlusion Based on Bolus Transtracheal Lung Inflation

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