Posture May Signal Respiratory Risk in Intractable Epilepsy

Ictal and post-ictal tonic postures (semiology) seen with generalized convulsive seizures were associated with electroencephalographic (EEG) suppression and respiratory depression in a prospective study of patients with intractable epilepsy who had video EEG monitoring.

This study adds to knowledge of sudden unexplained death in epilepsy patients (SUDEP), the leading cause of death in patients with intractable epilepsy.

“Peri-ictal brainstem posturing may be surrogate biomarkers for generalized convulsive seizure severity identifiable without in-hospital monitoring,” wrote Laura Vilella, MD, of the University of Texas Health Science Center at Houston, and coauthors, in Neurology.

Vilella and colleagues analyzed associations between peri-ictal brainstem semiology and post-ictal generalized EEG suppression (PGES) and breathing dysfunction — post-convulsive central apnea and other measures — in 295 generalized convulsive seizures recorded for 180 patients.

Seizures consist of an ictal phase, which may include a clonic and/or tonic component, followed by a post-ictal phase. While all seizures in the study had a clonic phase, no tonic phase was seen in about one-third of seizures.

The study authors found:

• Ictal tonic decerebration (bilateral symmetric tonic arm extension) in 41.4% of seizures, which was associated with PGES risk (P<0.001) and with longer PGES (P<0.011).
• Ictal tonic decortication (bilateral symmetric tonic arm flexion only) in 15.9%, which was associated with PGES risk (P<0.001).
• Ictal tonic hemi-decerebration (unilateral tonic arm extension with contralateral flexion) in 9.5%, which was associated with PGES risk (P<0.001).
• Post-ictal decerebration or decortication following the last clonic jerk of the seizure in 6.1%, which was associated with post-convulsive central apnea (P=0.004), longer hypoxemia (P=0.001), and SpO2 recovery (P=0.035).

“We found a clear gradation of semiological severity, such that presence of ictal decerebration, decortication and hemi-decerebration was associated with the most striking signs of compromise (presence of PGES and larger drops in SpO2), with ictal decerebration being associated with prolonged PGES,” Vilella and colleagues wrote. “Absence of generalized convulsive seizures tonic phase was associated with less profound changes.”

“We also made the novel observation that post-ictal ’brainstem’ type posturing is related to increased risk for post-convulsive central apnea and to longer hypoxemia duration and SpO2 recovery periods after generalized convulsive seizures,” they added.

“Since post-convulsive central apnea has been observed in SUDEP and near-SUDEP, post-ictal brainstem posturing may suggest a semiological marker of seizure severity and reflect a brainstem mechanism for SUDEP and near-SUDEP phenomena,” they wrote.

“Ictal semiology may prove valuable not only for seizure characterization, but also for an assessment of risk for adverse outcomes,” observed Alica Goldman, MD, PhD, MS, of Baylor College of Medicine in Houston, in an accompanying editorial.

“Importantly, the authors found that early administration of supplemental oxygen correlated with a faster recovery from hypoxemia which corresponds to an earlier report showing that timely nursing intervention reduced the duration of hypoxemia and PGES,” she added.

SUDEP risk is about 1/10,000 person years for newly diagnosed epilepsy and 1/1,000 person years for chronic epilepsy. A 2017 study concluded that, compared with autopsied non-SUDEP controls, people with SUDEP were more likely to live alone and die at home during the night, unwitnessed and in the prone position, often with a preceding seizure.

Prior research on SUDEP found that hypoxemia can lead to waves of brainstem depolarization and respiratory arrest in murine models. Structural changes accompany both generalized convulsive seizures (e.g., volume loss in the thalamus, hippocampus, and other structures) and SUDEP, and SUDEP is associated with disorganized autonomic and respiratory networks at the cortical and subcortical levels.

Post-ictal generalized EEG suppression has been linked to prolonged and more severe desaturation and hypercapnia than seizures without such suppression, illustrating the interplay of seizure phases and electrical activity with respiratory function in SUDEP pathophysiology.

In their study, Vilella and colleagues included patients 18 or older who had failed trials of two or more medications, who were monitored with video EEG between Feb. 2011 and April 2018. Participants had generalized tonic clonic, focal to bilateral tonic-clonic, or focal onset motor bilateral clonic seizures. Patients with a history of status epilepticus were excluded.

Half of the patients were female and mean age at the time of monitoring was about 37, with a mean epilepsy duration of 16.8 years. Epilepsy type was generalized in 16%, focal in 81%, and unknown in 3%. The largest proportion (32%) had >12 generalized convulsive seizures yearly, with 26% having 3-12 seizures and 19.4% 1-2 seizures each year.

No association was seen between anti-epileptic drug regimen and tonic phase semiology. Tonic phase duration was not associated with PGES presence, duration, oxygen saturations, or post-convulsive central apnea. “The lack of association of the tonic phase duration with PGES is contrary to prior findings and may be due to differences in sample size or PGES classification criteria,” the editorialist observed.

Overall, the findings encourage “scrutiny of the post-ictal video-EEG recording in patients with high-risk SUDEP phenotypes,” the researchers emphasized. The study did not include SUDEP outcomes, and prospective follow-up is required to shed more light on the role of peri-ictal semiology and SUDEP risk, they added.

1. Ictal and post-ictal tonic postures (semiology) seen with generalized convulsive seizures were associated with EEG suppression and respiratory depression in a prospective study of patients with intractable epilepsy who had video EEG monitoring.

2. The study adds to knowledge of sudden unexplained death in epilepsy patients (SUDEP), the leading cause of death in patients with intractable epilepsy.

Paul Smyth, MD, Contributing Writer, BreakingMED™

Cat ID: 34

Topic ID: 82,34,730,34,192,925