Near SUDEP in a patient with craniosynostosis syndrome and temporal lobe encephaloceles

Crouzon and Apert syndromes are rare genetic disorders characterized by craniosynostosis, a condition with premature fusion of sutures of the skull bones, which is occasionally associated with epilepsy. We report a case of a patient with Crouzon syndrome and medically refractory temporal lobe epilepsy with temporal encephaloceles that experienced a near sudden unexpected death in epilepsy (SUDEP) event. This case illuminates both the need to consider encephaloceles as a treatable lesional etiology of epilepsy in craniosynostosis syndromes and that postictal apnea may be an important mechanism of cardiorespiratory collapse seen in SUDEP, emphasizing the importance of cardiorespiratory monitoring.

The patient has a history of medically refractory focal presumed non-lesional epilepsy (onset age: 20 years old) and Crouzon syndrome. Informed consent was obtained from the patient. The patient suffers from focal seizures with impaired awareness (FIAS) and focal to bilateral tonic–clonic seizures (FBTCS). FIAS occur two to four times per month and have an aura of blurred vision, a sense of fear, and tachycardia at onset followed by dialepsis and oral automatisms. FBTCS occurs one to two times a year.

While in the EMU, the patient suffered a near SUDEP event (Figure 1). At the clinical onset, tachycardia (120 bpm) and oral automatisms were followed by versive left head and body turn before tonic stiffening, left lower extremity clonus, and generalized tonic–clonic convulsion. Electrographically there was rhythmic theta in the right frontotemporal region, evolving bilaterally. Postictally, he was apneic with a heart rate of 110 bpm and had diffuse postictal generalized EEG suppression (PGES). Within 12 s, he became bradycardic, and within another 40 s, he became asystolic for 17 s before a heart rate returned and quickly evolved into tachycardia (> 140 bpm). Stertorous breaths are observed for the first time 2 mins and 15 s after the seizure ended. Immediately following the return of respiratory effort, the rapid tachycardia and diffuse PGES resolve. An arm wearable device captured generalized seizure onset via sEMG and motion sensors. A rapid response was called, and the patient was intubated. While no cardiorespiratory resuscitation was performed (CPR, rescue breathing, etc.), the patient had a cardiorespiratory arrest with no other cause, consistent with a near SUDEP.¹

Temporal encephaloceles are increasingly recognized as a cause of drug-resistant temporal lobe epilepsy as surgical intervention renders patients seizure-free.² Because Apert and Crouzon³ syndromes have encephaloceles, this may be a prominent etiology of epilepsy in patients with these syndromes. As they frequently have medically refractory epilepsy, they are at higher risk for SUDEP.^{2, 3} Airway obstruction that is often associated with these syndromes may also put these patients at particular risk of SUDEP.⁴

The pathophysiology of SUDEP is unknown, and though it is a potentially heterogeneous process, increasing evidence suggests seizure-related respiratory dysfunction including ictal and postictal apneas may increase SUDEP risk.⁵ This case supports this evidence. Consistent with the findings in MORTEMUS and other reports, bradyarrhythmia in our patient was preceded by a period of apnea and increasing hypoxia.^{6, 7} Currently, it is difficult to determine patients who may be at increased risk, but the presence of cardiorespiratory dysfunction postictally, such as in our patient, may prove to be important biomarkers.

While attentive monitoring can prevent SUDEP in the EMU,⁷ the challenge is both determining those at elevated risk and mitigating it outside the hospital. In our case, the patient wore a seizure detection device as part of an ongoing study. Seizure detection devices have become more prominent and are frequently recommended to patients in hopes that they may decrease SUDEP risk, although this benefit is still unclear.⁸ Wearables that can monitor seizure activity, heart rate, respiration rate, and SpO2 as well as alert for seizures and associated cardiorespiratory dysfunctions can be a powerful tool to reduce SUDEP risk by alerting for life-threatening events and providing comprehensive quantitative data to patients, physicians, and caregivers. These devices can potentially assist physicians in stratifying SUDEP risk, optimizing antiseizure medications, and directing more aggressive non-medical treatment. The near SUDEP event in our patient has motivated expedited surgical work-up and a planned right temporal lobe resection and encephalocele repair.