Sudden Unexplained Death in Epilepsy During Physical Activity

Introduction Persons with epilepsy are at a higher risk of death than the general population. Sudden unexplained death in epilepsy (SUDEP) accounts for approximately 15% of the deaths among people with epilepsy [1]. Both pulmonary and cardiac derangements have been suggested as potential causes. Patients with uncontrolled seizures are at greatest risk for SUDEP, and those who experience tonic-clonic seizures, take multiple antiepileptic drugs, or have coexisting neurologic disease are at further increased risk of death. Physicians who care for young, active people should be aware of SUDEP and its associated mortality. Case Presentation The patient was a 33-year-old male Active Duty soldier with no past medical or surgical history who was noted to have seizure-like activity while running at Fort Benning, Georgia. About 1 mile into a routine 3-mile training run, he stated he felt like he was “going to pass out,” and he slowed his pace to be closer to the medic. Shortly after, he collapsed and was noted to have generalized, tonic-clonic seizure activity lasting 2 to 4 minutes. Upon arrival to the clinic, the patient had continued clonic activity, and was noted to be cyanotic and without a pulse. Basic life support was employed, an automated external defibrillator (AED) was applied, and the patient was cardioverted to a sinus rhythm. The patient required bag-valve-mask ventilatory support, and two large-bore intravenous lines were started. The patient was noted to have lost bowel control while in transit to the closest hospital. His initial vital signs showed a blood pressure of 167/95 mm Hg, heart rate of 142 beats per minute (bpm), and a temperature of 97.3°F, with an oxygen saturation of 99% with the addition of supplemental oxygenation. Upon arrival to the emergency room, concern for airway protection led to rapid-sequence intubation. Further laboratory work-up and noncontrast CT of the head were normal. The patient was transported to the regional medical center for further evaluation. On initial evaluation at the regional medical center his vital signs included a blood pressure of 167/100 mm Hg, heart rate of 102 bpm, temperature of 97.9°F, and an oxygen saturation of 99% on mechanical ventilation. His pulmonary and cardiac examinations, including echocardiogram, had normal results. Initial neurologic examination demonstrated pupils that were equal, round, and reactive to light and accommodation, with no nystagmus or rapid eye movements noted. The patient did demonstrate a gag reflex and produced a cough upon manipulation of the endotracheal tube. The patient had no purposeful movement to pain and demonstrated random single-extremity jerking movements, left side greater than the right. These movements were initially thought to be myoclonic jerks associated with a suspected anoxic brain injury. The critical care medicine team consulted a neurologist who, via telephone, agreed that the description of the patient's jerking movements were likely due to an anoxic brain injury, but could not rule out the possibility of status epilepticus versus seizure-like activity. The patient was administered lorazepam as well as a loading dose of fosphenytoin. After the first 10 minutes of anticonvulsant medication administration the patient's muscular activity had ceased and purposeful movements resumed, which required restraint and sedation. At this time status epilepticus was entertained more favorably and the patient was begun on valproic acid and admitted to the intensive care unit. The patient remained stable in the intensive care unit over the next 2 days and was weaned off of sedation and mechanical ventilation. No further seizure activity was observed. He was then transferred to the medical ward on hospital day 2, where further information was obtained from both the patient and another soldier who witnessed the event. It was discovered that the patient complained of stomach pain 2 days prior to presentation and had been scheduled for an ultrasound for suspected gallbladder disease. The patient denied recall of any of the events of the collapse. He denied any medical or surgical history, allergies, or drug use, and he specifically denied any over-the-counter medications or supplement use. There was no family history of seizure disorder. An inpatient neurologist was consulted for supplementary evaluation. Upon further inquiry into his past medical history, the soldier revealed a history of multiple mild closed head injuries associated with concussion, the most recent of which occurred after a mortar landed in close proximity to his tank in Iraq in 2004. His repeat neurologic evaluation only revealed brisk patellar and ankle-jerk reflexes, and was otherwise unremarkable. The result of his electroencephalogram, although performed while on anticonvulsant therapy, was also normal. Upon final review, given the history of witnessed seizure-like activity and of multiple prior closed head injuries, the patient was diagnosed with probable SUDEP. The patient was given strict seizure precautions, was to restrict his physical exertion, and was to remain on his antiseizure prophylaxis. The patient was referred to a cardiologist to have an electrophysiology study performed to rule out the remote possibility of an arrhythmia. Discussion SUDEP accounts for 7.5% to 17% of deaths among the epileptic population, and perhaps 50% of deaths among patients with refractory epilepsy [1–3]. Despite the high rate of death in young epileptics there seems to be a lack of understanding, although not knowledge, about this important cause of excess mortality. Only a small portion of SUDEP cases have been witnessed. Langan et al. [4] reported 15 cases of witnessed SUDEP and 80% of these patients seized immediately before death. Terrence et al. [5] reported 24% and Leetsma et al. [2] reported 38% of witnessed deaths to be an immediate consequence of a seizure attack. Kloster and Engelskjon [6] reported evidence of recent seizures (ie, witnessed, oral trauma, cyanosis) in 67% of victims. However, in all witnessed deaths, seizure activity ceased before death, and in many cases patients regained consciousness. The immediate event before death was typically respiratory arrest (obstructive and central) in a few witnessed cases. The majority of remaining victims were reported to have difficulty breathing before their deaths. Attempts at cardiopulmonary resuscitation in these cases were unsuccessful. Criteria have been suggested by a variety of investigators for making the diagnosis of SUDEP [3,4]. Synthesizing the existing criteria yields the following requirements: 1) the victim must have had epilepsy, defined as recurrent unprovoked seizures; 2) death must have occurred unexpectedly, with no obvious medical cause, with the patient in a reasonable state of health, in the absence of trauma or drowning; 3) death must have occurred suddenly when observed; and 4) there may or may not have been evidence of a seizure, but status epilepticus must not have occurred. Evidence for a seizure may consist of either a witnessed seizure or in the form of clinical findings such as a bitten tongue or cheek. An autopsy that does not reveal a cause for death is required for the diagnosis of definite SUDEP, whereas a diagnosis of probable SUDEP is given to those who fit the previously mentioned criteria without autopsy. Possible SUDEP would include cases in which SUDEP seems a reasonable diagnosis but when there is insufficient evidence regarding the circumstances of death and no autopsy is available. Early studies suggest that risk factors for SUDEP include male sex, cerebral lesions, developmental delay, a history of ongoing tonic-clonic seizures, and subtherapeutic anticonvulsant medication levels [2,7]. Subsequent work has been conflicting, but certain features seem to predominate. The majority of evidence supports the concept that patients with uncontrolled seizures, higher seizure frequency, and those who experience tonic-clonic are at greatest risk for SUDEP [1,7,8]. Different pathophysiologic events may contribute to SUDEP in different patients, and the mechanism is probably multifactorial. Respiratory events, including airway obstruction, central apnea, and neurogenic pulmonary edema, are probable terminal events. In addition, cardiac arrhythmia, during both the ictal and interictal periods, leading to arrest and acute cardiac failure, play an important role. Antiepileptic medication may be yet another risk factor. The exact mechanism of death in SUDEP remains unknown, although both cardiac and pulmonary abnormalities are suggested [6], and there is evidence supporting cardiac arrhythmias as the terminal event. Electrocardiographic studies during the ictal period, in addition to autopsy studies, find evidence for transient ictal conduction abnormalities and myocardial injury, respectively. Several reports have documented terminal arrhythmia or bradycardia in patients who died in monitored settings. Central apnea has also been hypothesized to produce SUDEP. There is one case report of post-ictal apnea leading to cardiac arrest [9], and one study demonstrated that status epilepticus in sheep was associated with death from hypoventilation [10]. Because both cardiac and pulmonary mechanisms can account for SUDEP, it is likely that the etiology is variable and is patient and seizure dependent. Overall, few guidelines for epileptic participation in sports are available and a common sense approach should be used to establish safety in participation [11]. There is no specific waiting period prior to allowing an athlete to return to action and any limitations should depend on how well the athlete's seizures are controlled [12]. Athletes whose seizures are poorly managed should avoid contact and collision sports and should also avoid high-risk activities, which may pose a risk of death to themselves or others, including swimming, weightlifting, archery, and riflery [13]. To our knowledge, this is the first witnessed case of probable SUDEP in an individual who was actively performing exercise. It is currently unknown whether or not epileptics are more vulnerable to SUDEP if they choose to engage in vigorous physical activity. However, one could postulate that as physical exertion can lead to dehydration, electrolyte imbalances, hyperventilation secondary to increased oxygen demand, and hyperthermia'all of which are well known to decrease the seizure threshold in an epileptic, there may be an increased risk of SUDEP in athletes. Conclusions Although all death is tragic, SUDEP seems especially tragic because it tends to strike young, otherwise healthy individuals. Progress will only be made when risk factors are defined and mechanisms of death better defined. Once this happens, appropriate preventive measures can be taken to minimize this complication of uncontrolled epilepsy. Until then, physicians should strive to completely control seizures, because even infrequent seizures can pose an increased risk of death.