Cause Of Death In Epilepsy Research Articles

Perspectives on the basis of seizure-induced respiratory dysfunction.

Epilepsy is an umbrella term used to define a wide variety of seizure disorders and sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in epilepsy. Although some SUDEP risk factors have been identified, it remains largely unpredictable, and underlying mechanisms remain poorly understood. Most seizures start in the cortex, but the high mortality rate associated with certain types of epilepsy indicates brainstem involvement. Therefore, to help understand SUDEP we discuss mechanisms by which seizure activity propagates to the brainstem. Specifically, we highlight clinical and pre-clinical evidence suggesting how seizure activation of: (i) descending inhibitory drive or (ii) spreading depolarization might contribute to brainstem dysfunction. Furthermore, since epilepsy is a highly heterogenous disorder, we also considered factors expected to favor or oppose mechanisms of seizure propagation. We also consider whether epilepsy-associated genetic variants directly impact brainstem function. Because respiratory failure is a leading cause of SUDEP, our discussion of brainstem dysfunction focuses on respiratory control.

Are SIDS, SUDC and SUDEP the different masks of the same great mystery?

The cases of sudden, unexpected child death against the background of relative clinical well-being, i.e., in the absence of apparent reasons take a special place in the structure of infant mortality. Sudden Infant Death Syndrome (SIDS), which is recognized as one of the leading causes of postnatal infant mortality in most developed countries, is the most common cause of unexpected out-ofhospital death of a child. Today SIDS remains one of the most mysterious problems in medicine. The lack of identifiable mechanisms causing SIDS has led to a large number of theories about the mechanisms responsible for death due to this syndrome. Also, sudden unexplained death in childhood (SUDC), which is the unexplained death of children over one- year-old, is currently distinguished among cases of unexpected death. The main clinical features of SUDC include: more common in boys; death occurs at night time, children are found in the early morning in a prone position, face down; children often have convulsions, including febrile ones in the clinical symptom complex during life. Several authors have noted that in some cases, the death due to SUDC resembles Sudden Death in Epilepsy (SUDEP), which is the leading cause of death in epilepsy. To date, it has already been shown that SUDEP is one of the forms of canalopathies characteristic of young children and it is associated with a high risk of sudden death. The mechanisms of thanatogenesis in SUDEP remain unknown. SIDS, SUDC, and SUDEP are a series of fatal syndromes united by multifactorial pathophysiological mechanisms, the causes of which are not fully understood. In fact, these syndromes represent a catastrophic multisystem failure, which is caused by an extremely unfavorable combination of autonomic, respiratory and cardiogenic disorders.

Cardioprotective effects of amiodarone in a rat model of epilepsy-induced cardiac dysfunction.

Cardiac dysfunction is one of the leading causes of death in epilepsy. The anti-arrhythmic drug, amiodarone, is under investigation for its therapeutic effects in epilepsy. We aimed to evaluate the possible effects of amiodarone on cardiac injury during status epilepticus, as it can cause prolongation of the QT interval. Five rat groups were enrolled in the study; three control groups (1) Control, (2) Control-lithium and (3) Control-Amio, treated with 150mg/kg/intraperitoneal amiodarone, (4) Epilepsy model, induced by sequential lithium/pilocarpine administration, and (5) the epilepsy-Amio group. The model group expressed a typical clinical picture of epileptiform activity confirmed by the augmented electroencephalogram alpha and beta spikes. The anticonvulsive effect of amiodarone was prominent, it diminished (p<0.001) the severity of seizures and hence, deaths and reduced serum noradrenaline levels. In the model group, the electrocardiogram findings revealed tachycardia, prolongation of the corrected QT (QTc) interval, depressed ST segments and increased myocardial oxidative stress. The in-vitro myocardial performance (contraction force and - (df/dt)max ) was also reduced. Amiodarone decreased (p<0.001) the heart rate, improved ST segment depression, and myocardial contractility with no significant change in the duration of the QTc interval. Amiodarone preserved the cardiac histological structure and reduced the myocardial injury markers represented by serum Troponin-I, oxidative stress and IL-1. Amiodarone pretreatment prevented the anticipated cardiac injury induced during epilepsy. Amiodarone possessed an anticonvulsive potential, protected the cardiac muscle and preserved its histological architecture. Therefore, amiodarone could be recommended as a protective therapy against cardiac dysfunction during epileptic seizures with favourable effect on seizure activity.

Hemosiderin, a possible biomarker for sudep?

Epilepsy is one of the neurological diseases of complex etiology that affects around 50 million people worldwide and is characterized by abnormal electrical activity and recurrent seizures. Uncontrolled generalized repetitive tonic-clonic seizures (GTCS) are the main causes of unexpected sudden death in epilepsy (SUDEP). Hypoxic stress induced by seizure results in neurocardiogenic dysfunctions, including iron overload and cardiomyopathy (IOC) which is related to severe lipid peroxidation caused by the production of reactive oxygen species (ROS). ROS induces recurrent seizure activity, favoring the overexpression of P glycoprotein (P-gp) in the heart. P-gp plays a depolarizing role in cardiomyocyte membranes and potassium (Kir) channels control cellular excitability regarding the repolarization of the cardiac action potential. All these events result in a possible appearance of severe bradycardia and fatal arrhythmia. Several studies have sought evidence for different possible biomarkers for potential prediction of the risk of SUDEP avoiding its fatal outcome.

Changes in epilepsy causes of death: A US population study.

Since 2000, medical treatment for epilepsy and cardiovascular risk-reduction strategies have advanced significantly in the United States (US). However, seizure-free rates remain unchanged, and people with epilepsy are at higher risk than the general population for heart disease and stroke. The purpose of this study is to determine how cardiovascular, epilepsy-related, and other causes of death are changing in epilepsy in comparison with the US population. Changes in the 15 underlying causes of death in epilepsy (ICD-10 G40-G40.9) and the US population were analyzed and compared from 2000 to 2018. The CDC multiple cause-of-death database was utilized as the primary data source. Changes in the relative proportions for each cause-of-death over were evaluated using logistic regression. The proportions of deaths in epilepsy due to heart disease declined 34.4% (p<.001), a rate similar to the general population (39.9%). Epilepsy-related deaths declined 25% as a percentage of all epilepsy deaths (p<.001). The proportions of deaths due to stroke and neoplasms increased significantly in epilepsy versus the US population (p<.001 linear trend). The reduction in ischemic heart disease in epilepsy is a novel and highly significant finding, which reflects widespread implementation of cardiovascular risk-factor reduction and treatment in the United States. Reductions in epilepsy-related deaths are an exciting development which requires further investigation into causality. The increase in deaths due to neoplasms and stroke relative to the US population is concerning, warranting vigilance and increased efforts at recognition, prevention, and treatment.

Suicidality in Epilepsy: Does It Share Common Pathogenic Mechanisms with Epilepsy?

Suicidality presents a major global health concern and its association with epilepsy has been suggested. The body of evidence is growing due to targeted epidemiological studies, genetic findings, and neuroimaging data, use of specific neuropsychiatric inventories, neuropsychological tests, and metabolic and immunological studies.Suicide tendencies and psychiatric comorbidity such as depression are not uncommon in chronic diseases, especially in epilepsy. Suicide is an important cause of death in epilepsy, and is usually underestimated. Persons with epilepsy have higher risk for suicide than healthy controls. It appears that some epilepsy types have stronger tendencies for suicide, in particular temporal lobe epilepsy. The suicidal risk factors in persons with epilepsy include difficult to treat epilepsies, onset of epilepsy at an earlier age, and comorbid depression.This clinical evidence is mostly based on observational studies in which we found an increased risk of suicidal ideation, suicidal attempts, and completed suicides in persons with epilepsy. However, we lack prospective and longitudinal studies on suicide in epilepsy. In this chapter we will examine recent research in neurobiological mechanisms between suicidality and epilepsy, and comorbid depression.

Why are epilepsy mortality rates rising in the United States? A population-based multiple cause-of-death study

IntroductionEpilepsy mortality rates are rising. It is unknown whether rates are rising due to an increase in epilepsy prevalence, changes in epilepsy causes of death, increase in the lethality or...

Pilocarpine-induced status epilepticus reduces chemosensory control of breathing

One of the possible causes of death in epilepsy is breathing disorders, especially apneas, which lead to an increase in CO2 levels (hypercapnia) and/or a decrease in O2 levels in arterial blood (hypoxemia). The respiratory neurons located in the ventral brainstem respiratory column are the main groups responsible for controlling breathing. Recent data from our group demonstrated respiratory changes in two experimental models of epilepsy, i.e. audiogenic epilepsy, and amygdala rapid kindling. Here, we aimed to evaluate respiratory changes in the classic model of temporal lobe epilepsy induced by intra-hippocampal injection of pilocarpine. Adult Wistar rats with stainless-steel cannulas implanted in the hippocampus region were used. The animals were submitted to pilocarpine injection (2.4 mg/μL, N = 12–15) or saline (N = 9) into the hippocampus. The respiratory parameters analyzed by whole-body plethysmography were respiratory rate (fR), tidal volume (VT) and ventilation (VE). Respiratory mechanics such as Newtonian airway resistance (Rn), viscance of the pulmonary parenchyma (G) and the elastance of the pulmonary parenchyma (H) were also investigated. No changes in baseline breathing were detected 15 or 30 days after pilocarpine-induced status epilepticus (SE). However, 30 days after pilocarpine-induced SE, a significant reduction in VE was observed during hypercapnic (7% CO2) stimulation, without affecting the hypoxia (8% O2) ventilatory response. We also did not observe changes in respiratory mechanics. The present results suggest that the impairment of the hypercapnia ventilatory response in pilocarpine-induced SE could be related to a presumable degeneration of brainstem respiratory neurons but not to peripheral mechanisms.

Seizure-related apneas have an inconsistent linkage to amygdala seizure spread.

Sudden unexpected death in epilepsy (SUDEP) is a frequent cause of death in epilepsy. Respiratory dysfunction is implicated as a critical factor in SUDEP pathophysiology. Human studies have shown that electrical stimulation of the amygdala resulted in apnea, indicating that the amygdala has a role in respiration control. Unilateral amygdala stimulation resulted in immediate onset of respiratory dysfunction occurring only during nose breathing. In small numbers of patients, some but not all spontaneous seizures resulted in apnea occurring shortly after seizure spread to the amygdala. With this study we aimed to determine whether seizure onset or spread to the amygdala was necessary and sufficient to cause apnea. We investigated the temporal relationship between apnea/hypopnea (AH) onset and initial seizure involvement within the amygdala in patients with implanted depth electrodes. Data from 17 patients (11 female) with 47 seizures were analyzed. With seven seizures (three patients), AH preceded amygdala seizure involvement by 2 to 55seconds. There was no AH with four seizures (three patients) that involved the amygdala. With eight seizures (four patients) AH occurred within 2seconds following amygdala seizure onset. With 28 seizures, AH started >2seconds after amygdala seizure onset (range 3-158seconds). Following seizure onset, there was a significant difference between AH onset time and amygdala seizure onset (P<.001). The mean ± standard deviation (SD) AH onset was 27.8±41.06seconds, and the mean time to amygdala involvement was 8.83±20.19seconds. There is a wide range of AH onset times relative to amygdala seizure involvement. With some seizures, amygdala seizure involvement occurs without AH. With other seizures, AH precedes amygdala seizures, suggesting that, with spontaneous seizures, involvement of the amygdala may not be crucial to induction of AH with all seizures. Other pathophysiology impacting brainstem respiratory networks may be of greater relevance to seizure-triggered apneas.

Altered A-type potassium channel function in the nucleus tractus solitarii in acquired temporal lobe epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is among the leading causes of death in people with epilepsy. Individuals with temporal lobe epilepsy (TLE) have a high risk for SUDEP because the seizures are often medically intractable. Neurons in the nucleus tractus solitarii (NTS) have been implicated in mouse models of SUDEP and play a critical role in modulating cardiorespiratory and autonomic output. Increased neuronal excitability of inhibitory, GABAergic neurons in the NTS develops during epileptogenesis, and NTS dysfunction has been implicated in mouse models of SUDEP. In this study we used the pilocarpine-induced status epilepticus model of TLE (i.e., pilo-SE mice) to investigate the A-type voltage-gated K+ channel as a potential contributor to increased excitability in GABAergic NTS neurons during epileptogenesis. Compared with age-matched control mice, pilo-SE mice displayed an increase in spontaneous action potential frequency and half-width 9-12 wk after treatment. Activity of GABAergic NTS neurons from pilo-SE mice showed less sensitivity to 4-aminopyridine. Correspondingly, reduced A-type K+ current amplitude was detected in these neurons, with no change in activation or inactivation kinetics. No changes were observed in Kv4.1, Kv4.2, Kv4.3, KChIP1, KChIP3, or KChIP4 mRNA expression. These changes contribute to the increased excitability in GABAergic NTS neurons that develops in TLE and may provide insight into potential mechanisms contributing to the increased risk for cardiorespiratory collapse and SUDEP in this model. NEW & NOTEWORTHY Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in epilepsy, and dysfunction in central autonomic neurons may play a role. In a mouse model of acquired epilepsy, GABAergic neurons in the nucleus tractus solitarii developed a reduced amplitude of the A-type current, which contributes to the increased excitability seen in these neurons during epileptogenesis. Neuronal excitability changes in inhibitory central vagal circuitry may increase the risk for cardiorespiratory collapse and SUDEP.

Strategies for non‐EEG seizure detection and timing for alerting and interventions with tonic–clonic seizures

Sudden unexpected death in epilepsy (SUDEP) is a common cause of death in epilepsy and frequently occurs following generalized tonic-clonic seizures (GTCS). Non-electroencephalography (EEG) seizure detection systems using mobile sensor devices permit caregivers to assist patients during seizures and may reduce risks for complications of seizures such as injuries and SUDEP. We review changes in accelerometry, electrodermal activity, and heart rate associated with tonic-clonic seizures and their use in detection systems, including multimodal detectors. We reviewed current and past publications reporting data on linkage between GTCS, post-ictal generalized EEG suppression (PGES), and ventilatory dysfunction. The timing and duration of postictal immobility and respiratory dysfunction associated with convulsions help identify which patients might benefit the most from seizure monitoring and from benchmarks for the timing of seizure detection, caregiver alerting, and interventions.

Postictal generalized EEG suppression and respiratory dysfunction following generalized tonic-clonic seizures in sleep and wakefulness.

Sudden unexpected death in epilepsy (SUDEP) is a common cause of death in epilepsy and frequently occurs following generalized tonic-clonic seizures (GTCS) in sleep. Postictal generalized electroencephalography (EEG) suppression (PGES), postictal immobility, and periictal respiratory dysfunction are potential risk factors for SUDEP. We sought to determine whether there was a difference in respiratory dysfunction, PGES, and postictal immobility for GTCS occurring during wakefulness or sleep. We retrospectively analyzed video-EEG telemetry data in the epilepsy-monitoring unit. Patients' state at seizure onset and seizure characteristics were identified. Respiratory parameters and heart rate were recorded. Presence and duration of PGES and time to first postictal nonrespiratory movement were recorded. There were 165 seizures in 67 patients. There was no significant difference in the duration of postictal immobility in GTCS occurring out of wakefulness or sleep (p=0.280). Oxygen desaturation nadir (p=0.572) and duration of oxygen desaturation were not significantly different for GTCS starting during sleep or wakefulness (p=0.992). PGES occurred more frequently when seizure onset was in sleep than in wakefulness (p=0.004; odds ratio [OR]2.760). There was no difference in the duration of PGES between the two groups. PGES occurs more commonly after GTCS in sleep than in wakefulness but, in the epilepsy-monitoring unit (EMU), a patient's state at seizure onset does not affect the degree of respiratory dysfunction or duration of postictal immobility. In sleep, outside the hospital setting, GTCS are likely to go unnoticed. Postictal immobility in prone patients prevents head repositioning and unimpeded air exchange. A positive feedback cycle ensues with increasing respiratory distress, potentiating postictal immobility and PGES and eventually leading to asystole. Our findings suggest that the high incidence of nocturnal SUDEP may be related to the unsupervised environment during sleep rather than the severity of sleep-related respiratory dysfunction or PGES duration in the immediate postictal period.

Cause of death in patients with poststroke epilepsy: Results from a nationwide cohort study.

The risk of death is increased for persons with epilepsy. The literature on causes of death in epilepsy is based mainly on cohorts with epilepsy of mixed aetiologies. For clinical purposes and improved understanding of mortality in different epilepsies, more information is needed on mortality in epilepsies of specific causes. In poststroke epilepsy (PSE), seizures occur in a setting of vascular disease and high mortality rates. The extent to which epilepsy contributes to mortality in this patient group is poorly understood. We therefore aimed to describe causes of death (COD) in PSE on a national scale. A previously identified cohort of 7740 patients with epilepsy or seizures after a stroke in 2005–2010 was investigated. A total of 4167 deaths occurred before the end of 2014. The standardized mortality ratio for the study cohort was 3.56 (95% CI: 3.45–3.67). The main underlying causes of death were disorders of the circulatory system (60%) followed by neoplasms (12%). Diseases of the nervous system were the sixth leading underlying COD (3%), and epilepsy or status epilepticus was considered the underlying COD in approximately a similar proportion of cases as neurodegenerative disorders (0.9% and 1.1%, respectively). Epilepsy was considered a contributing COD in 14% of cases. Our findings highlight the importance of optimal management of vascular morbidity in patients with PSE. The large proportion of patients with epilepsy as a contributing COD indicate the need of high ambitions also regarding the management of seizures in patients with PSE.

Seizure-Induced Sympathoexcitation Is Caused by Activation of Glutamatergic Receptors in RVLM That Also Causes Proarrhythmogenic Changes Mediated by PACAP and Microglia in Rats.

Sudden unexpected death in epilepsy is a major cause of death in epilepsy. Generally, seizures are accompanied by changes in brain function leading to uncontrolled nerve activity causing high blood pressure, rapid heart rate, and abnormal heart rhythm. Nevertheless, the brain chemicals causing these cardiovascular changes are unknown. Chemicals, such as glutamate and pituitary adenylate cyclase activating polypeptide, whose expression is increased after seizures, act on specific cardiovascular nuclei in the brain and influence the activity of the heart, and blood vessels. Microglia, which manage excitation in the brain, are commonly activated after seizure and produce pro- and/or anti-inflammatory factors. Hence, we aimed to determine the effects of blocking glutamate, pituitary adenylate cyclase activating polypeptide, and microglia in the RVLM and their contribution to cardiovascular autonomic dysfunction in seizure.

Discussing SUDEP: Have we improved?—A retrospective case note analysis

SummarySudden unexplained death in epilepsy (SUDEP) is the most common cause of death in epilepsy. Controversy surrounds its discussion with patients, with discrepancy between clinical practice and guideline recommendations; a previous audit of local practice in 2012 found that in only 4% of patients’ notes was there documented evidence of SUDEP discussion. The aim of this study was to evaluate current clinical practice and to determine whether there had been a change in practice following publication of the initial audit. A retrospective case note review was undertaken on all patients with a diagnosis of epilepsy attending a specialist epilepsy clinic in Tayside from January 1, 2012 to March 31, 2012. A documented discussion regarding SUDEP was recorded in 81 (34%) of 240 patients, an increase from previous review. Documented discussion was more likely to occur in new referrals and in those with ongoing generalized seizures, and conversely less likely to occur in those with a long history of seizures and drug‐resistant epilepsy. This repeat audit demonstrates improvement in practice; however, the minority of patients are still being informed, with those at higher risk statistically less likely to be informed.

Cardiopulmonary complications during pediatric seizures: A prelude to understanding SUDEP

Sudden unexpected death in epilepsy (SUDEP) is an important, unexplained cause of death in epilepsy. Role of cardiopulmonary abnormalities in the pathophysiology of SUDEP is unclear in the pediatric population. Our objective was to assess cardiopulmonary abnormalities during epileptic seizures in children, with the long-term goal of identifying potential mechanisms of SUDEP. We prospectively recorded cardiopulmonary functions using pulse-oximetry, electrocardiography (ECG), and respiratory inductance plethysmography (RIP). Logistic regression was used to evaluate association of cardiorespiratory findings with seizure characteristics and demographics. We recorded 101 seizures in 26 children (average age 3.9 years). RIP provided analyzable data in 78% and pulse-oximetry in 63% seizures. Ictal central apnea was more prevalent in patients with younger age (p = 0.01), temporal lobe (p < 0.001), left-sided (p < 0.01), symptomatic generalized (p = 0.01), longer duration seizures (p < 0.0002), desaturation (p < 0.0001), ictal bradycardia (p < 0.05), and more antiepileptic drugs (AEDs; p < 0.01), and was less prevalent in frontal lobe seizures (p < 0.01). Ictal bradypnea was more prevalent in left-sided (p < 0.05), symptomatic generalized seizures (p < 0.01), and in brain magnetic resonance imaging (MRI) lesions (p < 0.1). Ictal tachypnea was more prevalent in older-age (p = 0.01), female gender (p = 0.05), frontal lobe (p < 0.05), right-sided seizures (p < 0.001), fewer AEDs (p < 0.01), and less prevalent in lesional (p < 0.05) and symptomatic generalized seizures (p < 0.05). Ictal bradycardia was more prevalent in male patients (p < 0.05) longer duration seizures (p < 0.05), desaturation (p = 0.001), and more AEDs (p < 0.05), and was less prevalent in frontal lobe seizures (p = 0.01). Ictal and postictal bradycardia were directly associated (p < 0.05). Desaturation was more prevalent in longer-duration seizures (p < 0.0001), ictal apnea (p < 0.0001), ictal bradycardia (p = 0.001), and more AEDs (p = 0.001). Potentially life-threatening cardiopulmonary abnormalities such as bradycardia, apnea, and hypoxemia in pediatric epileptic seizures are associated with predictable patient and seizure characteristics, including seizure subtype and duration.

Anti-NMDA receptor encephalitis associated with ictal asystole

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis usually presents with psychiatric symptoms, behavioural changes, impaired consciousness, seizures and autonomic instability. Ictal asystole is a rare phenomenon associated with complex partial seizures. It is implicated as a potential cause of sudden unexpected death in epilepsy. We report a 41-year-old woman who presented with anti-NMDAR encephalitis. During continuous video electroencephalogram and cardiac monitoring, an episode of ictal asystole was detected. We discuss the potential link between anti-NMDAR encephalitis and ictal asystole. Treatment options for ictal asystole in the setting of anti-NMDAR encephalitis are also discussed.

A Nationwide Survey of the Extent of Autopsy in Sudden Unexplained Death in Epilepsy

Sudden unexplained death in epilepsy is a catastrophic event that requires autopsy for definitive diagnosis. Lack of awareness of sudden unexplained death in epilepsy as an important cause of death in epilepsy has been observed among coroners and pathologists. This survey study of US coroners and medical examiners (MEs) assesses their postmortem examinations of persons with epilepsy who had died suddenly without obvious cause. Analysis of the 510 survey responses shows that pathologists are significantly more likely than nonpathologists to inquire routinely about a history of cardiac disease, remove the brain for examination, or collect blood samples for determinations of anticonvulsant and psychotropic drugs. Urban coroners and MEs are significantly more likely than their nonurban colleagues to remove the brain for examination or collect blood samples for these determinations. Lack of family consent and the cost of autopsy are major reasons for not performing an autopsy of persons with epilepsy. Our study underscores the importance of promoting to all coroners and MEs and to the public the need for thorough autopsy of persons with epilepsy when the cause of death is not obvious.

Cardiac arrest: it's all in the head

In May, 2007, a 59-year-old man lost consciousness twice in 4 days. The fi rst episode occurred while he was watching a fi lm, and the second episode while he was at work, laying a carpet. Each episode started and ended abruptly, without warning or apparent triggers, and lasted less than 15 s. He did not bite his tongue or leak urine. After each episode, he was lucid, and felt well. He had no past history of loss of consciousness. He did, however, have diabetes and hypercholesterolaemia, for which he was being treated with miglitol and atorvastatin, respectively. The patient’s general practitioner provi sionally diagnosed syncope, and referred him to us. Cardiovascular and neurological examinations showed nothing abnormal; notably, the patient had no orthostatic hypotension. Blood tests, an electrocardiogram (ECG), transthoracic echocardiography, an exercise stress test, a 24 h ECG, and tilt-table testing also showed no abnormality. However, the day after the patient was admitted, he abruptly lost consciousness. Nurses observed tonic-clonic movements. The ECG monitor showed asystole, lasting 12 s. We provisionally diagnosed epilepsy. 5 days later, the patient lost consciousness again, during video-electroencephalography (video-EEG) monitoring. EEG showed ictal activity in the anterior part of the left temporal lobe, which became generalised. The seizure lasted 35 s. 10 s after the seizure began, the ECG monitor showed a sinus arrest, lasting 4·3 s (fi gure). Asystole was succeeded by sinus bradycardia (36 beats per min); the heart rate increased steadily thereafter, until it reached the pre-ictal rate of 66 beats per min; the heart rate was 47 beats per min when the seizure ceased. CT of the brain showed no abnormality. MRI showed sporadic bilateral white-matter changes, located near the insular cortex on both sides. These lesions were of vascular origin, but non-specifi c. Doppler ultrasonography of the carotid arteries showed no atherosclerosis. We prescribed levetiracetam, at a dose of 1000 mg per day. The patient remained in hospital for another week, during which time he did not lose consciousness; a further 24 h of combined videoEEG and ECG monitoring showed nothing abnormal. However, 4 months after discharge, the patient had another seizure, with bradycardia. We therefore implanted a cardiac pacemaker. When last seen, in March, 2008, the patient had not had a fi t or faint since the pacemaker was fi tted. Sinus tachycardia is common during epileptic fi ts. In one case series, 13 (30%) of 43 patients with intractable partial epilepsy had cardiac dysrhythmias, other than sinus tachycardia, during, or immediately after, fi ts. Ictal bradycardia tends to occur in (perhaps especially left) temporal-lobe epilepsy. The mechanism may be parasympathetic activation. Our patient had a seizure of the left temporal lobe, with secondary generalisation. Ictal bradycardia is rare, especially in women. However, it is likely to be substantially underdiagnosed. Moreover, it may be a major cause of sudden unexpected death in epilepsy, which kills an estimated 0·12% of people with epilepsy per year. This case illustrates that cardiac arrest can occur during the fi rst epileptic seizure. Pacemaker implantation can prevent death and disability.

Mortality of Epilepsy from National Vital Statistics and University Epilepsy Clinic in Taiwan

Where population-based studies of epilepsy mortality are impossible to conduct, other sources of data must be considered. We provide descriptive data on mortality and causes of death for epilepsy in Taiwan. Two settings in Taiwan were used. First, we evaluated the mortality ratio for epilepsy, using the national vital statistics for 1996 with the total population of Taiwan as the denominator. Second, we evaluated mortality in a cohort of prevalent epilepsy cases from a University outpatient clinic. For both, proportionate mortality was calculated to determine the relative contributions of different causes of death in epilepsy. One hundred and sixty-two deaths were correctly coded under ICD code 345 from the 1975 detailed diagnostic listing during the 1-year period of 1996. Epilepsy was the diagnosis in 0.8 deaths/100,000 population. Over an 11-year period, there were 54 deaths (0.9%) among 1,224 prevalent epilepsy cases from a University clinic during 5,704 person-years of follow-up. The most common underlying cause of death was epilepsy-related death in 129 (79.6%) out of 162 deaths from the vital statistics data. There were 13 deaths unrelated to epilepsy (8.0%). Acute reactive seizure as the cause of death was found in 9 patients (5.6%). The leading cause of death in the epilepsy clinic was disease unrelated to epilepsy in 21 deaths (38.9%), epilepsy-related death in 12 patients (22.2%), and death related to the cause of epilepsy in 9 patients (16.7%). Data derived from vital statistics are inadequate to evaluate mortality in people with epilepsy.