Short-Term Mortality After a First Epileptic Seizure: A Population-Based Study

PURPOSE: To determine the short-term mortality in a prospective incidence cohort of patients included after any kind of first afebrile epileptic seizure (i.e., provoked and unprovoked). METHODS: Information on death occurring within the first year of follow-up was collected in a cohort of 804 patients with a first seizure between March 1, 1984, and February 28, 1985, in southwest France. The variables analyzed were the etiology of seizure, cause of death, interval between seizure and death, and age of patients. RESULTS: By the end of the 1-year follow-up, there were 149 deaths among these patients as compared with 16 expected deaths [standardized mortality ratio (SMR), 9.3; 95% confidence interval (CI), 7.9-10.9]. There were no deaths in patients with idiopathic seizures. Patients with cryptogenic seizures had slightly increased mortality (SMR, 1.6; 95% CI, 0.4-4.1). Mortality was increased for patients with remote symptomatic seizures (SMR, 6.5; 95% CI, 3.8-10.5), provoked seizures (SMR, 10.1; 95% CI, 8.1-12.4), and seizures due to a progressive neurologic condition (SMR, 19.8; 95% CI, 14.0-27.3). Causes of death were underlying pathology (64%), unrelated condition (20%), unknown cause (9%), seizure-related death (6%), and one suicide. CONCLUSIONS: Early mortality clearly differed according to the etiology of the first seizure. The highest mortality was associated with provoked seizures and with seizures caused by progressive central nervous system disorders. Patients died far more often from underlying or unrelated conditions than from seizures.     

Mortality risk in an adult cohort with a newly diagnosed unprovoked epileptic seizure: a population-based study

PURPOSE: We sought to investigate mortality risk in an adult cohort with newly diagnosed unprovoked epileptic seizures. METHODS: One hundred seven patients who were at least 17 years old and had newly diagnosed unprovoked epileptic seizures were prospectively identified during a period of 20 months between 1985 and 1987. Patients were followed until the date of death or the end of 1996. The standard mortality ratio (SMR) was analyzed in the whole cohort and in the portion of the cohort with recurrent seizures at inclusion. The influences on the SMR of time since diagnosis, sex, age at diagnosis, seizure cause, seizure type, and cause of death were also investigated. RESULTS: The SMR was significantly increased (SMR, 2.5; 95% confidence interval [CI], 1. 2-3.2). This significantly increased risk was found during the first 2 years after diagnosis (year 1: SMR, 7.3; 95% CI, 4.4-12.1; year 2: SMR, 3.6; 95% CI, 1.6-8.1) and at years 9-11 (SMR, 5.4; 95% CI, 2. 7-11.2). The increased mortality risk was most pronounced when the seizures occurred before the age of 60 years. Mortality risk was elevated among patients with remote symptomatic epilepsy (SMR, 3.3; 95% CI, 2.4-4.5) but not idiopathic epilepsy. CONCLUSIONS: There is increased mortality risk in an adult cohort with newly diagnosed unprovoked epileptic seizures. This increase is found in symptomatic patients, young patients, and during the first 2 years after the diagnosis.     

One-Year Mortality in Bordeaux Cohort: The Value of Syndrome Classification

Summary:  Purpose: To evaluate the usefulness of the International Classification of Epilepsy Syndromes for 1-year mortality in a prospective incidence study of first epileptic seizures.
Methods: Date and cause of death from the treating physician in an incidence study of first afebrile seizures collected 15 years ago in Southwest France. Cases were classified by epilepsy syndrome. A total of 804 patients were included: acute symptomatic (n = 277), unprovoked (n = 439), or unclassifiable (n = 88).
Results: One hundred and fifty-one patients died within the first year: none with idiopathic partial or generalized epilepsy, 16/104 with symptomatic (standardized mortality ratio (SMR) 6.4, 95% CI 3.6–10.3), 1/59 with cryptogenic (SMR 1.7, 95% CI 0.1–9.7 CI) partial epilepsy, 1/14 (SMR 28.1, 95% CI 0.4–156.6) with symptomatic/cryptogenic generalized epilepsy, 2/23 with undetermined epilepsy, 1/135 with isolated seizure (SMR 0.6, 95% CI 0.1–3.1), and 90/277 (SMR 10.3, 95% CI 8.3–12.7) with acute symptomatic seizures. Unclassifiable seizures could not be classified as acute symptomatic or unprovoked: associated with alcohol abuse (death: 3/32, SMR 7.7, 95% CI 1.6–22.6), brain tumors (death: 31/39, SMR 41.5, 95% CI 28.2–58.9), and dementia (death: 6/17, SMR 5.4, 95% CI 2.0–11.7). Most deaths were due to progression of underlying disease, only 5.9% were seizure-related.
Conclusions: Although a syndromic diagnosis is important for treatment decisions and some prognostic aspects of seizure disorders, its value in mortality studies is limited. Mortality can be calculated only at the first (partial, generalized, and undetermined epilepsies, and special syndromes) and the second (idiopathic vs. symptomatic or cryptogenic) levels of the International Classification of Epilepsies.     

Mortality risk in adults with newly diagnosed and chronic epilepsy: a population‐based study

Background: We analyzed mortality in adult patients with newly diagnosed and chronic epilepsy over a 13‐year period. Methods: Eighty‐one patients aged ≥20 years with newly diagnosed epilepsy and 309 adult patients with chronic epilepsy were originally identified from population‐based incidence and prevalence studies conducted in Tartu between 1994 and 1996. Patients with epilepsy were followed until the date of death or until the end of 2007. The standardized mortality ratio (SMR) was analyzed for both cohorts. The influences of age at diagnosis, sex, epilepsy syndrome, seizure type, risk factors and treatment compliance on the SMR were also investigated. Results: The SMR was significantly increased in both cohorts, but was higher in patients with chronic epilepsy (SMR 3.1; 95% confidence interval [CI] 2.5–3.8) relative to patients with newly diagnosed epilepsy (SMR 2.6; 95% CI 1.8–3.5). In the newly diagnosed epilepsy cohort, the increased mortality risk was more pronounced in patients with complex partial seizures (SMR 5.6; 95% CI 2.4–11.0). In the chronic epilepsy cohort, the mortality risk was higher in patients with secondary generalized tonic‐clonic seizures (SMR 3.4; 95% CI 2.5–4.5). Non‐compliant patients had twice the mortality risk (SMR 4.2; CI 95% 2.7–6.2) compared to those who were on anticonvulsant treatment. Conclusions: Mortality rates are higher in people with newly diagnosed and chronic epilepsy. Mortality risks should be discussed with patients with epilepsy, especially if anticonvulsant treatment is refused despite recurrent seizures.     

Influence of Epilepsy on Mortality in Mental Retardation: An Epidemiologic Study

Summary: Purpose : A cohort consisting of all persons with known mental retardation (MR) and living in a Swedish province on December 31, 1985, was followed for 7 years (1987–1992) to study the mortality pattern.
Methods : A file of the cohort was linked to the cause-of-death pattern of the general population in the study area.
Results : One hundred twenty-four deaths (8.4%) occurred among the 1,478 persons with MR. Thirty deaths (10.1%) occurred among the 296 persons with epilepsy and MR. The standardized mortality ratio (SMR) in those with only MR was significantly increased as compared with that of the general population: 1.6 [95% confidence interval (CI) 1.3–2.01; MR and epilepsy, 5.0 (CI 3.3–7.5); and MR, epilepsy, and cerebral palsy (CP), 5.8 (CI 3.4–9.7). Mortality was increased both in patients with partial seizures without seizures secondarily generalized (SMR 3.7, CI 1.0–13.6) and in patients with seizures secondarily generalized (5.0, CI 2.3–11.0). The highest mortality occurred in patients who had seizures that were always generalized from the onset: 8.1 (CI 5.7–11.5). Mortality increased with increasing seizure frequency during the year preceding the prevalence date. In patients with epilepsy and MR, pneumonia was the most common cause of death and a seizure was the probable cause of death in 6.7%.
Conclusions : Epilepsy is associated with a significantly increased mortality in persons with MR. The increase is related to seizure type and seizure frequency. Death in persons with epilepsy and MR is seldom directly due to seizures. Other impairments associated with epilepsy and MR are important causes of death.     

Mortality in patients with epilepsy: a study of patients in long term residential care.

The causes of death in a group of patients with severe epilepsy in long term residential care over a period of 11 years were assessed and the standardised mortality rate (SMR) determined. A total of 3392 patient-years were surveyed. One hundred and thirteen deaths were recorded in the period and this represents an overall mortality rate which is almost twice the expected rate for this population (SMR = 1.9; 95% CI 1.6-2.3; p < 0.01). Most deaths were due to cancer (26%), bronchopneumonia (25%), circulatory diseases (24%), were seizure-related (12%) or due to sudden unexpected death (6%). The highest SMRs in the neoplasm sub-group were due to cancers of the pancreas (SMR = 6.2) and hepatobiliary tumours (SMR = 17.6). Twenty per cent of patients died of epilepsy or epilepsy related causes (that is accidents, during seizures, status or sudden unexpected death). One in every 480 patients died due to a sudden unexpected death. This study in a highly selected population seems to confirm suggestions that mortality rates are higher in patients with epilepsy than in the general population, but prospective studies are warranted to ascertain underlying mechanisms.     

A study of mortality after temporal lobe epilepsy surgery.

OBJECTIVE: To determine early and late mortality in a cohort of 305 consecutive patients who had temporal lobe epilepsy (TLE) surgery over a 20-year period. METHODS: Survival status, cause of death, and postoperative clinical details of those who died were ascertained in a cohort of 305 patients who had TLE surgery. Mortality was related to postoperative seizure status, operative pathology, and side of resection. RESULTS: The survival status of 299 patients was established. Twenty deaths occurred. Mortality was 1 per 136 person-years, with a standardized mortality ratio (SMR) of 4.5 (95% confidence interval [CI], 3.2 to 6.6). Six deaths were sudden and unexpected (SUDEP). The SUDEP rate was 1 per 455 person-years. The overall death and SUDEP rates were lower than those reported for similar patient populations with chronic epilepsy. Mortality in patients who had right-sided resections for mesial temporal sclerosis (MTS) remained considerably elevated with a mortality rate of 1 per 54 person-years, an SMR of 32.0 (95% CI, 24.7 to 40.5), and a SUDEP rate of 1 per 134 person-years. These patients had significantly lower seizure remission rates than left-sided patients, but the excess mortality was not simply explained by those patients whose partial seizures were uninfluenced by surgery. Patients who died had more severe or convulsive seizures despite an overall reduction in seizure frequency. CONCLUSIONS: The present findings confirm previous reports that TLE surgery lowers but does not normalize the overall mortality associated with chronic epilepsy. In patients with right-sided MTS, however, the postoperative mortality has remained similar to other groups with medically intractable seizures.     

Cause-specific mortality in adults with unprovoked seizures. A population-based incidence cohort study.

PURPOSE: To determine the cause-specific mortality relative to that expected in a population-based incidence cohort of people with unprovoked seizures. METHODS: The cohort comprises 224 inhabitants of Iceland first diagnosed as suffering from unprovoked seizures during a 5-year period from 1960 to 1964. The expected number of deaths was calculated by multiplying person-years of observation within 5-year age categories for each year from diagnosis through 1995 by cause-specific and sex-specific national death rates for those aged 20 years and above. The standardized mortality ratio (SMR) and 95% confidence intervals (95% CI) were calculated. RESULTS: All-cause mortality was increased among men (SMR 2.25, 95% CI 1.56-3.14) but not women (SMR 0.79, 95% CI 0.38-1.46). Among men, there were 8 deaths from accidents, poisoning and violence observed versus 2.82 expected (SMR 2.84, 95% CI 1.22-5.59) and 4 deaths from suicide versus 0.69 expected (SMR 5.80, 95% CI 1.56-14.84). All-cause mortality for men was still elevated after restriction of analysis to those with seizures of unknown etiology (SMR 1.73, 95% CI 1.05-2.67) with the excess deaths attributable to suicide (SMR 5.26, 95% CI 1.06-15.38). Both males and females with remote symptomatic unprovoked seizures had an increase in all-cause mortality due to excess mortality from all cancers, cerebrovascular disease and accidents. CONCLUSION: When compared with the age-, time-period- and gender-specific mortality in the general population, there is excess mortality in men but not women. The increased mortality for men is partly attributable to excess mortality from accidents and suicides.     

Mortality after temporal lobe epilepsy surgery

Purpose: To report mortality, after a longer interval, in a cohort of patients with drug‐resistant epilepsy treated by temporal lobe surgery between 1975 and 1995. A previous audit of these patients ending December 1, 1997 observed a standardized mortality ratio (SMR) of 4.5. Methods: We analyzed mortality in a cohort of 306 patients with temporal lobe epilepsy (TLE) who underwent temporal lobe resections between December 1, 1975 and December 1, 1995. Deaths occurring after December 1,1997 and until December 1, 2009 were evaluated. Medical records, death certificates, postmortem examination reports, coroner officer’s reports, and coroner’s inquest reports were sought, and causes of death were ascertained. Sudden unexpected death in epilepsy (SUDEP) cases were identified. Key Findings: In 3,569 person‐years of follow‐up 19 deaths occurred, [SMR 2.00, 95% confidence interval (CI) 1.27–3.13], 14 men (SMR 2.01, 95% CI 1.19–3.39) and 5 women (SMR 1.68, 95% CI 0.70–4.03). On analysis of subgroups, SMRs were significantly elevated in patients with mesial temporal sclerosis (MTS) (SMR 2.50, 95% CI 1.38–4.51), men with MTS (SMR 3.12, 95% CI 1.56–6.25), men with nonspecific lesions (SMR 2.68, 95% CI 1.00–7.09), and right‐sided resections in MTS (SMR 3.33, 95% CI 1.39–8.00). During follow‐up, six SUDEP cases were observed with a rate of 1/595 person‐years. Significance: In this cohort, the risk for premature death in patients undergoing TLE surgery decreased over time but remained above the standard population. Men had a slightly higher risk than women, as did right‐sided resections in MTS, confirming this observation in the original cohort. Although lower, the risk of SUDEP remained. Without up‐to‐date information on seizure outcome, we were unable to directly relate this to mortality.     

Mortality in Patients with a First Unprovoked Seizure

Summary:  Purpose: The mortality after a first epileptic seizure is affected by the source of cases, the intensity of the diagnostic work-up, the type and the presumed etiology of the seizure, the length of follow-up, and the modalities of data collection (retrospective vs. prospective). We review the four studies of this topic.
Methods: Four studies have been identified which focused on the mortality of the first unprovoked seizures or the first afebrile (provoked or unprovoked) seizure. These included two population-based surveys, one clinic-based community survey, and a randomized clinical trial on the treatment of the first unprovoked generalized tonic–clonic seizure.
Results: A standardized mortality ratio (SMR) of 2.3 (95% confidence interval, CI 1.5–3.3) for unprovoked first seizures was found in a retrospective cohort study in the population of Rochester, Minnesota. The SMR was higher during the first year after the seizures to progressively decrease thereafter. Acute symptomatic seizures carried the higher risk, followed by remote symptomatic seizures, while idiopathic and cryptogenic seizures carried no risk. The increased SMR found in women and in patients aged 0–19 years enrolled in the randomized trial differs from that seen in other mortality studies in epilepsy (SMR being highest in the youngest age groups) and may be a chance finding.
Conclusions: Mortality is increased in patients with a first unprovoked seizure, particularly during the first year after the seizure. This increased mortality is associated with known etiology of the seizure, and is not present when etiology is unknown.     

Long-Term Survival of People with Unprovoked Seizures: A Population-Based Study

Summary: Purpose : Few population-based studies of longterm survival in people with seizures or epilepsy have been made.
Methods: Between January 1, 1960 and December 31, 1964, we identified 224 incidence cases of unprovoked seizures in Iceland and determined survivorship status and date of death for the cases as of January 1, 1996. We compared survivorship with that expected based on data from age-/sex-specific life tables from the country for 1961–1990 and calculated the standardized mortality ratio (SMR).
Results: By 30 years after diagnosis, there were 45 deaths among patients with unprovoked seizures as compared with an expected 28 deaths [standardized mortality ratio (SMR) 1.6; 95% confidence interval (CI) 1.2–2.21. Patients with unprovoked seizures of unknown etiology did not have a significant increase in mortality overall (SMR 1.3, 95% CI 0.8–1.9) or in any time interval. For patients with remote symptomatic un provoked seizures, mortality was increased (SMR 2.3, 95% CI 1.4–3.5). This increase was attributable to excess mortality for the first 15 years after diagnosis (SMR 4.1, 95% CI 2.4–6.6), and SMR was not different after that time.
Conclusions: Survivorship was decreased for the population of patients with unprovoked seizures. The increased mortality was primarily due to excess mortality in patients with remote symptomatic seizures, occurring in the first 15 years after diagnosis. Overall mortality for idiopathic unprovoked seizures was not significantly increased.     

Cause-Specific Mortality in Epilepsy: A Cohort Study of More Than 9,000 Patients Once Hospitalized for Epilepsy

Summary: Purpose: We studied overall and cause-specific mortality rates in a large cohort of patients with epilepsy compared with mortality rates of the general population in the same geographic area.
Methods: The cohort consisted of all patients (N = 9,061) aged >15 years admitted with a diagnosis of epilepsy for inpatient care in Stockholm during the years 1980–1989. All patients were followed in the National Cause-of-Death Register, from which the causes of death were obtained, until December 31, 1992. Thus, 53,520 person-years were observed. Mortality rates were compared with those of the general population of Stockholm.
Results: We observed 4,001 deaths in the cohort, compared with an expected number of 1,109 deaths in the general population. This yielded a standardized mortality ratio (SMR) of 3.6 [95% confidence interval (CI) 3.5–3.71] Although highest in the younger patients, the SMR was significantly increased in all age groups. The excess mortality rate in the cohort was due to a wide range of causes of death, including malignant neoplasms [SMR 2.6 (2.4–2.8)], diseases of the circulatory system, [SMR 3.1 (3.0–3.3)], diseases of the respiratory system [SMR 4.0 (3.64.5)], diseases of the digestive system [SMR 5.1 (4.4–5.8)], and injuries and poisoning [SMR 5.6 (5.0–6.3)].
Conclusions: Our results demonstrate that this large subgroup of patients with a diagnosis of epilepsy, once hospitalized and discharged, is a population at risk, with an excess mortality rate due to several different causes.     

Mortality in adults with newly diagnosed and chronic epilepsy: a retrospective comparative study

BACKGROUND: People with epilepsy are at increased risk of premature death compared with the general population. Many clinicians are unsure whether and when this issue should be broached with their patients. We analysed mortality in patients with newly diagnosed and chronic epilepsy over a 20-year period. METHODS: Patients who attended the epilepsy service at the Western Infirmary in Glasgow, UK between 1981 and 2001, with newly diagnosed epilepsy (n=890) or referred after receiving unsuccessful treatment elsewhere (n=2689) were included in the study. Mortality data were obtained from the General Registrar Office for Scotland. Causes of death were ascertained from death certificates and primary care and health authority records. The two patient cohorts were compared with age-matched and sex-matched Scottish comparison groups. Standardised mortality ratios (SMR) were calculated for each epilepsy type, 10-year age band, and cause of death category. FINDINGS: Newly diagnosed patients had a 42% increase in mortality (SMR 1.42, 95% CI 1.16-1.72) compared with the comparison group. Increased mortality was recorded in those who had not responded to treatment, with no increase in risk observed in patients who were seizure free. In the chronic epilepsy cohort, there was more than double the expected number of deaths (2.05, 1.83-2.26). The incidence of sudden unexpected death in epilepsy was 1.08 and 2.46 per 1000 patient-years in patients with newly diagnosed and chronic epilepsy, respectively. The greatest excess in mortality was reported in patients younger than 30 years. INTERPRETATION: Mortality risks and preventive strategies should be discussed with patients with epilepsy when treatment fails or is refused despite recurrent seizures.     

Mortality by clinical characteristics in a tertiary care cohort of adult patients with chronic epilepsy

The authors evaluated the contribution of various clinical characteristics to mortality risk and underlying causes of death among all adult patients with epilepsy seen at the Department of Neurology, Oulu University Hospital in Finland during 1996 and 1997. Hazard ratios (HRs) for mortality in 1998–2006 relative to a population‐based reference cohort were estimated using Cox modeling, with adjustment for age and gender. The HR for total mortality was 2.66 (95% confidence interval [CI] 2.09–3.39). Infectious etiology of epilepsy (HR 5.77, 95% CI 2.52–13.2) and a seizure frequency of ≥1 per month (HR 4.42, 95% CI 3.00–6.52) related to high risks of death. Cancer (21%), ischemic heart disease (15%), and accidents (12%) caused most of the potential years of life lost. Despite recent advances in treatment of epilepsy and improved seizure control, chronic epilepsy still carries a substantially increased risk of death.     

Risk of mortality among patients with epilepsy in southern Taiwan

ObjectivePrevious studies suggested a higher risk of all-cause mortality in patients with epilepsy than in the general population. However, information on the age- and sex-specific risk of mortality, as well as on the cause-specific risk of mortality has been sparse. This study aims to determine sex-, age-, and cause-specific risk of mortality among patients with epilepsy from southern Taiwan.MethodsA total of 2180 patients treated in a tertiary hospital in southern Taiwan between 1989 and 2008 were compared to the general population of Taiwan for age-, sex- and cause-specific mortalities. The age-, sex-, and calendar year-standardized mortality ratios (SMRs) were calculated to estimate the relative risks of mortality associated with the epilepsy.ResultsThere are 266 (12.2%) deaths noted in the study period. The patients with epilepsy experienced a significantly increased SMR of all-cause mortality (SMR, 2.5; 95% confidence interval (CI), 2.2–2.8). The most significantly elevated age-specific SMR was 51.8 (95% CI, 6.2–187.2) and 8.6 (95% CI, 4.4–14.9) for male patients aged 0–9 years and female patients aged 20–29 years, respectively. Additionally, the most increased cause-specific SMR was noted for brain tumor (SMR, 21.4; 95% CI, 9.23–23.1), followed by accidental drowning (SMR, 8.8; 95% CI, 3.5–9.6) and falls (SMR, 5.7; 95% CI, 2.2–6.1).ConclusionYounger epilepsy should be the object of aggressive treatments. Advancement in treating brain tumors and prevention of accidental injuries may help improve the survival of patients with epilepsy.     

Mortality after Epilepsy Surgery

Summary:  Mortality rates are higher in people with refractory epilepsy than in the general population. We assessed mortality rates in a prospectively followed cohort who had epilepsy surgery, to examine the factors related to mortality and to assess the relationship between seizure control and mortality. Five hundred eighty-three patients were evaluated. Mortality was strongly related to seizure control (p = 0.001), with 18 deaths observed in patients with recurrent seizures (mortality rate = 11.4 per 1,000 person-years) and 1 death in patients with no recurrent seizures (mortality rate = 0.85 deaths per 1,000 person-years). Patients with generalized epilepsy who had corpus callosotomy had a higher mortality rate than patients who had resective or transective surgery. The side of surgery and gender did not influence mortality rates. The standardized mortality ratio was 5.75 for patients with recurrent seizures and was significantly higher for females than males. These data show that the excess mortality associated with refractory epilepsy is eliminated after epilepsy surgery when seizures are abolished and suggest that epilepsy surgery reduces the risk of epilepsy-associated death.     

Sudden unexpected death in epilepsy during cenobamate clinical development

Objective

We assessed mortality, sudden unexpected death in epilepsy (SUDEP), and standardized mortality ratio (SMR) among adults treated with cenobamate during the cenobamate clinical development program.

Methods

We retrospectively analyzed deaths among all adults with uncontrolled focal (focal to bilateral tonic–clonic [FBTC], focal impaired awareness, focal aware) or primary generalized tonic–clonic (PGTC) seizures who received ≥1 dose of adjunctive cenobamate in completed and ongoing phase 2 and 3 clinical studies. In patients with focal seizures from completed studies, median baseline seizure frequencies ranged from 2.8 to 11 seizures per 28 days and median epilepsy duration ranged from 20 to 24 years. Total person-years included all days that a patient received cenobamate during completed studies or up to June 1, 2022, for ongoing studies. All deaths were evaluated by two epileptologists. All-cause mortality and SUDEP rates were expressed per 1000 person-years.

Results

A total of 2132 patients (n = 2018 focal epilepsy; n = 114 idiopathic generalized epilepsy) were exposed to cenobamate for 5693 person-years. Approximately 60% of patients with focal seizures and all patients in the PGTC study had tonic–clonic seizures. A total of 23 deaths occurred (all in patients with focal epilepsy), for an all-cause mortality rate of 4.0 per 1000 person-years. Five cases of definite or probable SUDEP were identified, for a rate of .88 per 1000 person-years. Of the 23 overall deaths, 22 patients (96%) had FBTC seizures, and all 5 of the SUDEP patients had a history of FBTC seizures. The duration of exposure to cenobamate for patients with SUDEP ranged from 130 to 620 days. The SMR among cenobamate-treated patients in completed studies (5515 person-years of follow-up) was 1.32 (95% confidence interval [CI] .84–2.0), which was not significantly different from the general population.

Significance

These data suggest that effective long-term medical treatment with cenobamate may reduce excess mortality associated with epilepsy.     

Seizures after stroke: a prospective multicenter study

BACKGROUND: Studies of seizures after stroke have largely been retrospective, with small patient numbers and limited statistical analysis. Much of the doctrine about seizures after stroke is not evidenced based. OBJECTIVE: To determine the incidence, outcome, and risk factors for seizures after stroke. DESIGN: International, multicenter, prospective, analytic inception cohort study conducted for 34 months. PATIENTS AND SETTING: There were 2021 consecutive patients with acute stroke admitted to university teaching hospitals with established stroke units. After exclusion of 124 patients with previous epilepsy or without computed tomographic diagnosis, 1897 were available for analysis. Mean follow-up was 9 months. MAIN OUTCOME MEASURES: Occurrence of 1 or more seizures after stroke, stroke disability, and death after stroke. RESULTS: Seizures occurred in 168 (8.9%) of 1897 patients with stroke (28 [10.6%] of 265 with hemorrhagic and 140 [8.6%] of 1632 with ischemic stroke). On Kaplan-Meier survival analysis, patients with hemorrhagic stroke were at significantly greater risk of seizures (P =.002), with an almost 2-fold increase in risk of seizure after stroke (hazard ratio [HR], 1.85; 95% confidence interval [CI], 1.26-2.73; P =.002). On multivariate analysis, risk factors for seizures after ischemic stroke were cortical location of infarction (HR, 2.09; 95% CI, 1. 19-3.68; P<.01) and stroke disability (HR, 2.10; 95% CI, 1.16-3.82; P<.02). The only risk factor for seizures after hemorrhagic stroke was cortical location (HR, 3.16; 95% CI, 1.35-7.40; P<.008). Recurrent seizures (epilepsy) occurred in 47 (2.5%) of 1897 patients. Late onset of the first seizure was an independent risk factor for epilepsy after ischemic stroke (HR, 12.37; 95% CI, 4.74-32.32; P<. 001) but not after hemorrhagic stroke. CONCLUSIONS: Seizures occur more commonly with hemorrhagic stroke than with ischemic stroke. Only a small minority later develop epilepsy. Patients with a disabling cortical infarct or a cortical hemorrhage are more likely to have seizures after stroke; those with late-onset seizures are at greater risk of epilepsy.     

Suicide in people with epilepsy: How great is the risk?

Purpose:   Suicide is more common in populations with epilepsy, but estimates vary concerning the magnitude of the risk. We aimed to estimate the risk using meta-analysis.
Methods:   A literature search identified 74 articles (76 cohorts of people with epilepsy) in whom the number of deaths by suicide in people with epilepsy and the number of person–years at risk could be estimated. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated for each cohort, for groups of cohorts, and for the total population.
Results:   The overall SMR was 3.3 (95% CI 2.8–3.7) based on 190 observed deaths by suicide compared with 58.4 expected. The SMR was significantly increased in people with incident or newly diagnosed epilepsy in the community (SMR 2.1), in populations with mixed prevalence and incidence cases (SMR 3.6), in those with prevalent epilepsy (SMR 4.8), in people in institutions (SMR 4.6), in people seen in tertiary care clinics (SMR 2.28), in people with temporal lobe epilepsy (SMR 6.6), in those following temporal lobe excision (SMR 13.9), and following other forms of epilepsy surgery (SMR 6.4). The SMR was significantly low overall in two community-based studies of people with epilepsy and developmental disability.
Discussion:   We confirm that the risk of suicide is increased in most populations of people with epilepsy. Psychiatric comorbidity has been demonstrated to be a risk factor for suicide in the general population and in people with epilepsy, and such comorbidity should thus be identified and treated.     

Natural history and mortality of chronic epilepsy in an untreated population of rural Bolivia: A follow-up after 10 years

Purpose:   To evaluate the natural history and mortality of chronic epilepsy in an untreated prevalence cohort of people with epilepsy (PWE) in a rural area of Bolivia.
Methods:   During 1994–1996 we carried out an epidemiologic survey in a sample of 9,995 subjects in the Cordillera province. At the end of the survey we identified 130 PWE, of whom 118 were classified as having "active epilepsy." We revisited this cohort 10 years after the prevalence survey.
Results:   We were able to trace 103 (87.3%) of the 118 PWE previously identified. Ten of the 103 subjects died during the follow-up period. Of the 93 PWE still alive, adequate information on the occurrence of seizures was available for 71 subjects, of whom 31 (43.7%) were seizure-free for more than 5 years; only 3 of these 31 subjects have taken an antiepileptic drug (AED) for more than 1 year. Generalized seizures were associated with a better prognosis. Mortality rate in our prevalent cohort was 10.0/1,000 person-year at risk [95% confidence interval (CI) 5.5–18.3], without a significant increased risk respect to the general population [standardized mortality rate (SMR) 1.34; 95% CI 0.68–2.39]; a significant increased risk of death was found for patients with remote symptomatic epilepsy (SMR 3.0; 95% CI 1.2–6.3) but not with idiopathic epilepsy. Three of the 10 subjects died of causes possibly related to epilepsy.
Discussion:   Our data suggest that spontaneous remission of epilepsy occurs in a substantial proportion of untreated patients affected by chronic epilepsy; concerning mortality, we found a 3-fold increased mortality in patients with remote symptomatic epilepsy.