W. A. Hauser

A Population-Based Study of Seizures after Traumatic Brain Injuries

BACKGROUND The risk of seizures is increased after traumatic brain injury, but the extent and duration of the increase in risk are unknown. The purpose of this study was to identify the characteristics of brain injuries that are associated with the development of seizures. METHODS We identified 4541 children and adults with traumatic brain injury (characterized by loss of consciousness, post-traumatic amnesia, or skull fracture) in Olmsted County, Minnesota, during the period from 1935 through 1984. Injuries were classified as mild (loss of consciousness or amnesia lasting less than 30 minutes), moderate (loss of consciousness for 30 minutes to 24 hours or a skull fracture), or severe (loss of consciousness or amnesia for more than 24 hours, subdural hematoma, or brain contusion). We compared the incidence of new unprovoked seizures in this cohort with population rates, using standardized incidence ratios and Cox proportional-hazards analysis. RESULTS The overall standardized incidence ratio was 3.1 (95 percent confidence interval, 2.5 to 3.8). The standardized incidence ratio was 1.5 (95 percent confidence interval, 1.0 to 2.2) after mild injuries but with no increase over the expected number after five years, 2.9 (95 percent confidence interval, 1.9 to 4.1) after moderate injuries, and 17.0 (95 percent confidence interval, 12.3 to 23.6) after severe injuries. In the multivariate analysis, significant risk factors for later seizures were brain contusion with subdural hematoma, skull fracture, loss of consciousness or amnesia for more than one day, and an age of 65 years or older. CONCLUSIONS The increased risk of seizures after traumatic brain injury varies greatly according to the severity of the injury and the time since the injury.

Incidence and risk factors in sudden unexpected death in epilepsy: A prospective cohort study

Objective: To determine incidence of and risk factors for sudden unexpected death in epilepsy (SUDEP). Methods: Three epilepsy centers enrolled 4,578 patients and prospectively followed these patients for 16,463 patient-years. The cohort was screened for death annually. Deaths were investigated to determine whether SUDEP occurred. Potential risk factors were compared in SUDEP cases and in controls enrolled contemporaneously at the same center. Results: Incidence of SUDEP was 1.21/1,000 patient-years and was higher among women (1.45/1,000) than men (0.98/1,000). SUDEP accounted for 18% of all deaths. Occurrence of tonic-clonic seizures, treatment with more than two anticonvulsant medications, and full-scale IQ less than 70 were independent risk factors for SUDEP. The number of tonic-clonic seizures was a risk factor only in women. The presence of cerebral structural lesions and use of psychotropic drugs at the last visit were not risk factors for SUDEP in this cohort. Subtherapeutic anticonvulsant levels at the last visit were equally common in the two groups. No particular anticonvulsant appeared to be associated with SUDEP. Conclusions: These results support the idea that tonic-clonic seizures are an important proximate cause of SUDEP. This information creates a risk profile for SUDEP that may help direct preventative efforts.

Race-ethnic disparities in the impact of stroke risk factors: the northern Manhattan stroke study.

Background and Purpose— Stroke risk factors have been determined in large part through epidemiological studies in white cohorts; as a result, race-ethnic disparities in stroke incidence and mortality rates remained unexplained. The aim in the present study was to compare the prevalence, OR, and etiological fraction (EF) of stroke risk factors among white, blacks, and Caribbean Hispanics living in the same urban community of northern Manhattan. Methods— In this population-based incident case-control study, cases (n=688) of first ischemic stroke were prospectively matched 1:2 by age, sex, and race-ethnicity with community controls (n=1156). Risk factors were determined through in-person assessment. Conditional logistic regression was used to calculate adjusted ORs in each race-ethnic group. Prevalence and multivariate EFs were determined in each race-ethnic group. Results— Hypertension was an independent risk factor for whites (OR 1.8, EF 25%), blacks (OR 2.0, EF 37%), and Caribbean Hispanics (OR 2.1, EF 32%), but greater prevalence led to elevated EFs among blacks and Caribbean Hispanics. Greater prevalence rates of diabetes increased stroke risk in blacks (OR 1.8, EF 14%) and Caribbean Hispanics (OR 2.1 P <0.05, EF 10%) compared with whites (OR 1.0, EF 0%), whereas atrial fibrillation had a greater prevalence and EF for whites (OR 4.4, EF 20%) compared with blacks (OR 1.7, EF 3%) and Caribbean Hispanics (OR 3.0, EF 2%). Coronary artery disease was most important for whites (OR 1.3, EF 16%), followed by Caribbean Hispanics (OR 1.5, EF 6%) and then blacks (OR 1.1, EF 2%). Prevalence of physical inactivity was greater in Caribbean Hispanics, but an elevated EF was found in all groups. Conclusions— The prevalence, OR, and EF for stroke risk factors vary by race-ethnicity. These differences are crucial to the etiology of stroke, as well as to the design and implementation of stroke prevention programs.

POPULATION – BASED STUDY OF SEIZURE DISORDERS AFTER CEREBRAL INFARCTION

We performed the first population-based study that determined the magnitude of the risk and identified the factors predictive of developing seizure disorders after cerebral infarction. Five hundred thirty-five consecutive persons without prior unprovoked seizures were followed from their first cerebral infarctions until death or migration out of Rochester, Minnesota. Thirty-three patients (6%) developed early seizures (within 1 week), 78% of which occurred within the first 24 hours after infarction. Using multivariate analysis, the only factor predictive of early seizure occurrence was anterior hemisphere location of infarct (odds ratio 4.0, 95% CI 1.2 to 13.7). Twenty-seven patients developed an initial late seizure (past 1 week), whereas 18 developed epilepsy (recurrent late seizures). Compared with the population in the community, the risk during the first year was 23 times higher for initial late seizures and 17 times higher for epilepsy. The cumulative probability of developing initial late seizures was 3.0% by 1 year, 4.7% by 2 years, 7.4% by 5 years, and 8.9% by 10 years. Independent predictive factors on multivariate analysis for initial late seizures were early seizure occurrence (hazard ratio of 7.8 [95% CI 2.8 to 21.7]) and stroke recurrence (3.1 [1.2 to 8.3]). Both early seizure occurrence (16.4 [5.5 to 49.2]) and stroke recurrence (3.5 [1.2 to 10.5]) independently predicted the development of epilepsy as well. We also found that early seizure occurrence predisposed those with initial late seizures to develop epilepsy. NEUROLOGY 1996; 46 350-355

Practice Parameter update: Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): Teratogenesis and perinatal outcomes Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. Methods: Systematic review of relevant articles published between January 1985 and June 2007. Results: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. Recommendations: If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of <7 (Level C).

Epilepsy, vagal nerve stimulation by the NCP system, mortality, and sudden, unexpected, unexplained death.

Summary: Purpose: To determine rates of all‐cause mortality and of sudden, unexpected, unexplained deaths in epilepsy (SUDEP) in a cohort of individuals treated with the Neuro Cybernetic Prosthesis (NCP) System for intractable epilepsy, and; to contrast the NCP experience with other epilepsy cohorts.

The risk of unprovoked seizures after encephalitis and meningitis

A population-based cohort of 714 survivors of encephalitis or meningitis between 1935 and 1981 was followed in order to evaluate the risks of unprovoked seizures after CNS infections. The 20-year risk of developing unprovoked seizures was 6.8%, and the ratio of observed to expected cases of unprovoked seizures was 6.9. The increased incidence of unprovoked seizures was highest during the first 5 years after the CNS infection but remained elevated over the next 15 years of follow-up. The type of CNS infection and the presence or absence of seizures during the acute phase of the CNS infection greatly influenced the risks of subsequent unprovoked seizures. The 20-year risk of developing unprovoked seizures was 22% for patients with viral encephalitis and early seizures, 10% for patients with viral encephalitis without early seizures, 13% for patients with bacterial meningitis and early seizures, and 2.4% for patients with bacterial meningitis without early seizures. The 20-year risk of 2.1% for patients with aseptic meningitis was not increased over the general population incidence of unprovoked seizures.

Dementia and adult-onset unprovoked seizures

OBJECTIVE We tested the hypothesis that dementia increases the risk of unprovoked seizure among adults. Partial- and generalized-onset seizures were considered together and separately. Additionally, we explored whether the increased risk was restricted to Alzheimers disease (AD), as previously shown. DESIGN Subjects in this population-based case-control study were 145 incident cases of first unprovoked seizure (without prior stroke, CNS infection, brain tumor, head trauma, mental retardation, or cerebral palsy) aged 55 years or older and 290 controls matched to cases on age, gender, and duration of medical follow-up. Using the records-linkage system of the Rochester Epidemiology Project, we obtained, for both cases and matched controls, information on dementia prior to onset of unprovoked seizure. Subjects were classified as having dementia if they met ad hoc criteria equivalent to those in the DSM-III. AD was distinguished from other dementias. RESULTS Both a diagnosis of AD and a diagnosis of other dementia were associated with at least a six-fold increased risk of unprovoked seizure when controlling for age, sex, and length of medical follow-up in Rochester. There was no difference in risk when comparing generalized-onset seizures with partial-onset seizures. CONCLUSIONS In the absence of other prior neurologic insult, both AD and other dementias increase the risk of generalized- and partial-onset unprovoked seizures.

Pregnancies of Women with Epilepsy: A Population‐Based Study in Iceland

Summary: Purpose: Women with epilepsy who become pregnant are commonly considered to be at high risk for complications during pregnancy or delivery. The offspring are also considered o have increased risk of perinatal mortality, congenital malformations, and maturational delay. Because few of these studies are population based, potential bias exists because of selection.

Long-term mortality after a first episode of status epilepticus

ObjectiveTo evaluate long-term mortality among people with status epilepticus (SE). MethodsThe authors performed a population-based retrospective cohort study to determine long-term mortality after SE. Between January 1, 1965, and December 31, 1984, all first episodes of SE receiving medical attention were ascertained through the Rochester Epidemiology Project Records-Linkage System. Cases surviving the first 30 days (n = 145) were followed until death or study termination (February 1996). ResultsAt 10 years, cumulative mortality among 30-day survivors was 43%. The standardized mortality ratio (SMR) at 10 years was 2.8 (95% CI, 2.1–3.5). The mortality rate of those with idiopathic/cryptogenic SE was not increased (SMR = 1.1; 95% CI, 0.5–2.3). The following characteristics of SE increased long-term risk for mortality: SE ≥ 24 hours in duration vs SE < 2 hours (relative risk [RR] = 2.3; 95% CI, 1.1–5.1); acute symptomatic etiology vs idiopathic/cryptogenic etiology (RR = 2.2; 95% CI, 1.0–5.1) SE; myoclonic SE vs generalized convulsive SE (RR = 4.0; 95% CI, 1.3–13). ConclusionForty percent of subjects who survived the first 30 days after an incident episode of SE die within the next 10 years. The long-term mortality rate was threefold that of the general population over the same time period. The long-term mortality rate at 10 years was worse for those with myoclonic SE, for those who presented with SE lasting more than 24 hours, and for those with acute symptomatic SE. The long-term mortality rate was not altered in those with idiopathic/cryptogenic SE. We conclude that SE alone does not modify long-term mortality.