John F. Annegers

Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935-1984.

Summary: The incidence of epilepsy and of all unprovoked seizures was determined for residents of Rochester, Minnesota U.S.A. from 1935 through 1984. Ageadjusted incidence of epilepsy was 44 per 100,000 personyears. Incidence in males was significantly higher than in females and was high in the first year of life but highest in persons aged ≥75years. Sixty percent of new cases had epilepsy manifested by partial seizures, and two thirds had no clearly identified antecedent. Cerebrovascular disease was the most commonly identified antecedent, accounting for 11% of cases. Neurologic deficits from birth, mental retardation and/or cerebral palsy, observed in 8% of cases, was the next most frequently identified preexisting condition. The cumulative incidence of epilepsy through age 74 years was 3.1%. The age‐adjusted incidence of all unprovoked seizures was 61 per 100,000 person‐years. Age‐and gender‐specific incidence trends were similar to those of epilepsy, but a higher proportion of cases was of unknown etiology and was characterized by generalized onset seizures. The cumulative incidence of all unprovoked seizures was 4.1% through age 74 years. With time, the incidence of epilepsy and of unprovoked seizures decreased in children and increased in the elderly.

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.

Prevalence of Epilepsy in Rochester, Minnesota: 1940–1980

Summary: : The prevalence of epilepsy in Rochester, Minnesota has been determined for a specific date in each of 5 decennial census years. Individuals with a diagnosis of epilepsy (recurrent unprovoked seizures) who were known to have experienced a seizure or who had received antiepileptic medication in the preceding 5 years were considered active prevalence cases. By this definition, the age‐adjusted prevalence per 1,000 population, increased steadily from 2.7 in 1940 to 6.8 in 1980. At each of five prevalence dates, for all prevalence cases, 60% had epilepsy manifest by partial seizures, and 75% had no known etiology. Prevalence was higher for males than females for all except the last prevalence day. After 1950, prevalence tended to increase with advancing age and was highest in the oldest age groups. On the average, the 1980 prevalence cases had epilepsy <10 years and >50% had their first diagnosis in the first 20 years of life.

Factors prognostic of unprovoked seizures after febrile convulsions.

We evaluated the risk of unprovoked seizures after febrile convulsions and the factors prognostic of them in a cohort of 687 children who had an initial febrile seizure while residing in Rochester, Minnesota. Overall, children with febrile convulsions had a fivefold excess of unprovoked seizures, and the risk until the age of 25 was 7 percent. The risk ranged from 2.4 percent among children with simple febrile convulsions to 6 to 8 percent among children with a single complex feature--i.e., focal or prolonged seizures or repeated episodes of febrile convulsions with the same illness. For children with any two of the complex features, the risk was 17 to 22 percent, and for those with all three features, 49 percent. The occurrence of subsequent partial unprovoked seizures was strongly associated with all three of the complex features, whereas the occurrence of subsequent unprovoked seizures of generalized onset was associated with the number of febrile convulsions and a family history of unprovoked seizures. These results are consistent with the view that the increased risk of generalized-onset unprovoked seizures reflects a predisposition to both simple febrile convulsions and generalized-onset unprovoked seizures. The association between complex febrile convulsions and partial seizures, on the other hand, may reflect either a causal association or the presence of preexisting brain disease that is responsible for both the complex febrile seizures and later partial seizures.

The cost of epilepsy in the United States: an estimate from population-based clinical and survey data.

Summary: Purpose: To provide 1995 estimates of the lifetime and annual cost of epilepsy in the United States using data from patients with epilepsy, and adjusting for the effects of comorbidities and socioeconomic conditions.

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.

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

Seizure recurrence after a 1st unprovoked seizure An extended follow‐up

We followed 208 patients identified on the day of their 1st unprovoked seizure for a mean duration of 4 years. Seizures recurred in 64. Recurrence risks were estimated to be 14%, 29%, and 34% at 1, 3, and 5 years following the 1st episode. A history of previous neurologic insult (remote symptomatic) was associated with a 2.5-fold increased risk of recurrence. Among idiopathic cases, a sibling with epilepsy, a generalized spike and wave EEG, or a history of acute symptomatic seizure increased risk for recurrence. Among remote symptomatic cases, status epilepticus, a prior acute symptomatic seizure, or Todds paresis increased risk. Depending upon clinical features, recurrence risk at 5 years following a 1st seizure ranged from 23% to 80%. Treatment with anticonvulsant medication was not associated with a decrease in recurrence risks.

Sudden Unexplained Death in Epilepsy: Observations from a Large Clinical Development Program

Summary: Purpose: The present study was conducted to determine the rate of sudden unexplained death in epilepsy (SUDEP) in a well‐defined cohort of patients included in the lamotrigine (LTG) clinical development database.

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.