Newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden: First report from the Stockholm Incidence Registry of Epilepsy (SIRE)

Purpose:   To describe and report initial findings of a system for prospective identification and follow-up of patients with newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden, the Stockholm Incidence Registry of Epilepsy (SIRE).
Methods:   From September 2001 through August 2004, a surveillance system has been in use to identify incident cases of first unprovoked seizures (neonatal seizures excluded) and epilepsy among residents of Northern Stockholm, an urban area with approximately 998,500 inhabitants. Potential cases are identified through multiple mechanisms: Network of health care professionals, medical record screening in specific hospital units, including outpatient clinics, emergency room services, and review of requests for electroencephalography (EEG) examination. Potential cases are classified 6 months after the index seizure based on review of medical records.
Results:   After screening approximately 10,500 EEG requests and 3,300 medical records, 1,015 persons met the criteria for newly diagnosed unprovoked seizures (430 single seizures; 585 epilepsy). The crude incidence for first unprovoked seizures and epilepsy was 33.9/100,000 person years, (the same adjusted to the European Standard Million), highest the first year of life (77.1/100,000) and in the elderly. No cause could be identified in 62.4%.
Conclusions:   We have established a sustainable system for prospective identification of new onset epilepsy cases in Stockholm. Despite a possible under-ascertainment, the registry provides a useful starting point for follow-up studies.     

How accurate is ICD coding for epilepsy?

Purpose:   Assess the validity of ICD-9-CM and ICD-10 epilepsy coding from an emergency visit (ER) and a hospital discharge abstract database (DAD).
Methods:   Two separate sources of patient records were reviewed and validated. (1) Charts of patients admitted to our seizure monitoring unit over 2 years (n = 127, ICD-10 coded records) were reviewed. Sensitivity (Sn), specificity (Sp), and positive and negative predictive values (PPV and NPV) were calculated. (2) Random sample of charts for patients seen in the ER or admitted to hospital under any services, and whose charts were coded with epilepsy or an epilepsy-like condition, were reviewed. Two time-periods were selected to allow validation of both ICD-9-CM (n = 486) and ICD-10 coded (n = 454) records. Only PPV and NPV were calculated for these records. All charts were reviewed by two physicians to confirm the presence/absence of epilepsy and compare to administrative coding.
Results:   Sample 1: Sn, Sp, PPV, and NPV of ICD-10 epilepsy coding from the seizure monitoring unit (SMU) chart review were 99%, 70%, 85%, and 97% respectively. Sample 2: The PPV and NPV for ICD-9-CM coding from the ER database were, respectively, 99% and 97% and from the DAD were 98% and 99%. The PPV and NPV for ICD-10 coding from the ER database were, respectively, 100% and 90% and from the DAD were 98% and 99%. The epilepsy subtypes grand mal status and partial epilepsy with complex partial seizures both had PPVs >75% (ICD-9-CM and ICD-10 data).
Discussion:   Administrative emergency and hospital discharge data have high epilepsy coding validity overall in our health region.     

Seizure recency and quality of life in adolescents with childhood-onset epilepsy

Health-related quality of life (HRQOL) is associated with seizure recency among adults with epilepsy. In a prospective, community-based study of long-term outcomes of childhood-onset epilepsy, we evaluated whether worse HRQOL is associated with more recent seizures among children and adolescents with epilepsy. We used the Child Health Questionnaire (CHQ), a generic measure with child and parent-proxy versions, to measure HRQOL. Among 277 children with epilepsy (CWE) assessed 9 years after diagnosis, parent-proxy reported but not child self-reported HRQOL was significantly worse for those having seizures in the prior year than for those who were seizure free ≥1 year across the majority of scales. There were no differences between CWE in remission for 1-5 years and those seizure free ≥5 years for child and parent-proxy reported HRQOL with the exception of the parent Emotional Impact scale, suggesting that HRQOL differences related to seizure recency level off after the initial year of remission.     

Early versus late remission in a cohort of patients with newly diagnosed epilepsy

Purpose:  To count patients with newly diagnosed epilepsy entering early and late remission and to identify prognostic predictors of late remission.
Methods:  Children and adults with previously untreated epilepsy from two Italian tertiary centers (Monza, Bari) were the study population. All patients received monotherapy at treatment start; drug choice and schedule were left to the physician's judgment. A retrospective audit was performed and the following prognostic predictors were identified: age, gender, putative etiology, first electroencephalography (EEG) record, neurologic and psychiatric examination, disease duration at diagnosis, seizure type(s) and number prior to starting treatment, epilepsy syndrome, and first antiepileptic drug. Early remission was defined by 2-year seizure control immediately after treatment start. Late remission was defined by 2-year seizure control achieved at least 24 months after treatment start. Prognostic predictors were assessed by logistic regression analysis, adjusting for age, gender, and center.
Results:  One hundred seventy-four women and 178 men (mean age 31.5 years) were included and followed for 2399.6 person-years. The cumulative time-dependent probability of 2-year remission was 56.3% at 2 years after treatment start, and 62.6, 69.4, and 79.5% at 3, 5, and 10 years. One hundred fifteen patients (23.0%) achieved early remission and 38 patients (10.8%) achieved late remission. The interaction between partial seizures and number of seizures prior to treatment was the only independent predictor of late remission.
Discussion:  The course of epilepsy and the chance of remission are together a complex and dynamic process, possibly explained by the diversity of the mechanisms underlying drug response and the use of an increasing number of drugs.     

Efficacy and safety of felbamate in children under 4 years of age: a retrospective chart review

Background and purpose:  To review our experience of the efficacy and tolerability of felbamate in children younger than 4 years.
Methods:  We used a retrospective chart review to identify 53 children with seizures who were younger than 4 years. Efficacy was evaluated based on the occurrence of responsiveness, defined as seizure frequency reduction of more than 50% for a minimum period of 4 months. Tolerability was based on parent-reported side effects.
Results:  Twenty-two (41%) patients resulted to be responders and 31 (59%) did not. By univariate analysis, those achieving seizure remission were probably much older, to have a shorter history of epilepsy and a lower frequency of seizures before felbamate therapy. The number of antiepileptic drugs (AEDs) used before felbamate therapy was the only significant predictor of the duration of response to felbamate, with a longer responsiveness to the drug seen in those who were placed under fewer than three AEDs before felbamate compared with those who had taken more than three (median, 16 months vs. 7 months; P  < 0.0084). Side effects occurred in 30% of the subjects, but these did not require discontinuation of the drug.
Discussion:  Felbamate is an effective medication for a wide range of epilepsy syndromes in children younger than 4 years. Although caution is necessary when the drug is used in children, felbamate might represent a possible option for the treatment of epilepsy in this age group.     

Patients with epilepsy: Cognitively compromised before the start of antiepileptic drug treatment?

Purpose:   To compare the cognitive profile of newly diagnosed untreated epilepsy patients with healthy volunteers using a comprehensive neuropsychological test battery.
Methods:   A total of 155 untreated patients with newly diagnosed epilepsy, and no known brain pathology, were assessed before the start of treatment with antiepileptic medication. Their scores across the neuropsychological measures were compared with 87 healthy volunteers from the general population equated for age and sex.
Results:   After adjusting for age, sex, and education, patients with epilepsy performed significantly worse than healthy volunteers on 6 of 14 cognitive measures, particularly in the domains of memory and psychomotor speed. Cognitive performance was not related to the number of seizures, type of epilepsy, or mood. When an impairment index was calculated, 53.5% patients had a least one abnormal score [>2 standard deviations (SD) below the control mean] on the test battery compared with 20.7% of healthy volunteers.
Discussion:   Newly diagnosed untreated patients with epilepsy are cognitively compromised before the start of antiepileptic drug medication. The domains most affected are memory and psychomotor speed. More than one-half of the patients had at least one abnormal test score across the test battery. There were no differences in epilepsy-related or mood variables between those who demonstrated dysfunction and those that did not.     

Vagus nerve stimulation for refractory epilepsy in children: More to VNS than seizure frequency reduction

Purpose :  Vagus nerve stimulation (VNS) is used increasingly as adjunctive therapy for refractory epilepsy. Studies of VNS in children report mainly seizure frequency reduction as a measure of efficacy and clinical details are often scanty. We report our experience with VNS in children with refractory epilepsy and emphasize the positive effects of VNS in terms of seizure severity.
Methods :  We reviewed 26 consecutive children who had VNS with a minimum follow-up period of 18 months. We examined their clinical characteristics, seizure types, seizure frequency, epilepsy syndrome diagnosis, and response to VNS in terms of seizure frequency and seizure severity.
Results :  Fifty-four percent of patients responded to VNS with ≥50% seizure frequency reduction. Patients with Lennox-Gastaut syndrome (LGS) and tonic seizures had a higher responder rate; 78% (seven of nine patients) (p < 0.01). Status epilepticus (SE) episodes were reduced or ceased in the four patients with recurrent SE. Seizure severity, duration, and recovery time decreased in all responders. Increased alertness was reported in all responders and three nonresponders.
Conclusion :  Decreased seizure severity, recovery time, abolition of daytime drop attacks, and reduced hospitalization due to SE improved patients' lives over and above the benefit from seizure frequency reduction.     

Localized transmeningeal muscimol prevents neocortical seizures in rats and nonhuman primates: Therapeutic implications

Purpose:   To determine whether muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)–induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity.
Methods:   Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys. Via the implants, either a control solution (artificial cerebrospinal fluid, ACSF) or muscimol (0.25–12.5 m m ) was delivered locally as a "pretreatment," followed by the similar delivery of a seizure-inducing concentration of Ach. In five additional rats, the quantities of food-pellets consumed during epidural ACSF and muscimol (2.5 m m ) exposures were measured. In a last group of four rats, muscimol (0.8–2.5 m m ) was delivered epidurally during the ongoing, Ach-induced EEG seizure.
Results:   In contrast to ACSF pretreatments, epidural muscimol pretreatment in rats completely prevented the seizures at and above 2.5 m m . In the monkeys, subarachnoid muscimol pretreatments at 2.5 m m completely prevented the focal-seizure–inducing effect of Ach, whereas similar deliveries of ACSF did not affect the seizures. Furthermore, 2.5 m m epidural muscimol left the eating behavior of rats intact and caused only slight changes in the EEG power spectra. Finally, muscimol delivery during Ach-induced EEG seizures terminated the seizure activity within 1–3 min.
Conclusions:   The results of this study suggest that muscimol is a viable candidate for the transmeningeal pharmacotherapy of intractable focal epilepsy.     

EEG features of absence seizures in idiopathic generalized epilepsy: Impact of syndrome, age, and state

Purpose:   Factors influencing the electroencephalography (EEG) features of absence seizures in newly presenting children with idiopathic generalized epilepsy (IGE) have not been rigorously studied. We examined how specific factors such as state, provocation, age, and epilepsy syndrome affect the EEG features of absence seizures.
Methods:   Children with untreated absence seizures were studied using video-EEG recording. The influence of state of arousal, provocation (hyperventilation, photic stimulation), age, and epilepsy syndrome on specific EEG features was analyzed.
Results:   Five hundred nine seizures were evaluated in 70 children with the following syndromes: childhood absence epilepsy (CAE) 37, CAE+ photoparoxysmal response (PPR) 10, juvenile absence epilepsy (JAE) 8, juvenile myoclonic epilepsy (JME) 6, and unclassified 9. Polyspikes occurred in all syndromes but were more common in JME. They were brought out by drowsiness and sleep in fragments of generalized spike and wave (GSW). Polyspikes were more likely to occur during photic stimulation, but were not influenced by age independently. GSW was more likely to be disorganized in JME than JAE, and in JAE than CAE. Increasing age and levels of arousal were more likely to result in organized GSW. Factors specific to each child independently influenced EEG features; the nature of these factors has not been identified.
Discussion:   The EEG features of absence seizures are influenced by a complex interaction of age, epilepsy syndrome, level of arousal, provoking factors, and other intrinsic factors. Epilepsy syndrome alone cannot predict specific features of GSW; however, JME is more frequently associated with polyspikes and disorganization of the paroxysm.     

Multidrug-resistant genotype (ABCB1) and seizure recurrence in newly treated epilepsy: Data from international pharmacogenetic cohorts

Purpose:   The association between a specific polymorphism ( 3435C > T ) in the ABCB1 gene, coding for the membrane drug transporter P-glycoprotein (PgP), and pharmacoresistance to seizure control is controversial. Studies have been limited by multiple drug use, chronic cohorts with varying definitions, and retrospective clinical data. Herein we examine the relationship of this polymorphism with seizure recurrence in three independent international cohorts of patients newly treated for epilepsy.
Methods:   Data were collected on demographics, medication details, and seizure control after 12 months of treatment. The distribution of ABCB1 3435C>T genotypes was compared between patients with and without recurrent unprovoked seizures.
Results:   Five hundred forty-two newly treated patients were enrolled (212 from Australia, 285 from Scotland, and 45 from Hong Kong). A total of 38.4% had recurrent unprovoked seizures after starting antiepileptic drug (AED) treatment. Genotype frequencies and ethnicity did not differ between the Scottish and Australian cohorts, but both were significantly different in the Hong Kong cohort. There was no significant relationship between the ABCB1 3435C > T genotype and the rate of recurrence of unprovoked seizures in the three cohorts individually or combined; however the epilepsy syndrome and a greater number of seizures pretreatment was associated with an increased risk of seizure recurrence.
Conclusions:   The ABCB1 3435C > T genotype does not have a major role in determining the efficacy of seizure control with initial AED therapy. The study highlights issues that arise in combining pharmacogenetic datasets from different ethnic regions and health systems, an approach that is essential to advance this field.     

Labor market participation following onset of seizures and early epilepsy: Findings from a UK cohort

Purpose:   Previous studies have reported a considerable employment disadvantage among people with epilepsy. In a cohort of men and women who had experienced a single seizure or had early epilepsy at study entry we explored employment status and social mobility over 4 years and investigated whether employment outcomes were more disadvantageous for certain social groups.
Methods:   Analyses were based on 350 individuals of working age identified via the UK Multicentre Study of Early Epilepsy and Single Seizures. Employment rates were calculated for the cohort and general population. Employment trajectories over 4 years were explored according to occupational social class. The relative risk of employment was calculated by clinical features of seizures and social class.
Results:   Individuals with single seizures or early epilepsy had significantly lower employment rates than the general population at study entry, and 2- and 4-year follow-up. Employment rates of men and women in the cohort did not differ significantly. Although little social class mobility occurred during follow-up, there was evidence of some downward mobility between first seizure(s) and study entry. In the fully adjusted model, nonemployment was predicted at all time points by having fair/poor self-rated health and experiencing four or more seizures. We observed that some individuals continued to work in hazardous occupations or drive professionally within a year of experiencing seizure(s).
Discussion:   People who have recently experienced a single seizure or who have early epilepsy are exposed to substantial employment disadvantage. Greater efforts are necessary to help these people return to work and stay employed.     

Quality of life in pediatric epilepsy: demographic and disease-related predictors and comparison with healthy controls

The purpose of the present study was to compare the health-related quality of life (HRQOL) of children with epilepsy with that of healthy controls and to examine predictors of HRQOL, including current treatment, seizure severity, and comorbid neurological impairments. The epilepsy group consisted of 41 children, aged 4-19 years. The control group consisted of 41 age-matched healthy children seen for well child care in a community pediatric practice. Results demonstrated that the HRQOL of the epilepsy group was significantly more limited than that of the control group. For children with epilepsy, comorbid neurological impairments and number of antiepileptic medications were associated with diminished HRQOL. Duration of illness, age of onset, seizure severity, and treatment type were not predictive of diminished HRQOL. The present findings suggest that presence of comorbid neurological impairments and number of medications are the best predictors of reduced HRQOL in children with epilepsy and may present a subgroup of patients with additional treatment needs.     

Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in Chinese patients with refractory partial-onset seizures

Purpose:   To evaluate efficacy and tolerability of levetiracetam (LEV; Keppra^®) as add-on therapy in Chinese patients with refractory partial-onset seizures.
Methods:   In this multicenter, double-blind, randomized, placebo-controlled trial, 206 patients aged 16–70 years with uncontrolled partial-onset seizures were randomized to receive LEV (n =103) or placebo (n =103); 202 patients (LEV, n =102; placebo, n = 100) comprised the intent-to-treat population. An 8-week historical baseline period confirmed eligibility according to seizure count. The 16-week treatment period consisted of a 4-week up-titration period (LEV, 1,000–3,000 mg/day in two equal divided doses) followed by a 12-week maintenance period. Efficacy assessments were based on weekly frequency of partial-onset seizures during the 16-week treatment period.
Results:   LEV significantly decreased weekly partial-onset seizure frequency over placebo by 26.8% (p  < 0.001). Median percentage reductions in weekly partial-onset seizure frequency from historical baseline were 55.9% for LEV and 13.7% for placebo (p  < 0.001). The ≥50% responder rates were 55.9% for LEV, compared with 26.0% for placebo (p  < 0.001). Freedom from partial-onset seizures during treatment period was achieved by 11 LEV patients (10.8%) and 2 placebo patients (2.0%) (p = 0.012). Adverse events were reported by 65 LEV-treated patients (63.1%) and 62 placebo-treated patients (60.2%); most were of mild-to-moderate intensity. The most common adverse events were somnolence (LEV, 17.5%; placebo, 17.5%), decreased platelet count (LEV, 9.7%; placebo, 9.7%), and dizziness (LEV, 7.8%; placebo, 13.6%).
Discussion:   Add-on LEV was effective and well-tolerated in Chinese patients with refractory partial-onset seizures.     

Language in pediatric epilepsy

Purpose:   This study examined the severity and range of linguistic impairments in young, intermediate, and adolescent youth with epilepsy and how these deficits were associated with illness effects, nonverbal intelligence, psychopathology, and reading.
Methods:   Tests of language, intelligence, achievement, and structured psychiatric interviews were administered to 182 epilepsy youth, aged 6.3–8.1, 9.1–11.7, and 13.0–15.2 years, as well as to 102 age- and gender-matched normal children. Parents provided demographic, seizure-related, and behavioral information on their children.
Results:   Significantly more epilepsy subjects had language scores 1 standard deviation (SD) below average than the age-matched control groups did. The intermediate and adolescent epilepsy groups also had significantly lower mean language scores compared to their matched controls. The older compared to the younger epilepsy groups had more language impairment and a wider range of linguistic deficits. Longer duration of illness, childhood absence epilepsy, psychiatric diagnosis, and socioeconomic status were associated with linguistic deficits in the young group. Prolonged seizures, lower Performance IQ, and minority status predicted low language scores in the intermediate epilepsy group. In the adolescent group, language impairment was associated with poor seizure control, decreased Performance IQ, and lower socioeconomic status. Linguistic and reading deficits were significantly related in each epilepsy group.
Conclusions:   The age-related increase in linguistic impairment, different profiles of predictors in each age group, and the relationship of linguistic deficits with poor reading skills have important clinical, developmental, theoretical, and academic implications.     

The Prevalence and Incidence of Convulsive Disorders in Children

Summary: Each year, about 150,000 children and adolescents in the United States will come to medical attention for evaluation of a newly occurring seizure disorder of some type. Between 2% and 4% of all children in Europe and the United States experience at least one convulsion associated with a febrile illness before the age of 5 years. The cumulative incidence of febrile convulsions among children ranges from about 1% in China to more than 8% in Japan and 14% in Guam. The peak incidence of a first febrile convulsion occurs in the second year of life. Between 0.5% and 1% of children and adolescents experience a seizure associated with other acute metabolic or neurologic insults; most of these occur in the neonatal period. The incidence of epilepsy (recurrent unprovoked seizures) in children and adolescents seems relatively consistent across all populations studied, ranging from 50 to 100/100,000. The highest incidence of epilepsy is in the first year of life. West syndrome accounts for about 2% of all childhood epilepsy, Lennox-Gastaut syndrome for 1–2%, childhood absence epilepsy (pyknolepsy) for 10–15%, juvenile myoclonic epilepsy for 5%, and idiopathic localization-related epilepsy for 10%. Between 0.5 and 1% of children experience a nonrecurrent, single, unprovoked convulsive episode. Following are the estimated numbers of children and adolescents with newly diagnosed convulsive disorders in the United States for the year 1990: febrile seizures, 100,000; neonatal seizures, 4,000; other provoked seizures, 6,000; single unprovoked seizures, 10,000; and epilepsy, 30,000.     

Stigma, seizure frequency and quality of life: the impact of epilepsy in late adulthood.

Epilepsy is one of the most common neurological disorders of late adulthood, yet little research has examined the impact of epilepsy on the quality of life of older people. Current measures of health-related quality of life (HRQOL) have been developed and used almost exclusively in adults under the age of 65. The issues, which affect HRQOL in younger adults, may differ from those which affect older adults who may have age-related physical limitations and multiple co-morbidities. This study sought to explore the HRQOL and psychosocial function of a community dwelling sample of 64 older adults with epilepsy compared with a similar, age-matched control group. An additional objective of the study was to examine the impact of perceived stigma and seizure frequency on HRQOL and psychosocial well-being. Results indicated that HRQOL and psychosocial functioning in the epilepsy group was significantly impaired relative to normal controls. A greater perception of stigma and more frequent seizures was also strongly related to poor quality of life and reduced psychosocial function. Although more than two thirds of the sample had seizure frequency of less than one per year, it was apparent that even infrequent seizures had the facility to impair HRQOL, suggesting that in older adults, the apprehension induced by even the possibility of a seizure may be sufficient to reduce HRQOL. The results have implications for the clinical management of epilepsy and suggest the need for further research in older populations.     

Seizure-related injuries in children with newly diagnosed and untreated epilepsy

PURPOSE: Patients with epilepsy are reported to have an increased risk of physical injury. One of clinicians' concerns for diagnosing epilepsy early is to try to prevent such injuries and also to allay parental anxiety that seizures may cause injuries. The purpose of this study was to investigate injuries in children with newly diagnosed epilepsy and before starting antiepileptic medication. METHODS: A prospective study was undertaken of all newly diagnosed and untreated patients with at least two unprovoked, afebrile seizures of any type, aged 1-16 years, presenting consecutively to seven paediatric/paediatric neurology outpatient departments over a 12-month period. Information was collected on the duration of epilepsy before diagnosis, the epilepsy syndrome, the seizure type causing the injury, how and the age at which the injury was sustained, and whether hospital treatment was required for the injury. RESULTS: One hundred ninety-eight patients (116 boys) were surveyed. No patient died as a result of an injury. Twenty-five (12.6%) children experienced an injury before the diagnosis of epilepsy was established. Only four of the 25 patients (2% of all 198 patients) required medical attention for the injury. The injuries occurred at a mean age of 10.3 years (range, 4-15.1 years), and epilepsy was diagnosed at a mean age of 11.1 (range, 4.2-15.8) years. Fifteen patients were injured at home, six at school, and four outside the home. The seizures causing the injuries were tonic-clonic (17), complex partial (four), myoclonic (one), and of uncertain type (three). None of the 32 patients with childhood-onset typical absence epilepsy had accidental injuries. CONCLUSIONS: Injuries caused by epileptic seizures were uncommon in this newly diagnosed and untreated, consecutive paediatric outpatient series. These unique data could help to reassure clinicians that the diagnosis of epilepsy should not be influenced by any concern that accidental injuries caused by seizures are common in children before starting medication.     

High seizure frequency prior to antiepileptic treatment is a predictor of pharmacoresistant epilepsy in a rat model of temporal lobe epilepsy

Purpose:   Progress in the management of patients with medically intractable epilepsy is impeded because we do not fully understand why pharmacoresistance happens and how it can be predicted. The presence of multiple seizures prior to medical treatment has been suggested as a potential predictor of poor outcome. In the present study, we used an animal model of temporal lobe epilepsy to investigate whether pharmacoresistant rats differ in seizure frequency from pharmacoresponsive animals.
Methods:   Epilepsy with spontaneous recurrent seizures (SRS) was induced by status epilepticus. Frequency of SRS was determined by video/EEG (electroencephalography) monitoring in a total of 33 epileptic rats before onset of treatment with phenobarbital (PB).
Results:   Thirteen (39%) rats did not respond to treatment with PB. Before treatment with PB, average seizure frequency in PB nonresponders was significantly higher than seizure frequency in responders, which, however, was due to six nonresponders that exhibited > 3 seizures per day. Such high seizure frequency was not observed in responders, demonstrating that high seizure frequency predicts pharmacoresistance in this model, but does not occur in all nonresponders.
Discussion:   The data from this study are in line with clinical experience that the frequency of seizures in the early phase of epilepsy is a dominant risk factor that predicts refractoriness. However, resistance to treatment also occurred in rats that did not differ in seizure frequency from responders, indicating that disease severity alone is not sufficient to explain antiepileptic drug (AED) resistance. These data provide further evidence that epilepsy models are useful in the search for predictors and mechanisms of pharmacoresistance.     

Which patients become seizure free with antiepileptic drugs? An observational study in 821 patients with epilepsy

Objectives –  Analysis of factors influencing seizure outcome in antiepileptic drug treatment of epilepsy.
Patients and methods –  Retrospective analysis of 500 patients with complete seizure control and 321 patients with refractory epilepsy (mean ages 33.3 and 32.1 years respectively).
Results –  The seizure-free group consisted of 377 patients with symptomatic/cryptogenic epilepsy (SCE; mean seizure control 45 months) and 123 patients with idiopathic generalized epilepsy (IGE; mean seizure control 61 months) ( P  = 0.02). Of the patients with SCE, 35.7% had achieved seizure control with monotherapy (MT), 29.6% with ≥2 AEDs. No single AED was superior in MT. Of the patients with IGE, 35.9% had become seizure free with MT, 15.6% on combination therapy (CT). Valproate MT was more commonly associated with seizure freedom than lamotrigine ( P  < 0.05).
Conclusions –  The results indicate that, in SCE, seizures can be controlled with carefully selected CT more commonly than suggested by previous studies. The seizure prognosis of patients with IGE presenting to a specialist in epilepsy may be worse than previously thought.     

Prevalence of epilepsy and seizures in the Navajo Nation 1998–2002

Purpose:  To determine the prevalence of epilepsy and seizures in the Navajo.
Methods:  We studied 226,496 Navajo residing in the Navajo Reservation who had at least one medical encounter between October 1, 1998 and September 30, 2002. We ascertained and confirmed cases in two phases. First, we identified patients with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes signifying epilepsy or seizures using Indian Health Service (IHS) administrative data. Second, we reviewed medical charts of a geographic subpopulation of identified patients to confirm diagnoses and assess the positive predictive value of the ICD-9-CM codes in identifying patients with active epilepsy.
Results:  Two percent of Navajo receiving IHS care were found to have an ICD-9-CM code consistent with epilepsy or seizures. Based on confirmed cases, the crude prevalence for the occurrence of any seizure (including febrile seizures and recurrent seizures that may have been provoked) in the geographic subpopulation was 13.5 per 1,000 and the crude prevalence of active epilepsy was 9.2 per 1,000. Prevalence was higher among males, children under 5 years of age, and older adults.
Discussion:  The estimated prevalence of active epilepsy in the Navajo Nation is above the upper limit of the range of reported estimates from other comparable studies of U.S. communities.