A multistate joint model for interval-censored event-history data subject to within-unit clustering and informative missingness, with application to neurocysticercosis research.

We propose a multistate joint model to analyze interval-censored event-history data subject to within-unit clustering and nonignorable missing data. The model is motivated by a study of the neurocysticercosis (NC) cyst evolution at the cyst-level, taking into account the multiple cysts phases with intermittent missing data and loss to follow-up, as well as the intra-brain clustering of observations made on a predefined data collection schedule. Of particular interest in this study is the description of the process leading to cyst resolution, and whether this process varies by antiparasitic treatment. The model uses shared random effects to account for within-brain correlation and to explain the hidden heterogeneity governing the missing data mechanism. We developed a likelihood-based method using a Monte Carlo EM algorithm for the inference. The practical utility of the methods is illustrated using data from a randomized controlled trial on the effect of antiparasitic treatment with albendazole on NC cysts among patients from six hospitals in Ecuador. Simulation results demonstrate that the proposed methods perform well in the finite sample and misspecified models that ignore the data complexities could lead to substantial biases.

Folic acid use by women with epilepsy: Findings of the Epilepsy Birth Control Registry.

PURPOSE: To determine the prevalence and predictors of folic acid (FA) use by women with epilepsy (WWE) at risk of unintended pregnancy. METHODS: These retrospective data come from the Epilepsy Birth Control Registry (EBCR) web-based survey of 1144 WWE in the community, 18-47years, who provided demographic, epilepsy, AED, contraception, pregnancy, healthcare visits and FA data. We report prevalence and predictors of FA use in relation to risk of pregnancy (not at risk, at risk, seeking pregnancy, pregnant), demographics, seizure types and AED and contraception categories. RESULTS: 368 (47.6%) of the 773 WWE at risk of unintended pregnancy in the EBCR took FA supplement. Being at risk was a significant predictor in comparison to WWE not at risk (OR=1.464 [1.103-1.944], p=0.008). In comparison to WWE at risk, FA use trended greater for WWE actively seeking pregnancy (29/47, 61.7% v 368/773, 47.6%; p=0.0605) and was greater for pregnant WWE (17/19, 89.5% v 368/773, 47.6%; p=0.0007). Demographic predictors for WWE at risk were race (p=0.003), education (p=0.012) and income (0.043) with significantly greater FA use by Caucasians than minorities and direct correlations between FA use and levels of education and household income. Seizure type, AED use, category and dosage, polytherapy and contraceptive category were not predictors. A healthcare provider visit during the year prior to the survey was not a predictor. Prevalence of FA use was similar following visits with gynecologists - 51.7%, neurologists - 48.7% and primary care - 48.6%. FA supplementation by prescription was greater for WWE at risk on AED versus no AED (190/355, 53.5% v 3/13, 23.1%; p=0.045). CONCLUSION: Low prevalence of preconception FA use may reflect a need for more education. In addition, further research is needed to provide definitive evidence that FA reduces congenital malformations in the offspring of WWE.

Remission and relapse in a drug-resistant epilepsy population followed prospectively.

PURPOSE: We investigated the cumulative probability of seizure remission and relapse in an adult population with drug-resistant epilepsy and frequent seizures. In addition, we determined clinical predictors of remission and relapse in this population. METHODS: IN 2003, we identified 246 patients at a single center with drug-resistant epilepsy defined as at least one seizure per month and failure of at least two antiepileptic drugs. These patients were followed prospectively (cohort design). We examined the cumulative probability of seizure remission and relapse in this population using Kaplan-Meier methodology. Clinical predictors of remission and relapse were also evaluated using Cox regression analysis. KEY FINDINGS: The estimated cumulative probability of 12-month seizure remission was 34.6% at 7 years in the entire population and 33.4% when limited to those without surgery. The risk for relapse after a 12-month period of seizure remission was 71.2% at 5 years. Negative predictors of seizure remission included developmental delay, symptomatic generalized epilepsy syndrome, duration of intractability, and number of antiepileptic drugs failed. Localization-related epilepsy was the only negative predictor of relapse. SIGNIFICANCE: Among patients with drug-resistant epilepsy, 5% per year enter seizure remission even with a follow-up of 6 years. However, a substantial proportion of these patients relapse after the first year following a remission. The large proportion of patients entering a significant remission gives these patients hope; however, caution should be advised when discussing the likelihood of future seizures.

Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.

To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.

Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): I. Obstetrical complications and change in seizure frequency: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. The committee evaluated the available evidence according to a structured literature review and classification of relevant articles. For WWE who are taking antiepileptic drugs (AEDs), there is probably no substantially increased risk (>2 times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (>1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. WWE should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84-92%) of remaining seizure-free during pregnancy. WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery.

Early Recurrence of First Unprovoked Seizures in Children.

OBJECTIVES: The risk of early seizure recurrences after first unprovoked seizures in children is largely unknown. We aimed to determine the rate of seizure recurrence within 14 days of first unprovoked seizures in children and identify associated risk factors. Secondarily, we aimed to determine the risk of recurrence at 48 hours and 4 months. METHODS: We conducted a secondary analysis of a multicenter cohort study of children 29 days to 18 years with first unprovoked seizures. Emergency department (ED) clinicians completed standardized histories and physical examinations. The primary outcome, recurrent seizure at 14 days, and the secondary outcomes, recurrence at 48 hours and 4 months, were assessed by telephone follow-up and medical record review. For each recurrence time point, we excluded those patients for whom no seizure had recurred but chronic antiepileptic drugs had been initiated. RESULTS: A total of 475 patients were enrolled in the parent study. Of evaluable patients for this secondary analysis, 26 of 392 (6.6%, 95% confidence interval [CI] = 4.4%-9.6%) had recurrences within 48 hours of the incident seizures, 58 of 366 (15.8%, 95% CI = 12.3%-20.0%) had recurrences within 14 days, and 107 of 340 (31.5%, 95% CI = 26.6%-36.7%) had recurrences within 4 months. On logistic regression analysis, age younger than 3 years was independently associated with a higher risk of 14-day recurrence (adjusted odds ratio [OR] = 2.1, 95% CI = 1.2-3.7; p = 0.01). Having had more than one seizure within the 24 hours prior to ED presentation was independently associated with a higher risk of seizure recurrence at 48 hours (adjusted OR = 4.3, 95% CI = 1.9-9.8; p < 0.001). CONCLUSIONS: Risk of seizure recurrence 14 days after first unprovoked seizures in children is substantial, with younger children at higher risk. Prompt completion of an electroencephalogram and evaluation by a neurologist is appropriate for these children.

An estimate of the prevalence of psychogenic non-epileptic seizures.

The prevalence of psychogenic non-epileptic seizures is difficult to estimate. We propose an estimate based on a calculation. We used the following data, which are known or have been estimated, and are generally accepted. A prevalence of epilepsy of 0.5-1%; a proportion of intractable epilepsy of 20-30%; a percentage of these referred to epilepsy centers of 20-50%; and a percentage of patients referred to epilepsy centers that are psychogenic non-epileptic seizures: 10-20%. Using the low estimates, the prevalence of psychogenic non-epileptic seizures would be 1/50 000. Using the high estimates, the prevalence of psychogenic non-epileptic seizures would be 1/3000. The prevalence of psychogenic non-epileptic seizures is somewhere between 1/50 000 and 1/3000, or 2 to 33 per 100 000, making it a significant neurologic condition.

The association of living conditions and lifestyle factors with burden of cysts among neurocysticercosis patients in Ecuador.

We used baseline data on 154 symptomatic neurocysticercosis (NCC) patients in Ecuador to identify predictors of the burden of cysts. We ran logistic regression models with the burden of cysts as the outcome, defined as the number of cysts in the brain (1 vs >1), and having cysts in all 3 phases of evolution (active, transitional and calcifications) vs <3. These two outcomes are thought to be indicators of exposure dose and/or repeated exposure over time. The predictors examined were: living in a rural area, living on a dirt road, living in an adobe or wood house (vs brick/cement), no running water in the house, no bathroom in the house, having a domestic employee cook in the home, eating most meals at restaurants or street vendors, working in a manual labour job. We found that the odds of having multiple NCC cysts was higher among those working in manual labour (OR=3.5, p=0.004), and those who ate most meals outside the home had higher odds of having cysts in all 3 phases (OR=5.0, p=0.007). Burden of cysts may be a useful outcome when looking to identify exposure risk factors in the absence of an uninfected control group.

The descriptive epidemiology of epilepsy-a review.

Epilepsy is a chronic disease experienced by millions and a cause of substantial morbidity and mortality. This review summarizes prevalence and incidence studies of epilepsy that provided a clear definition of epilepsy and could be age-adjusted: requirements if comparisons across studies are to be made. Although few exceptions, age-adjusted prevalence estimates from record-based studies (2.7-17.6 per 1000), are lower than those from door-to-door surveys (2.2-41.0 per 1000). Age-adjusted incidence ranged from 16 to 51 per 100,000, with one exception in Chile, where incidence was 111 per 100,000. Variation in reported prevalence and incidence may be related to factors such as access to health care, regional environmental exposures, or socioeconomic status. A higher proportion of epilepsy characterized by generalized seizures was reported in most prevalence studies. Epilepsy characterized by partial seizures accounted for 20-66% of incident epilepsies. Virtually all prevalence and incidence studies report a preponderance of seizures of unknown cause. Additional prevalence studies are needed in regions where data does not exist, and additional incidence studies in all regions. Interpretation of differences in prevalence and incidence will require understanding of the role of cultural, social and economic factors influencing epilepsy and its care.

Are MRI-detected brain abnormalities associated with febrile seizure type?

OBJECTIVE: Whether magnetic resonance imaging (MRI) is informative in febrile seizures (FS) is unknown. We undertook a study to determine the frequency of MRI-detected brain abnormalities and to evaluate their association with FS type and with specific features of complex FS. METHODS: A prospective cohort study, from 1999 to 2004, included children with first FS from one Pediatric Emergency Department. MRI of the brain was performed within 1 week of the seizure. FS type was categorized by experts blind to the prior clinical history and MRI results. MRI examinations were read blind to the child's clinical history and FS type, and interviewers were blind to MRI results. RESULTS: In 159 children with a first FS, imaging abnormalities occurred in 12.6% (N = 20). Eight of the 54 with complex FS had imaging abnormalities compared to 12 of the 105 with simple FS (n.s.). Compared to children with simple FS, children with both focal and prolonged FS (N = 14) were more likely to have imaging abnormality (OR = 4.3, 95% CI = 1.2-15.0), even after adjustment for abnormal neurological examination. Imaging abnormalities included those known to be associated with seizures (e.g., focal cortical dysplasia) and those not typically associated with seizures (e.g., subcortical focal hyperintensities > or = 5 mm). DISCUSSION: Our data suggest that brain abnormalities may lower seizure threshold in febrile children, predisposing to the development of FS. Clinical management was unaffected and therefore these data do not alter the recommendation that MRI is unnecessary in children with FS, without some other neurological indication.