Utility of EEG Activation Procedures in Epilepsy: A Population-Based Study.

PURPOSE: No previous population-based study has addressed the contribution of activation procedures to the yield of epileptiform abnormalities on serial EEGs. We assessed yield of activation-related epileptiform abnormalities and predictors of finding an activation-related abnormality with multiple EEGs in a population-based study of newly diagnosed epilepsy. METHODS: We used the resources of the Rochester Epidemiology Project to identify 449 residents of Rochester, Minnesota with a diagnosis of newly diagnosed epilepsy at age 1 year or older, between 1960 and 1994, who had at least one EEG. Information on all activation procedures (i.e., sleep, hyperventilation, and photic activation) and seizure/epilepsy characteristics was obtained by comprehensive review of medical records. RESULTS: At the first EEG, the yield of epileptiform abnormalities was greatest for individuals 1 to 19 years of age at diagnosis, for each activation procedure. The yield in patients aged 1 to 19 versus ≥20 years was 21.6% versus 10.3% for sleep, 6.5% versus 3.3% for photic stimulation, and 10.3% versus 5% for hyperventilation. Among young people (aged 1-19 years), sleep was associated with an increased likelihood of finding an activation-related abnormality on any EEG. The likelihood of finding an activation-related abnormality on any EEG was decreased for postnatal symptomatic and for unknown etiology. CONCLUSIONS: Among activation procedures, sleep showed the highest yield of epileptiform abnormalities. There was a low yield for photic stimulation and hyperventilation. Within each activation procedure, younger age at diagnosis had the greatest yield. Sleep is the most effective activation procedure, especially in younger patients, and should be performed when possible.

Comparative safety of antiepileptic drugs during pregnancy.

OBJECTIVE: To assess the safety of the newer antiepileptic drugs (AEDs) during pregnancy. METHODS: The study population was pregnant women who enrolled in the North American AED Pregnancy Registry between 1997 and 2011. Data on AED use and maternal characteristics were collected through phone interviews at enrollment, at 7 months' gestation, and postpartum. Malformations were confirmed by medical records. The risk of major malformations was calculated among infants exposed to specific AEDs in monotherapy during the first trimester of pregnancy and among an unexposed group. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated with logistic regression. RESULTS: The risk of major malformations was 9.3% (30 of 323) for valproate, 5.5% (11 of 199) for phenobarbital, 4.2% (15 of 359) for topiramate, 3.0% (31 of 1.033) for carbamazepine, 2.9% (12 of 416) for phenytoin, 2.4% (11 of 450) for levetiracetam, and 2.0% (31 of 1,562) for lamotrigine. Compared with lamotrigine, the RR was 5.1 (95% CI 3.0-8.5) for valproate, 2.9 (1.4-5.8) for phenobarbital, and 2.2 (1.2-4.0) for topiramate. The proportion of women with epilepsy who had seizures during pregnancy ranged from 23% for valproate to 31% for lamotrigine. Valproate was associated with a higher risk of neural tube defects, hypospadias, cardiac defects, and oral clefts and phenobarbital with a higher risk of cardiac defects and oral clefts; 5 infants exposed to topiramate (1.4%) had a cleft lip. CONCLUSIONS: AEDs such as valproate and phenobarbital were associated with a higher risk of major malformations than newer AEDs such as lamotrigine and levetiracetam. Topiramate was associated with an increased risk of cleft lip compared with that of a reference population.

Accuracy of family history information on epilepsy and other seizure disorders.

BACKGROUND: In epilepsy as in other disorders, family history information is often obtained by asking patients about the medical histories of their relatives rather than interviewing or examining the relatives directly. The accuracy of this type of information for epilepsy and other seizure disorders is unclear. METHODS: This study used data from the Genetic Epidemiology of Seizure Disorders in Rochester study, a population-based investigation including all Rochester, MN, residents born ≥1920 with incidence of unprovoked seizures from 1935 to 1994 (case probands) and control probands matched by age, gender, and prior Rochester residency period. Seizure disorders in the first-degree relatives of case and control probands were ascertained by reviewing the relatives' medical records. Case and control probands were interviewed about seizures in their first-degree relatives using a validated 9-question screening interview. Interviewers were blinded to case-control status. RESULTS: Sensitivity of the family history (i.e., proportion of relatives with medical record-documented seizures who screened positive in the proband interview) was 62% (32/52) for epilepsy, 50% (7/14) for isolated unprovoked seizures, and 56% (9/16) for febrile seizures. Sensitivity did not differ by case/control status of the proband. Sensitivity was much higher for probands reporting on their offspring or siblings than their parents. Among relatives with epilepsy, 90% of offspring and 80% of siblings but only 32% of parents screened positive. CONCLUSIONS: Family histories of epilepsy are reasonably accurate for siblings and offspring, but are underreported in parents. Family histories of other seizure disorders are underreported.

Estimating risk for developing epilepsy: a population-based study in Rochester, Minnesota.

OBJECTIVES: Previous studies that have assessed the risk of developing epilepsy have failed to account for the competing risk of death, significant in the elderly where epilepsy incidence is highest. We report the lifetime risk for epilepsy, accounting for the competing risk of mortality. METHODS: Lifetime risk and cumulative incidence of epilepsy were examined among Rochester, MN, residents between 1960 and 1979. Age-, gender-, and calendar year-specific deaths were obtained for Rochester, MN. Lifetime risk was calculated as the conditional probability of developing epilepsy by a specific age for a person reaching that age who had not yet developed epilepsy. Lifetime risk and cumulative incidence were compared for age and time period. RESULTS: We identified 412 individuals with incident epilepsy diagnosed between January 1, 1960, and December 31, 1979. Lifetime risk was 1.6% to age 50 and 3.0% to age 80; cumulative incidence was 1.7% to age 50 and 3.4% to age 80. Similar differences were seen across epilepsy etiologies. Lifetime risk through 87 years of age increased over time from 3.5% in 1960-1969 to 4.2% in 1970-1979. CONCLUSIONS: One in 26 people will develop epilepsy during their lifetime. Lifetime risk provides an estimate of an individual's risk for epilepsy over his or her remaining lifetime, translates into the number of people who are expected to develop epilepsy, and assists health care planners as they estimate service needs for epilepsy.

Adverse antiepileptic drug effects in new-onset seizures: a case-control study.

OBJECTIVE: Adverse effects (AEs) are a major concern when starting antiepileptic drug (AED) treatment. This study quantified the extent to which AE reporting in people with new-onset seizures started on AEDs is attributable to the medication per se, and investigated variables contributing to AE reporting. METHODS: We pooled data from 2 large prospective studies, the Multicenter Study of Early Epilepsy and Single Seizures and the Northern Manhattan Study of incident unprovoked seizures, and compared adverse event profile (AEP) total and factor scores between adult cases prescribed AEDs for new-onset seizures and untreated controls, adjusting for several demographic and clinical variables. Differences in AEP scores were also tested across different AED monotherapies and controls, and between cases and controls grouped by number of seizures. RESULTS: A total of 212 cases and 206 controls were identified. Most cases (94.2%) were taking low AED doses. AEP scores did not differ significantly between the 2 groups. Depression, female gender, symptomatic etiology, younger seizure onset age, ≥2 seizures, and history of febrile seizures were associated with higher AEP scores. There were no significant differences in AEP scores across different monotherapies and controls. AEP scores increased in both cases and controls with increasing number of seizures, the increment being more pronounced in cases. CONCLUSIONS: When AED treatment is started at low doses following new-onset seizures, AE reporting does not differ from untreated individuals. Targeting specific factors affecting AE reporting could lead to improved tolerability of epilepsy treatment.

Novel susceptibility locus at chromosome 6q16.3-22.31 in a family with GEFS+.

BACKGROUND: Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with extremely variable expressivity. Mutations in 5 genes that raise susceptibility to GEFS+ have been discovered, but they account for only a small proportion of families. METHODS: We identified a 4-generation family containing 15 affected individuals with a range of phenotypes in the GEFS+ spectrum, including febrile seizures, febrile seizures plus, epilepsy, and severe epilepsy with developmental delay. We performed a genome-wide linkage analysis using microsatellite markers and then saturated the potential linkage region identified by this screen with more markers. We evaluated the evidence for linkage using both model-based and model-free (posterior probability of linkage [PPL]) analyses. We sequenced 16 candidate genes and screened for copy number abnormalities in the minimal genetic region. RESULTS: All 15 affected subjects and 1 obligate carrier shared a haplotype of markers at chromosome 6q16.3-22.31, an 18.1-megabase region flanked by markers D6S962 and D6S287. The maximum multipoint lod score in this region was 4.68. PPL analysis indicated an 89% probability of linkage. Sequencing of 16 candidate genes did not reveal a causative mutation. No deletions or duplications were identified. CONCLUSIONS: We report a novel susceptibility locus for genetic epilepsy with febrile seizures plus at 6q16.3-22.31, in which there are no known genes associated with ion channels or neurotransmitter receptors. The identification of the responsible gene in this region is likely to lead to the discovery of novel mechanisms of febrile seizures and epilepsy.

The association of host age and gender with inflammation around neurocysticercosis cysts.

The results of previous investigations indicate that age and gender may influence the strength of the human host's immune response to infection of the central nervous system with the larvae of Taenia solium. Most of the relevant research on such neurocysticercosis (NCC) has, however, been conducted on hospital-based samples in developing countries, where differential access to healthcare may bias the study results. Using data from 171 NCC patients participating in a treatment trial, the associations of patient age and gender with the presence of inflammation around NCC cysts (i.e. cysts in the transitional phase) have recently been explored, after controlling for measures of economic and geographical access to healthcare. Data on cysts were collected from computed-tomography or magnetic-resonance images taken at four time-points, from baseline to 12-months post-treatment. The odds of having transitional cysts were evaluated by logistic regression whereas Poisson regression was used to explore the numbers of transitional cysts, with generalised estimating equations (GEE) used to account for the multiple observations over time. After controlling for healthcare access, the odds of having transitional cysts were found to be 1.5-fold higher for the female patients than for the male, although this association was not statistically significant (P = 0.136). In the Poisson model, however, the number of transitional cysts was found to be 1.8-fold higher in the female patients than in the male, and this gender effect was not only statistically significant (P = 0.002) but also constant over time. The association of host age with transitional cysts was more complicated, with significant interaction between age and time. It therefore appears that there are significant gender and age differences in the local immune response to NCC, even after adjusting for differences in healthcare access.

Management issues for women with epilepsy--focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding: 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 preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast-milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: 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, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. METHODS: A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007. RESULTS: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. RECOMMENDATIONS: Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations.

Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): 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 American Epilepsy Society.

OBJECTIVE: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. METHODS: A 20-member committee including general neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and February 2008. RESULTS: For WWE taking antiepileptic drugs, there is probably no substantially increased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 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. 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. RECOMMENDATIONS: Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%-92%) of remaining seizure-free during pregnancy (Level B). However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy (Level C).

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).

Pregnancy registries in epilepsy: a consensus statement on health outcomes.

Most pregnant women with epilepsy require antiepileptic drug (AED) therapy. Present guidelines recommend optimizing treatment prior to conception, choosing the most effective AED for seizure type and syndrome, using monotherapy and lowest effective dose, and supplementing with folate. The Epilepsy Therapy Project established the international Health Outcomes in Pregnancy and Epilepsy (HOPE) forum to learn more about the impact of AEDs on the developing fetus, particularly the role of pregnancy registries in studying AED teratogenicity. The primary outcome of interest in these registries is the occurrence of major congenital malformations, with some data collected on minor malformations. Cognitive and behavioral outcomes are often beyond the timeframe for follow-up of these registries and require independent study. The HOPE consensus report describes the current state of knowledge and the limitations to interpretations of information from the various sources. Data regarding specific risks for both older and newer AEDs need to be analyzed carefully, considering study designs and confounding factors. There is a critical need for investigations to delineate the underlying mechanisms and explain the variance seen in outcomes across AEDs and within a single AED.

Effects of albendazole treatment on neurocysticercosis: a randomised controlled trial.

AIM: The aim of this trial was to evaluate the effects of albendazole (ALB) on cyst disappearance, reduction of the number of cysts and seizure recurrence. METHODS: 178 patients with new onset symptoms due to active or transitional neurocysticercosis were randomly assigned to receive either 800 mg of ALB daily or placebo for 8 days. All patients also received prednisone. Imaging studies were done at baseline and at months 1, 6 and 12 of follow-up. RESULTS: Active cysts were identified in 59 of 88 people randomised to ALB and 57 of the 90 in the placebo arm. By 1 month, 31% were free of active cysts in the treatment group compared with 7% in the placebo group (p = 0.001). In addition, the ALB group had a greater reduction in the number of active cysts compared with the placebo group (p = 0.001). After 1 month following treatment there was no additional gain by treatment group in the disappearance or reduction in the number of active cysts. ALB treatment had little effect on cysts in the transitional or calcification stage. We found no difference between the ALB and placebo groups in symptoms during treatment or in seizure recurrence during the 12 months after treatment. CONCLUSION: Albendazole plus symptomatic treatment leads to the disappearance of active cysts in 31% of patients compared with 7% of those with symptomatic treatment alone. This treatment effect occurs within the first 30 days after treatment. TRIAL REGISTRATION NUMBER: NCT00283699.

Inconsistency between prospectively and retrospectively reported febrile seizures.

This study compared the incidence of febrile seizures (FS) reported prospectively up to 5 years of age, with the prevalence of FS by parental recall in the same cohort using the same questionnaire at 12 years of age. Both prospective and retrospective data were available for 807 children (389 males, 418 females). The number of children reported to have experienced FS in the prospective study was 57, and in the retrospective study was 45, yielding a cumulative incidence of 7.1 and 5.6% respectively. In the retrospective study there was an under-reporting of 19 children, over-reporting of eight children, and one child misreported by age at onset. Overall sensitivity of the retrospective approach was 65% and specificity was 99%. Positive predictive value was 82% and negative predictive value was 97%. Retrospective data underestimate the frequency of FS with high specificity but low sensitivity. Recall data suggest that some children with FS were not reported in the prospective data. These biases should be considered when evaluating the value of FS as a predictor of future health effects.

Recurrence of afebrile status epilepticus in a population-based study in Rochester, Minnesota.

OBJECTIVE: To determine the risk of recurrence of status epilepticus (SE) in a population-based sample and to identify risk factors for recurrence. METHODS: We ascertained all first episodes of afebrile SE in residents of Rochester, MN, through the Rochester Epidemiology Project's records-linkage system between January 1, 1965, and December 31, 1984. Information was collected on age, gender, duration, seizure type, etiology, therapeutic response to initial antiepileptic drug medication, and subsequent episodes of SE. RESULTS: Among the 183 episodes of first afebrile SE, the risk of recurrent SE was 31.7% over a 10-year follow-up period. The risk of recurrence was about 25% for those with acute symptomatic SE, remote symptomatic SE, and idiopathic cryptogenic SE. Recurrence was 100% for those with progressive symptomatic SE. Female gender (rate ratio [RR] = 2.3, 95% CI = 1.1 to 5.0) and progressive symptomatic etiology (RR = 2.4, 95% CI = 0.6 to 8.9) increased the risk for recurrent SE. Both partial SE (RR = 0.5, 95% CI = 0.2 to 1.1) and good therapeutic response to the initial antiepileptic drug therapy (RR = 0.3, 95% CI = 0.1 to 0.7) were associated with a decreased risk of recurrent SE. CONCLUSIONS: Status epilepticus (SE) recurs in about one-third of individuals with a first episode of SE. Except for SE occurring in the setting a progressive brain disorder, the risk of recurrence is about 25%, regardless of the underlying etiology. Female gender and lack of response to the first antiepileptic drug medication after the initial episode of SE identify those individuals at greatest risk for recurrence.

Classification of partial seizure symptoms in genetic studies of the epilepsies.

OBJECTIVES: To develop standardized definitions for classification of partial seizure symptoms for use in genetic research on the epilepsies, and evaluate inter-rater reliability of classifications based on these definitions. METHODS: The authors developed the Partial Seizure Symptom Definitions (PSSD), which include standardized definitions of 41 partial seizure symptoms within the sensory, autonomic, aphasic, psychic, and motor categories. Based on these definitions, two epileptologists independently classified partial seizures in 75 individuals from 34 families selected because one person had ictal auditory symptoms or aphasia. The data used for classification consisted of standardized diagnostic interviews with subjects and family informants, and medical records obtained from treating neurologists. Agreement was assessed by kappa. RESULTS: Agreement between the two neurologists using the PSSD was "substantial" or "almost perfect" for most symptom categories. CONCLUSIONS: Use of standardized definitions for classification of partial seizure symptoms such as those in the Partial Seizure Symptom Definitions should improve reliability and accuracy in future genetic studies of the epilepsies.

Subarachnoid hemorrhage incidence among Whites, Blacks and Caribbean Hispanics: the Northern Manhattan Study.

American blacks and Hispanics may have a greater incidence of subarachnoid hemorrhage (SAH) than whites, but incidence data are scant. We used an active hospital and community surveillance program and autopsy reports to identify incident SAH cases among white, black and Hispanic adults living in Northern Manhattan between July 1993 and June 1997. The annual incidence adjusted for age and sex to the 1990 US Census was 9.7 per 100,000 (95% CI 7.5-12.0). Compared with whites (9 cases, age- and sex-adjusted annual incidence 8.2 per 100,000), the rate ratio of SAH was 1.3 (95% CI 0.7-2.4) for Hispanics (34 cases, incidence 10.9), and 1.6 (95% CI 0.8-2.8) for blacks (9 cases, incidence 12.8). The 30-day case fatality rate was 26%. Risk of death increased significantly with age and severity at onset but was not influenced by gender or race-ethnicity.

The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and Hispanics.

BACKGROUND: Black and Hispanic Americans have a greater risk of primary intracerebral hemorrhage (ICH) than whites. Deep ICH is most often associated with hypertension, while lobar ICH is associated with cerebral amyloid angiopathy. The authors conducted a population-based incidence study to directly compare the incidence of deep vs lobar ICH in all three race-ethnic groups. METHODS: The authors used an active hospital and community surveillance program and autopsy reports to identify incident ICH cases among white, black, and Caribbean Hispanic adults in Northern Manhattan between July 1993 and June 1997. Incidence rates were adjusted for age and sex to the 1990 US Census. CIs for risk ratios (RR) were calculated with Byar's chi2 approximation of the Poisson distribution. RESULTS: The authors identified 155 cases of ICH for an annual incidence of 30.9/100,000 (26.7 to 35.0). Men had a higher risk of ICH than women (RR 1.5, 95% CI 1.2 to 1.8), driven entirely by the incidence of deep ICH (RR 1.8) rather than lobar ICH (RR 1.0). Compared with whites, RR for blacks was all ICH 3.8 (2.2 to 8.9), deep 4.8 (2.3 to 21.1), lobar 2.8 (1.2 to 14.4); RR for Hispanics was all 2.6 (1.4 to 6.1), deep 3.7 (1.7 to 16.5), lobar 1.4 (0.4 to 7.4). CONCLUSIONS: ICH is a heterogeneous disease with deep and lobar subtypes distinguishable on an epidemiologic basis. The different patterns of these two subtypes in our race-ethnically diverse population lend credence to the notion that ICH should no longer be treated as a single entity.

Epilepsy and mortality in Africa: a review of the literature.

PROBLEM: The prevalence of epilepsy is high in many areas of Africa. This condition is stigmatized, and there are limited health personnel and facilities for diagnosis and treatment. A huge treatment gap is suspected for epilepsy, and data suggest that nearly 80-85% of people with epilepsy have never been diagnosed or treated. It is reported worldwide that the mortality among people with epilepsy is two- to threefold higher than in general population. An increase of at least this magnitude is suspected in Africa, but there are very few data. Verbal autopsy studies may be one way of carrying out studies of mortality for epilepsy in Africa because these methods do not rely on autopsies, which are rare, or upon death certificates, which are a poor source of information on death in Africa. METHODS: This paper presents the literature on mortality after seizures in Africa, although there are few studies of mortality among people with epilepsy in Africa. RESULTS: The existing studies suggest an increased risk of dying and a greater proportion of deaths that are epilepsy-related. One study reports a sixfold increase in mortality in people with epilepsy. This is higher than the two- to threefold increase reported in developed countries. CONCLUSIONS: Considering the high prevalence of this condition, the public health impact of epilepsy mortality is likely to be enormous.