Incidence and prevalence of epilepsy and associated factors in a health district in North-West Cameroon: A population survey.

This population-based cross-sectional survey with a follow-up case-control study assessed the prevalence, incidence, and risk factors for epilepsy in a rural health district in the North-West Region of Cameroon. Community-based epilepsy screening targeted all inhabitants, six years and older, in all 16 health areas in the Batibo Health District. During door-to-door visits, trained fieldworkers used a validated questionnaire to interview consenting household heads to screen for epilepsy in eligible residents. Trained physicians subsequently assessed people with suspected seizures. After clinical assessment, they confirmed or refuted the diagnosis and estimated the date of epilepsy onset. A trained nurse interviewed people with epilepsy and randomly selected healthy individuals, obtaining relevant demographic details and information on exposure to risk factors for epilepsy. Out of 36,282 residents screened, 524 had active epilepsy. The age-standardized prevalence of active epilepsy was 33.9/1,000 (95% CI: 31.0-37.1/1,000). We estimated the one-year age-standardized epilepsy incidence at 171/100,000 (95%CI: 114.0-254.6). Active epilepsy prevalence varied widely between health areas, ranging between 12 and 75 per 1,000. The peak age-specific prevalence was in the 25-34 age group. In adults, multivariate analysis showed that having a relative with epilepsy was positively associated with epilepsy. Epilepsy characteristics in this population, geographical heterogeneity, and the age-specific prevalence pattern suggest that endemic neurocysticercosis and onchocerciasis may be implicated. Further investigations are warranted to establish the full range of risk factors for epilepsy in this population.

Epilepsy in a health district in North-West Cameroon: Clinical characteristics and treatment gap.

INTRODUCTION: Epilepsy is a common yet misunderstood condition in Cameroon, including in the Batibo Health district. METHODS: This cross-sectional study describes epilepsy clinical characteristics, the treatment gap, and associated factors in a rural district in Cameroon. After screening for epilepsy using a door-to-door survey, physicians confirmed suspected cases of epilepsy. Detailed information on the medical, seizure, and treatment history was collected from everyone with epilepsy, followed by a general and neurological examination. RESULTS: We diagnosed 546 people with active epilepsy (at least one seizure in the previous 12 months). The mean age of people with active epilepsy was 25.2 years (SD: 11.1). The mean age at first seizure was 12.5 years (SD: 8.2). Convulsive seizures (uncertain whether generalized or focal) were the most common seizure types (60%), while 41% had focal-onset seizures. About 60% of people had seizures at least monthly. One-quarter of participants had had at least one episode of status epilepticus. Anti-seizure medication (ASM) was taken by 85%, but most were receiving inappropriate treatment or were non-adherent, hence the high treatment gap (80%). Almost a third had had seizure-related injuries. Epilepsy was responsible for low school attendance; 74% of school dropouts were because of epilepsy. CONCLUSION: The high proportion of focal-onset seizures suggests acquired causes (such as neurocysticercosis and onchocerciasis, both endemic in this area). The high epilepsy treatment gap and the high rates of status epilepticus and epilepsy-related injuries underscore the high burden of epilepsy in this rural Cameroonian health district.

Parasites and epilepsy: Understanding the determinants of epileptogenesis.

There is a large body of evidence suggesting that parasites could be a major preventable risk factor for epilepsy in low- and middle-income countries. We review potentially important substrates for epileptogenesis in parasitic diseases. Taenia solium is the most widely known parasite associated with epilepsy, and the risk seems determined mainly by the extent of cortical involvement and the evolution of the primary cortical lesion to gliosis or to a calcified granuloma. For most parasites, however, epileptogenesis is more complex, and other favorable host genetic factors and parasite-specific characteristics may be critical. In situations where cortical involvement by the parasite is either absent or minimal, parasite-induced epileptogenesis through an autoimmune process seems plausible. Further research to identify important markers of epileptogenesis in parasitic diseases will have huge implications for the development of trials to halt or delay onset of epilepsy.

Factors affecting seizure outcome after epilepsy surgery: an observational series.

IMPORTANCE: Surgical treatment can bring seizure remission in people with focal epilepsy but requires careful selection of candidates. OBJECTIVES: To determine which preoperative factors are associated with postoperative seizure outcome. DESIGN: We audited seizure outcome of 693 adults who had resective epilepsy surgery between 1990 and 2010 and used survival analysis to detect preoperatively identifiable risk factors of poor seizure outcome. RESULTS: Seven factors were significantly associated with increased probability of recurrence of seizures with impaired awareness postsurgery: MRI findings (eg, HR adjusted for other variables in the model 2.5; 95% CI 1.6 to 3.8 for normal MRI compared with hippocampal sclerosis), a history of secondarily generalised convulsive seizures (2.3; 95% CI 1.7 to 3.0 for these seizures in the previous year vs never), psychiatric history (1.3; 95% CI 1.1 to 1.7), learning disability (1.8; 95% CI 1.2 to 2.6) and extratemporal (vs temporal) surgery (1.4; 95% CI 1.02, 2.04). People with an older onset of epilepsy had a higher probability of seizure recurrence (1.01; 95% CI 1.00, 1.02) as did those who had used more antiepileptic drugs (1.05; 95% CI 1.01 to 1.09). Combinations of variables associated with seizure recurrence gave overall low probabilities of 5-year seizure freedom (eg, a normal MRI and convulsive seizures in the previous year has a probability of seizure freedom at 5 years of approximately 0.19). CONCLUSIONS AND RELEVANCE: Readily identified clinical features and investigations are associated with reduced probability of good outcome and need consideration when planning presurgical evaluation.

Somatic complications of epilepsy surgery over 25 years at a single center.

INTRODUCTION: Epilepsy surgery is an effective treatment for refractory focal epilepsy. Risks of surgery need to be considered when advising individuals of treatment options. We describe the frequency and nature of physical adverse events associated with epilepsy surgery in a single center. MATERIAL AND METHODS: We reviewed the prospectively maintained records of adults who underwent epilepsy surgery at our center between 1990 and 2014 to identify peri/postsurgical adverse events. These were categorized into neurological deficits and those related to surgery (e.g. wound infections). Neurological deficits were categorized as expected or unexpected and into transient (≤3 months) or persistent (>3 months), RESULTS: There were 911 procedures with no peri-operative deaths. Persistent neurological adverse events were seen following 157 (17.2%) procedures. The most common persistent expected complication was quadrantanopia after temporal lobe resections (72/764, 9.4%). Unexpected persistent neurological complications occurred in 20 procedures (2.2%) and included: quadrantanopia (6, 0.7%); hemianopia (2, 0.2%); hemi/mono-paresis/sensory loss (9, 1%); dysphasia (10, 1%); frontalis muscle weakness (2, 0.2%); and oculomotor weakness (1, 0.1%). 106 surgery related adverse events occurred in 83 procedures, with severe infections requiring bone-flap removal in 24 (2.6%) procedures and intracranial infections in 8 (0.9%). The risk of post-resective severe infection increased by 4 fold (OR 4.32, 95% CI 2.1-8.9, p<0.001) with use of subdural EEG monitoring prior to resection. In consequence, in August 2011 we introduced antibiotic coverage in all individuals undergoing intracranial monitoring. Also, after August 2011 there was greater use of Stereo-EEG (SEEG) than subdural (OR 9.0 CI 0.36-224.2, p=0.18ns). One complicated by severe infection. Other surgical complications included haematoma (0.3%), hydrocephalus (0.3%) and CSF leak (1.2%). None had permanent complications. CONCLUSIONS: Adverse event rates are similar to other series. Epilepsy surgery carries well defined surgical and neurological risks. The risks of somatic adverse events, in addition to neuropsychiatric and neuropsychological complications need to be made clear to individuals considering this treatment option.

The long-term course of temporal lobe epilepsy: From unilateral to bilateral interictal epileptiform discharges in repeated video-EEG monitorings.

INTRODUCTION: Bilateral interictal epileptiform discharges (IED) and ictal patterns are common in temporal lobe epilepsy (TLE) and have been associated with decreased chances of seizure freedom after epilepsy surgery. It is unclear whether secondary epileptogenesis, although demonstrated in experimental models, exists in humans and may account for progression of epilepsy. MATERIAL AND METHODS: We reviewed consecutive video-EEG recordings from 1992 to 2014 repeated at least two years apart (mean interval 6.14years) in 100 people diagnosed with TLE. RESULTS: Ictal EEG patterns and IED remained restricted to one hemisphere in 36 people (group 1), 46 exhibited bilateral abnormalities from the first recording (group 2), 18 progressed from unilateral to bilateral EEG pathology over time (group 3). No significant differences between the three groups were seen with respect to age at epilepsy onset, duration, or underlying pathology. Extra-temporal IED during the first EEG recording were associated with an increased risk of developing bilateral epileptiform changes over time (hazard ratio 3.67; 95% CI 1.4, 9.4). CONCLUSION: Our findings provide some support of progression in TLE and raise the possibility of secondary epileptogenesis in humans. The development of an independent contra-lateral epileptogenic focus is known to be associated with a less favorable surgical outcome. We defined reliable EEG markers for an increased risk of progression to more widespread or independent bitemporal epileptogenicity at an early stage, thus allowing for individualized pre-surgical counselling.

Outcome of seizures in the general population after 25†years: a prospective follow-up, observational cohort study.

OBJECTIVES: We investigated long-term (to 25 years) seizure prognosis and survival in people with newly diagnosed epilepsy in the community. We explored whether prognosis is different in those with epilepsy (>2 unprovoked seizures) and those with a single seizure at presentation. METHODS: This is a prospective observational cohort study of people with newly diagnosed seizures. We investigated seizure outcome and survival in people presenting with a single seizure and in those presenting with >2 seizures (epilepsy). RESULTS: 695 people (median follow-up 23.6 years) had unprovoked epileptic seizures. For seizure analysis we excluded 38 people with missing data leaving 657 (309 male, and 249 aged <18 years). Seizures recurred in 67%. The 354 people with epilepsy were only slightly more likely to have further seizure recurrence than the 302 people with a single seizure at presentation (HR 1.32, 95% CI 1.09 to 1.59). In 327 people with complete follow-up, 268 (82%, 95% CI 77% to 86%) were in terminal remission; (80%, (95% CI 73% to 85%) in those with epilepsy at presentation). Premature mortality was increased in people with epilepsy (standardised mortality ratio 1.67; 95% CI 1.40 to 1.99) and those with a single seizure at presentation (standardised mortality ratio 2.65; 95% CI 2.23 to 3.15). It is also high in those with early remission. CONCLUSIONS: People with epilepsy and with single seizures at presentation in the community generally have good prognosis for seizure control with prolonged follow-up. The risk of premature mortality is significantly increased in both groups.

Cause of death and predictors of mortality in a community-based cohort of people with epilepsy.

OBJECTIVE: The risk of premature mortality is increased in people with epilepsy. The reasons for this and how it may relate to epilepsy etiology remain unclear. METHODS: The National General Practice Study of Epilepsy is a prospective, community-based cohort that includes 558 people with recurrent unprovoked seizures of whom 34% died during almost 25 years of follow-up. We assessed the underlying and immediate causes of death and their relationship to epilepsy etiology. Psychiatric and somatic comorbidities of epilepsy as predictors of mortality were scrutinized using adjusted Cox proportional hazards models. RESULTS: The 3 most common underlying causes of death were noncerebral neoplasm, cardiovascular, and cerebrovascular disease, accounting for 59% (111/189) of deaths, while epilepsy-related causes (e.g., sudden unexplained death in epilepsy) accounted for 3% (6/189) of deaths. In 23% (43/189) of individuals, the underlying cause of death was directly related to the epilepsy etiology; this was significantly more likely if death occurred within 2 years of the index seizure (percent ratio 4.28 [95% confidence interval 2.63-6.97]). Specific comorbidities independently associated with increased risk of mortality were neoplasms (primary cerebral and noncerebral neoplasm), certain neurologic diseases, and substance abuse. CONCLUSIONS: Comorbid diseases are important causes of death, as well as predictors of premature mortality in epilepsy. There is an especially strong relationship between cause of death and epilepsy etiology in the first 2 years after the index seizure. Addressing these issues may help stem the tide of premature mortality in epilepsy.

Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy.

OBJECTIVE: Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter 'integrity'. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy. METHODS: Three hundred people with epilepsy attending specialist clinics and 90 healthy controls were included in this cross-sectional cohort study. RNFL imaging was performed using spectral-domain optical coherence tomography (OCT). Drug resistance was defined as failure of adequate trials of two antiepileptic drugs to achieve sustained seizure freedom. RESULTS: The average RNFL thickness and the thickness of each of the 90° quadrants were significantly thinner in people with epilepsy than healthy controls (p<0.001, t test). In a multivariate logistic regression model, drug resistance was the only significant predictor of abnormal RNFL thinning (OR=2.09, 95% CI 1.09 to 4.01, p=0.03). Duration of epilepsy (coefficient -0.16, p=0.004) and presence of intellectual disability (coefficient -4.0, p=0.044) also showed a significant relationship with RNFL thinning in a multivariate linear regression model. CONCLUSIONS: Our results suggest that people with epilepsy with no previous exposure to vigabatrin have a significantly thinner RNFL than healthy participants. Drug resistance emerged as a significant independent predictor of RNFL borderline attenuation or abnormal thinning in a logistic regression model. As this is easily assessed by OCT, RNFL thickness might be used to better understand the mechanisms underlying drug resistance, and possibly severity. Longitudinal studies are needed to confirm our findings.

The performance of three mortality risk-adjustment comorbidity indices in a community epilepsy cohort.

Mortality risk-adjustment comorbidity indices are an efficient means of controlling for the important confounding effect of somatic and psychiatric comorbidities in observational mortality studies. We carried out an external validation study and compared the performance of the Charlson, Elixhauser and Epilepsy-specific (ES) indices using the National General Practice Study of Epilepsy, a community-based prospective cohort of 558 people with incident epilepsy followed for 23.3 years (median). The minimum and maximum crude mortality rates were similar between the three indices, but mid-range Elixhauser scores predicted lower rates relative to the two other indices. Two of the stratified Charlson Kaplan-Meier survival probability curves crossed, and a low Elixhauser score was associated with a counterintuitive increase in mortality. Each comorbidity index was a significant predictor of mortality in the Cox proportional hazards models, although there was evidence that the unadjusted Charlson regression model violated the proportionality assumption. Harrell's c-statistics were >0.87 in all adjusted models. All three indices performed well, but there is evidence that the ES index may be more discriminating and have a better model fit than the Charlson or Elixhauser indices in a community-based clinical cohort of people with epilepsy.

Long term retention of retigabine in a cohort of people with drug resistant epilepsy.

PURPOSE: To assess the utility of retigabine (RTG) for epilepsy in clinical practice at a single UK tertiary centre. METHODS: We identified all individuals who were offered RTG from April 2011 to May 2013. We collected demographics, seizure types, previous and current antiepileptic drugs (AEDs), starting and maximum attained daily dose of RTG, clinical benefits, side effects, and reason to discontinue RTG from in- and outpatient encounters until February 28, 2014. RESULTS: 145 people who had failed a median of 11 AEDs took at least one dose of RTG. One year retention was 32% and decreased following the safety alert by the US Federal Drug Administration (FDA) in April 2013. None became seizure free. 34 people (24%) reported a benefit that was ongoing at last assessment in five (3%). The most relevant benefit was the significant reduction or cessation of drop attacks or seizure-related falls in four women, this persisted at last assessment in two. The presence of simple partial seizures was associated with longer retention, as was a higher attained dose of RTG. Adverse effects were seen in 74% and largely CNS-related or nonspecific and affected the genitourinary system in 13%. CONCLUSION: Retention of RTG was less favourable compared to data from open label extension studies of the regulatory trials. In comparison with historical data on similar retention audits retention of RTG at one year appears to be less than lamotrigine, topiramate, levetiracetam, pregabalin, zonisamide, and lacosamide, and slightly higher than gabapentin.

An unknown quantity--the worldwide prevalence of epilepsy.

The reported incidence (rate of new cases in a population) of epilepsy is consistently lower in high-income than in lower-income economies, whereas opinions vary regarding comparative prevalence rates (proportion of the population with epilepsy). For any condition that does not influence mortality, lifetime prevalence should approximate to the cumulative incidence. We suspected that epilepsy prevalence might be uniform throughout the world, whereas incidence is higher in resource-poor countries. To test whether our suspicion was reasonable, we conducted a Medline search to estimate the prevalence of active and lifetime epilepsy in different economic areas throughout the world. We found that the range of estimated prevalence of epilepsy may be broadly similar throughout the world, but comparison is limited by lack of door-to-door studies in high-income economies and by variations in the definitions of active epilepsy. We contend that any inconsistencies between incidence and prevalence are due largely to the excess premature death rate in people with epilepsy in lower-income economies. Much of the variability in epidemiologic indices arises from differences in study methodology, definitions, and risk factors. The epidemiology of epilepsy, and particularly its mortality, needs thorough investigation using uniform definitions that do not include antiepileptic drug use; causes of death should be identified and actions, including treatment and education, should be taken to avoid preventable deaths.

Network meta-analyses of antiepileptic drug efficacy and tolerability in drug-resistant focal epilepsies: a clinical perspective.

PURPOSE: Network meta-analysis (NMA) is a new technique that allows multiple treatment comparisons and provides estimates of effect sizes for all possible pair-wise comparisons. Several NMAs of antiepileptic drug (AED) efficacy and tolerability in individuals with refractory focal epilepsy, however, came to non-specific and, in some cases, divergent conclusions. We review some clinical factors that may be responsible for these inconsistent findings. RESULTS: A major issue is the small number of individuals included in the meta-analyses with consequent wide confidence intervals and lack of ability to achieve significant results. Further issues are lack of robustness of the measured efficacy outcome-the responder ratio (the percentage of individuals with a >50 % improvement in seizure frequency); the selection of randomized studies (RCTs) included, i.e., the inclusion of studies with heterogeneous populations (children and adults); and inclusion of people treated with different doses of the experimental drug. Some methods of analysing data from RCTs, such as the last observation carried forward (LOCF) analysis, the choice of different phases of the study to compare to baseline, and the year in which the trial was conducted, selectively affect measurement of efficacy outcomes. Titration speed and other methodological aspects selectively affect tolerability. CONCLUSION: Several factors restrict the analysis of clinically useful estimates of the comparative efficacy of AEDs, while analysis of tolerability may be easier to accomplish.

Web-search trends shed light on the nature of lunacy: relationship between moon phases and epilepsy information-seeking behavior.

In old and modern times and across cultures, recurrent seizures have been attributed to the lunar phase. It is unclear whether this relationship should be classified as a myth or whether a true connection exists between moon phases and seizures. We analyzed the worldwide aggregated search queries related to epilepsy health-seeking behavior between 2005 and 2012. Epilepsy-related Internet searches increased in periods with a high moon illumination. The overall association was weak (r=0.11, 95% confidence interval: 0.07 to 0.14) but seems to be higher than most control search queries not related to epilepsy. Increased sleep deprivation during periods of full moon might explain this positive association and warrants further study into epilepsy-related health-seeking behavior on the Internet, the lunar phase, and its contribution to nocturnal luminance.