Falling status epilepticus mortality rates in England and Wales: 2001-2013?

Status epilepticus (SE) is associated with significant mortality and accounts for ~10% of epilepsy-related deaths. Epilepsy and SE mortality data from 2001 to 2013, in addition to annual age group populations for England and Wales, were obtained from the Office of National Statistics website (www.ons.gov.uk). Age-adjusted mortality rates for epilepsy and SE with 95% confidence intervals (CIs) were calculated using the European Standard Population. Trends in mortality rates for both epilepsy and SE were investigated using the Spearman coefficient. The crude mean epilepsy mortality rate per 100,000 person-years between 2001 and 2013 was 1.87 (95% CI 1.83-1.91), with a corresponding SE mortality rate of 0.14 (95% CI 0.13-0.15). The mean age-adjusted epilepsy mortality rate per 100,000 person years was 3.24 (95% CI 3.12-3.35), with a corresponding SE mortality rate of 0.24 (95% CI 0.21-0.27). All epilepsy deaths significantly decreased from 2001 to 2013 (Spearman's ρ -0.733, p = 0.004); this decrease was predominantly due to a decrease in SE deaths (Spearman's ρ -0.917, p < 0.001). In summary, our finding supports the hypothesis that the policy of early and aggressive treatment of SE may be improving the prognosis of this condition in England and Wales

The association between alcohol consumption and sleep disorders among older people in the general population

The relationship between alcohol consumption and sleep disturbance is complex. The association of alcohol dependence with insomnia is likely to be bidirectional in nature. Alcohol use is common among older people in many societies and the prevalence of insomnia tends to increase with age, therefore this group warrants particular consideration. We explored the cross sectional and long term (30 years) associations between alcohol drinking (volume and hazardous drinking) and sleep duration and insomnia in a general population study of older adults (6,117 male and female civil servants followed for 30 years). For men, drinking more than 21 units (approximately 168 grams) of alcohol per week, compared with not drinking, was associated with waking several times a night (odds ratio 1.30, confidence intervals 1.02-1.66). Men who maintained a heavy volume of drinking over the three decades of observation, or who had an unstable consumption pattern, tended to have worse sleep profiles in terms of waking tired and waking several times. Sustained male hazardous drinking (as measured by the AUDIT-C scale) was also associated with worse sleep profiles. Findings for women were not so clear. In this population based setting, drinking high volumes of alcohol may contribute to the prevalence of sleep problems in older age, particularly for men. People in this age group should be discouraged from using alcohol as a sleep aid

Advances in the management of generalized convulsive status epilepticus: what have we learned?

Convulsive status epilepticus is the most serious manifestation of an epileptic diathesis. In the early stages (5-30 min), there exists class A evidence to support the efficacy of benzodiazepines as first-line treatment. As status epilepticus progresses into the later stages, the evidence for treatment becomes less robust until we are depending upon short case series and case reports for the treatment of refractory status epilepticus. However, the past year saw the publication of three randomized controlled trials in the setting of benzodiazepine-resistant established convulsive status epilepticus: the EcLiPSE and ConSEPT studies, compared levetiracetam to phenytoin in children; and the ESETT study compared fosphenytoin, levetiracetam and sodium valproate in adults and children. In addition, the emergence of data from the SENSE study, a multicentre multinational prospective cohort study and the publication of a systematic review and meta-analysis of the mortality of status epilepticus over the past 30 years, has brought the treatment of status epilepticus into sharp focus. In this update we provide a detailed analysis of these studies and their impact on clinical practice. We review contentious areas of management in status epilepticus where a consensus is lacking and advance the case for more research on existing and alternative treatment strategies

The long-term prognosis of epilepsy

The five studies presented in this thesis consider different aspects of the long-term prognosis of epilepsy and febrile seizures. The studies were: 1). A systemic review to examine a) how the risk of premature mortality in an individual with epilepsy changes over time and b) whether population mortality rates due to epilepsy have changed over time. (Study 1) 2). An extension of the National General Practice Study of Epilepsy (NGPSE), a prospective community-based incident cohort study to examine a) long-term seizure prognosis and mortality in people with epilepsy and b) seizure prognosis in children with febrile seizures (Study 2) 3). Two retrospective hospital-based cohort studies examining prognosis of chronic epilepsy with regard to a) frequency of different seizure patterns (Study 3) and mediumterm seizure outcome following anti-epileptic drug changes (Study 4). 4). A systematic review examining the impact of aetiology and others factors on outcome in status epilepticus (Study 5). Amongst the findings were: 1): There is no conclusive evidence that either the overall standardised mortality ratio (SMR) or the mortality rate of people with epilepsy has changed significantly over time. The SMR is highest soon after diagnosis and subsequently decreases with a possible late increase after 10 years. In the NGPSE cohort the SMR remains significantly elevated after 20 years despite over 80% currently being in terminal remission. 2): 6.7% (95% CI 4, 11%) of children with febrile seizures developed epilepsy after 20 years. 3): Approximately one-third of people with chronic epilepsy have a history of at least one significant period of seizure freedom (two or more years) while a comparable number with apparent drug-resistant epilepsy attain at least one year of seizure freedom after medication change, although approximately half subsequently relapse. 4). Aetiology and, to a lesser extent, age are the primary determinants of prognosis in status epilepticus

Bone protection and anti-epileptic drugs: The effect of audit and computer messaging on supplementation prescribing practices

AbstractObjectiveThis audit assessed the impact of individualised written recommendations and a computer message, on repeat prescriptions for calcium and vitamin D supplements, for patients on long term AEDs.Methods1041 adult patients with epilepsy were retrospectively followed from 2004, from the time of the introduction of the Quality and Outcomes Framework (QOF) and the publication of the National Institute of Clinical Evidence (NICE) guidelines for epilepsy, up until 2011. In 2009 a clinical notes review of 414 of the above patients, in Ellesmere Port and Neston (13 practices) was performed, suggesting supplementation, where appropriate, in a written report. A computer message was added to relevant prescriptions also recommending supplements, in the above practices plus all 26 practices in Chester and the surrounding area. The number of patients receiving repeat prescription for supplements in each area between 2004 and 2011 was analysed.ResultsThere was a significant increase in the repeat prescriptions of supplements in 2010/11 after the interventions, the increase being most marked in Ellesmere Port and Neston where both written recommendations and computer message had occurred compared with the two areas with the computer message only.ConclusionQuality audit with written recommendations, and a message added to the General Practice (GP) computer systems significantly increased the number of repeat prescriptions of calcium and vitamin D supplements in this group of patients.Practice ImplicationsWhere clear guidelines are established, this study demonstrates that continuing education and counselling of GPs and use of computer messaging would result in improved compliance with such guidelines

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

A retrospective cohort study of super-refractory status epilepticus in a tertiary neuro-ICU setting

PURPOSE: Over the last decade, the range of treatments available for the management of super-refractory status epilepticus (SRSE) has expanded. However, it is unclear whether this has had an impact on its high mortality and morbidity. The aim of this study was to investigate whether there has been a change in the outcome of SRSE over time in a neurological intensive care unit (ICU) within a tertiary centre. METHODS: Analysis of a retrospective cohort of 53 admissions from 45 patients to the neurological ICU at the National Hospital for Neurology and Neurosurgery, Queen Square, London, between January 2004 and September 2018. RESULTS: Significant reductions were observed in both duration of SRSE over time and in the time spent in ICU, suggesting that treatment quality has improved over time. A median of four antiseizure drugs (ASDs) were given prior to seizure resolution. In 23 % resolution of SRSE occurred following optimisation of current treatment rather than introduction of a new ASD. The mortality rate was very low at 11 % by 6 months; however, there was no indication of improvement in outcome as all surviving patients had a modified Rankin scale score of 3-5 upon discharge from ICU, classified as moderate-to-severe disability. CONCLUSION: Neither the survival rate nor the outcome score changed significantly over time, suggesting that changes in the treatment of SRSE have had no impact on patient outcome

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

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 (&gt;2 unprovoked seizures) and those with a single seizure at presentation. 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 &gt;2 seizures (epilepsy). 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 &lt;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. 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

Treatment resistant trigeminal neuralgia relieved with oral sumatriptan: a case report

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Pharmacological Blockade of the Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus in Rats

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury as characterized by Fluoro Jade C labeling was observed in critical brain areas including the dentate gyrus, parietal cortex, amygdala, and thalamus. Dantrolene and carisbamate treatment provided significant neuroprotection against delayed neuronal damage in these brain regions when administered one-hour after POX-SE. These results indicate that dantrolene or carisbamate could be effective adjuvant therapies to the existing countermeasures to reduce neuronal injury and behavioral morbidities post OP SE survival