The burden of comorbidity in people with epilepsy is high. Several diseases, including depression, anxiety, dementia, migraine, heart disease, peptic ulcers, and arthritis are up to eight times more common in people with epilepsy than in the general population. Several mechanisms explain how epilepsy and comorbidities are associated, including shared risk factors and bidirectional relations. There is a pressing need for new and validated screening instruments and guidelines to help with the early detection and treatment of comorbid conditions. Preliminary evidence suggests that some conditions, such as depression and migraine, negatively aff ect seizure outcome and quality of life. Further investigation is needed to explore these relations and the eff ects of targeted interventions. Future advances in the investigation of the comorbidities of epilepsy will strengthen our understanding of epilepsy and could play an important part in stratifi cation for genetic studies.

Background: Stroke is one of the leading causes of acquired epilepsy in adults. An

Findings from randomised controlled trials, along with more than 100 case series and observational studies, support the efficacy and safety of resective surgery and, more recently, non-resective surgical interventions for the treatment of drug-resistant epilepsy in appropriately selected individuals. There is an argument that epilepsy surgery remains underused, but the evidence to support this assertion is at times unclear. Results from longitudinal studies show a stagnant or declining rate of epilepsy surgery over time, despite the evidence and guidelines supporting its use. Some suggest that this stagnation is due to a decreasing pool of eligible surgical candidates, whereas others emphasise the numerous barriers to epilepsy surgery. Strategies exist to increase access to surgery and to improve communication about the effectiveness of this potentially life-changing procedure. Further investigation into the nature and causes of the presumed underuse of epilepsy surgery and the elaboration of strategies to address this treatment gap are necessary and pressing.

Objective:In order to evaluate the incidence and prevalence of drug-resistant epilepsy (DRE) as well as its predictors and correlates, we conducted a systematic review and meta-analysis of observational studies.Methods:Our protocol was registered with PROSPERO and the PRISMA and MOOSE reporting standards were followed. We searched MEDLINE, Embase, and Web of Science. We used a double arcsine transformation and random-effects models to carry out our meta-analyses. We performed random-effects meta-regressions using study-level data.Results:Our search strategy identified 10,794 abstracts. Of these, 103 articles met our eligibility criteria. There was high inter-study heterogeneity and risk of bias. The cumulative incidence of DRE was 25.0 % (95% CI: 16.8, 34.3) in child studies but 14.6% (95% CI: 8.8, 21.6) in adult/mixed ages studies. The prevalence of DRE was 13.7% (95% CI: 9.2, 19.0) in population/community-based populations but 36.3% (95% CI: 30.4, 42.4) in clinic-based cohorts. Meta-regression confirmed that the prevalence of DRE was higher in clinic-based populations and in focal epilepsy. Multiple predictors and correlates of DRE were identified. The most reported of these were having a neurological deficit, an abnormal EEG, and symptomatic epilepsy. The most reported genetic predictors of DRE were polymorphisms of the ABCB1 gene.Conclusions:Our observations provide a basis for estimating the incidence and prevalence of DRE, which vary between populations. We identified numerous putative DRE predictors and correlates. These findings are important to plan epilepsy services, including epilepsy surgery, a crucial treatment option for people with disabling seizures and DRE.

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.

The case of a 51-year-old man diagnosed with two acquired cavernous hemangiomas 17 years after cranial irradiation for a cerebellar astrocytoma is reported. A review of 84 cases of radiation-induced cavernous hemangiomas found in the literature is presented. In this series the mean age at the time of irradiation (±SD) was 10.4 ± 2.0 years (median = 8 years), while the mean time to cavernous hemangioma diagnosis (±SD) was 10.3 ± 1.9 years (median = 8 years). Time to cavernous hemangioma diagnosis was found to be inversely related to radiation dose. Hemorrhage from radiation-induced cavernous hemangiomas was found in 40.0% of patients, with an incidence of 3.9% per patient year. An inverse trend was identified between radiation dose and symptomatic presentation, cavernous hemangioma hemorrhage or surgical resection. This review of radiation-induced cavernous hemangiomas confirms that both younger patients and those who received a larger dose of radiation are at increased risk of radiation-induced cavernous hemangiomas. Our results suggest that, based on an assessment of CT or MR images, there may be an increased risk of hemorrhage when comparing radiation-induced to congenital cavernous hemangiomas. Increasing radiation doses appear to stabilize these lesions, decreasing the risk of a symptomatic presentation, cavernous hemangioma hemorrhage and surgical intervention.

There is a significant shortfall in suitably powered studies to provide sufficient evidence for safe prescribing of AEDs to people with ID.

The basic pathophysiology of epilepsy is still not fully understood. Epidemiological evidence for epilepsy seems to suggest that it may not only be the propensity for seizures to occur. The high prevalence of comorbidity and the finding that premature mortality is still increased in those who are in long-term remission, suggest that there is a systemic component to the condition. This systemic component is an additional shared risk factor that can explain an important proportion of the comorbidities of epilepsy as well as how an individual with inactive epilepsy remains at an elevated risk of premature mortality. This systemic component can be viewed from the perspective of a number of fundamental pathophysiological processes: inflammation, oxidative stress, glycation, and methylation capacity. These processes are associated with all-cause mortality and there is also a growing understanding of their impact on seizure processes. We propose that epilepsy be considered as the sum of seizures and comorbidities caused by systemic dysfunction, and that the comprehensive management of epilepsy should also include the management of the systemic dysfunction.