An evaluation of the effectiveness of perampanel in people with epilepsy who have previously undergone resective surgery and/or implantation of a vagal nerve stimulator.

About 30% of people with epilepsy (PWE) are drug-resistant. Those with focal seizures may be suitable for epilepsy surgery. Those not amenable to resective surgery can be considered for vagus nerve stimulation (VNS). However, after operative procedures, around 50% of patients continue to experience seizures. A multi-center retrospective study assessing perampanel effectiveness and tolerability for PWE who have undergone surgical resection and/or VNS implantation was performed. The primary outcome was ≥50% reduction in seizure frequency while secondary outcomes included side effects (SEs), dose-related effectiveness, and toxicity. The median perampanel dose was 6 mg. Only one PWE became seizure free. A ≥50% decrease in seizure frequency was observed in 52.8% of the post-resection group and 16.9% of the VNS group (p < 0.001), while SEs were seen in 44.8% and 41.1%, respectively. Perampanel doses greater than 8 mg led to better response in both groups, especially in the post-VNS cohort. SEs were not dose-related and the safety profile was similar to previous observational studies. Perampanel can be beneficial in these two super-refractory epilepsy groups, particularly in PWE with seizures after surgical resection. Doses of more than 8 mg appear to be well tolerated and may be more effective than lower doses in PWE after surgical interventions.

Prevalence of all epilepsies in urban informal settlements in Nairobi, Kenya: a two-stage population-based study.

BACKGROUND: WHO estimates that more than 50 million people worldwide have epilepsy and 80% of cases are in low-income and middle-income countries. Most studies in Africa have focused on active convulsive epilepsy in rural areas, but there are few data in urban settings. We aimed to estimate the prevalence and spatial distribution of all epilepsies in two urban informal settlements in Nairobi, Kenya. METHODS: We did a two-stage population-based cross-sectional study of residents in a demographic surveillance system covering two informal settlements in Nairobi, Kenya (Korogocho and Viwandani). Stage 1 screened all household members using a validated epilepsy screening questionnaire to detect possible cases. In stage 2, those identified with possible seizures and a proportion of those screening negative were invited to local clinics for clinical and neurological assessments by a neurologist. Seizures were classified following the International League Against Epilepsy recommendations. We adjusted for attrition between the two stages using multiple imputations and for sensitivity by dividing estimates by the sensitivity value of the screening tool. Complementary log-log regression was used to assess prevalence differences by participant socio-demographics. FINDINGS: A total of 56 425 individuals were screened during stage 1 (between Sept 17 and Dec 23, 2021) during which 1126 were classified as potential epilepsy cases. A total of 873 were assessed by a neurologist in stage 2 (between April 12 and Aug 6, 2022) during which 528 were confirmed as epilepsy cases. 253 potential cases were not assessed by a neurologist due to attrition. 30 179 (53·5%) of the 56 425 individuals were male and 26 246 (46·5%) were female. The median age was 24 years (IQR 11-35). Attrition-adjusted and sensitivity-adjusted prevalence for all types of epilepsy was 11·9 cases per 1000 people (95% CI 11·0-12·8), convulsive epilepsy was 8·7 cases per 1000 people (8·0-9·6), and non-convulsive epilepsy was 3·2 cases per 1000 people (2·7-3·7). Overall prevalence was highest among separated or divorced individuals at 20·3 cases per 1000 people (95% CI 15·9-24·7), unemployed people at 18·8 cases per 1000 people (16·2-21·4), those with no formal education at 18·5 cases per 1000 people (16·3-20·7), and adolescents aged 13-18 years at 15·2 cases per 1000 people (12·0-18·5). The epilepsy diagnostic gap was 80%. INTERPRETATION: Epilepsy is common in urban informal settlements of Nairobi, with large diagnostic gaps. Targeted interventions are needed to increase early epilepsy detection, particularly among vulnerable groups, to enable prompt treatment and prevention of adverse social consequences. FUNDING: National Institute for Health Research using Official Development Assistance.

An Investigation of Levetiracetam in Alzheimer's Disease (ILiAD): a double-blind, placebo-controlled, randomised crossover proof of concept study.

BACKGROUND: Although Alzheimer's disease affects around 800,000 people in the UK and costs almost £23 billion per year, currently licenced treatments only offer modest benefit at best. Seizures, which are more common in patients with Alzheimer's disease than age matched controls, may contribute to the loss of nerve cells and abnormal brain discharges can disrupt cognition. This aberrant electrical activity may therefore present potentially important drug targets. The anti-seizure medication levetiracetam can reduce abnormal cortical discharges and reverse memory deficits in a mouse model of Alzheimer's disease. Levetiracetam has also been shown to improve memory difficulties in patients with mild cognitive impairment, a precursor to Alzheimer's disease. Clinical use of levetiracetam is well-established in treatment of epilepsy and extensive safety data are available. Levetiracetam thus has the potential to provide safe and efficacious treatment to help with memory difficulties in Alzheimer's disease. METHODS: The proposed project is a proof of concept study to test whether levetiracetam can help cognitive function in people with dementia. We plan to recruit thirty patients with mild to moderate Alzheimer's disease with no history of previous seizures or other significant co-morbidity. Participants will be allocated to a double-blind placebo-controlled crossover trial that tests levetiracetam against placebo. Standardised scales to assess cognition and a computer-based touchscreen test that we have developed to better detect subtle improvements in hippocampal function will be used to measure changes in memory. All participants will have an electroencephalogram (EEG) at baseline. The primary outcome measure is a change in the computer-based touchscreen cognitive task while secondary outcomes include the effect of levetiracetam on mood, quality of life and modelling of the EEG, including time series measures and feature-based analysis to see whether the effect of levetiracetam can be predicted. The effect of levetiracetam and placebo will be compared within a given patient using the paired t-test and the analysis of covariance adjusting for baseline values. DISCUSSION: This is the first study to evaluate if an anti-seizure medication can offer meaningful benefit to patients with Alzheimer's disease. If this study demonstrates at least stabilisation of memory function and/or good tolerability, the next step will be to rapidly progress to a larger study to establish whether levetiracetam may be a useful and cost-effective treatment for patients with Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03489044 . Registered on April 5, 2018.

Development of EpiRisk: An online clinical tool for estimating the risk of major congenital malformations in pregnant women treated for epilepsy.

Antiepileptic drugs (AEDs) are known to associate with an increased risk of major congenital malformations (MCMs) in children born to women who become pregnant while taking them. As the indications for AEDs continue to diversify, novel AEDs emerge, and polytherapy becomes more prevalent, the volume and complexity of the information relating to teratogenic risk can become unmanageable for the clinician. This in turn makes accurate education of pregnant women treated with AEDs regarding the risk of MCMs challenging. To enable clinicians to provide better information regarding the potential teratogenic risk of AEDs, we outline here the method we have employed to underpin a new system of real-time risk analysis, "EpiRisk." When launched, EpiRisk will offer a user-friendly, online clinical tool, compatible with all modern Internet browsers, smart phones, and personal computers. Using the most current published data, as well as "real world" data from the UK and the Australian Pregnancy Registers, EpiRisk will enable clinicians to quickly and accurately assess the teratogenic risk of AEDs in mono- and polytherapy. EpiRisk may thus provide a future-proof central hub for empowering patients, clinicians, and registries by delivering evidence-based information on the teratogenic risk of the AEDs in pregnant women with epilepsy through an easily accessible platform.