Epilepsy treatment priorities: answering the questions that matter

Objective To identify research priorities that have been answered, six years after being identified as important to people with epilepsy and epilepsy professionals. Background The DUETs database collates key unanswered questions identified by patients and professionals. In 2011, 398 questions were created using focus group methodologies. We wanted to know whether published research has since answered these important questions. Design The top 20 ranked questions for both patients and clinicians were studied. The PubMed and Cochrane databases were searched for published papers and NICE, SIGN and ILAE guidance for authoritative statements. The number of papers targeted at answering these research priorities was recorded

Phenotyping paroxysmal conditions to empower genetic research

I describe the process of preparing cohorts of individuals with two paediatric onset paroxysmal disorders – hyperekplexia and juvenile myoclonic epilepsy – for second generation sequencing. This involves: i) listening to the individual; ii) identifying subgroups; iii) using non-­‐core features to create subgroups; iv) and assessing the importance of copy number variation. Using focus groups and an interpretative phenomenological approach clinicians and people with epilepsy produced 398 questions focused on epilepsy treatment. The most important themes for the professionals were – teatment pogrammes or non-­‐epileptic attack disorder and concerns about side effectsinutero.For patients cognitive drug side effects and managing the consequences of drug side effects were most important. Studying ninety-­‐seven individuals with hyperekplexia confirmed that all gene-­‐positive cases present in the neonatal period and that clonazepam is the treatment of choice (95% found it efficacious). Patients with SLC6A5 and GLRB mutations were more likely to have developmental delay (RR1.5 p<0.01; RR1.9 p<0.03) than those with GLRA1 mutations; 92% of GLRB cases reported a mild to severe delay in speech acquisition. Juvenile myoclonic epilepsy is challenging to subdivide based on seizure and EEG features. The neuropsychological profile of limited number of patients 39) as examined in great detail including tests Q WAIS), emory TYM,WMS),executive function (BADS, DKEFS), affect (HADS). TYM was as sensitive as a full WMS for identifying cognitive errors and the zoo map and key search tests were performed particularly poorly. Personality profiling (EPQ-­‐BV) identifies the cohort as having high levels of neurotic and introvert traits. Three atypical ‘hyperekplexia’ cases had alternative diagnoses suggested by copy number analysis. The juvenile myoclonic epilepsy patients had an 8% frequency of recognised pathogenic CNVs– but no recurrent variants were identified.A number of non-­‐epilepsy related findings were identified including a potentially preventable cause of SUDEP

Sudden death in epilepsy: insights from the last 25 years

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in patients with refractory epilepsy, and as such has been a major research focus over the last 25 years. The earliest SUDEP research papers were published in Seizure, as have scores of SUDEP papers since. In this review we discuss the efforts to try and describe the pathophysiological basis of SUDEP, the drive to discover the clinical risk factors that increase the likelihood of SUDEP, and the motivation to increase awareness of SUDEP. These three areas are the prime factors that, when answered, will allow us to better mitigate against SUDEP and help individuals monitor their personal risk. The field has benefited from strong definitions, multinational collaboration, the use of cutting edge genetic analysis, and ensuring that bereaved families are able to take part in research when this is appropriate. Clearly there is much that we do not know and yet, has any area of epilepsy research come so far in the last 25 years

On the road again: assessing driving ability in patients with neurological conditions

Clinicians may not be aware of the specialised methods and adaptations that are used to help people with disabilities to drive a car. We describe a driving assessment process as carried out by one of the UK’s flagship assessment centres, including an overview of the available assessments, adaptations and relevant legislation to guide practitioners about how best to signpost and counsel their patients appropriately about driving

Weight change associated with antiepileptic drugs

Aim To investigate antiepileptic drug (AED)-related weight changes in patients with epilepsy through a retrospective observational study. Method We analysed the anonymised electronic primary care records of 1.1 million adult patients in Wales. We included patients aged 18 years and over with a diagnosis of epilepsy, whose body weight had been measured up to 12 months before starting, and between 3 and 12 months after starting, one of five AEDs. We calculated the weight difference after starting the AED for each patient. Results 1423 patients were identified in total. The mean difference between body weight after and before starting each AED (together with 95% CI and p values for no difference) were: carbamazepine (CBZ) 0.43 (−0.19 to 1.05) p=0.17; lamotrigine (LTG) 0.31 (−0.38 to 1.00) p=0.38; levetiracetam (LEV) 1.00 (0.16 to 1.84) p=0.02; sodium valproate (VPA) 0.74 (0.10 to 1.38) p=0.02; topiramate (TPM) −2.30 (−4.27 to −0.33) p=0.02. Conclusions LEV and VPA were associated with significant weight gain, TPM was associated with significant weight loss, and LTG and CBZ were not associated with significant weight change

Genetic epilepsy with febrile seizures plus: definite and borderline phenotypes

Generalised epilepsy with febrile seizures plus (GEFS+) is the most studied familial epilepsy syndrome. However, characteristics of UK families have not previously been reported. Among the first 80 families recruited to our families study, four broad subphenotypes were identified: families with classical GEFS+; families with borderline GEFS+; families with unclassified epilepsy; and families with an alternative syndromal diagnosis. Borderline GEFS+ families shared many characteristics of classical GEFS+ families—such as prominent febrile seizures plus and early onset febrile seizures—but included more adults with focal epilepsies (rather than the idiopathic generalised epilepsies predominating in GEFS+) and double the prevalence of migraine. Thus the authors believe that a novel and robust familial epilepsy phenotype has been identified. Subcategorising families with epilepsy is helpful in targeting both clinical and research resources. Most families with GEFS+ have no identified causal mutation, and so predicting genetic homogeneity by identifying endophenotypes becomes more important

Defining causality in COVID-19 and neurological disorders.

When faced with acute neurological presentations in a patient with COVID-19, how confident can one be that SARS-CoV2 is causal