Summary Background Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy. Methods We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5–12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). Findings 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0–94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96–1·47]); non-inferiority margin 1·314. The PP analysis showed t...

Summary Background Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. Methods This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). Findings 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95–1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamot...

Aims: To investigate the diagnoses made for children referred to a ''fits, faints, and funny turns'' clinic. Methods: Prospective study of 380 children referred to a dedicated secondary care clinic over an eight year period. Results: Twenty three per cent of children were given a final diagnosis of one of the childhood epilepsies, with 48% of these having a specific epilepsy syndrome. Syncope was the commonest cause of a nonepileptic event (syncope and reflex anoxic seizures comprised 100/238, 42%) but there were a wide variety of other causes. Fifty three events (14%) were unclassified and managed without a diagnostic label or treatment. Conclusions: In children with funny turns referred to secondary care, the diagnostic possibilities are numerous; among non-epileptic events, syncopes predominate. The majority do not have epilepsy. Unclassifiable events with no clear epileptic or non-epileptic cause are common and can be safely managed expectantly. E pilepsies of childhood can be confused with other intermittent unusual behaviours of varied cause. This contributes to the misdiagnosis of epilepsy, particularly its over-diagnosis. [1][2][3][4][5] This paper describes the diagnoses reached for children referred with ''fits, faints, and funny turns'' (FFAFT) to a dedicated secondary care clinic in a district general hospital over an eight year period (1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003). METHODSThe clinic received referrals from the local borough of Bury and some from surrounding districts. Referrals came from GPs, paediatricians, child psychiatrists, paediatric neurologists (usually for ongoing care), and acute hospital admissions. Referrals included those presenting for the first time with events, and those where a diagnosis of epilepsy had already been made but where further classification and management were required. The clinic did not care for all children with epilepsy in the district (for example, some of those with straightforward diagnoses or stable epilepsy); the data presented therefore cannot be compared directly with population based studies.Clinics were held weekly. The same clinician saw all the children (all age ,16 years) and made or confirmed most of the diagnoses. A record of the diagnoses was kept prospectively. Where diagnosis was unclear, further opinions from visiting paediatric neurologists were sought. Electroencephalograms (EEGs) were done at a tertiary centre (Royal Manchester Children's Hospital) and reported by paediatric neurologists.Diagnoses were made primarily on clinical information, sometimes augmented by home videos of events using a camcorder loaned by the clinic to families. Families were primed by a letter sent with the appointment asking them to bring a direct witnessed account of a typical event to the first consultation and details of any relevant family history. RESULTS Figure 1 present categories of diagnoses.New diagnosis of epilepsy Epilepsy was newly diagnosed in 89 children (50 boys and 39 girls) (fig 2). The median age of onset was 5 years (range 0...