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Background: Convulsive status epilepticus is the most common neurological emergency in children. Its management is important to avoid or minimise neurological morbidity and death. The current first-choice second-line drug is phenytoin (Epanutin, Pfizer Inc., New York, NY, USA), for which there is no robust scientific evidence., Objective: To determine whether phenytoin or levetiracetam (Keppra, UCB Pharma, Brussels, Belgium) is the more clinically effective intravenous second-line treatment of paediatric convulsive status epilepticus and to help better inform its management., Design: A multicentre parallel-group randomised open-label superiority trial with a nested mixed-method study to assess recruitment and research without prior consent., Setting: Participants were recruited from 30 paediatric emergency departments in the UK., Participants: Participants aged 6 months to 17 years 11 months, who were presenting with convulsive status epilepticus and were failing to respond to first-line treatment., Interventions: Intravenous levetiracetam (40 mg/kg) or intravenous phenytoin (20 mg/kg)., Main Outcome Measures: Primary outcome - time from randomisation to cessation of all visible signs of convulsive status epilepticus. Secondary outcomes - further anticonvulsants to manage the convulsive status epilepticus after the initial agent, the need for rapid sequence induction owing to ongoing convulsive status epilepticus, admission to critical care and serious adverse reactions., Results: Between 17 July 2015 and 7 April 2018, 286 participants were randomised, treated and consented. A total of 152 participants were allocated to receive levetiracetam and 134 participants to receive phenytoin. Convulsive status epilepticus was terminated in 106 (70%) participants who were allocated to levetiracetam and 86 (64%) participants who were allocated to phenytoin. Median time from randomisation to convulsive status epilepticus cessation was 35 (interquartile range 20-not assessable) minutes in the levetiracetam group and 45 (interquartile range 24-not assessable) minutes in the phenytoin group (hazard ratio 1.20, 95% confidence interval 0.91 to 1.60; p  = 0.2). Results were robust to prespecified sensitivity analyses, including time from treatment commencement to convulsive status epilepticus termination and competing risks. One phenytoin-treated participant experienced serious adverse reactions., Limitations: First, this was an open-label trial. A blinded design was considered too complex, in part because of the markedly different infusion rates of the two drugs. Second, there was subjectivity in the assessment of 'cessation of all signs of continuous, rhythmic clonic activity' as the primary outcome, rather than fixed time points to assess convulsive status epilepticus termination. However, site training included simulated demonstration of seizure cessation. Third, the time point of randomisation resulted in convulsive status epilepticus termination prior to administration of trial treatment in some cases. This affected both treatment arms equally and had been prespecified at the design stage. Last, safety measures were a secondary outcome, but the trial was not powered to demonstrate difference in serious adverse reactions between treatment groups., Conclusions: Levetiracetam was not statistically superior to phenytoin in convulsive status epilepticus termination rate, time taken to terminate convulsive status epilepticus or frequency of serious adverse reactions. The results suggest that it may be an alternative to phenytoin in the second-line management of paediatric convulsive status epilepticus. Simple trial design, bespoke site training and effective leadership were found to facilitate practitioner commitment to the trial and its success. We provide a framework to optimise recruitment discussions in paediatric emergency medicine trials., Future Work: Future work should include a meta-analysis of published studies and the possible sequential use of levetiracetam and phenytoin or sodium valproate in the second-line treatment of paediatric convulsive status epilepticus., Trial Registration: Current Controlled Trials ISRCTN22567894 and European Clinical Trials Database EudraCT number 2014-002188-13., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 58. See the NIHR Journals Library website for further project information.

Cerebral palsy (CP) is not a disease, but a neurological syndrome, a combination of signs and symptoms, some of which may occur in neurodegenerative or metabolic disorders, particularly those with an onset in the first 2 years of life. There are many different causes of the syndrome. All children with CP should undergo brain MRI, even with an identified antenatal or perinatal insult. Children with CP should be referred to a paediatric neurologist or a clinical geneticist, or both, if appropriate and particularly in the absence of a known perinatal cerebral insult, with brain MRI that is reported to be normal, a progression in, or new, signs or where there is a reported 'family history of CP'. Finally, a few of the CP syndromes may be readily treatable and potentially prevent irreversible neurological and cognitive impairment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus., Methods: This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894., Findings: Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91-1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction])., Interpretation: Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus., Funding: National Institute for Health Research Health Technology Assessment programme., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Convulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE., Methods/design: This is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up., Discussion: This clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting., Trial Registration: ISRCTN identifier, ISRCTN22567894 . Registered on 27 August 2015 EudraCT identifier, 2014-002188-13 . Registered on 21 May 2014 NIHR HTA Grant: 12/127/134.

Investigators from the National Infantile Spasms Consortium (NISC) in the USA studied the etiology of new-onset infantile spasms (IS) in 251 infants (mean age at onset, 7.1, range, 0.1-22.7 months).

Objective: Evaluation of efficacy of vigabatrin as the first drug in infants with previously untreated infantile spasms (IS) and reporting the long-term outcome., Methods: We analyzed a cohort of 180 infants with infantile spasms treated with vigabatrin as the first drug. Following initial evaluation and a 48-h basal period for counting the spasms, vigabatrin was administered using the same protocol in all. After 14 days all infants were assessed for therapeutic response (primary outcome). Psychomotor development was evaluated by a psychologist and neurologist prior to the initiation of treatment and during the follow-up. Seizure outcomes were followed prospectively, by seizure types and epilepsy syndromes. Long-term (secondary) outcomes included neurologic status, occurrence of late epilepsy, and developmental/cognitive status., Results: Vigabatrin terminated the spasms in 101 patients (56.9%) at a mean period of 5 days. Patients with normal psychomotor development prior to the onset of spasms responded best. After follow-up of 2.4 to 18.9 years (mean 10.64; standard deviation [SD] 4.40), 38.1% of responders, treated with vigabatrin, had severe neurologic dysfunction, 42% had epilepsy, and 42.2% had unfavorable intellectual outcome. The group with symptomatic etiology and abnormal neurologic status at presentation demonstrated a significantly worse prognosis and a more unfavorable outcome than cryptogenic or idiopathic cases (85.1% and 81.6% versus 14.9% and 0%-p = 0.001). Idiopathic patients treated with vigabatrin were all intellectually normal, except the youngest patient who had borderline cognitive function., Significance: The most important prognostic factors were the underlying etiology and preexisting developmental profile. Long-term outcome in the patients treated with vigabatrin was similar to the outcome in patients treated with adrenocorticotropic hormone (ACTH) or corticosteroids, as reported in earlier studies. The long-term prognosis of idiopathic cases treated with vigabatrin was favorable., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)