Intravenous levetiracetam in acute repetitive seizures and status epilepticus in children: experience from a children's hospital.

PURPOSE: To report the effectiveness and safety of intravenous levetiracetam in the treatment of children with acute repeated seizures, and status epilepticus in a children's hospital. METHODS: This two-year observational study evaluated all in-patients who received intravenous levetiracetam to treat acute repeated seizures (ARS) or convulsive and non-convulsive status epilepticus (SE). Information was collected on seizure type, epilepsy syndrome and underlying cause, the initial loading dose of intravenous levetiracetam, its effectiveness and safety and whether the patient remained on the drug at final follow-up. Analysis was descriptive. RESULTS: Fifty-one patients aged 0.2-18.8 (mean 7.1) years were evaluated, including 45 with acute ARS or SE and six unable to continue their usual orally administered anti-epileptic medication. The median initial dose of levetiracetam was 14.4 (range 5-30)mg/kg in the 45 patients treated for acute seizures and SE. Twenty three of the 39 (59%) patients with ARS became and remained seizure-free. Levetiracetam terminated status in three of four (75%) patients with convulsive, and the two patients with non-convulsive status epilepticus. Aggressive behaviour occurred in three children, one of whom discontinued treatment. Forty-two patients (81%), including 34 of the 45 patients (76%) treated for ARS or SE remained on levetiracetam at the time of final follow-up, between two and 18 months after receiving the drug. CONCLUSION: This observational study has confirmed previous data that intravenous levetiracetam seems to be effective and safe in the treatment of acute repeated seizures and status epilepticus. A randomised clinical trial is justified to determine whether intravenous levetiracetam should replace intravenous phenytoin as the first long-acting anticonvulsant in the management of acute repetitive seizures and status epilepticus.

Treatment of difficult epilepsy.

Most of the epilepsies that occur in children are relatively straightforward to manage, including suppression of the seizures. However, in at least 30% of children, seizures will not be fully controlled by one or two antiepileptic drugs (AEDs); these children may also have additional physical, educational or behavioural problems. This population is often labelled as having a "difficult" or an "intractable" epilepsy. The approach to these children must always begin with ensuring that the diagnosis of epilepsy is accurate, that the correct seizure type or types and epilepsy syndrome have been identified and that an underlying cause has been considered. Treatment must be holistic, considering the child as a person and not just someone having seizures; the AED regimen must be appropriate and not excessive; and surgery must always be considered a viable option.

Mutating the anchor residues associated with MHC binding inhibits and deviates CD8+ T cell mediated protective immunity against malaria.

We investigated whether immune responses induced by immunization with plasmid DNA are restricted predominantly to immunodominant CD8+ T cell epitopes, or are raised against a breadth of epitopes including subdominant CD8+ and CD4+ T cell epitopes. Site-directed mutagenesis was used to change one or more primary anchor residues of the immunodominant CD8+ T cell epitope on the Plasmodium yoelii circumsporozoite protein, and in vivo protective efficacy and immune responses against defined PyCSP CD8+ and/or CD4+ epitopes were determined. Mutation of the P2 but not P9 or P10 anchor residues decreased protection and completely abrogated the antigen-specific CD8+ CTL activity and CD8+ dependent IFN-gamma responses to the immunodominant CD8+ epitope and overlapping CD8+/CD4+ epitope. Moreover, mutation deviated the immune response towards a CD4+ T cell IFN-gamma dependent profile, with enhanced lymphoproliferative responses to the immunodominant and subdominant CD4+ epitopes and enhanced antibody responses. Responses to the subdominant CD8+ epitope were not induced. Our data demonstrate that protective immunity induced by PyCSP DNA vaccination is directed predominantly against the single immunodominant CD8+ epitope, and that although responses can be induced against other epitopes, these are mediated by CD4+ T cells and are not capable of conferring optimal protection against challenge.