Article, Cardiology

Lack of efficacy of phenytoin in children presenting with febrile status epilepticus

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  • Lack of efficacy of phenytoin in children presenting with febrile status epilepticus

    To the Editor,

    We read with interest a recently published article by Ismail et al [1] reporting the lack of efficacy of phenytoin in children presenting with febrile status epilepticus (FSE). The authors, by retrospective medical record review, conclude that phenytoin is rarely effective in controlling

    FSE in children and that exposure to phenytoin results in increased seizure duration and risk of brain injury. We would like to comment on a few issues:

    The authors hypothesize that phenytoin could be ineffective in treatment of FSE based on the observation that Sodium channel mutations have been linked to atypical Febrile seizures and that the sodium channel blocking effect of phenytoin may be impaired in the presence of a mutation. Sodium channel mutations have been reported in severe myoclonic epilepsy of infancy (Dravet syndrome) and in some families with generalized epilepsy with febrile seizures plus (GEFS+), and children with these syndromes may present with FSE [2]. Howev- er, most children presenting with FSE do not have these epilepsy syndromes, and long-term outcome studies have shown a good outcome after FSE, with only a small proportion developing epilepsy [3]. Also, as discussed by the authors, some studies have demonstrated a lack of efficacy of phenytoin in preventing febrile seizures, but none of these studies investigated the efficacy of phenytoin in acute treatment of seizures.
  • The authors report that 9 episodes (14.5%) had a
  • positive response, 25 episodes (40.3%) had a negative response, and 28 episodes (45.2%) had a nonevaluable response to phenytoin (because phenytoin was administered in combination with another anticonvulsant). We feel that the group with nonevaluable response should be excluded from the analysis because it is impossible to determine which anticonvulsant was effective in terminating the seizures. The results then show that

    9 (26.5%) of 34 episodes had a positive response to phenytoin, which is comparable with the reported 16.5% to 50% efficacy of second-line treatment of convulsive status epilepticus (CSE) in children [4-6].

    The authors also report that the median seizure duration was also significantly more prolonged in patients who did not respond to phenytoin (median, 90 [first quartile-third quartile, 60-155] minutes) com- pared with those who responded (median, 50 [45-70] minutes). This is not unexpected because the seizures not responding to any second-line treatment will have a longer seizure duration compared with the ones that respond. The authors do not provide the seizure duration before drug administration and also the number of doses of benzodiazepines administered in each group. The current evidence suggests that delay in treatment of seizures and lack of response to first- line treatment result in longer seizure duration [7]. Recent studies have reported that delay in administra- tion of second-line treatment (phenytoin, phenobarbi- tone, or sodium valproate) significantly increases the

    risk of refractory CSE [6,8]. It is possible that children not responding to phenytoin had a longer seizure duration before treatment and/or had received more than 1 dose of benzodiazepines and therefore were progressing to be refractory to treatment.

    Convulsive status epilepticus is the most common medical neUrologic emergency in childhood, and FSE is the single most common cause of CSE in children [9]. Phenytoin is used as the second-line drug in most CSE management protocols in children. Any study reporting the efficacy of phenytoin is likely to be read with interest by clinicians and therefore have a significant impact on clinical management of children with FSE. We agree that it is possible that children presenting with FSE may have yet unidentified genetic mutations, and also phenytoin may be ineffective in individuals with sodium channel mutations. We, however, feel strongly that it is inappropriate and misleading to generalize this to all children with FSE and conclude that there is a lack of efficacy of phenytoin based on a retrospective case note review with a small sample size. Further evidence from randomized controlled studies confirming the lack of efficacy of phenytoin in children with FSE is needed before recommending any change in CSE Treatment protocols.

    Suresh S. Pujar MRCPCH

    Neurosciences Unit, Institute of Child Health

    University College London and Great Ormond

    Street Hospital for Children NHS Trust

    WC1N 3LU, London, UK

    Young Epilepsy, Lingfield, Surrey, UK E-mail address: [email protected]

    Rod C. Scott MRCPCH

    Neurosciences Unit, Institute of Child Health

    University College London and Great Ormond

    Street Hospital for Children NHS Trust

    WC1N 3LU, London, UK

    Young Epilepsy, Lingfield, Surrey, UK

    Department of Neurology Dartmouth Medical School, Hanover, NH

    Richard F.M. Chin MRCPCH

    Neurosciences Unit, Institute of Child Health

    University College London and Great Ormond

    Street Hospital for Children NHS Trust

    WC1N 3LU, London, UK

    Muir Maxwell Epilepsy Research Centre, Child Life and Health

    University of Edinburgh

    Edinburgh, UK

    http://dx.doi.org/10.1016/j.ajem.2012.07.005

    References

    1. Ismail S, Levy A, Tikkanen H, et al. Lack of efficacy of phenytoin in children presenting with febrile status epilepticus. Am J Emerg Med 2012.
    2. Nakayama J, Arinami T. Molecular genetics of febrile seizures. Epilepsy Res 2006;70(S1):190-8.
    3. Raspall-Chaure M, Chin RF, Neville BG, et al. Outcome of paediatric convulsive status epilepticus: a systematic review. Lancet Neurol 2006; 5(9):769-79.
    4. Eriksson K, Metsaranta P, Huhtala H, et al. treatment delay and the risk of prolonged status epilepticus. Neurology 2005;65(8):1316-8.
    5. Chin RF, Neville BG, Peckham C, et al. Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population- based study. Lancet Neurol 2008;7(8):696-703.
    6. Lambrechtsen FA, Buchhalter JR. Aborted and refractory status epilepticus in children: a comparative analysis. Epilepsia 2008;49(4): 615-25.
    7. Yoong M, Chin RF, Scott RC. Management of convulsive status epilepticus in children. Arch Dis Child Educ Pract Ed 2009;94(1):1-9.
    8. Agarwal P, Kumar N, Chandra R, et al. Randomized study of intravenous valproate and phenytoin in status epilepticus. Seizure 2007;16(6): 527-32.
    9. Chin RF, Neville BG, Peckham C, et al. Incidence, cause, and short- term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet 2006;368(9531):222-9.

      Implications of early and accurate imaging for suspected transient ischemic attack

      To the Editor,

      Over and above the fact that the old definition of Transient ischemic attack was sometimes associated with “waiting to determine whether symptoms resolve in less than 24 hours to rule out stroke” and that this could delay treatment for Stroke prevention [1], there was also the danger that stroke patients who experienced rapid symptomatic improvement that fell short of full resolution of symptoms could misdiagnosed as TIA, thereby being denied thrombo- lytic treatment. This was the case in 12912 of 93517 patients who arrived in hospital within 2 hours of the onset of focal neurological symptoms, but did not receive Thrombolytic treatment. Despite initial symptomatic improvement, 26.7% of those 12912 patients subsequently deteriorated, and were no longer independently mobile on discharge [2]. In addition to the observation made by the authors that diffusion weighted imaging is superior to computed tomography for identification of brain infarcts (1) what also needs to be stressed is that magnetic resonance imaging is at least comparable to computed tomography for identification of acute intracranial hemorrhage within the 3 hour thrombolytic therapy time window [3]. Furthermore, in one study, ” even raters with limited film reading experience reached good accuracy” in identifying hyperacute intracerebral hemorrhage in patients who were imaged within 6 hours of symptom onset [4].

      Accordingly, for early and accurate diagnosis of ischemic and hemorrhagic stroke, so as to distinguish those two entities

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