Febrile Seizures: clinical and genetic studies

Febrile seizures are described as a temporary seizure disorder of childhood; the attacks occur by definition in association with fever and are usually accompanied by sudden tonic-clonic muscle contractions and reduced consciousness, usually lasting not longer than 5 to 10 minutes. According to the commonly accepted definition of the National Institutes of Health consensus meeting of febrile seizures in 1980, 'a febrile seizure (an abnormal, sudden, excessive electrical discharge of neurons [grey malter] which propagates down the neuronal processes [white matter] to affect an end organ in a clinically measurable fashion) is an event in infancy or childhood, usually occurring between three months and five years of age, associated with fever but without evidence of intracranial infection or defined cause. Seizures with fever in children who have suffered a previous nonfebrile seizure are excluded. Febrile seizures are to be distinguished from epilepsy, which is characterised by recurrent non febrile seizures'. 1 In the context of this thesis, fever has been defined as a rectally measured body temperature of 38.5 °C or higher. Complex febrile seizures have one or more of the foHowing characteristics: the seizure lasts for more than 15 minutes (prolonged) or 30 minutes or more (febrile status epilepticus); there are one or more recurrences within 24 hours (multiple type febrile seizures); the seizure has partial features, i.e. a focal onset of the seizure or a postictal Todd paresis of facial muscles or Iimbs. Seizures are referred to as simple, if they last less than 15 minutes, do not recur within 24 hours (single-type) and are generalised

Randomized, controlled trial of ibuprofen syrup administered during febrile illnesses to prevent febrile seizure recurrences

OBJECTIVES: Febrile seizures recur frequently. Factors increasing the risk of febrile seizure recurrence include young age at onset, family history of febrile seizures, previous recurrent febrile seizures, time lapse since previous seizure <6 months, relative low temperature at the initial seizure, multiple type initial seizure, and frequent febrile illnesses. Prevention of seizure recurrences serves two useful purposes: meeting parental fear of recurrent febrile seizures in general and reducing the (small) risk of a long-lasting and eventually injurious recurrent seizure. In daily practice, children with febrile seizures often are treated with antipyretics during fever to prevent febrile seizure recurrences. Thus far, no randomized placebo-controlled trial has been performed to assess the efficacy of intermittent antipyretic treatment in the prevention of seizure recurrence. METHODS: We performed a randomized, double-blind, placebo-controlled trial. Children 1 to 4 years of age who had had at least one risk factor for febrile seizure recurrence were enrolled. They were randomly assigned to either ibuprofen syrup, 20 mg/mL, 0.25 mL (= 5 mg) per kilogram of body weight per dose, or matching placebo, to be administered every 6 hours during fever (temperature, >/=38.5 degrees C). Parents were instructed to take the child's rectal temperature immediately when the child seemed ill or feverish and to promptly administer the study medication when the temperature was >/=38.5 degrees C. Doses were to be administered every 6 hours until the child was afebrile for 24 hours. The parents were instructed not to administer any other antipyretic drug to the child. For measuring rectal temperature, a Philips HP5316 digital thermometer (Philips, Eindhoven, The Netherlands) was distributed. During subsequent treatment of the fever episode, parents had to call the investigator at least once each day to notify the investigator in case of febrile seizure recurrence. The investigator could be contacted by parents 24 hours per day. The primary outcome was the first recurrence of a febrile seizure. Kaplan-Meier curves and Cox regression were used for the statistical analysis. The treatment effect on the course of the temperature was assessed using analysis of covariance, with temperature at fever onset as covariate. Two analyses were performed. In an intention-to-treat analysis, all first recurrences were considered regardless of study medication compliance. A per-protocol analysis was limited to those recurrences that occurred in the context of study medication compliance. RESULTS: Between October 1, 1994, and April 1, 1996, 230 children were randomly assigned to ibuprofen syrup (111 children) or placebo (119 children). Median follow-up time was 1.04 years (25th-75th percentiles; 0.7-1.8 years) in the ibuprofen group and 0.98 years (0.7-1.6 years) in the placebo group. Of all children, 67 had a first febrile seizure recurrence, with 31 in the ibuprofen group and 36 in the placebo group. The 2-year recurrence probabilities were 32% and 39%,

Frequency of fever episodes related to febrile seizure recurrence

The aim of this study was to assess the number of fever episodes as a risk factor for febrile seizure recurrence during the first 6 months after the last previous febrile seizure. In a 6-month follow-up study of 155 children, aged 3 months to 5 y, with a first or a recurrent febrile seizure, the occurrence of fever episodes and febrile seizure recurrences was prospectively documented. Using logistic regression analysis the association between the baseline characteristics and the number of fever episodes and the outcome, a febrile seizure recurrence, was studied. In total, 260 fever episodes were registered; 29 children experienced 1 or more febrile seizure recurrence during follow-up. Two factors were associated with febrile seizure recurrence: the number of fever episodes [odds ratio (OR)= 1.8; 95% confidence interval (CI): 1.4-2.4)] and age at study entry (OR=0.6; 95% CI: 0.3-1.1). In a multivariable model, only the number of fever episodes remained significant. In conclusion, the number of fever episodes increases the risk of a febrile seizure recurrence with a factor of 1.8 per fever episode in the first 6 months after a febrile seizure

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent

Temperature, age, and recurrence of febrile seizure

OBJECTIVE: Prediction of a recurrent febrile seizure during subsequent episodes of fever. DESIGN: Study of the data of the temperatures, seizure recurrences, and baseline patient characteristics that were collected at a randomized placebo controlled trial of ibuprofen syrup to prevent febrile seizure recurrences. SETTING: Two pediatric hospitals in the Netherlands. PATIENTS: A total of 230 children with an increased risk of febrile seizure recurrence. MAIN OUTCOME MEASURE: Seizure recurrence during a subsequent fever episode. RESULTS: A total of 509 episodes of fever were registered with 67 recurrences; 35 (52%) recurrences within the first 2 hours after fever of onset had a lower median temperature (39.3 degrees C) than 32 (48%) after more than 2 hours of fever (40.0 degrees C, P<.001). Poisson regression analysis resulted in 3 univariably significant (P<.05) predictors of a recurrence of sei

Migration of Umbilical Venous Catheters

OBJECTIVE:  Migration of umbilical venous catheters (UVCs) after initial correct position has been described. The aim of this study was to assess the incidence of malposition of the tip of the UVCs at 24 to 36 hours postinsertion. STUDY DESIGN:  Retrospective analysis of all neonates who had UVC placement in a 14-month period. The primary outcome was the rate of UVCs incorrectly positioned 24 to 36 hours after initial correct placement, defined as the UVC tip below or more than 5 mm above the level of the right diaphragm on a thoracoabdominal X-ray. RESULTS:  We included 86 neonates with a median (range) birth weight of 1,617 (535-5,000) grams, and gestational age of 31 (24-42) weeks. Of the 80 UVCs that were further analyzed, only in 38 (48%) of 80 patients, the tip of the UVC still had a correct position 24 to 36 hours after initial placement. In 22 (28%) of 80 patients, the UVCs had a position that was too high and in 20 (25%) that was too low. CONCLUSION:  More than half of UVCs migrated at 24 to 36 hours postinsertion to positions known to have higher complication rates. We, therefore, recommend follow-up evaluation at 24 to 36 hours postinsertion, to prevent complications from malposition