Paralytic syndromes in children: epidemiology and relationship to vaccination.

Acute flaccid paralysis is a standard outcome for detection of poliomyelitis globally and an ongoing potential vaccine-associated adverse event concern for polio, influenza, and meningococcal vaccines. No systematic population-based data on the epidemiologic and clinical features of this condition, or its potential association with immunization, have been reported from the United States. The present retrospective cohort study of acute flaccid paralysis in the Southern and Northern California Kaiser Permanente Health Care Plans was conducted using computerized diagnosis data and medical record review of potential cases among children aged 1 month to <15 years and diagnosed from January 1, 1992 through December 31, 1998. In all, 3297 potential cases were identified; of these, 2682 cases (81%) did not meet the case definition, and of the remaining 615 cases, 245 (7% of the total) were included. The incidence of disease was 1.4 per 100,000 children/year (95% confidence interval = 1.2-1.6); predicting approximately 844 children/year in the United States. Disease incidence did not vary with season or sex, varied inversely with age, and declined 28% during the study period. No cases of vaccine-associated acute flaccid paralysis were identified. In nonendemic countries, ongoing acute flaccid paralysis surveillance is often conducted, because of the risk of poliovirus importation, but this practice may be difficult to justify, given low disease incidence and breadth of clinical presentation.

A follow-up study of MPS I patients treated with laronidase enzyme replacement therapy for 6 years.

Recombinant human alpha-L-iduronidase (Aldurazyme, laronidase) was approved as an enzyme replacement therapy for patients with the lysosomal storage disorder, mucopolysaccharidosis I (MPS I). In order to assess the long-term safety and efficacy of laronidase therapy, 5 of 10 patients in the original laronidase Phase 1/2 clinical trial were re-evaluated after 6 years of treatment. Lysosomal storage was further improved at 6 years (urinary glycosaminoglycans (GAG) excretion decreased 76%; mean liver size at 1.84% of body weight). Shoulder maximum range of motion was maintained or further increased and reached a mean 33.2 (R) and 25.0 (L) degrees gained in flexion and 34.0 (R) and 27.3 (L) degrees gained in extension. Sleep apnea was decreased in four of five patients and the airway size index improved. Cardiac disease evaluations showed no progression to heart failure or cor pulmonale but pre-existing significant valve disease did progress in some patients. Substantial growth was observed for the pre-pubertal patients, with a gain of 33 cm (27%) in height and a gain of 31 kg in weight (105%). In general, the evaluated patients reported an improved ability to perform normal activities of daily living. Overall these data represent the first evidence that laronidase can stabilize or reverse many aspects of MPS I disease during long-term therapy and that early treatment prior to the development of substantial cardiac and skeletal disease may lead to better outcomes.

A randomized, double-blinded, placebo-controlled trial of phenytoin for the prevention of early posttraumatic seizures in children with moderate to severe blunt head injury.

STUDY OBJECTIVE: We determine the efficacy of prophylactic phenytoin in preventing early posttraumatic seizures in children with moderate to severe blunt head injury. METHODS: Children younger than 16 years and experiencing moderate to severe blunt head injury were randomized to receive phenytoin or placebo within 60 minutes of presentation at 3 pediatric trauma centers. The primary endpoint was posttraumatic seizures within 48 hours; secondary endpoints were survival and neurologic outcome 30 days after injury. A Bayesian decision-theoretic clinical trial design was used to determine the probability of remaining posttraumatic seizure free for each treatment group. RESULTS: One hundred two patients were enrolled, with a median age of 6.1 years. Sixty-eight percent were boys. The 2 treatment groups were well matched. During the 48-hour observation period, 3 (7%) of 46 patients given phenytoin and 3 (5%) of 56 patients given placebo experienced a posttraumatic seizure. There were no significant differences between the treatment groups in survival or neurologic outcome after 30 days. According to these results, the probability that phenytoin has the originally hypothesized effect of reducing the rate of early posttraumatic seizures by 12.5% is 0.0053. The probability that phenytoin has any prophylactic efficacy is 0.383. The median effect size in this trial was -0.015 (seizure rate increased by 1.5% in the phenytoin group), 95% probability interval -0.127 to 0.091 (12.7% higher rate of posttraumatic seizures to a 9.1% lower rate of posttraumatic seizures with phenytoin). CONCLUSION: The rate of early posttraumatic seizures in children may be much lower than previously reported. Phenytoin did not substantially reduce that rate.

Neurologic outcome score for infants and children.

OBJECTIVES: To develop and validate a practical outcome instrument applicable to a broad range of neurologic deficits in children. METHODS: Reliability testing of a draft version of the Neurologic Outcome Scale for Infants and Children (NOSIC) in 100 children with a wide range of ages and levels of neurologic function was performed. After review of the reliability data by a panel of experts, the NOSIC was revised. Validity and reliability testing of the final NOSIC was performed in a new population of 157 children, 52 with cerebral palsy, motor delay, or language delay. Interrater reliability was assessed using Spearman rank correlation coefficients of two investigators' scores. NOSIC scores were correlated with scores on criterion-standard neuropsychological tests to assess validity. RESULTS: The median NOSIC score for normal children was 98, interquartile range 96-100; the median score for abnormal children was 87, interquartile range 58-96. Interrater reliability of the NOSIC scores of 84 patients rated by both raters demonstrated excellent reliability (rho = 0.77, 95% confidence interval [CI] = 0.62 to 0.88). Correlation of the NOSIC scores of the 127 patients who had neuropsychological testing with applicable criterion standards was rho = 0.63, 95% CI = 0.50 to 0.74. CONCLUSIONS: The NOSIC is a practical, reliable, valid, instrument applicable to infants and children with a broad range of neurologic deficits. It should be a useful research tool when neurologic function is an important outcome measure.