Ellen Wood

The Gross Motor Function Classification System for Cerebral Palsy: a study of reliability and stability over time

Children with cerebral palsy (CP) experience a change in motor function with age and development. It is important to consider this expected change in offering a prognosis, or in assessing differences in motor function after an intervention. The Gross Motor Function Classification System for CP (GMFCS) has been developed for these purposes. This study was based on a retrospective chart review of 85 children with CP followed from ≤2 to ≥12 years of age. The GMFCS was applied to clinical notes by two blinded raters four times throughout the study. Interrater reliability was high (G=0.93). Test‐retest reliability was high (G=0.79). The positive predictive value of the GMFCS at 1 to 2 years of age to predict walking by age 12 years was 0.74. The negative predictive value was 0.90. The GMFCS can validly predict motor function for children with CP. The results are discussed in terms of their implications for clinical practice and future research.

Increasing Prevalence of Cerebral Palsy Among Very Preterm Infants: A Population-Based Study

OBJECTIVES. It is unclear whether declines in neonatal and infant mortality have led to changes in the occurrence of cerebral palsy. We conducted a study to examine and investigate recent temporal changes in the prevalence of cerebral palsy in a population-based cohort of very preterm infants who were 24 to 30 weeks of gestational age. METHODS. A population-based cohort of very preterm infants who were born between January 1, 1993, and December 31, 2002, was evaluated by the Perinatal Follow-up Program of Nova Scotia. Follow-up extended to age 2 years to ascertain the presence or absence of cerebral palsy and for overall survival. Infant survival and cerebral palsy rates were compared by year and also in two 5-year periods, 1993–1997 and 1998–2002. Logistic regression analyses were used to identify factors that potentially were responsible for temporal changes in cerebral palsy rates. RESULTS. A total of 672 liveborn very preterm infants were born to mothers who resided in Nova Scotia between 1993 and 2002. Infant mortality among very preterm infants decreased from 256 per 1000 live births in 1993 to 114 per 1000 live births in 2002, whereas the cerebral palsy rates increased from 44.4 per 1000 live births in 1993 to 100.0 per 1000 live births in 2002. Low gestational age, postnatal dexamethasone use, patent ductus arteriosus, severe hyaline membrane disease, resuscitation in the delivery room, and intraventricular hemorrhage were associated with higher rates of cerebral palsy, whereas antenatal corticosteroid use was associated with a lower rate. CONCLUSION. Cerebral palsy has increased substantially among very preterm infants in association with and possibly as a consequence of large declines in infant mortality.

Stability of the Gross Motor Function Classification System in adults with cerebral palsy

To determine the stability of Gross Motor Function Classification System (GMFCS) levels between approximately 12 years of age and adulthood (i.e. > 16y) using a matched chart review. Adult health records from the Ottawa Rehabilitation Centre were matched with childhood health records from the Ottawa Childrens Treatment Centre (OCTC). Health records were available for 103 adults (52 males, 51 females) with cerebral palsy (CP; age range 17–38y; mean age 22y [SD 4y]) who had also been seen at the OCTC at a mean age of 12 years (SD 1y). GMFCS levels as adults were: Level I, n= 10; Level II, n= 24; Level III, n= 21; Level IV, n= 30; and Level V, n= 18. Adult participants were classified using the GMFCS at the time they were last seen by a rehabilitation specialist, sometime between June 2002 and June 2005. Corresponding paediatric charts were reviewed and classified by two independent raters blinded to the adult GMFCS levels. GMFCS levels around age 12 were: Level I, n= 20; Level II, n= 13; Level III, n= 22; Level IV, n= 35; and Level V, n= 13. Interrater reliability for childhood health records was determined with a quadratic weighted kappa and was 0.978. Stability of GMFCS levels was also assessed using the quadratic weighted kappa and was 0.895. The positive predictive value of the GMFCS at 12 years of age to predict walking without mobility aids by adulthood is 0.88. If the child is a wheelchair user at around age 12 years, the positive predictive value is 0.96 that the individual will still be a wheelchair user as an adult. This study supports previous findings that interrater reliability when using the GMFCS is very high. It also shows that the GMFCS level observed around the age of 12 years is highly predictive of adult motor function. This provides important information for individuals with CP, their families, and care providers as they plan for future care needs and rehabilitation intervention.

Relation of Pregnancy and Neonatal Factors to Subsequent Development of Childhood Epilepsy: A Population-Based Cohort Study

OBJECTIVE. We examined the effect of pregnancy and neonatal factors on the subsequent development of childhood epilepsy in a population-based cohort study. PATIENTS AND METHODS. Children born between January 1986 and December 2000 in Nova Scotia, Canada were followed up to December 2001. Data on pregnancy and neonatal events and on diagnoses of childhood epilepsy were obtained through record linkage of 2 population-based databases: the Nova Scotia Atlee Perinatal Database and the Canadian Epilepsy Database and Registry. Factors analyzed included events during the prenatal, labor and delivery, and neonatal time periods. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals. RESULTS. There were 648 new cases of epilepsy diagnosed among 124207 live births, for an overall rate of 63 per 100000 person-years. Incidence rates were highest among children <1 year of age. In adjusted analyses, factors significantly associated with an increased risk of epilepsy included eclampsia, neonatal seizures, central nervous system (CNS) anomalies, placental abruption, major non-CNS anomalies, neonatal metabolic disorders, neonatal CNS diseases, previous low birth weight infant, infection in pregnancy, small for gestational age, unmarried, and not breastfeeding infant at the time of discharge from hospital. CONCLUSIONS. Our study supports the concept that prenatal factors contribute to the occurrence of subsequent childhood epilepsy.

Self‐Reported Headache Frequency in Canadian Adolescents: Validation and Follow‐Up

Objective.—To validate our previous estimates of the prevalence of frequent headache and associated factors in a new sample of 12‐ to 13‐year‐old adolescent Canadians, and to explore if estimates of the prevalence of frequent headache and associated factors remain stable within the original cohort after a two‐year interval.

Does the risk of cerebral palsy increase or decrease with increasing gestational age

BackgroundIt is generally accepted that the risk of cerebral palsy decreases with increasing gestational age of live born infants. However, recent studies have shown that cerebral palsy often has prenatal antecedents including congenital malformations, vascular insults and maternal infection. Cerebral palsy is therefore better viewed as occurring among fetuses, rather than among infants. We explored the epidemiologic implications of this change in perspective.MethodsWe used recently published data from Shiga Prefecture, Japan and from North-East England to examine the pattern of gestational age-specific rates of cerebral palsy under these alternative perspectives. We first calculated gestational age-specific rates of cerebral palsy as per convention, by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of live births in that gestational age category. Under the alternative formulation, we calculated gestational age-specific rates of cerebral palsy by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of fetuses who were at risk of being born at that gestation and being afflicted with cerebral palsy.ResultsUnder the conventional formulation, cerebral palsy rates decreased with increasing gestational age from 63.9 per 1,000 live births at <28 weeks gestation to 0.9 per 1,000 live births at 37 or more weeks gestation. When fetuses were viewed as potential candidates for cerebral palsy, cerebral palsy rates increased with increasing gestational age from 0.08 per 1,000 fetuses at risk at <28 weeks gestation to 0.9 per 1,000 fetuses at risk at 37 or more weeks gestation.ConclusionsThe fetuses-at-risk approach is the appropriate epidemiologic formulation for calculating the gestational age-specific rate of cerebral palsy from a causal perspective. It shows that the risk of cerebral palsy increases as gestational duration increases. This compelling view of cerebral palsy risk may help refocus research aimed at understanding and preventing cerebral palsy.

The epidemiology of infantile spasms

OBJECTIVE The aim of this study was to estimate population based incidence rates for infantile spasms (IS) and to study our clinical impression that the incidence of IS has recently decreased in the Canadian Provinces of Nova Scotia and Prince Edward Island. METHODS Birth cohorts from 1978 to 1998, identified through the hospital health records, EEG records and physician computerized databases, were followed for two years for the development of IS. Disease incidence rates were calculated using denominators derived from Statistics Canadas reported annual live birth rates. RESULTS The inclusion criteria for IS were fulfilled by 75 patients. The overall incidence of IS was 30.7/100,000 live births (95% Cl 24.3, 38.8). Etiologic classification was symptomatic for 51 cases (68%), cryptogenic for 18 (24%), and idiopathic in six children (8%). Although there were more males (N=44) than females (N=31), the incidence rates were similar. There was a marked variability in annual and five-year incidence rates. CONCLUSIONS Although the clinical characteristics of our patients were similar to other reported IS populations, the instability in IS incidence rates indicates a need for caution in interpreting smaller IS epidemiologic studies.

The utility of the physical examination and investigations in the pediatricneurology consultation

For most consultations the diagnosis is established by a thorough clinical history. We prospectively assessed the impact of each component of the pediatric neurologic consultation in 500 consecutive referrals to a tertiary care pediatric neurology clinic. Diagnosis and management decisions were declared for each patient by the consultant after each stage of the consultation process (1: receipt of consultation letter, 2: history, 3: physical examination and 4: receipt of investigation results). We found that the physical examination and investigations influenced management decisions for less than 6%. Specifically the examination was never influential for children with headaches, Tourette syndrome, developmental delay or attention-deficit-hyperactivity disorder (ADHD). Investigations never influenced management for those with Tourette syndrome, ADHD, or cerebral palsy. Therefore for the majority of children the critical component of the pediatric neurology consultation is a detailed clinical history.

Successful treatment of severe infantile hyperekplexia with low-dose clobazam.

We report two cases of severe infantile hyperekplexia successfully treated with low-dose clobazam. The first case presented at 6 weeks of age with multiple episodes consisting of difficulty diapering because of stiffness and loud inspiratory noises followed by breath-holding in inspiration. She was diagnosed with hyperekplexia and started on clonazepam 0.05 mg daily. This was discontinued because of excessive sleepiness. The second case presented at 3 weeks of age with episodes of crying that would change in pitch and then abruptly stop, followed by leg and arm extension and stiffening. On occasion, there was cyanosis, and she received mouth-to-mouth resuscitation. She was diagnosed with hyperekplexia at 9 months of age. Both infants were treated with clobazam (0.25 and 0.3 mg/kg/day respectively), resulting in resolution of symptoms with no side effects. During treatment, both had minimal startle response to various stimuli and have now been successfully weaned from clobazam. Low-dose clobazam is effective in the treatment of hyperekplexia and is well tolerated in infants. (J Child Neurol 2002;17:154-156).

A novel rearrangement of occludin causes brain calcification and renal dysfunction

Pediatric intracranial calcification may be caused by inherited or acquired factors. We describe the identification of a novel rearrangement in which a downstream pseudogene translocates into exon 9 of OCLN, resulting in band-like brain calcification and advanced chronic kidney disease in early childhood. SNP genotyping and read-depth variation from whole exome sequencing initially pointed to a mutation in the OCLN gene. The high degree of identity between OCLN and two pseudogenes required a combination of multiplex ligation-dependent probe amplification, PCR, and Sanger sequencing to identify the genomic rearrangement that was the underlying genetic cause of the disease. Mutations in exon 3, or at the 5–6 intron splice site, of OCLN have been reported to cause brain calcification and polymicrogyria with no evidence of extra-cranial phenotypes. Of the OCLN splice variants described, all make use of exon 9, while OCLN variants that use exons 3, 5, and 6 are tissue specific. The genetic rearrangement we identified in exon 9 provides a plausible explanation for the expanded clinical phenotype observed in our individuals. Furthermore, the lack of polymicrogyria associated with the rearrangement of OCLN in our patients extends the range of cranial defects that can be observed due to OCLN mutations.