Mortality from childhood stroke in England and Wales, 1921-2000.

OBJECTIVE: Stroke is an important but under-recognised cause of childhood mortality. The authors aimed to describe the trends in mortality from childhood stroke in England and Wales between 1921 and 2000. DESIGN: The study searched the Office for National Statistics mortality database for the years 1921-2000 using appropriate, previously validated International Classification of Diseases codes. Mortality rates were analysed by period of death, gender, age at death, birth cohort and stroke subtype. RESULTS: 6029 deaths from childhood stroke were found between 1921 and 2000. Analysis by period of death demonstrated an initial decline in mortality followed by a steep rise in the 1940s. Subsequently, rates declined from the late 1960s onwards. At all time points males had a higher mortality rate than females. Infants had a relatively high mortality rate (24.5 per million person years) but rates fell steeply in early childhood (2.5 per million person years at age 5-9 years) before rising again in late adolescence (7.5 per million person years at age 15-19 years). An increased rate was found for males at all ages (RR = 1.24, p<0.0001) but was greatest in infancy (RR = 1.45, p<0.0001). Haemorrhagic stroke accounted for 71% of stroke deaths. Birth cohort analysis showed a trend of declining mortality with each successive generation since the 1950s. CONCLUSIONS: This study describes characteristics and temporal changes in childhood stroke mortality in the 20(th) century. In particular, the higher mortality rates in males and infants, the importance of deaths from haemorrhagic stroke and the finding of a decline in birth cohort mortality since the 1950s provide aetiological insights.

Running an international paediatric non-commercial clinical trial.

The current regulations for conducting non-commercial clinical trials in Europe are many and complex. These are explored from the perspective of a UK based non-commercial international clinical trial. The reasons for the difficulties encountered are discussed and suggestions made as to how best to overcome them. Improvements are suggested for our law makers and competent authorities. It is argued that the current regulatory environment could be considered unethical as it inhibits and delays research.

Subependymal nodules, giant cell astrocytomas and the tuberous sclerosis complex: a population-based study.

OBJECTIVES: (1) In a population-based study of tuberous sclerosis (TSC), to identify the number of patients presenting with symptomatic giant cell astrocytomas (GCAs); (2) within a subset of this population, to identify the number who would be diagnosed with GCAs on predetermined radiological criteria. METHODS: Patients with TSC in Wessex (a geographical region of England) were identified, and their medical history determined. A subset were invited to have a cranial MRI if they did not have a history of a symptomatic GCA and if they were likely to tolerate cranial imaging without a general anaesthetic. Scans were performed according to a standard protocol on a single scanner and were reported blindly by a neuroradiologist. RESULTS: 179 people were identified with TSC. Ten of these had a history of treatment for a symptomatic GCA. Forty-one of the remainder had a cranial MRI. Thirty-nine of these had subependymal nodules, of whom 24 (59%) had at least one (maximum 11) that showed enhancement with gadolinium. In seven (17%), the lesion was >1 cm, and all of these lesions showed gadolinium enhancement. CONCLUSIONS: In this study, the proportion of patients with TSC who had a history of symptomatic GCA was 5.6%. In the subset without such a history, who underwent imaging, the number diagnosed as having a GCA on radiological criteria was much higher (59% gadolinium enhancement and 17% >1 cm in size). Screening for GCAs (performing scans on asymptomatic patients with TSC) would therefore identify large numbers of patients who had not presented with symptoms. This finding leads us to recommend that screening should not be undertaken.

The relation of infantile spasms, tubers, and intelligence in tuberous sclerosis complex.

BACKGROUND: The aetiology of the learning difficulty in tuberous sclerosis is debated. It may be related to the amount of tubers in the brain or caused by the infantile spasms that occur in early life. AIMS: To examine the relative contributions to final intelligence (IQ) made by both cerebral tubers and infantile spasms. METHODS: As part of an epidemiological study of tuberous sclerosis in the south of England, patients were recruited who were able to undergo magnetic resonance imaging (MRI) without the need for an anaesthetic. Epilepsy history was determined by interview and review of clinical records. IQ was assessed using either Wechsler intelligence scales or Raven's matrices. RESULTS: A total of 41 patients consented to have an MRI scan. IQ scores were normally distributed about a mean of 91. Twenty six patients had a positive history of epilepsy, and 11 had suffered from infantile spasms. There was a significant relation between the number of tubers and IQ. Infantile spasm status partly confounded the relation between tubers and IQ, but did not render the relation statistically insignificant. The relation between infantile spasms and learning difficulty remained strong even when controlling for the number of tubers.