Setting Sleep centres and paediatric neurology centres in England.Participants Children and young people aged 4-18 with onset of narcolepsy from January 2008. Main outcome measuresThe odds of vaccination in those with narcolepsy compared with the age matched English population after adjustment for clinical conditions that were indications for vaccination. The incidence of narcolepsy within six months of vaccination compared with the incidence outside this period measured with the self controlled cases series method.Results Case notes for 245 children and young people were reviewed; 75 had narcolepsy (56 with cataplexy) and onset after 1 January 2008. Eleven had been vaccinated before onset; seven within six months. In those with a diagnosis by July 2011 the odds ratio was 14.4 (95% confidence interval 4.3 to 48.5) for vaccination at any time before onset and 16.2 (3.1 to 84.5) for vaccination within six months before onset. The relative incidence from the self controlled cases series analysis in those with a diagnosis by July 2011 with onset from October 2008 to December 2010 was 9.9 (2.1 to 47.9). The attributable risk was estimated as between 1 in 57 500 and 1 in 52 000 doses. ConclusionThe increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children. IntroductionNarcolepsy is a chronic disorder presenting with excessive daytime sleepiness, often accompanied by a transient loss of muscle tone triggered by strong emotion (cataplexy). Diagnosis is based on clinical criteria and can be confirmed by polysomnography followed by a multiple sleep latency test. 1 Estimates of prevalence generally range between 25 and 50 per 100 000, though might be less in some populations, possibly because of differences in genetic susceptibility or exposure to aetiological risk factors.2 Information on incidence is more limited. Onset can occur at any age 2 but is commonest in those aged 10-19, in whom an incidence of 3.84 per 100 000 person years has been reported. 3 The interval between onset and diagnosis can be long, with a median of 10.5 years in one study. 4 Diagnostic delay is less in those with cataplexy and in younger patients. 5 There is a strong association with human leucocyte antigen (HLA) DQB1*0602 and reported associations with environmental factors such as streptococcal infection, 6 seasonal influenza, 7 and more recently pandemic A/H1N1 2009 influenza. 8 In England, a monovalent pandemic strain vaccine containing the oil-in-water adjuvant AS03 (Pandemrix) was introduced in October 2009 during the second wave of infection, initially for people with high risk clinical conditions 9 10 and then in healthy 12 A second pandemic vaccine was used (Celvepan) but accounted for less than 1% of the total.In August 2010 concerns were raised in Finland and Sweden about a possible associat...

Aim  To report the demographic, phenotypic, and time‐to‐diagnosis characteristics of children with GM2 gangliosidosis referred to the UK study of Progressive Intellectual and Neurological Deterioration. Method  Case notification is made via monthly surveillance card, administered by the British Paediatric Surveillance Unit to all UK‐based paediatricians; children with GM2 gangliosidosis were identified from cases satisfying inclusion in the UK study of Progressive Intellectual and Neurological Deterioration and analysed according to phenotypic and biochemical categories. Results  Between May 1997 and January 2010, 73 individuals with GM2 gangliosidoses were reported: 40 with Tay–Sachs disease, 31 with Sandhoff disease, and two with GM2 activator protein deficiency. Together they account for 6% (73/1164) of all diagnosed cases of progressive intellectual and neurological deterioration. The majority (62/73) were sporadic index cases with no family history. Children of Pakistani ancestry were overrepresented in all subtypes, particularly juvenile Sandhoff disease, accounting for 10 of 11 notified cases. Infantile‐onset variants predominated (55/73); the mean age at onset of symptoms was 6.2 and 4.7 months for infantile‐onset Tay–Sachs and Sandhoff disease respectively, and 26.2 and 34.7 months for the corresponding juvenile‐onset variants. Time to diagnosis averaged 7.4 months and 28.0 months in infantile‐ and juvenile‐onset disease respectively. Interpretation  GM2 gangliosidosis is a significant cause of childhood neurodegenerative disease; timely diagnosis relies upon improved clinical recognition, which may be increasingly important as specific therapies become available. There is a potential benefit from the introduction of screening programmes for high‐risk ethnic groups.

Although this study does not ascertain all UK cases, it provides a novel insight into the epidemiology of the neurodegenerative diseases that cause PIND in children. It is reassuring that in general these children are carefully investigated and that active surveillance has found only six children with vCJD. However, there is concern that more childhood vCJD cases may appear, possibly with a different genotype from those identified so far.

Aim To report on the epidemiology of the brain white matter disorders of children identified via a national prospective study. Method Since 1997 a study of UK children with progressive intellectual and neurological deterioration (PIND) has used the British Paediatric Surveillance Unit system to identify children with progressive neurodegenerative disease. This paper reports on children in the study with brain white matter disorders. Results Between May 1997 and November 2014 the PIND study identified 349 children with diagnosed leukodystrophies, giving an estimated UK lifetime risk of 31/million live births. There were 18 specific diseases in the group and relatively large numbers of affected children came from consanguineous Pakistani families. In addition there were 454 children with genetic leukoencephalopathies – in this group there were 38 diseases. 5.8% of children with scan evidence of brain white matter disorders did not receive a specific diagnosis. Interpretation These unique prospectively‐obtained national data avoid the selection bias inherent in reports from single centres. White matter disorders of the central nervous system comprise more than half of UK paediatric neurodegenerative diseases meeting the PIND criteria. This paper reports the lifetime risk/million live births for the commonest leukodystrophies, providing a basis for comparison with future studies.

Aim  Our aim was to study the clinical presentation, mode of diagnosis, and epidemiology of mitochondrial disorders in children from the UK who have progressive intellectual and neurological deterioration (PIND). Method  Since April 1997, we have identified patients aged 16 years or younger with suspected PIND through the monthly notification card sent to all UK consultant paediatricians by the British Paediatric Surveillance Unit. Clinical details obtained from reporting paediatricians are classified by an Expert Group. Results  By July 2008, 2493 cases of PIND had been reported, among which there were 112 children (69 males, 43 females) with mitochondrial diseases presenting between birth and 14 years 7 months (median 12mo), divided into 13 subgroups. In some instances, clinical features were characteristic of mitochondrial disease, but many children presented non‐specifically with combinations of developmental delay, hypotonia, failure to thrive, and seizures; 16 children had multisystem disease at presentation. Mortality was high: 40 children had died. Blood and/or cerebrospinal fluid lactate measurements were abnormal in 87 children, and 47 of 78 brain magnetic resonance images showed increased basal ganglia signal. Definite diagnoses were usually made by muscle enzyme or genetic studies. Interpretation  This is a unique population‐based study of the mitochondrial disorders that cause childhood neurodegenerative disease. It provides detailed information about the clinical presentation and investigation of these complex cases.