Narcolepsy In Children Research Articles

Chapter 18 - Autoimmune sleep disorders

A number of autoantibodies, some paraneoplastic, are associated with sleep disorders. Morvan syndrome and limbic encephalitis, associated with voltage-gated potassium channel-complex antibodies, principally against CASPR2 and LGI1, can result in profound insomnia and rapid eye movement sleep behavior disorder (RBD). Patients with aquaporin-4 antibodies and neuromyelitis optica may develop narcolepsy in association with other evidence of hypothalamic dysfunction, sometimes as the initial presentation. Central sleep apnea and central neurogenic hypoventilation are found in patients with anti-N-methyl-d-aspartate receptor antibody encephalitis, and obstructive sleep apnea, stridor, and hypoventilation are prominent features of a novel tauopathy associated with IgLON5 antibodies. In addition, paraneoplastic diseases may involve the hypothalamus and cause sleep disorders, particularly narcolepsy and RBD in those with Ma1 and Ma2 antibodies. Patients with antineuronal nuclear autoantibodies type 2 may develop stridor. Several lines of evidence suggest that narcolepsy is an autoimmune disorder. There is a strong relationship with the human leukocyte antigen (HLA) DQB1*06:02 haplotype and polymorphisms in the T-cell receptor alpha locus and purinergic receptor P2Y11 genes. Patients with recent-onset narcolepsy may have high titers of antistreptococcal or other antibodies, although none has yet been shown to be disease-specific but, supporting an immune basis, recent evidence indicates that narcolepsy in children can be precipitated by one type of vaccination against the 2009-2010 H1N1 influenza pandemic.

Utility of nocturnal SOREMP for diagnosing narcolepsy in children

Utility of nocturnal SOREMP for diagnosing narcolepsy in children

Clinical features of obese children with narcolepsy

Objective To analyze the clinical characteristics of narcolepsy in children with obesity, and to evaluate the impact of obesity on narcoleptic children clinically. Methods Forty cases first diagnosed as narcolepsy were recruited in the study who to see doctors at the Department of Neurology, Children's Hospital of Capital Institute of Pediatrics, from July 2012 to January 2015.According to diagnostic criteria for obesity by the body mass index(BMI)growth curve for the Chinese children and adolescents, they were divided into the obese group and the nonobese group.The general clinical data of 2 groups were analyzed, and the related metabolic indexes and the whole night polysomnography(PSG) of 2 groups were studied. Results In this group, male versus female 3:1, obesity was found in 21 cases(52.5%) and nonobesity was found in 19 cases(47.5%) from the samples.The mean BMI of all patients was(21.55±3.11) kg/m2.The average BMI of the obese group was(23.09±2.46) kg/m2, and BMI of the non-obese group was(19.85±2.89) kg/m2.Obese children were younger at the onset of disease and by the time of diagnosis age [(7.94±2.22)years old, (8.76±2.36) years old] than nonobese children[(10.75±3.10)years old, (12.51±2.88) years old]. The fasting blood glucose and blood lipid in all patients were normal, and there was no significant difference between 2 groups.The total sleep time, sleep efficiency and the ratio of rapid eye movement(REM) phase of the obese group[(397.45±53.76) min, (68.70±8.90)%, (18.37±4.39)%]were significantly lower than those of the non-obese group [(449.95±86.49) min, (76.58±13.60)%, (22.19±6.34)%]. According to the sleep structure, the percentage of stageⅠnon rapid eye movement(NREM) sleep in the obese group[(20.90±6.38)%] was more than that in non-obese group[(16.26±4.22)%]. There was no difference between the percentage of stage ⅡNREM sleep in the obese group[(42.59±5.52)%]and the non-obese group[(38.54±8.74)%]. Stage Ⅲ+ Ⅳ(slow wave sleep) NREM sleep ratio in the obese group[(18.14±6.97)%] was significantly lower than that in the non-obese group[(22.60±5.69)%]. Conclusions Obesity is one of the most common comorbids in narcolepsy, which affects more than 50% of narcoleptic children, mostly younger at disease onset.The narcolepsy children with obesity has total sleep time decreased, sleep efficiency reduced and sleep structure disorder is more obvious.To improve the realization of obesity in narcolepsy children and early treatment is the key to the success of the therapy. Key words: Narcolepsy; Obesity; Child

Methylphenidate use among medical students at Ben-Gurion University of the Negev.

Introduction:Methylphenidate is a psychotropic agent commonly used for the treatment of attention deficit disorder with or without hyperactivity and narcolepsy in children and adults. The awareness to attention deficit disorder as well as the non-medical use of methylphenidate for cognitive enhancement has increased during the past years.Objectives:To evaluate the medical and non-medical use of methylphenidate among medical students in the Ben-Gurion University of the Negev.Materials and Methods:Medical students were asked to report methylphenidate use, symptoms and diagnosis of attention deficit disorder using a structured questionnaire.Results:A total of 229 students participated in the study, out of which 105 (45.9%) were in the pre-clinical years of medical school. Twenty-two students (9.6%) were previously diagnosed with attention deficit disorder. Lifelong use of methylphenidate was reported by 39 (17%) students, while 31 students (13.5%) reported using methylphenidate during the preceding 12 month. In the beginning of medical school, only 7% of the students used methylphenidate, most of them began using it during pre-clinical academic years.Discussion:High rates of attention deficit disorder compared to the general population were reported by medical students. The rate of methylphenidate use is similar to recent report from a US medical school, and is considerably higher than in college students population.Conclusions:Many medical students are using methylphenidate without a medical indication. Further study is needed to evaluate the effect of methylphenidate on academic performance of healthy adults.

Clinical Profile of Narcolepsy in Children in India

Clinical Profile of Narcolepsy in Children in India

Neuroimmunology: Disease mechanisms in narcolepsy remain elusive.

A pandemic influenza vaccine with a specific type of vaccine antigen has been linked to an increased incidence of narcolepsy in children from 2009–2010. However, the recent retraction of an article that reported a putative autoantigen means that the search for the mechanisms behind the vaccine–narcolepsy connection continues.

IS-012 Narcolepsy In Children, Clinical Aspects

Narcolepsy gives rise to a complex picture of symptoms that range from daytime sleepiness and REM-associated cataplexies, hypnagogic hallucinations and sleep paralysis into severe sleep disturbances, metabolic disturbances and psychological as well as social problems. The compound symptoms influence the well-being of the growing and maturing young person in a way that may impair the development of the personality, self-confidence and esteem. It is of great value if the treatment can be run within a multi-disciplinary team including neuropaediatrician, endocrinologist, dietician, nurse, physiotherapist, social worker and psychologist. Treatment of narcolepsy is best started with wake-supporting steps. Sleep hygiene and power naps are part of the strategy but central stimulant medication is most often needed. The cataplectic attacks are the symptoms considered most disturbing by the patients. They may improve by reduced daytime sleepiness but specific treatment is needed and is difficult to make efficient. Night sleep disturbances may respond well to sodium oxybate, a drug that also influences daytime wakefulness and cataplexies. This far no curative therapy has been found. Future development may lead to specific agents that can influence the hypocretine/orexine system and ways to influence the autoimmune mechanism underlying the disease.

Clinical features of narcolepsy in children vaccinated with AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine in England.

AimThe aim of this study was to investigate whether children in England with narcolepsy who received the ASO3 adjuvanted pandemic A/H1N1 2009 influenza vaccine (Pandemrix) differed clinically from unvaccinated patients.MethodA retrospective review was conducted in children with narcolepsy diagnosed by sleep centres and paediatric neurologists in 16 English hospitals. The inclusion criteria were patient age 4 to 18 years, onset of narcolepsy after January 2008, and diagnosis by the time of the key data-gathering visit in 2011. Clinical data came from hospital notes and general practitioner questionnaires. An expert panel validated the diagnoses.ResultsSeventy-five patients with narcolepsy were identified (43 males, 32 females; mean age at onset 10y 4mo, range 3–18y). Of these patients, 11 received the Pandemrix vaccine before narcolepsy onset. On first presentation, there were more frequent reports of cataplexy, among other features, in vaccinated than in unvaccinated patients (82% vs 55%), but only excessive weight gain (55% vs 20%) was significantly more frequent (p=0.03). Facial hypotonia (p=0.03) and tongue protrusion (p=0.01) were eventually seen more frequently in vaccinated children. When considering patients diagnosed within a year of onset, vaccinated children were not diagnosed more rapidly than unvaccinated children.InterpretationSome symptoms and signs of narcolepsy were more frequently reported in Pandemrix–vaccinated patients. There was no evidence of the more rapid diagnosis in vaccinated patients that has been reported in Finland and Sweden.

The diagnosis and treatment of pediatric narcolepsy.

Narcolepsy in children is a serious disorder marked by a chronic course and lifelong handicap in school performance and choice of employment, by free time activity limitation, and by behavior and personality changes, all of which constitute a major influence on the quality of life. Increased daytime sleepiness may be the only sign at the disease onset, with attacks of sleep becoming longer and lasting up to hours. Also present may be confusional arousals with features of sleep drunkenness. Paradoxically, preschool and young children may show inattentiveness, emotional lability, and hyperactive behavior. Cataplexy may develop after onset of sleepiness and affect mainly muscles of the face. Hypnagogic hallucinations and sleep paralysis are seldom present. Multiple Sleep Latency Test criteria are not available for children younger than 6 years. The haplotype (HLA-DQB1:0602) can be associated with the disorder; however, the best predictor of narcolepsy-cataplexy is hypocretin deficiency. The treatment generally used in adults is regarded as off-label in childhood, which is why the management of pediatric narcolepsy is difficult.

G342(P) Weak at the knees with laughter

Narcolepsy is a chronic neurological disorder characterised by excessive daytime sleepiness, cataplexy, hallucinations in sleep-wake phase and sleep paralysis.Case reports (methods)We present a case series of children with narcolepsy from...

EPA-0748 – Methylphenidate abuse: results of a french survey

Introduction Methylphenidate (MPH) abuse is well established especially among young people in USA. In France, MPH is indicated in treatment for attention deficit/hyperactivity disorder (ADHD) in children and narcolepsy in children and adults. Since its release onto the market, MPH abuse has been progressively increasing by individuals close to children treated with MPH and especially by patients to whom MPH is prescribed offlabel or obtained in black market. Objectives We report the results of a national survey on abuse and off-label use of methylphenidate. Methods Assessment of data collected between 2000 and 2011 from the Nots, OPPIDUM and OPEMA databases (tools for monitoring psychoactive substance misuse). Results MPH abuse and misuse were identified in 245 patients (168 in NotS, 68 in Oppidum and 9 in Opema). In NotS database, subjects were predominantly males (65%), aged between 12 and 74 years. When specified (122 cases), the sustained release form was used in 83% of cases and maximum daily MPH intake reached 2520 mg. MPH was injected (20%) or snorted (4%). Polydrug use was noted in 77% of cases. Regarding Oppidum and Opema databases, patients were exclusively adults and supported for drug addiction. In these cases, MPH was obtained by medical prescription (61%) and/or in black market (36%). Conclusion The medical practice of off-label prescription of MPH to treat ADHD or drug addiction in adults is the main problem in France. Another new aspect is that MPH is also diverted by teenagers, with or without ADH, for its stimulant and concentration-enhancing properties.

Modafinil for the treatment of idiopathic hypersomnia – results of a randomized, double-blind, placebo controlled study

The European Medicines Agency withdrew modafinil for the indications idiopathic hypersomnia (IH) and narcolepsy in children due to the lack of sufficient evidence based literature. The literature provides mainly retrospective data. Lavault et al. (Sleep Medicine 2011) found modafinil to be the medication of first choice in 96% of IH patients resulting in a reduction of ESS of 2.6–3 points. The purpose of our study was to study the effects of modafinil on ESS and sleep latency in the MWT (primary variables) of IH patients. In this investigator initiated study only drug naïve IH patients without long sleep according to ICSD2 criteria were included. Disease onset had to be before the age of 30 years. Patients were consecutively recruited from 3 German Sleep Centers and randomized to placebo or 200 mg modafinil once daily in the morning. Visit 1 on day 1 (drug naïve) included vital signs, ESS, medical history, physical investigation and laboratory tests. Throughout the 28 days patients filled in evening morning protocols. Patients were on medication from days 8–21. On days 7, 14 and 21 MWT, ESS and CGI were performed. 14 IH were randomized to modafinil (10 m, 4f, mean age 38.4 ± 12.7 years), 17 (9 m, 8f, mean age 34.8 ± 13.5 years) to placebo. One patient was excluded due to protocol violation. In the intention to treat analysis ESS was significantly reduced in the modafinil group by 5.4 points, compared to 1.9 points in the placebo group ( p < 0.023, effect size 0.64), sleep latency in the MWT was not significantly prolonged (4.9 vs. 1.5 min.), CGI was significantly improved (−01.4 vs. −0.36, p < 0.028, effect size 0.61). Manovas showed no interaction of gender and ESS, but the differences were smaller for men than for women. There was no age effect. Modafinil 200 mg improves ESS and CGI significantly when compared to placebo. The increase of sleep latency in the MWT is not significant. There is no interaction with age and gender. Modafinil is an effective medication in adult patients with idiopathic hypersomnia without long sleep. This investigator initiated study was financed by Cephalon Germany.

Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France

An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects aged<18 years, and 4.7 (1.6-13.9) in those aged 18 and over. Sensitivity analyses considering date of referral for diagnosis or the date of onset of symptoms as the index date gave similar results, as did analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n=32; mostly AS03-adjuvanted vaccine, n=28) to non-exposed cases (n=30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In this sub-analysis, H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association cannot be completely ruled out, the associations appeared robust to sensitivity analyses, and a specific analysis focusing on ASO3-adjuvanted vaccine found similar increase.

Fall-Kontroll-Studie zu Risikofaktoren von Narkolepsie in Deutschland

Through June 2010 several cases of narcolepsy were reported in Sweden and Finland in children and adolescents from 12 to 16 years after immunisation with Pandemrix®, so that an association was suspected. To test this hypothesis, multiple studies were initiated. Within the scope of several European epidemiological studies, an association between the vaccination with Pandemrix® and the occurrence of narcolepsy in children and adolescents was demonstrated. An increased risk of narcolepsy in vaccinated adults compared to non-vaccinated individuals was also reported in France. The Paul-Ehrlich-Institut is conducting a nationwide epidemiological study on the risk factors of narcolepsy in collaboration with the German Sleep Society (DGSM). The study started in May 2011 and is still ongoing. An amendment was approved by the local Ethics Committee in December 2012. The study design is a retrospective matched multicentre case–control study. The recruitment of suspected cases of narcolepsy is performed in German sleep centres identifying in the clinic’s information system patients who were referred from 1 April 2009 to 31 December 2012 to a sleep centre to have a multiple sleep latency test performed due to excessive daytime sleepiness. Suspected cases of narcolepsy are validated according to the preliminary case definition proposed by the Brighton Collaboration (BC) by two independent experts. As soon as a case is validated, age- and gender-matched population-based controls are recruited from the same postal code area (first two digits of the postal code). A second control group comprises so-called test-negative controls, i.e. patients with excessive daytime sleepiness, in whom narcolepsy was definitely excluded. Via telephone interview information on preceding medical conditions, infections and immunisations are recorded. The statistical analysis is performed by a multivariate conditional logistic regression. This article reports the present state of knowledge on the association between the vaccination with pandemic influenza vaccine and narcolepsy and describes the amended study design.

Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis

Objective To evaluate the risk of narcolepsy in children and adolescents in England targeted for vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine (Pandemrix) from October 2009.Design Retrospective analysis. Clinical...

The incidence of narcolepsy in Europe: Before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns

BackgroundIn August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification. MethodsWe used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000–2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom. ResultsOverall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90–0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women>men) and around 60 years of age. In the age group 5–19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1–3.1) in Denmark, 6.4 (95% CI: 4.2–9.7) in Finland and 7.5 (95% CI: 5.2–10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time. ConclusionsThe results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.

Decreased incidence of childhood narcolepsy 2 years after the 2009 H1N1 winter flu pandemic

increased several fold in China following the H1N1 winter flu pandemic (pH1N1). 1 In parallel with this report, increased incidence was also reported in several countries in Northern Europe, with many children developing the disease following administration of Pandemrix, an adjuvanted pH1N1 vaccine. Studies in Sweden, Finland, and Norway have shown a 4- to 13fold increased risk of developing childhood narcolepsy following Pandemrix (only 1 of 16,000 vaccinated children developed narcolepsy, however). 2–4 These results bolster the claim that narcolepsy, an autoimmune disease caused by hypocretin cell loss, could be triggered by H1N1 vaccination or infection. Further evidence of causality may come from studying narcolepsy incidence following the 2009 pandemic, as H1N1 infections decreased in subsequent seasons. In the Figure, we report on the evolution of new onset cases at Beijing University People’s Hospital. For better comparison, we only present data on cases diagnosed within 1 year of onset, so that data are comparable to prior years. Data from 2012 are also included, although curtailed after September, so that a few cases with onset in the first 3 months of 2012 will still be identified (denoted with a star and not used in any statistical analysis). As can be seen, a return to baseline is evident, suggesting that the 2009–2010 winter was a unique event. We next examined whether patients identified following the pH1N1 pandemic season differed clinically. As before, to avoid issues pertaining to evaluation time since onset, we only compared subjects diagnosed within 1 year of onset. In 1998–2009, 2010, and 2011 respectively, 187, 201, and 49 subjects were identified (mean 6 standard error of the mean delay to diagnosis: 4.7 6 0.3, 4.4 6 0.2, and 4.6 6 0.4 months). Sex, body mass index, age at diagnosis, occurrence and age of onset of each narcolepsy symptom (ie, sleepiness, cataplexy, sleep paralysis, hypnagogic hallucination, and disturbed nocturnal sleep), and sleep recording findings (Multiple Sleep Latency Test, Apnea Hypopnea Index) were next compared across the 3 groups. Remarkably few differences were found. First, although mean age of onset in subjects diagnosed in 2010 was younger than in those diagnosed before and after 2010, differences were not statistically significant (8.7 6 0.4 years in 2010 vs 10.0 6 0.7 years before and 10.1 6 1.7 years in 2011, p ¼ 0.2). Second, sleep-onset rapid eye movement periods during the multiple latency tests were more numerous in cases diagnosed in 2010 versus others, whether or not controlled with age (4.65 6 0.05 in 2010 vs 4.32 6 0.05 before and 4.00 6 0.18 years in 2011, p < 0.001), suggesting increased severity. All other parameters were similar across groups. We conclude that pH1N1 infections during the 2009–2010 season have likely played a role in triggering narcolepsy in children, but that the phenotypes of these cases is not distinguishable from prior cases.

Late-Onset Obsessive-Compulsive Disorder With Comorbid Narcolepsy After Perfect Blend of Thalamo-Striatal Stroke and Post-Streptococcal Infection

Late-Onset Obsessive-Compulsive Disorder With Comorbid Narcolepsy After Perfect Blend of Thalamo-Striatal Stroke and Post-Streptococcal Infection

Vaccines for preventing influenza in healthy children.

The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years of age. To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children, assess vaccine efficacy (prevention of confirmed influenza) and effectiveness (prevention of influenza-like illness (ILI)) and document adverse events associated with influenza vaccines. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3) which includes the Acute Respiratory Infections Group's Specialised Register, OLD MEDLINE (1950 to 1965), MEDLINE (1966 to November 2011), EMBASE (1974 to November 2011), Biological Abstracts (1969 to September 2007), and Science Citation Index (1974 to September 2007). Randomised controlled trials (RCTs), cohort and case-control studies of any influenza vaccine in healthy children under 16 years of age. Four review authors independently assessed trial quality and extracted data. We included 75 studies with about 300,000 observations. We included 17 RCTs, 19 cohort studies and 11 case-control studies in the analysis of vaccine efficacy and effectiveness. Evidence from RCTs shows that six children under the age of six need to be vaccinated with live attenuated vaccine to prevent one case of influenza (infection and symptoms). We could find no usable data for those aged two years or younger.Inactivated vaccines in children aged two years or younger are not significantly more efficacious than placebo. Twenty-eight children over the age of six need to be vaccinated to prevent one case of influenza (infection and symptoms). Eight need to be vaccinated to prevent one case of influenza-like-illness (ILI). We could find no evidence of effect on secondary cases, lower respiratory tract disease, drug prescriptions, otitis media and its consequences and socioeconomic impact. We found weak single-study evidence of effect on school absenteeism by children and caring parents from work. Variability in study design and presentation of data was such that a meta-analysis of safety outcome data was not feasible. Extensive evidence of reporting bias of safety outcomes from trials of live attenuated influenza vaccines (LAIVs) impeded meaningful analysis. One specific brand of monovalent pandemic vaccine is associated with cataplexy and narcolepsy in children and there is sparse evidence of serious harms (such as febrile convulsions) in specific situations. Influenza vaccines are efficacious in preventing cases of influenza in children older than two years of age, but little evidence is available for children younger than two years of age. There was a difference between vaccine efficacy and effectiveness, partly due to differing datasets, settings and viral circulation patterns. No safety comparisons could be carried out, emphasising the need for standardisation of methods and presentation of vaccine safety data in future studies. In specific cases, influenza vaccines were associated with serious harms such as narcolepsy and febrile convulsions. It was surprising to find only one study of inactivated vaccine in children under two years, given current recommendations to vaccinate healthy children from six months of age in the USA, Canada, parts of Europe and Australia. If immunisation in children is to be recommended as a public health policy, large-scale studies assessing important outcomes, and directly comparing vaccine types are urgently required. The degree of scrutiny needed to identify all global cases of potential harms is beyond the resources of this review. This review includes trials funded by industry. An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry-funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favourable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in the light of this finding.

Narcolepsy in children

Narcolepsy in children