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Sample records for pediatric narcolepsy diagnosis

  1. Pediatric narcolepsy.

    PubMed

    Peterson, Paul C; Husain, Aatif M

    2008-11-01

    Narcolepsy is a disabling disease with a prevalence of 0.05%. It is characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnogogic hallucinations, automatic behavior, and disrupted nocturnal sleep. The presentation can be very variable, making diagnosis difficult. Loss of hypocretin containing neurons in the lateral hypothalamus has been noted in autopsy studies, and the cerebrospinal fluid level of hypocretin is reduced in patients with narcolepsy with cataplexy. New treatment options are available for the many symptoms of this disease. Early recognition and treatment can greatly improve the quality of life of patients with narcolepsy. A detail review of the epidemiology, pathophysiology, and management of narcolepsy in children is presented.

  2. Delayed diagnosis of narcolepsy: characterization and impact.

    PubMed

    Thorpy, Michael J; Krieger, Ana C

    2014-05-01

    Narcolepsy, a chronic neurologic condition resulting from dysregulation of the sleep-wake cycle, usually has an onset at an early age. However, a long delay until diagnosis has been consistently reported in the literature across countries and several publications have focused on characterizing this delay. Most studies report a mean delay to diagnosis of up to 15 years, with individual cases of >60 years, although a trend over time toward a shorter diagnostic delay has been suggested. While variables associated with this delay have been identified, a lack of symptom recognition resulting in misdiagnosis prior to reaching the narcolepsy diagnosis is the likely underlying reason. This lack of symptom recognition is especially relevant considering the high comorbidity burden that has been shown in patients with narcolepsy as some disorders manifest with symptoms that overlap with narcolepsy. A consequence of delayed diagnosis is delayed treatment, which affects the burden of disease. Substantial detrimental effects on health-care resource utilization, employment, and quality of life have been described after narcolepsy onset and prior to the diagnosis of narcolepsy. This review highlights the importance of closing the diagnostic gap by expanding awareness of narcolepsy and its symptoms.

  3. Narcolepsy.

    PubMed

    Kornum, Birgitte R; Knudsen, Stine; Ollila, Hanna M; Pizza, Fabio; Jennum, Poul J; Dauvilliers, Yves; Overeem, Sebastiaan

    2017-02-09

    Narcolepsy is a chronic sleep disorder that has a typical onset in adolescence and is characterized by excessive daytime sleepiness, which can have severe consequences for the patient. Problems faced by patients with narcolepsy include social stigma associated with this disease, difficulties in obtaining an education and keeping a job, a reduced quality of life and socioeconomic consequences. Two subtypes of narcolepsy have been described (narcolepsy type 1 and narcolepsy type 2), both of which have similar clinical profiles, except for the presence of cataplexy, which occurs only in patients with narcolepsy type 1. The pathogenesis of narcolepsy type 1 is hypothesized to be the autoimmune destruction of the hypocretin-producing neurons in the hypothalamus; this hypothesis is supported by immune-related genetic and environmental factors associated with the disease. However, direct evidence in support of the autoimmune hypothesis is currently unavailable. Diagnosis of narcolepsy encompasses clinical, electrophysiological and biological evaluations, but simpler and faster procedures are needed. Several medications are available for the symptomatic treatment of narcolepsy, all of which have quite good efficacy and safety profiles. However, to date, no treatment hinders or slows disease development. Improved diagnostic tools and increased understanding of the pathogenesis of narcolepsy type 1 are needed and might lead to therapeutic or even preventative interventions.

  4. Circadian Rest-Activity Rhythm in Pediatric Type 1 Narcolepsy

    PubMed Central

    Filardi, Marco; Pizza, Fabio; Bruni, Oliviero; Natale, Vincenzo; Plazzi, Giuseppe

    2016-01-01

    Study Objectives: Pediatric type 1 narcolepsy is often challenging to diagnose and remains largely undiagnosed. Excessive daytime sleepiness, disrupted nocturnal sleep, and a peculiar phenotype of cataplexy are the prominent features. The knowledge available about the regulation of circadian rhythms in affected children is scarce. This study compared circadian rest-activity rhythm and actigraphic estimated sleep measures of children with type 1 narcolepsy versus healthy controls. Methods: Twenty-two drug-naïve type 1 narcolepsy children and 21 age- and sex- matched controls were monitored for seven days during the school week by actigraphy. Circadian activity rhythms were analyzed through functional linear modeling; nocturnal and diurnal sleep measures were estimated from activity using a validated algorithm. Results: Children with type 1 narcolepsy presented an altered rest-activity rhythm characterized by enhanced motor activity throughout the night and blunted activity in the first afternoon. No difference was found between children with type 1 narcolepsy and controls in the timing of the circadian phase. Actigraphic sleep measures showed good discriminant capabilities in assessing type 1 narcolepsy nycthemeral disruption. Conclusions: Actigraphy reliably renders the nycthemeral disruption typical of narcolepsy type 1 in drug-naïve children with recent disease onset, indicating the sensibility of actigraphic assessment in the diagnostic work-up of childhood narcolepsy type 1. Citation: Filardi M, Pizza F, Bruni O, Natale V, Plazzi G. Circadian rest-activity rhythm in pediatric type 1 narcolepsy. SLEEP 2016;39(6):1241–1247. PMID:27091539

  5. Circadian Rest-Activity Rhythm in Pediatric Type 1 Narcolepsy.

    PubMed

    Filardi, Marco; Pizza, Fabio; Bruni, Oliviero; Natale, Vincenzo; Plazzi, Giuseppe

    2016-06-01

    Pediatric type 1 narcolepsy is often challenging to diagnose and remains largely undiagnosed. Excessive daytime sleepiness, disrupted nocturnal sleep, and a peculiar phenotype of cataplexy are the prominent features. The knowledge available about the regulation of circadian rhythms in affected children is scarce. This study compared circadian rest-activity rhythm and actigraphic estimated sleep measures of children with type 1 narcolepsy versus healthy controls. Twenty-two drug-naïve type 1 narcolepsy children and 21 age- and sex- matched controls were monitored for seven days during the school week by actigraphy. Circadian activity rhythms were analyzed through functional linear modeling; nocturnal and diurnal sleep measures were estimated from activity using a validated algorithm. Children with type 1 narcolepsy presented an altered rest-activity rhythm characterized by enhanced motor activity throughout the night and blunted activity in the first afternoon. No difference was found between children with type 1 narcolepsy and controls in the timing of the circadian phase. Actigraphic sleep measures showed good discriminant capabilities in assessing type 1 narcolepsy nycthemeral disruption. Actigraphy reliably renders the nycthemeral disruption typical of narcolepsy type 1 in drug-naïve children with recent disease onset, indicating the sensibility of actigraphic assessment in the diagnostic work-up of childhood narcolepsy type 1. © 2016 Associated Professional Sleep Societies, LLC.

  6. Pharmacological management of narcolepsy and cataplexy in pediatric patients.

    PubMed

    Lecendreux, Michel

    2014-10-01

    Narcolepsy is a neurological disorder frequently occurring from childhood and persisting through adolescence and adulthood. Individuals suffering from narcolepsy exhibit excessive daytime somnolence, sleep attacks, cataplexy, dysomnia, metabolic perturbations including weight gain, and problems in social interaction and academic performance. The prevalence of narcolepsy in childhood is not known but can be estimated from adult studies to be greater than 20-60 per 100,000 in Western countries. The 2009 (A) H1N1 vaccination campaign led to an increase of narcoleptic cases both in children and in adults, supporting the autoimmune hypothesis of the disease. This article focuses on the epidemiology, etiology, and particularities of treatment in pediatric narcolepsy and details the effects of the drugs used to treat this condition, including recent trends in the field. Future therapeutic directions are also discussed. At present, medications used to treat children or adolescents have shown efficacy mostly based on clinical experience, given the lack of level 1 evidence-based studies in the pediatric population. Therefore, most compounds used in adult narcolepsy to target clinical symptoms such as wake-promoting or anticataplectic agents are prescribed off-label in pediatric patients. Published research shows the benefit of drug therapy for narcoleptic children, but these must be dispensed with caution in the absence of well conducted clinical trials.

  7. Narcolepsy and cataplexy: a pediatric case report

    PubMed Central

    Savaş, Tülin; Erol, ilknur; Saygı, Semra; Habeşoğlu, Mehmet Ali

    2016-01-01

    Narcolepsy is characterized by excessive sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis during the rapid eye movement period of sleep. Herein, we present a boy aged eight years who was diagnosed as having narcolepsy and cataplexy about thirteen months after his first presentation. He was admitted with symptoms of daytime sleepiness. In the follow-up, cataplexy in the form of head dropping attacks developed seven months after the first admission. The patient was investigated for different prediagnoses and was eventually diagnosed as having narcolepsy and cataplexy through polysomnography and multiple sleep latency tests thirteen months after the first presentation. He is being followed up and is under drug therapy; his symptoms have improved substantially. PMID:28123336

  8. Narcolepsy and cataplexy: a pediatric case report.

    PubMed

    Savaş, Tülin; Erol, Ilknur; Saygı, Semra; Habeşoğlu, Mehmet Ali

    2016-12-01

    Narcolepsy is characterized by excessive sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis during the rapid eye movement period of sleep. Herein, we present a boy aged eight years who was diagnosed as having narcolepsy and cataplexy about thirteen months after his first presentation. He was admitted with symptoms of daytime sleepiness. In the follow-up, cataplexy in the form of head dropping attacks developed seven months after the first admission. The patient was investigated for different prediagnoses and was eventually diagnosed as having narcolepsy and cataplexy through polysomnography and multiple sleep latency tests thirteen months after the first presentation. He is being followed up and is under drug therapy; his symptoms have improved substantially.

  9. Narcolepsy

    PubMed Central

    Murray, T. J.; Foley, Anita

    1974-01-01

    Narcolepsy is a disorder of sleep control characterized by a tetrad of symptoms: sleep attacks, cataplexy, sleep paralysis and hypnagogic hallucinations. A diagnosis is made from a careful history. The incidence is estimated as high as 0.3% of the population. Unfortunately patients go for many years before the diagnosis is made and often have experienced disruption of their employment, social and family life, and may have experienced a number of car accidents because of falling asleep at the wheel. An unknown number of narcoleptics kill themselves on the highways before the diagnosis is ever made. Sleep attacks can usually be controlled by methylphenidate, and if the other symptoms persist they can often be effectively managed by imipramine. PMID:4809449

  10. Narcolepsy

    MedlinePlus

    ... with narcolepsy don't sleep well at night. Exams and Tests Your health care provider will do ... sure your bed and pillows are comfortable. Avoid caffeine, alcohol, and heavy meals several hours before bedtime. ...

  11. The Impact of Gender on Timeliness of Narcolepsy Diagnosis

    PubMed Central

    Won, Christine; Mahmoudi, Mandana; Qin, Li; Purvis, Taylor; Mathur, Aditi; Mohsenin, Vahid

    2014-01-01

    Study Objectives: To examine the impact of gender in narcoleptic patients on timeliness of diagnosis, symptomology, and health and lifestyle impairment Methods: This is a cross-sectional study of 109 consecutive patients (68 women) with newly diagnosed narcolepsy with and without cataplexy, from a University sleep disorders center. Consecutive patients were administered an 8-page questionnaire at the time of their diagnosis regarding sleep habits, medications, and medical conditions, lifestyle impairments, as well as details regarding narcolepsy-related symptoms. Results: Men and women presented with remarkably similar narcolepsy related symptoms, yet women were more likely to be delayed in diagnosis; 85% of men were likely to be diagnosed by 16 years after symptom onset, compared to 28 years in women. More women were likely to remain undiagnosed at any given time point after symptom onset (hazard ratio for diagnosis of men compared to women 1.53; 95% CI 1.01-2.32; p = 0.04). Men and women reported similar degree of subjective sleepiness as measured by the Epworth Sleepiness Scale (mean 16.2 ± 4.5; p = 0.18), though women demonstrated significantly more severe objective sleepiness on multiple sleep latency testing (MSLT) (mean sleep latency in women = 5.4 min (± 4.1), in men 7.4 min (± 3.5); p = 0.03). Despite being more objectively sleepy, women were less likely to report lifestyle impairments in the areas of personal relationships (71% men, 44% women, p = 0.01) and physical activity (36% men, 16% women, p = 0.02), but were also more likely to self-medicate with caffeine (63.4% men, 82.4% women; p = 0.03). Conclusions: Narcolepsy impacts men and women's health and lifestyle differently, and may cause delays diagnosis for women. Citation: Won C; Mahmoudi M; Qin L; Purvis T; Mathur A; Mohsenin V. The impact of gender on timeliness of narcolepsy diagnosis. J Clin Sleep Med 2014;10(1):89-95. PMID:24426826

  12. Diagnosis and management of narcolepsy in the Indian scenario

    PubMed Central

    Sureshbabu, Sachin; Muniem, Abdul; Bhatia, Manvir

    2016-01-01

    Introduction: The diagnosis and management of narcolepsy in the Indian context needs to be revisited especially in the wake of concerns raised by sleep medicine experts that the entity could be formidably underdiagnosed, as well as undertreated in our setting. Materials and Methods: The history, clinical records, polysomnographic/multiple sleep latency test data, and treatment records of five hundred consecutive patients attending a dedicated sleep clinic between the years 2013 and 2016 were retrospectively analyzed. The response to treatment measures and improvement in daytime functioning were periodically assessed by personal/telephonic interview and E-mail communication. Results: Thirteen patients were diagnosed with narcolepsy based on the standard criteria of which three had cataplexy. The mean age of presentation was 23.23 years and the male:female ratio was 2.25:1. The mean duration from the onset of symptoms to diagnosis was 4.2 years. Two patients responded to nonpharmacological interventions alone, and six to modafinil, while two patients remained symptomatic and required treatment with methylphenidate. One patient was lost to follow-up, while two others are due for their first follow-up. Conclusion: A refurbished outlook of the diagnostic methodology and treatment paths tailored to our clinical scenario can potentially impact the future of narcolepsy management and research in our country. PMID:27994353

  13. Usefulness of a Nocturnal SOREMP for Diagnosing Narcolepsy with Cataplexy in a Pediatric Population

    PubMed Central

    Reiter, Joel; Katz, Eliot; Scammell, Thomas E.; Maski, Kiran

    2015-01-01

    Study Objectives: We investigated the diagnostic accuracy of a nocturnal sleep onset rapid eye movement sleep period (nSOREMP) for the identification of narcolepsy with cataplexy (N+C) among children and adolescents referred to the sleep laboratory for an overnight polysomnography (PSG) and multiple sleep latency test (MSLT). Design: Retrospective chart review of sleep clinic notes and PSG and MSLT reports. Setting: Boston Children's Hospital sleep laboratory and outpatient clinics. Patients: All patients 6–18 y old, referred for consecutive PSG and MSLT for the evaluation of central hypersomnias, between January 2005 and January 2014. Measurements and Results: We analyzed the records of 148 patients and established diagnostic categories using the International Classification of Sleep Disorders, 2nd Edition. Patient diagnoses included narcolepsy with cataplexy (28.4%), narcolepsy without cataplexy (8.1%), other hypersomnia conditions (9.5%), delayed sleep phase syndrome (12.2%), behaviorally induced insufficient sleep syndrome (4.1%), other sleep disorders (obstructive sleep apnea, periodic limb movements of sleep; 6.8%), isolated cataplexy (2%), and various diagnoses (29.1%). There were 54.8% of the N+C patients who had an nSOREMP, but only 2.4% of all other patients had an nSOREMP. The specificity of an nSOREMP for detection of N+C was high at 97.3% (95% confidence interval [CI]: 92.2–99.4%), but the sensitivity was moderate at 54.8% (95% CI: 38.7–70.2%). Overall, the positive predictive value of an nSOREMP for the diagnosis of N+C was 88.5% (95% CI: 69.8–97.4%). Conclusions: In children, the presence of an nocturnal sleep onset rapid eye movement sleep period is highly suggestive of narcolepsy with cataplexy and provides further evidence of rapid eye movement sleep dysregulation in this condition. Citation: Reiter J, Katz E, Scammell TE, Maski K. Usefulness of a nocturnal SOREMP for diagnosing narcolepsy with cataplexy in a pediatric population. SLEEP

  14. Intravenous Immunoglobulin Therapy in Pediatric Narcolepsy: A Nonrandomized, Open-Label, Controlled, Longitudinal Observational Study

    PubMed Central

    Lecendreux, Michel; Berthier, Johanna; Corny, Jennifer; Bourdon, Olivier; Dossier, Claire; Delclaux, Christophe

    2017-01-01

    Study Objectives: Previous case reports of intravenous immunoglobulins (IVIg) in pediatric narcolepsy have shown contradictory results. Methods: This was a nonrandomized, open-label, controlled, longitudinal observational study of IVIg use in pediatric narcolepsy with retrospective data collection from medical files obtained from a single pediatric national reference center for the treatment of narcolepsy in France. Of 56 consecutively referred patients with narcolepsy, 24 received IVIg (3 infusions administered at 1-mo intervals) in addition to standard care (psychostimulants and/or anticataplectic agents), and 32 continued on standard care alone (controls). Results: For two patients in each group, medical files were unavailable. Of the 22 IVIg patients, all had cerebrospinal fluid (CSF) hypocretin ≤ 110 pg/mL and were HLA-DQB1*06:02 positive. Of the 30 control patients, 29 were HLA-DQB1*06:02 positive and of those with available CSF measurements, all 12 had hypocretin ≤ 110 pg/mL. Compared with control patients, IVIg patients had shorter disease duration, shorter latency to sleep onset, and more had received H1N1 vaccination. Mean (standard deviation) follow-up length was 2.4 (1.1) y in the IVIg group and 3.9 (1.7) y in controls. In multivariate-adjusted linear mixed-effects analyses of change from baseline in Ullanlinna Narcolepsy Scale (UNS) scores, high baseline UNS, but not IVIg treatment, was associated with a reduction in narcolepsy symptoms. On time-to-event analysis, among patients with high baseline UNS scores, control patients achieved a UNS score < 14 (indicating remission) less rapidly than IVIg patients (adjusted hazard ratio 0.18; 95% confidence interval: 95% confidence interval: 0.03, 0.95; p = 0.043). Shorter or longer disease duration did not influence treatment response in any analysis. Conclusions: Overall, narcolepsy symptoms were not significantly reduced by IVIg. However, in patients with high baseline symptoms, a subset of IVIg

  15. Attention-Deficit/Hyperactivity Disorder (ADHD) Symptoms in Pediatric Narcolepsy: A Cross-Sectional Study

    PubMed Central

    Lecendreux, Michel; Lavault, Sophie; Lopez, Régis; Inocente, Clara Odilia; Konofal, Eric; Cortese, Samuele; Franco, Patricia; Arnulf, Isabelle; Dauvilliers, Yves

    2015-01-01

    Study Objectives: To evaluate the frequency, severity, and associations of symptoms of attention-deficit/hyperactivity disorder (ADHD) in children with narcolepsy with and without cataplexy. Design: Cross-sectional survey. Setting: Four French national reference centers for narcolepsy. Patients: One hundred eight consecutively referred children aged younger than 18 y with narcolepsy, with (NwC, n = 86) or without cataplexy (NwoC, n = 22), and 67 healthy controls. Interventions: The participants, their families, and sleep specialists completed a structured interview and questionnaires about sleep, daytime sleepiness, fatigue, and ADHD symptoms (ADHD-rating scale based upon Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR] symptoms), and use of psychostimulants for the treatment of narcolepsy (administered in 68.2%). Polysomnographic measures were collected. Measurements and Results: Clinically significant levels of ADHD symptoms were found in 4.8% of controls compared with 35.3% in patients with NwoC (P < 0.001) and 19.7% in patients with NwC (P < 0.01). Total ADHD scores were 6.4 (95% confidence interval [CI]: 4.5, 9.0) in controls compared with 14.2 (95% CI: 10.6, 18.9; P < 0.001), in patients with NwoC and 12.2 (95% CI: 9.8, 15.3; P < 0.01) in patients with NwC; subscores of inattention and hyperactivity/impulsivity were also significantly higher in both narcolepsy groups compared with controls. No difference was found between the NwC and NwoC groups for any ADHD measure. ADHD symptom severity was associated with increased levels of sleepiness, fatigue, and insomnia. Compared with the 34 untreated patients, the 73 patients treated with psychostimulants (modafinil in 91%) showed a trend toward lower narcolepsy symptoms but not lower ADHD symptoms. Conclusions: Pediatric patients with narcolepsy have high levels of treatment-resistant attention-deficit/hyperactivity disorder (ADHD) symptoms. The optimal treatment for

  16. Attention-Deficit/Hyperactivity Disorder (ADHD) Symptoms in Pediatric Narcolepsy: A Cross-Sectional Study.

    PubMed

    Lecendreux, Michel; Lavault, Sophie; Lopez, Régis; Inocente, Clara Odilia; Konofal, Eric; Cortese, Samuele; Franco, Patricia; Arnulf, Isabelle; Dauvilliers, Yves

    2015-08-01

    To evaluate the frequency, severity, and associations of symptoms of attention-deficit/hyperactivity disorder (ADHD) in children with narcolepsy with and without cataplexy. Cross-sectional survey. Four French national reference centers for narcolepsy. One hundred eight consecutively referred children aged younger than 18 y with narcolepsy, with (NwC, n = 86) or without cataplexy (NwoC, n = 22), and 67 healthy controls. The participants, their families, and sleep specialists completed a structured interview and questionnaires about sleep, daytime sleepiness, fatigue, and ADHD symptoms (ADHD-rating scale based upon Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR] symptoms), and use of psychostimulants for the treatment of narcolepsy (administered in 68.2%). Polysomnographic measures were collected. Clinically significant levels of ADHD symptoms were found in 4.8% of controls compared with 35.3% in patients with NwoC (P < 0.001) and 19.7% in patients with NwC (P < 0.01). Total ADHD scores were 6.4 (95% confidence interval [CI]: 4.5, 9.0) in controls compared with 14.2 (95% CI: 10.6, 18.9; P < 0.001), in patients with NwoC and 12.2 (95% CI: 9.8, 15.3; P < 0.01) in patients with NwC; subscores of inattention and hyperactivity/impulsivity were also significantly higher in both narcolepsy groups compared with controls. No difference was found between the NwC and NwoC groups for any ADHD measure. ADHD symptom severity was associated with increased levels of sleepiness, fatigue, and insomnia. Compared with the 34 untreated patients, the 73 patients treated with psychostimulants (modafinil in 91%) showed a trend toward lower narcolepsy symptoms but not lower ADHD symptoms. Pediatric patients with narcolepsy have high levels of treatment-resistant attention-deficit/hyperactivity disorder (ADHD) symptoms. The optimal treatment for ADHD symptoms in these patients warrants further evaluation in longitudinal intervention studies.

  17. [Narcolepsy in childhood and adolescence: symptoms, diagnosis, and therapy. A case report].

    PubMed

    Gehrmann, Jochen; Siegler, Dominik; Ignacy, Evelin; Reimer, Inga

    2017-03-01

    Narcolepsy is a rare, multifactorial disease of the hypothalamus characterized by its leading symptoms of excessive daytime sleepiness and cataplexy. Sleep-EEG and a HLA-DR-genotype serve to secure the diagnosis. We report here on a 14-year-old girl suffering from anxieties, depression, school refusal, social withdrawal as well as very frequent attacks of sleep during the day and cataplexy. Currently, there is no approved drug for children and adolescents suffering from narcolepsy. Our patient benefited significantly and quickly from an off-label treatment with methylphenidate in combination with psychoeducation, cognitive behavioral therapy, and family therapy. Narcolepsy is a very rare but probably underestimated differential diagnosis applied to unclear daytime sleepiness, anxieties, or depression in childhood and adolescence. Both the key symptoms and the comorbid symptoms improve significantly under treatment with stimulants, albeit at a higher dosage.

  18. Reducing the Clinical and Socioeconomic Burden of Narcolepsy by Earlier Diagnosis and Effective Treatment.

    PubMed

    Thorpy, Michael; Morse, Anne Marie

    2017-03-01

    The burden of narcolepsy is likely the result of 2 main aspects: the clinical difficulties and disability incurred as a direct effect of the disorder and the socioeconomic burden. The clinical burden includes the symptoms, diagnosis, comorbidities, treatment, and even mortality that can be associated with narcolepsy. Lifelong therapy is necessary for these patients. Effective treatment results in long-term benefits from both patient and societal perspectives by improving clinical outcomes, potentially enabling improved education and increased employment and work productivity, and quality of life. Thus, reducing the time to appropriate management results in improved outcomes in these patients.

  19. Usefulness of a Nocturnal SOREMP for Diagnosing Narcolepsy with Cataplexy in a Pediatric Population.

    PubMed

    Reiter, Joel; Katz, Eliot; Scammell, Thomas E; Maski, Kiran

    2015-06-01

    We investigated the diagnostic accuracy of a nocturnal sleep onset rapid eye movement sleep period (nSOREMP) for the identification of narcolepsy with cataplexy (N+C) among children and adolescents referred to the sleep laboratory for an overnight polysomnography (PSG) and multiple sleep latency test (MSLT). Retrospective chart review of sleep clinic notes and PSG and MSLT reports. Boston Children's Hospital sleep laboratory and outpatient clinics. All patients 6-18 y old, referred for consecutive PSG and MSLT for the evaluation of central hypersomnias, between January 2005 and January 2014. We analyzed the records of 148 patients and established diagnostic categories using the International Classification of Sleep Disorders, 2(nd) Edition. Patient diagnoses included narcolepsy with cataplexy (28.4%), narcolepsy without cataplexy (8.1%), other hypersomnia conditions (9.5%), delayed sleep phase syndrome (12.2%), behaviorally induced insufficient sleep syndrome (4.1%), other sleep disorders (obstructive sleep apnea, periodic limb movements of sleep; 6.8%), isolated cataplexy (2%), and various diagnoses (29.1%). There were 54.8% of the N+C patients who had an nSOREMP, but only 2.4% of all other patients had an nSOREMP. The specificity of an nSOREMP for detection of N+C was high at 97.3% (95% confidence interval [CI]: 92.2-99.4%), but the sensitivity was moderate at 54.8% (95% CI: 38.7-70.2%). Overall, the positive predictive value of an nSOREMP for the diagnosis of N+C was 88.5% (95% CI: 69.8-97.4%). In children, the presence of an nocturnal sleep onset rapid eye movement sleep period is highly suggestive of narcolepsy with cataplexy and provides further evidence of rapid eye movement sleep dysregulation in this condition. © 2015 Associated Professional Sleep Societies, LLC.

  20. Listening to the Patient Voice in Narcolepsy: Diagnostic Delay, Disease Burden, and Treatment Efficacy

    PubMed Central

    Maski, Kiran; Steinhart, Erin; Williams, David; Scammell, Thomas; Flygare, Julie; McCleary, Kimberly; Gow, Monica

    2017-01-01

    Study Objectives: Describe common symptoms, comorbidities, functional limitations, and treatment responsiveness among patients with narcolepsy. Investigate the effect of pediatric onset of narcolepsy symptoms on time to diagnosis of narcolepsy and presence of comorbid depression. Methods: Cross-sectional survey of 1,699 people in the United States with self-reported diagnosis of narcolepsy. We utilized mixed-methods data analyses to report study findings. Results: Most participants reported receiving a diagnosis of narcolepsy more than 1 y after symptom onset. We found that the strongest predictor of this delayed diagnosis was pediatric onset of symptoms (odds ratio = 2.4, p < 0.0005). Depression was the most common comorbidity but we detected no association with pediatric onset of narcolepsy symptoms. Overall, participants reported that fatigue and cognitive difficulties were their most burdensome symptoms in addition to sleepiness and cataplexy. The majority of participants reported residual daytime fatigue and/or sleepiness despite treatment. Most participants reported they could not perform at work or school as well as they would like because of narcolepsy symptoms. Conclusions: This study provides unique insight into the narcolepsy disease experience. The study quantifies the problem of diagnostic delay for narcolepsy patients in the United States and highlights that symptoms are more likely to be missed if they develop before 18 y of age. These results suggest that narcolepsy awareness efforts should be aimed at parents, pediatric health care providers, school professionals, and children/adolescents themselves. Disease burden is high because of problems with fatigue, cognition, and persistence of residual symptoms despite treatment. Citation: Maski K, Steinhart E, Williams D, Scammell T, Flygare J, McCleary K, Gow M. Listening to the patient voice in narcolepsy: diagnostic delay, disease burden and treatment efficacy. J Clin Sleep Med. 2017;13(3):419–425

  1. Narcolepsy in pediatric age – Experience of a tertiary pediatric hospital

    PubMed Central

    Dias Costa, Filipa; Barreto, Maria Inês; Clemente, Vanda; Vasconcelos, Mónica; Estêvão, Maria Helena; Madureira, Núria

    2014-01-01

    Narcolepsy, a chronic disorder of the sleep–wake cycle of multifactorial etiology, is characterized by excessive daytime sleepiness, often associated with cataplexy, hypnagogic/hypnopompic hallucinations and sleep paralysis. Both early clinical suspicion and therapeutic approach are essential for promotion of cognitive development and social integration of these children. The authors present a descriptive retrospective study of a series of eight children in whom symptoms first started between 6.8 and 10.5 years of age. Diagnostic delay ranged from 4 months to 2 years. One child had H1N1 flu vaccination eight months before the clinical onset. The first multiple sleep latency test was positive in 6 of 8 cases. All cases were treated with methylphenidate, and venlafaxine was associated in 4 of them. In one case the initial therapy was exclusively behavioral. In all cases, symptomatic improvement, better school performance and social integration were achieved after therapeutic adjustment. PMID:26483902

  2. Pediatrics: diagnosis of neuroblastoma.

    PubMed

    Sharp, Susan E; Gelfand, Michael J; Shulkin, Barry L

    2011-09-01

    Neuroblastoma is the most common pediatric extracranial soft-tissue tumor, accounting for approximately 8% of childhood malignancies. Its prognosis is widely variable, ranging from spontaneous regression to fatal disease despite multimodality therapy. Multiple imaging and clinical tests are needed to accurately assess patient risk with risk groups based on disease stage, patient age, and biological tumor factors. Approximately 60% of patients with neuroblastoma have metastatic disease, most commonly involving bone marrow or cortical bone. Metaiodobenzylguanidine (mIBG) scintigraphy plays an important role in the assessment of neuroblastoma, allowing whole-body disease assessment. mIBG is used to define extent of disease at diagnosis, assess disease response during therapy, and detect residual and recurrent disease during follow-up. mIBG is highly sensitive and specific for neuroblastoma, concentrating in >90% of tumors. mIBG was initially labeled with (131)I, but (123)I-mIBG yields higher quality images at a lower patient radiation dose. (123)I-mIBG (AdreView; GE Healthcare, Arlington Heights, IL) was approved for clinical use in children by the Food and Drug Administration in 2008 and is now commercially available throughout the United States. The use of single-photon emission computed tomography and single-photon emission computed tomography/computed tomography in (123)I-mIBG imaging has improved certainty of lesion detection and localization. Fluorodeoxyglucose positron-emission tomography has recently been compared with mIBG and found to be most useful in neuroblastomas which fail to or weakly accumulate mIBG.

  3. Increased mortality in narcolepsy.

    PubMed

    Ohayon, Maurice M; Black, Jed; Lai, Chinglin; Eller, Mark; Guinta, Diane; Bhattacharyya, Arun

    2014-03-01

    To evaluate the mortality rate in patients with narcolepsy. Data were derived from a large database representative of the US population, which contains anonymized patient-linked longitudinal claims for 173 million individuals. Symphony Health Solutions (SHS) Source Lx, an anonymized longitudinal patient dataset. All records of patients registered in the SHS database between 2008 and 2010. None. Identification of patients with narcolepsy was based on ≥ 1 medical claim with the diagnosis of narcolepsy (ICD-9 347.xx) from 2002 to 2012. Dates of death were acquired from the Social Security Administration via a third party; the third party information was encrypted in the same manner as the claims data such that anonymity is ensured prior to receipt by SHS. Annual all-cause mortality rates for 2008, 2009, and 2010 were calculated retrospectively for patients with narcolepsy and patients without narcolepsy in the database, and standardized mortality ratios (SMR) were calculated. Mortality rates were also compared with the general US population (Centers for Disease Control data). SMRs of the narcolepsy population were consistent over the 3-year period and showed an approximate 1.5-fold excess mortality relative to those without narcolepsy. The narcolepsy population had consistently higher mortality rates relative to those without narcolepsy across all age groups, stratified by age decile, from 25-34 years to 75+ years of age. The SMR for females with narcolepsy was lower than for males with narcolepsy. Narcolepsy was associated with approximately 1.5-fold excess mortality relative to those without narcolepsy. While the cause of this increased mortality is unknown, these findings warrant further investigation.

  4. [NARCOLEPSY WITH CATAPLEXY: TYPE 1 NARCOLEPSY].

    PubMed

    Dauvilliers, Yves; Lopez, Régis

    2016-06-01

    Narcolepsy with cataplexy or narcolepsy type 1 in a rare, disabling sleep disorder, with a prevalence of 20 to 30 per 100,000. Its onset peaks in the second decade. The main features are excessive daytime sleepiness and cataplexy or sudden less of muscle tone triggered by emotional situations. Other less consistent symptoms include hypnagogic hallucinations, sleep paralysis, disturbed nighttime sleep, and weight gain. Narcolepsy with cataplexy remains a clinical diagnosis but nighttime and daytime polysomnography (multiple sleep latency tests) are useful to document mean sleep latency below 8 min and at least two sleep-onset REM periods. HLA typing shows an association with HLA DQB1*0602 in more than 92% of cases but was not included in the new diagnostic criteria. In contrast, a low hypocretin-1/orexin-A levels (values below 110 pg/mL) in the cerebrospinal fluid was highly specific for narcolepsy with cataplexy and was included in the recent diagnostic criteria for narcolepsy. The deficiency of the hypocretin system is well-established in human narcoleptics with a reduction of cerebrospinal fluid hypocretin levels in relation with an early loss of hypocretin neurons. The cause of human narcolepsy remains unknown, however an autoimmune process in most probable acting on a highly genetic background with environmental factors such as streptococcal infections, and H1N1 AS03-adjuvanted vaccine named Pandemrix.

  5. Tolerance and Efficacy of Sodium Oxybate in Childhood Narcolepsy with Cataplexy: A Retrospective Study

    PubMed Central

    Lecendreux, Michel; Poli, Francesca; Oudiette, Delphine; Benazzouz, Fatima; Donjacour, Claire E.H.M; Franceschini, Christian; Finotti, Elena; Pizza, Fabio; Bruni, Oliviero; Plazzi, Giuseppe

    2012-01-01

    Narcolepsy with cataplexy is a sleep disorder characterized by excessive daytime sleepiness, irresistible sleep episodes, and sudden loss of muscle tone (cataplexy) mostly triggered by emotions. Narcolepsy with cataplexy is a disabling lifelong disorder frequently arising during childhood. Pediatric narcolepsy often results in severe learning and social impairment. Improving awareness about this condition increases early diagnosis and may allow patients to rapidly access adequate treatments, including pharmacotherapy and/or non-medication-based approaches. Even though children currently undergo pharmacotherapy, data about safety and efficacy in the pediatric population are scarce. Lacking international guidelines as well as drugs registered for childhood narcolepsy with cataplexy, physicians have no other alternative but to prescribe in an off-label manner medications identical to those recommended for adults. We retrospectively evaluated 27 children ranging from 6 to 16 years old, suffering from narcolepsy with cataplexy, who had been treated with off-label sodium oxybate and had been followed in a clinical setting. Throughout a semi-structured interview, we documented the good efficacy and tolerability of sodium oxybate in the majority of the patients. This study constitutes a preliminary step towards a further randomized controlled trial in childhood narcolepsy with cataplexy. Citation: Lecendreux M; Poli F; Oudiette D; Benazzouz F; Donjacour CEHM; Franceschini C; Finotti E; Pizza F; Bruni O; Plazzi G. Tolerance and efficacy of sodium oxybate in childhood narcolepsy with cataplexy: a retrospective study. SLEEP 2012;35(5):709-711. PMID:22547897

  6. Delayed Diagnosis, Range of Severity, and Multiple Sleep Comorbidities: A Clinical and Polysomnographic Analysis of 100 Patients of the Innsbruck Narcolepsy Cohort

    PubMed Central

    Frauscher, Birgit; Ehrmann, Laura; Mitterling, Thomas; Gabelia, David; Gschliesser, Viola; Brandauer, Elisabeth; Poewe, Werner; Högl, Birgit

    2013-01-01

    frequent comorbidity of narcolepsy with many other sleep disorders. Our study is the first to evaluate the percentage of patients with high frequency leg movements and excessive fragmentary myoclonus in narcolepsy and is the first to demonstrate EMG evidence of RBD in the MSLT. These findings add to the growing body of literature suggesting that motor instability is a key feature of narcolepsy. Citation: Frauscher B; Ehrmann L; Mitterling T; Gabelia D; Gschliesser V; Brandauer E; Poewe W; Högl B. Delayed diagnosis, range of severity, and multiple sleep comorbidities: a clinical and polysomnographic analysis of 100 patients of the Innsbruck narcolepsy cohort. J Clin Sleep Med 2013;9(8):805-812. PMID:23946711

  7. Pediatric insomnia: clinical, diagnosis, and treatment.

    PubMed

    Miano, Silvia; Peraita-Adrados, Rosa

    2014-01-01

    Pediatric insomnia is an extrinsic sleep disorder subdivided into two categories: behavioral insomnia and insomnia related to medical, neurological, and psychiatric diseases. This review will cover several types of insomnia, comorbidities and specific pediatric therapies according to clinical characteristics and age. Behavioral insomnia should be differentiated from pediatric insomnia due to medical conditions, mostly occurring during the first year of life. Multiple night awakenings and diurnal hypersomnolence are strong indicators of insomnia due to medical conditions. Insomnia during adolescence and pediatric insomnia associated with psychiatric comorbidity, cognitive disabilities and epilepsy, will be discussed in terms of diagnosis, clinical features and implications for treatment.

  8. Narcolepsy Following Yellow Fever Vaccination: A Case Report

    PubMed Central

    Rosch, Richard E.; Farquhar, Michael; Gringras, Paul; Pal, Deb K.

    2016-01-01

    Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the pediatric age group probably linked to the use of the Pandemrix influenza vaccine in 2009, has increased awareness that different environmental factors can “trigger” narcolepsy with cataplexy in a genetically susceptible population. Here, we describe the case of a 13-year-old boy with narcolepsy following yellow fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy. Polysomnography showed rapid sleep onset with rapid eye movement (REM) latency of 47 min, significant sleep fragmentation and a mean sleep latency of 1.6 min with sleep onset REM in four out of four nap periods. Together with the clinical history, these findings are diagnostic of narcolepsy type 1. The envelope protein E of the yellow fever vaccine strain 17D has significant amino acid sequence overlap with both hypocretin and the hypocretin receptor 2 receptors in protein regions that are predicted to act as epitopes for antibody production. These findings raise the question whether the yellow fever vaccine strain may, through a potential molecular mimicry mechanism, be another infectious trigger for this neuro-immunological disorder. PMID:27559330

  9. Narcolepsy Following Yellow Fever Vaccination: A Case Report.

    PubMed

    Rosch, Richard E; Farquhar, Michael; Gringras, Paul; Pal, Deb K

    2016-01-01

    Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the pediatric age group probably linked to the use of the Pandemrix influenza vaccine in 2009, has increased awareness that different environmental factors can "trigger" narcolepsy with cataplexy in a genetically susceptible population. Here, we describe the case of a 13-year-old boy with narcolepsy following yellow fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy. Polysomnography showed rapid sleep onset with rapid eye movement (REM) latency of 47 min, significant sleep fragmentation and a mean sleep latency of 1.6 min with sleep onset REM in four out of four nap periods. Together with the clinical history, these findings are diagnostic of narcolepsy type 1. The envelope protein E of the yellow fever vaccine strain 17D has significant amino acid sequence overlap with both hypocretin and the hypocretin receptor 2 receptors in protein regions that are predicted to act as epitopes for antibody production. These findings raise the question whether the yellow fever vaccine strain may, through a potential molecular mimicry mechanism, be another infectious trigger for this neuro-immunological disorder.

  10. Insomnia, parasomnias, and narcolepsy in children: clinical features, diagnosis, and management.

    PubMed

    Maski, Kiran; Owens, Judith A

    2016-10-01

    Sleep problems are frequently encountered as presenting complaints in child neurology clinical practice. They can affect the functioning and quality of life of children, particularly those with primary neurological and neurodevelopmental disorders, since coexisting sleep problems can add substantially to neurocognitive and behavioural comorbidities. Additionally, symptoms of some sleep disorders such as parasomnias and narcolepsy can be confused with those of other neurological disorders (eg, epilepsy), posing diagnostic challenges for paediatric neurologists. The understanding of the neurophysiology of sleep disorders such as insomnia, parasomnias, and narcolepsy is still evolving. There is a complex relation between the sleeping brain and its waking function. The interplay among genetic factors, alterations in neurotransmitters, electrophysiological changes, and environmental factors potentially contribute to the genesis of these sleep disorders.

  11. Narcolepsy in African Americans.

    PubMed

    Kawai, Makoto; O'Hara, Ruth; Einen, Mali; Lin, Ling; Mignot, Emmanuel

    2015-11-01

    Although narcolepsy affects 0.02-0.05% of individuals in various ethnic groups, clinical presentation in different ethnicities has never been fully characterized. Our goal was to study phenotypic expression across ethnicities in the United States. Cases of narcolepsy from 1992 to 2013 were identified from searches of the Stanford Center for Narcolepsy Research database. International Classification of Sleep Disorders, Third Edition diagnosis criteria for type 1 and type 2 narcolepsy were used for inclusion, but subjects were separated as with and without cataplexy for the purpose of data presentation. Information extracted included demographics, ethnicity and clinical data, HLA-DQB1*06:02, polysomnography (PSG), multiple sleep latency test (MSLT) data, and cerebrospinal fluid (CSF) hypocretin-1 level. 182 African-Americans, 839 Caucasians, 35 Asians, and 41 Latinos with narcolepsy. Sex ratio, PSG, and MSLT findings did not differ across ethnicities. Epworth Sleepiness Scale (ESS) score was higher and age of onset of sleepiness earlier in African Americans compared with other ethnicities. HLA-DQB1*06:02 positivity was higher in African Americans (91.0%) versus others (76.6% in Caucasians, 80.0% in Asians, and 65.0% in Latinos). CSF hypocretin-1 level, obtained in 222 patients, was more frequently low (≤ 110 pg/ml) in African Americans (93.9%) versus Caucasians (61.5%), Asians (85.7%) and Latinos (75.0%). In subjects with low CSF hypocretin-1, African Americans (28.3%) were 4.5 fold more likely to be without cataplexy when compared with Caucasians (8.1%). Narcolepsy in African Americans is characterized by earlier symptom onset, higher Epworth Sleepiness Scale score, higher HLA-DQB1*06:02 positivity, and low cerebrospinal fluid hypocretin-1 level in the absence of cataplexy. In African Americans, more subjects without cataplexy have type 1 narcolepsy. © 2015 Associated Professional Sleep Societies, LLC.

  12. Diagnosis of narcolepsy and idiopathic hypersomnia. An update based on the International classification of sleep disorders, 2nd edition.

    PubMed

    Billiard, Michel

    2007-10-01

    Defining the precise nosological limits of narcolepsy and idiopathic hypersomnia is an ongoing process dating back to the first description of the two conditions. The most recent step forward has been done within the preparation of the second edition of the "International classification of sleep disorders" published in June 2005. Appointed by Dr Emmanuel Mignot, the Task Force on "Hypersomnias of central origin, not due to a circadian rhythm sleep disorder, sleep related breathing disorder, or other causes of disturbed nocturnal sleep" thoroughly revisited the nosology of narcolepsy and of idiopathic hypersomnia. Narcolepsy is now distinguished into three different entities, narcolepsy with cataplexy, narcolepsy without cataplexy and narcolepsy due to medical condition, and idiopathic hypersomnia into two entities, idiopathic hypersomnia with long sleep time and idiopathic hypersomnia without long sleep time. Nevertheless there are still a number of pending issues. What are the limits of narcolepsy without cataplexy? Is there a continuum in the pathophysiology of narcolepsy with and without cataplexy? Should sporadic and familial forms of narcolepsy with cataplexy appear as subgroups in the classification? Are idiopathic hypersomnia with long sleep time and idiopathic hypersomnia without long sleep time, two forms of the same condition or two different conditions? Is there a pathophysiological relationship between narcolepsy without cataplexy and idiopathic hypersomnia without long sleep time?

  13. Narcolepsy in a three-year-old girl: A case report.

    PubMed

    Park, Eu Gene; Lee, Jiwon; Joo, Eun Yeon; Lee, Munhyang; Lee, Jeehun

    2016-01-01

    Narcolepsy is characterized by excessive daytime somnolence associated with sleep paralysis, hallucinations when falling asleep or awakening, and cataplexy. Early recognition of pediatric narcolepsy is essential for growth and development. We experienced a case of narcolepsy in a three-year-old girl. The patient underwent brain MRI and 24h video-electroencephalogram (EEG) monitoring. Polysomnography (PSG) with multiple sleep latency test (MSLT) and human leukocyte antigen (HLA) DQ typing was performed. The brain MRI was normal. 24h video-EEG monitoring revealed no abnormal slow or epileptiform discharge on interictal EEG, and no EEG change during tongue thrusting, dropping head with laughter, or flopping down, which was consistent with cataplexy associated with narcolepsy. A mean sleep latency of 2.5 min and four episodes of sleep-onset REM periods in five naps were observed in PSG with MSLT. She was positive in HLA-DQB1*0602. Based on these findings, she was diagnosed as narcoleptic with cataplexy. The history, combined with PSG and MSLT, was helpful in the diagnosis of narcolepsy. We report a case of early-onset narcolepsy presenting with excessive sleepiness and cataplexy. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  14. Narcolepsy in African Americans

    PubMed Central

    Kawai, Makoto; O'Hara, Ruth; Einen, Mali; Lin, Ling; Mignot, Emmanuel

    2015-01-01

    Study Objectives: Although narcolepsy affects 0.02–0.05% of individuals in various ethnic groups, clinical presentation in different ethnicities has never been fully characterized. Our goal was to study phenotypic expression across ethnicities in the United States. Design/Setting: Cases of narcolepsy from 1992 to 2013 were identified from searches of the Stanford Center for Narcolepsy Research database. International Classification of Sleep Disorders, Third Edition diagnosis criteria for type 1 and type 2 narcolepsy were used for inclusion, but subjects were separated as with and without cataplexy for the purpose of data presentation. Information extracted included demographics, ethnicity and clinical data, HLA-DQB1*06:02, polysomnography (PSG), multiple sleep latency test (MSLT) data, and cerebrospinal fluid (CSF) hypocretin-1 level. Patients: 182 African-Americans, 839 Caucasians, 35 Asians, and 41 Latinos with narcolepsy. Results: Sex ratio, PSG, and MSLT findings did not differ across ethnicities. Epworth Sleepiness Scale (ESS) score was higher and age of onset of sleepiness earlier in African Americans compared with other ethnicities. HLA-DQB1*06:02 positivity was higher in African Americans (91.0%) versus others (76.6% in Caucasians, 80.0% in Asians, and 65.0% in Latinos). CSF hypocretin-1 level, obtained in 222 patients, was more frequently low (≤ 110 pg/ml) in African Americans (93.9%) versus Caucasians (61.5%), Asians (85.7%) and Latinos (75.0%). In subjects with low CSF hypocretin-1, African Americans (28.3%) were 4.5 fold more likely to be without cataplexy when compared with Caucasians (8.1%). Conclusions: Narcolepsy in African Americans is characterized by earlier symptom onset, higher Epworth Sleepiness Scale score, higher HLA-DQB1*06:02 positivity, and low cerebrospinal fluid hypocretin-1 level in the absence of cataplexy. In African Americans, more subjects without cataplexy have type 1 narcolepsy. Citation: Kawai M, O'Hara R, Einen M, Lin L

  15. Prenatal diagnosis: essentials for the pediatric surgeon.

    PubMed

    Rice, H E; Adzick, N S

    1993-05-01

    Prenatal diagnosis is a rapidly growing field that has supported new treatments for the developing fetus. Improved methods of diagnosing anatomic, biochemical, and molecular defects of the fetus have fostered a parallel growth of better techniques of fetal therapy. A fundamental knowledge of the basic uses and limitation of prenatal diagnosis is essential for the practicing pediatric surgeon. This review summarizes clinical uses and recent advances in various methods of prenatal diagnosis, including ultrasound, fetal echocardiography, amniocentesis, chorionic villus sampling, fetal blood sampling, alpha-fetoprotein, and DNA analysis. For each technique, the common indications, risks, and clinical utility are discussed.

  16. Incidence of Narcolepsy in Germany

    PubMed Central

    Oberle, Doris; Drechsel-Bäuerle, Ursula; Schmidtmann, Irene; Mayer, Geert; Keller-Stanislawski, Brigitte

    2015-01-01

    Study Objectives: Following the 2009 pandemic, reports of an association between an AS03 adjuvanted H1N1 pandemic influenza vaccine and narcolepsy were published. Besides determining background incidence rates for narcolepsy in Germany this study aimed at investigating whether there was a change in incidence rates of narcolepsy between the pre-pandemic, pandemic, and the post-pandemic period on the population level. Design: Retrospective epidemiological study on the incidence of narcolepsy with additional capture-recapture analysis. Setting: German sleep centers. Patients or Participants: Eligible were patients with an initial diagnosis of narcolepsy (ICD10 Code G47.4) within the period from January 1, 2007 to December 31, 2011. Interventions: None; observational study. Measurements and Results: A total of 342 sleep centers were invited to participate in the study. Adequate and suitable data were provided by 233 sleep centers (68.1%). A total of 1,198 patients with an initial diagnosis of narcolepsy within the observed period were included, of whom 106 (8.8%) were children and adolescents under the age of 18 years and 1,092 (91.2%) were adults. In children and adolescents, the age-standardized adjusted incidence rate significantly increased from 0.14/100,000 person-years in the pre-pandemic period to 0.50/100,000 person-years in the post-pandemic period (incidence density ratio, IDR 3.57; 95% CI 1.94–7.00). In adults, no significant change was detectable. This increase started in spring 2009. Conclusions: For the years 2007–2011, valid estimates for the incidence of narcolepsy in Germany were provided. In individuals under 18, the incidence rates continuously increased from spring 2009. Citation: Oberle D, Drechsel-Bäuerle U, Schmidtmann I, Mayer G, Keller-Stanislawski B. Incidence of narcolepsy in Germany. SLEEP 2015;38(10):1619–1628. PMID:25902804

  17. Diagnosis and treatment of pediatric osteoporosis.

    PubMed

    Bachrach, Laura K

    2014-12-01

    Progress toward identifying and treating disorders of bone fragility in pediatric patients has been considerable in recent years. This article will summarize several key advances in the management of osteoporosis in children and adolescents. Recommendations from the 2013 pediatric Position Development Conference provide expert guidance for evaluating bone health in younger patients. The diagnosis of pediatric osteoporosis can be made in a child with low-trauma vertebral fractures or a combination of low bone mass and long bone fractures. Management of bone fragility includes optimizing nutrition, activity, and treatment of the underlying disease. Pharmacologic agents can be considered if these measures fail to prevent further bone loss or fractures. Although the efficacy and safety of several intravenous and oral bisphosphonates have been examined, there is still no consensus on the optimal drug, dose, or duration of treatment. Observational studies of children with secondary osteoporosis provide insight into risk factors for fracture or the potential for recovery. Despite advances in the diagnosis and treatment of pediatric osteoporosis, more research is needed. Randomized controlled trials of pharmacologic agents should be defined to target those identified at the highest risk by observational studies. http://links.lww.com/COE/A9

  18. [Narcolepsy-cataplexy].

    PubMed

    Deflandre, E; Roelants, F; Cambron, L; Poirrier, R

    2002-08-01

    The diagnosis of narcolepsy-cataplexy is based on three axes: 1) the medical history is strongly suggestive when diurnal sleep attacks (narcolepsy) and drop attacks (cataplexy) are reported or observed; 2) the polysomnography is mandatory and shows nocturnal and diurnal (multiple sleep latency test) REM sleep onsets; 3) HLA typing, practically helps to exclude the diagnosis when HLA DR15-DQB1*0602 is not present. New pathogenetic hypotheses have been proposed, mostly based the absence of hypocretin in narcoleptic cerebrospinal fluid. This neurotransmitter was previously known exclusively by its involvement in alimentary behaviours. The new therapies remain symptomatic, but they are powerful to prevent somnolence, daytime sleepiness, cataplexy and insomnia associated with this syndrome.

  19. How Is Narcolepsy Treated?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Narcolepsy Treated? Narcolepsy has no cure. However, medicines, lifestyle ... Video Dr. Emmanuel Mignot talks about advances in narcolepsy research and care 03/07/2013 Dr. Michael ...

  20. What Is Narcolepsy?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Narcolepsy? Narcolepsy (NAR-ko-lep-se) is a disorder ... Video Dr. Emmanuel Mignot talks about advances in narcolepsy research and care 03/07/2013 Dr. Michael ...

  1. Incidence of Narcolepsy in Germany.

    PubMed

    Oberle, Doris; Drechsel-Bäuerle, Ursula; Schmidtmann, Irene; Mayer, Geert; Keller-Stanislawski, Brigitte

    2015-10-01

    Following the 2009 pandemic, reports of an association between an AS03 adjuvanted H1N1 pandemic influenza vaccine and narcolepsy were published. Besides determining background incidence rates for narcolepsy in Germany this study aimed at investigating whether there was a change in incidence rates of narcolepsy between the pre-pandemic, pandemic, and the post-pandemic period on the population level. Retrospective epidemiological study on the incidence of narcolepsy with additional capture-recapture analysis. German sleep centers. Eligible were patients with an initial diagnosis of narcolepsy (ICD10 Code G47.4) within the period from January 1, 2007 to December 31, 2011. None; observational study. A total of 342 sleep centers were invited to participate in the study. Adequate and suitable data were provided by 233 sleep centers (68.1%). A total of 1,198 patients with an initial diagnosis of narcolepsy within the observed period were included, of whom 106 (8.8%) were children and adolescents under the age of 18 years and 1,092 (91.2%) were adults. In children and adolescents, the age-standardized adjusted incidence rate significantly increased from 0.14/100,000 person-years in the pre-pandemic period to 0.50/100,000 person-years in the post-pandemic period (incidence density ratio, IDR 3.57; 95% CI 1.94-7.00). In adults, no significant change was detectable. This increase started in spring 2009. For the years 2007-2011, valid estimates for the incidence of narcolepsy in Germany were provided. In individuals under 18, the incidence rates continuously increased from spring 2009. © 2015 Associated Professional Sleep Societies, LLC.

  2. Component-Resolved Diagnosis in Pediatrics

    PubMed Central

    Wolthers, Ole D.

    2012-01-01

    Component resolved diagnosis is a new concept in the investigation of pediatric allergic disease. The aim of the present paper is to review the available data on component resolved diagnosis with respect to implications for investigation of children with allergic disease. In most conditions head-to-head comparisons of component resolved diagnosis with traditional IgE testing have not been performed. Rather than alternatives the molecular methods should be seen as adjuncts to the cheaper traditional specific IgE tests. It may be appropriate to determine IgE antibodies to components as part of the diagnostic work-up in selected cases of peanut and birch pollen allergy and in hymenoptera allergy. However, cost benefit analyses of component resolved diagnosis compared with traditional work-up of allergy are needed. Prospectively planned protocols for assessment of the extent to which component resolved diagnosis may be able to improve the selection of children to immunotherapy and, thus, the efficacy of immunotherapy, are needed. Finally, studies of component resolved diagnosis with microarray technology in screening panels with hundreds of components should be undertaken before it can be determined to which extent such panel screening, if at all, may be helpful in children. PMID:22919510

  3. Secondary narcolepsy following neurocysticercosis infection.

    PubMed

    Watson, Nathaniel F; Doherty, Michael J; Zunt, Joseph R

    2005-01-15

    The authors describe a case of secondary narcolepsy resulting from neurocysticercosis infection. Neurocysticercosis is a common central nervous system parasitic disease endemic to Central and South America caused by ingestion of eggs from a host with intestinal taeniasis. Neurological deficits depend on lesion location. Our case developed a hypothalamic cyst causing severe sleepiness and sleep-onset rapid eye movement periods on both polysomnography and multiple sleep latency testing. The cerebrospinal fluid hypocretin-1 level was normal indicating secondary narcolepsy can result without failure of hypocretin production. The diagnosis of neurocysticercosis should be considered in any individual with excessive sleepiness and recent travel to endemic regions of the world.

  4. Diagnosis dialog for pediatric physical therapists: hypotonia, developmental coordination disorder, and pediatric obesity as examples.

    PubMed

    Martin, Kathy S; Westcott, Sarah; Wrotniak, Brian H

    2013-01-01

    To clarify what diagnosis means for pediatric physical therapists, to provide several examples of human movement dysfunction syndromes, and to offer guidance for how pediatric physical therapists may continue this work in any clinical setting. The importance of diagnosis in pediatric physical therapy is presented along with examples of 3 different processes used to develop diagnostic labels. These processes included surveys to identify consensus opinion of clinicians, a literature review, and a combination of these 2. Hypotonia, developmental coordination disorder, and pediatric obesity are presented as examples. The 3 diagnoses serve as a basis for ongoing dialogue, discussion, and development of diagnostic labels for human movement syndromes identified by pediatric physical therapists.

  5. Challenges in Diagnosing Narcolepsy without Cataplexy: A Consensus Statement

    PubMed Central

    Baumann, Christian R.; Mignot, Emmanuel; Lammers, Gert Jan; Overeem, Sebastiaan; Arnulf, Isabelle; Rye, David; Dauvilliers, Yves; Honda, Makoto; Owens, Judith A.; Plazzi, Giuseppe; Scammell, Thomas E.

    2014-01-01

    Background: Diagnosing narcolepsy without cataplexy is often a challenge as the symptoms are nonspecific, current diagnostic tests are limited, and there are no useful biomarkers. In this report, we review the clinical and physiological aspects of narcolepsy without cataplexy, the limitations of available diagnostic procedures, and the differential diagnoses, and we propose an approach for more accurate diagnosis of narcolepsy without cataplexy. Methods: A group of clinician-scientists experienced in narcolepsy reviewed the literature and convened to discuss current diagnostic tools, and to map out directions for research that should lead to a better understanding and more accurate diagnosis of narcolepsy without cataplexy. Recommendations: To aid in the identification of narcolepsy without cataplexy, we review key indicators of narcolepsy and present a diagnostic algorithm. A detailed clinical history is mainly helpful to rule out other possible causes of chronic sleepiness. The multiple sleep latency test remains the most important measure, and prior sleep deprivation, shift work, or circadian disorders should be excluded by actigraphy or sleep logs. A short REM sleep latency (≤ 15 minutes) on polysomnography can aid in the diagnosis of narcolepsy without cataplexy, although sensitivity is low. Finally, measurement of hypocretin levels can helpful, as levels are low to intermediate in 10% to 30% of narcolepsy without cataplexy patients. Citation: Baumann CR, Mignot E, Lammers GJ, Overeem S, Arnulf I, Rye D, Dauvilliers Y, Honda M, Owens JA, Plazzi G, Scammell TE. Challenges in diagnosing narcolepsy without cataplexy: a consensus statement. SLEEP 2014;37(6):1035-1042. PMID:24882898

  6. Diagnosis and management of allergic conjunctivitis in pediatric patients.

    PubMed

    Berger, William E; Granet, David B; Kabat, Alan G

    2017-01-01

    Allergic conjunctivitis (AC), although one of the most common ocular disorders in pediatric patients, is frequently overlooked, misdiagnosed, and undertreated in children. To guide pediatric health care professionals in the optimal diagnosis and management of AC in pediatric patients. To identify any existing best practice guidelines for the diagnosis and treatment of AC in pediatric patients, a review of the literature published between 2004 and January 2015 was conducted. Diagnosis and treatment algorithms and guidelines for pediatric patient referrals were then developed. A literature search to identify best practice guidelines for the treatment of AC in pediatric patients failed to return any relevant articles, which highlighted the need for best practice recommendations. Based on publications on adult AC and clinical experience, this review provides step-by-step guidance for pediatric health care professionals, including recognizing clinical features of AC, establishing a comprehensive medical history, and performing a thorough physical examination to ensure a correct diagnosis and the optimal treatment or referral to an eye care specialist or allergist when required. In addition to established drug treatments, the role of subcutaneous and sublingual immunotherapy is discussed to inform pediatric health care professionals about alternative treatment options for patients who do not tolerate pharmacotherapy or who do not respond sufficiently. The diagnostic and treatment algorithms and guidelines provided in this review help address the current literature and educational gap and may lead to improvements in diagnosis and management of pediatric AC.

  7. Diagnosis and treatment of pediatric benign pneumoperitoneum

    PubMed Central

    Duan, Shou-Xing; Sun, Zong-Bo; Wang, Guang-Huan; Zhong, Jun; Ou, Wen-Hui; Fu, Ma-Xian; Wang, Fu-Sheng; Ma, Shu-Hua; Li, Jian-Hong

    2017-01-01

    Abstract Introduction: Benign pneumoperitoneum (BPPT) is defined as asymptomatic free intraabdominal air or as pneumoperitoneum without peritonitis. Symptomatic free air requires surgical anagement, but management of asymptomatic pneumoperitoneum is controversial. In this study, we investigate the diagnosis and treatment of BPPT in children. Clinical Findings: The clinical data of 9 pediatric patients with BPPT who were admitted to our hospital from January 2000 to January 2015 were retrospectively analyzed to summarize the diagnosis and treatment. Overall, 9 cases were included with 8 males and 1 female, aged from 4 days to 4 years. Among them there were 6 newborns (including 1 premature infant). Patients were all admitted to hospital with the major clinical symptom of abdominal distension, including 2 cases accompanied by tachypnea, 2 cases with vomiting, 1 case with diarrhea, and 2 cases with fever. No previous constipation or obstructive defecation existed. Six newborns had meconium defecation within 24 hours after birth. Physical examination revealed all patients with relaxed abdominal wall except 1 patient with abdominal distension had slight muscle stiffness and hyperactive bowel sounds. Abdominal X-ray suggested free air under the diaphragm in all cases. Interventions/Outcomes: All patients except for one case of laparotomy were conservatively treated and cured with fasting, infection prevention, rehydration, abdominocentesis, and close observation. Nine cases of patients were all discharged with no death occurrence. After discharge follow-up of 7 months to 6 years was conducted. There was no recurrence of similar symptoms, and children were in good growth and development. Conclusion: The diagnosis of BPPT mainly relies on clinical symptoms in patient, careful abdominal examination, abdominal X-ray combined with abdominocentesis, and the exclusion of gastrointestinal perforation for confirmation. Conservative treatment can cure the disease. Attention

  8. Challenges in diagnosing narcolepsy without cataplexy: a consensus statement.

    PubMed

    Baumann, Christian R; Mignot, Emmanuel; Lammers, Gert Jan; Overeem, Sebastiaan; Arnulf, Isabelle; Rye, David; Dauvilliers, Yves; Honda, Makoto; Owens, Judith A; Plazzi, Giuseppe; Scammell, Thomas E

    2014-06-01

    Diagnosing narcolepsy without cataplexy is often a challenge as the symptoms are nonspecific, current diagnostic tests are limited, and there are no useful biomarkers. In this report, we review the clinical and physiological aspects of narcolepsy without cataplexy, the limitations of available diagnostic procedures, and the differential diagnoses, and we propose an approach for more accurate diagnosis of narcolepsy without cataplexy. A group of clinician-scientists experienced in narcolepsy reviewed the literature and convened to discuss current diagnostic tools, and to map out directions for research that should lead to a better understanding and more accurate diagnosis of narcolepsy without cataplexy. To aid in the identification of narcolepsy without cataplexy, we review key indicators of narcolepsy and present a diagnostic algorithm. A detailed clinical history is mainly helpful to rule out other possible causes of chronic sleepiness. The multiple sleep latency test remains the most important measure, and prior sleep deprivation, shift work, or circadian disorders should be excluded by actigraphy or sleep logs. A short REM sleep latency (≤ 15 minutes) on polysomnography can aid in the diagnosis of narcolepsy without cataplexy, although sensitivity is low. Finally, measurement of hypocretin levels can helpful, as levels are low to intermediate in 10% to 30% of narcolepsy without cataplexy patients.

  9. Pediatric enteric neuropathies: diagnosis and current management.

    PubMed

    Westfal, Maggie L; Goldstein, Allan M

    2017-06-01

    Neurointestinal diseases are increasingly recognized as causes of significant gastrointestinal morbidity in children. This review highlights the most common pediatric enteric neuropathies and their diagnosis and management, emphasizing insights and discoveries from the most recent literature available. The embryologic and histopathologic causes of enteric neuropathies are varied. They range from congenital aganglionosis in Hirschsprung disease, to autoimmune-mediated loss of neuronal subtypes in esophageal achalasia and Chagas disease, to degenerative neuropathies in some cases of chronic intestinal pseudo-obstruction and gastroparesis. Increased awareness of the clinical presentation and diagnostic evaluation of these conditions is essential as it allows for earlier initiation of treatment and improved outcomes. Most current therapies, which include medical management, neurostimulation, and operative intervention, aim to minimize the symptoms caused by these conditions. The evidence base for many of these treatments in children is poor, and multiinstitutional prospective studies are needed. An innovative therapy on the horizon involves using neuronal stem cell transplantation to treat the underlying disorder by replacing the missing or damaged neurons in these diseases. Although recent advances in basic and clinical neurogastroenterology have significantly improved our awareness and understanding of enteric neuropathies, the efficacy of current treatment approaches is limited. The development of novel therapies, including pharmacologic modulators of neurointestinal function, neurostimulation to enhance gut motility, and neuronal cell-based therapies, is essential to improve the long-term outcomes in children with these disorders.

  10. Narcolepsy in children: a diagnostic and management approach.

    PubMed

    Babiker, Mohamed O E; Prasad, Manish

    2015-06-01

    To provide a diagnostic and management approach for narcolepsy in children. Narcolepsy is a chronic disabling disorder characterized by excessive daytime sleepiness, cataplexy, hypnogogic and/or hypnopompic hallucinations, and sleep paralysis. All four features are present in only half of the cases. Excessive daytime sleepiness is the essential feature of narcolepsy at any age and is usually the first symptom to manifest. A combination of excessive daytime sleepiness and definite cataplexy is considered pathognomonic of narcolepsy syndrome. New treatment options have become available over the past few years. Early diagnosis and management can significantly improve the quality of life of patients with narcolepsy with cataplexy. This review summarizes the pathophysiology, clinical features, and management options for children with narcolepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Sleep in the Pediatric Population.

    PubMed

    Hintze, Jonathan P; Paruthi, Shalini

    2016-03-01

    This article provides an overview of common pediatric sleep disorders encountered in the neurology clinic, including restless legs syndrome, narcolepsy, parasomnias, sleep-related epilepsy, and sleep and headaches. An overview of each is provided, with an emphasis on accurate diagnosis and treatment. It is important in comprehensive neurologic care to also obtain a sleep history, because treating the underlying sleep condition may improve the neurologic disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Pediatric Traumatic Brain Injury: Characteristic Features, Diagnosis, and Management

    PubMed Central

    ARAKI, Takashi; YOKOTA, Hiroyuki; MORITA, Akio

    2017-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability in children. Pediatric TBI is associated with several distinctive characteristics that differ from adults and are attributable to age-related anatomical and physiological differences, pattern of injuries based on the physical ability of the child, and difficulty in neurological evaluation in children. Evidence suggests that children exhibit a specific pathological response to TBI with distinct accompanying neurological symptoms, and considerable efforts have been made to elucidate their pathophysiology. In addition, recent technical advances in diagnostic imaging of pediatric TBI has facilitated accurate diagnosis, appropriate treatment, prevention of complications, and helped predict long-term outcomes. Here a review of recent studies relevant to important issues in pediatric TBI is presented, and recent specific topics are also discussed. This review provides important updates on the pathophysiology, diagnosis, and age-appropriate acute management of pediatric TBI. PMID:28111406

  13. Altered Brain Microstate Dynamics in Adolescents with Narcolepsy

    PubMed Central

    Drissi, Natasha M.; Szakács, Attila; Witt, Suzanne T.; Wretman, Anna; Ulander, Martin; Ståhlbrandt, Henriettae; Darin, Niklas; Hallböök, Tove; Landtblom, Anne-Marie; Engström, Maria

    2016-01-01

    Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13–20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional MRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics. PMID:27536225

  14. The Acute Pediatric Scrotum: Presentation, Differential Diagnosis and Management

    PubMed Central

    Vasdev, Nikhil; Chadwick, David; Thomas, David

    2012-01-01

    Both pediatric and adult urologists frequently evaluate pediatric patients with an acute scrotum. We present a detailed review on the acute pediatric scrotum highlighting the clinical presentation, differential diagnosis and management of this common clinical condition. It is important to highlight that a testicular torsion is the most important differential diagnosis and the main priority in each case is to diagnosis and treat a potential testicular torsion is of the essence. The aim of our extensive review is to update/review the appropriate evaluation and management of the acute scrotum and to guide the clinician in distinguishing testicular torsion from the other conditions that commonly mimic this surgical emergency. This review is useful for trainees in UK and Europe who plan to take the FRCS (Urol) examination. PMID:24917714

  15. Sociodemographic differences in diagnosis and treatment of pediatric headache.

    PubMed

    Stevens, Jack; Harman, Jeffrey; Pakalnis, Ann; Lo, Warren; Prescod, Jessica

    2010-04-01

    The authors investigated the sociodemographic differences in receiving a headache diagnosis for pediatric health care visits using 2 nationally representative databases--the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. For those visits involving a headache diagnosis, the authors explored 2 possible disparities in care--being diagnosed by a neurologist and being prescribed an evidence-based medication. A headache diagnosis was less common during visits for private insurance patients versus Medicaid patients. In addition, while a headache diagnosis was equally likely for visits by Caucasian American children versus African American children and children of other races, visits for the latter 2 groups were less likely to involve a headache diagnosis from a neurologist. Finally, only 37% of the headache visits involved a prescription of an evidence-based medication. The authors conclude that some sociodemographic disparities exist in pediatric headache care across the United States.

  16. The Humanistic and Economic Burden of Narcolepsy

    PubMed Central

    Flores, Natalia M.; Villa, Kathleen F.; Black, Jed; Chervin, Ronald D.; Witt, Edward A.

    2016-01-01

    Study Objectives: To evaluate the burden of narcolepsy--with respect to psychiatric comorbidities, Health-Related Quality of Life (HRQoL), direct costs for healthcare resource utilization, and indirect costs for reported work loss–through comparison of patients to matched controls. Methods: This analysis was conducted on data from the 2011, 2012, and 2013 US National Health and Wellness Survey (NHWS; 2011 NHWS n = 75,000, 2012 NHWS n = 71,157, and 2013 NHWS n = 75,000). Patients who reported a narcolepsy diagnosis (n = 437) were matched 1:2 with controls (n = 874) on age, sex, race/ethnicity, marital status, education, household income, body mass index, smoking status, alcohol use, exercise, and physical comorbidity. Chi-square tests and one-way analyses of variance were used to assess whether the narcolepsy and control groups differed on psychiatric comorbidities, HRQoL, labor force participation, work productivity, and healthcare resource utilization. Results: Patients with narcolepsy, in comparison to matched controls, reported substantially (two to four times) greater psychiatric comorbidity, HRQoL impairment, prevalence of long-term disability, absenteeism, and presenteeism, and greater resource use in the past 6 mo as indicated by higher mean number of hospitalizations, emergency department visits, traditional healthcare professional visits, neurologist visits, and psychiatrist visits (each p < 0.05). Conclusions: These population-based data suggest that a narcolepsy diagnosis is associated with substantial adverse impact on mental health, HRQoL, and key economic burdens that include work impairment, resource use, and both direct and indirect costs. Although this study is cross-sectional, the results highlight the magnitude of the potential opportunity to improve mental health, lower costs, and augment work-related productivity through effective assessment and treatment of narcolepsy. Citation: Flores NM, Villa KF, Black J, Chervin RD, Witt EA. The

  17. Narcolepsy: new understanding of irresistible sleep.

    PubMed

    Krahn, L E; Black, J L; Silber, M H

    2001-02-01

    Recently, low levels of a newly identified neuropeptide, hypocretin 1, were described in the cerebrospinal fluid of patients with narcolepsy. This neurochemical finding furthers our understanding of this enigmatic sleep disorder typically characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Narcolepsy appears to be fundamentally related to abnormally regulated rapid eye movement sleep. The diagnosis of this disorder remains challenging because of multiple other conditions that can cause daytime sleepiness and the difficulties in recognizing cataplexy based on patient report. The role of hypocretins in narcolepsy is unclear but intriguing because the cell bodies are restricted to the lateral hypothalamus, a brain region long associated with sleep regulation, with neuronal widespread projections to areas including the locus ceruleus, ventral tegmental area, amygdala, and dorsal raphe. Hypocretins potentially modulate the activity of monoamines and acetylcholine, and therefore their absence leads to the multiple symptoms of narcolepsy. This article reviews the current understanding of the diagnosis and treatment of narcolepsy and discusses the possible implications of the hypocretin discovery.

  18. [Atelectasis: mechanisms, diagnosis and treatment in the pediatric patient].

    PubMed

    Johnston, Cíntia; Carvalho, Werther Brunow de

    2008-01-01

    To review the literature about mechanisms, diagnosis and treatment of atelectasis in the pediatric patient. An electronic data search was carried out in Medline and Scielo using the following inclusion criteria for articles published between 1960 and 2007 about: atelectasis etiology, physiopathology, functional consequences, evaluation, prevention, treatment and complications, in pediatrics. The used key words were atelectasis, children, pediatrics, mucus plugs, chest physiotherapy; 45 pulmonary atelectasis articles were analyzed, 17 of them in pediatrics. Of the pediatric, 13 were case series, 3 literature reviews and one a case report. This demonstrates that there were few articles on atelectasis during the reviewed period and that these articles were at the D and E evidence level. No clinical trials were performed to identify s the most efficient treatment for atelectasis in the pediatric patient. Although clinical practice for treatment of atelectasis has evolved, mostly due to improvement of bronchoscopy and chest physiotherapy techniques, there is still a need to perform randomized clinical trials to address treatment of atelectasis in the pediatric patient.

  19. Animal models of narcolepsy.

    PubMed

    Chen, Lichao; Brown, Ritchie E; McKenna, James T; McCarley, Robert W

    2009-08-01

    Narcolepsy is a debilitating sleep disorder with excessive daytime sleepiness and cataplexy as its two major symptoms. Although this disease was first described about one century ago, an animal model was not available until the 1970s. With the establishment of the Stanford canine narcolepsy colony, researchers were able to conduct multiple neurochemical studies to explore the pathophysiology of this disease. It was concluded that there was an imbalance between monoaminergic and cholinergic systems in canine narcolepsy. In 1999, two independent studies revealed that orexin neurotransmission deficiency was pivotal to the development of narcolepsy with cataplexy. This scientific leap fueled the generation of several genetically engineered mouse and rat models of narcolepsy. To facilitate further research, it is imperative that researchers reach a consensus concerning the evaluation of narcoleptic behavioral and EEG phenomenology in these models.

  20. Pediatric prenatal diagnosis of congenital heart disease.

    PubMed

    Killen, Stacy A S; Mouledoux, Jessica H; Kavanaugh-McHugh, Ann

    2014-10-01

    Fetal cardiology is a rapidly evolving field. Imaging technology continues to advance as do approaches to in-utero interventions and care of the critically ill neonate, with even greater demand for improvement in prenatal diagnosis of congenital heart disease (CHD) and arrhythmias. Reviewing the advances in prenatal diagnosis of CHD in such a rapidly developing field is a broad topic. Therefore, we have chosen to focus this review of recent literature on challenges in prenatal detection of CHD, challenges in prenatal counseling, advances in fetal arrhythmia diagnosis, and potential benefits to patients with CHD who are identified prenatally. As methods and tools to diagnose and manage CHD and arrhythmias in utero continue to improve, future generations will hopefully see a reduction in both prenatal and neonatal morbidity and mortality. Prenatal diagnosis can and should be used to optimize location and timing of delivery and postnatal interventions.

  1. Narcolepsy and disorders of excessive somnolence.

    PubMed

    Dyken, Mark E; Yamada, Thoru

    2005-06-01

    Recent studies provide valid criteria that help differentiate idiopathic narcolepsy from other disorders of excessive daytime somnolence [3]. Research to date suggests that idiopathic narcolepsy might properly be considered a disorder of excessive sleepiness with dysfunctional REM-sleep mechanisms, clinically evidenced as cataplexy and electrophysiologically recognized as SOREMPs. Given these criteria, a diagnosis can generally be made using a combination of history, PSG, and MSLT. Traditionally, the medical treatment of idiopathic narcolepsy has centered on a two-drug regimen (stimulants for sleepiness and TCAs for cataplexy and auxiliary symptoms). Some newer medications are proving efficacious for sleepiness with minimal adverse effects, whereas others may provide a single-drug regimen that simultaneously addresses sleepiness and cataplexy [18]. New research has allowed some experts to hypothesize that idiopathic narcolepsy may be the result of a genetic predisposition to autoimmune disease [176]. It is possible that aberrant genetic coding of elements in the hypocretin/orexin systems allows a sensitivity to inducible and possibly virally mediated changes, which leave cells in the lateral hypothalamus susceptible to autoimmune attack [96]. As such, genetic screening of high-risk individuals might eventually rationalize the prophylactic use of immunosuppressants in some instances. In the future, for atypical cases(poorly responsive to therapy), genetic, CSF, and brain imaging studies, and possibly even neuronal transplantation may prove beneficial in the assessment and treatment of idiopathic narcolepsy.

  2. Diagnosis and management of pediatric appendicitis, intussusception, and Meckel diverticulum.

    PubMed

    Pepper, Victoria K; Stanfill, Amy B; Pearl, Richard H

    2012-06-01

    Three of the most common causes of surgical abdominal pain in pediatric patients include appendicitis, Meckel diverticulum, and intussusception. All 3 can present with right lower quadrant pain, and can lead to significant morbidity and even mortality. Although ultrasound is the preferred method of diagnosis with appendicitis and intussusception, considerable variety exists in the modalities needed in the diagnosis of Meckel diverticulum. This article discusses the pathways to diagnosis, the modes of treatment, and the continued areas of controversy. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. [Pediatric ependymomas: Current diagnosis and therapy].

    PubMed

    Frappaz, Didier; Vasiljevic, Alexandre; Beuriat, Pierre-Aurelien; Alapetite, Claire; Grill, Jacques; Szathmari, Alexandru; Faure-Conter, Cécile

    2016-10-01

    Ependymomas represent 10% of pediatric brain tumors. In the recent WHO 2016 classification, pathology is enriched by localization and molecular biology. Whatever the age, total removal by one or several looks when required remains a major prognostic factor. In children, focal radiation remains a standard, while the role of chemotherapy is matter of randomized studies. In infants, front line chemotherapy is the standard. Inclusion in the SIOP ependymoma II protocol is encouraged. In case of relapse, further surgery and radiation are advised, while inclusion in innovative trials including re-irradiation, and phase I-II should be encouraged. A better understanding of underlying mechanisms of ependymoma cell will provide in the close future, the key to use targeted therapies at time of relapse, and very soon as first line therapy for some subgroups of patients.

  4. The Humanistic and Economic Burden of Narcolepsy.

    PubMed

    Flores, Natalia M; Villa, Kathleen F; Black, Jed; Chervin, Ronald D; Witt, Edward A

    2016-03-01

    To evaluate the burden of narcolepsy--with respect to psychiatric comorbidities, Health-Related Quality of Life (HRQoL), direct costs for healthcare resource utilization, and indirect costs for reported work loss-through comparison of patients to matched controls. This analysis was conducted on data from the 2011, 2012, and 2013 US National Health and Wellness Survey (NHWS; 2011 NHWS n = 75,000, 2012 NHWS n = 71,157, and 2013 NHWS n = 75,000). Patients who reported a narcolepsy diagnosis (n = 437) were matched 1:2 with controls (n = 874) on age, sex, race/ethnicity, marital status, education, household income, body mass index, smoking status, alcohol use, exercise, and physical comorbidity. Chi-square tests and one-way analyses of variance were used to assess whether the narcolepsy and control groups differed on psychiatric comorbidities, HRQoL, labor force participation, work productivity, and healthcare resource utilization. Patients with narcolepsy, in comparison to matched controls, reported substantially (two to four times) greater psychiatric comorbidity, HRQoL impairment, prevalence of long-term disability, absenteeism, and presenteeism, and greater resource use in the past 6 mo as indicated by higher mean number of hospitalizations, emergency department visits, traditional healthcare professional visits, neurologist visits, and psychiatrist visits (each p < 0.05). These population-based data suggest that a narcolepsy diagnosis is associated with substantial adverse impact on mental health, HRQoL, and key economic burdens that include work impairment, resource use, and both direct and indirect costs. Although this study is cross-sectional, the results highlight the magnitude of the potential opportunity to improve mental health, lower costs, and augment work-related productivity through effective assessment and treatment of narcolepsy. © 2016 American Academy of Sleep Medicine.

  5. Allergies and Disease Severity in Childhood Narcolepsy: Preliminary Findings

    PubMed Central

    Aydinoz, Secil; Huang, Yu-Shu; Gozal, David; Inocente, Clara O.; Franco, Patricia; Kheirandish-Gozal, Leila

    2015-01-01

    Introduction: Narcolepsy frequently begins in childhood, and is characterized by excessive daytime sleepiness, with the presence of cataplexy reflecting a more severe phenotype. Narcolepsy may result from genetic predisposition involving deregulation of immune pathways, particularly involving T helper 2 cells (Th2). Increased activation of Th2 cells is usually manifested as allergic conditions such as rhinitis, atopic dermatitis, and asthma. We hypothesized that the presence of allergic conditions indicative of increased Th2 balance may dampen the severity of the phenotype in children with narcolepsy. Methods: A retrospective chart review of childhood narcolepsy patients was conducted at three major pediatric sleep centers. Patients were divided into those with narcolepsy without cataplexy (NC−) and narcolepsy with cataplexy (NC+). Demographics, polysomnographic and multiple sleep latency test data, and extraction of information on the presence of allergic diseases such allergic rhinitis, atopic dermatitis, and asthma was performed. Results: There were 468 children identified, with 193 children in NC− group and 275 patients in the NC+ group. Overall, NC+ children were significantly younger, had higher body mass index, and had shorter mean sleep latencies and increased sleep onset rapid eye movement events. The frequency of allergic conditions, particularly asthma and allergic rhinitis, was markedly lower in NC+ (58/275) compared to NC− patients (94/193; P < 0.0001). Conclusion: Involvement of the immune system plays an important role in the pathophysiology of narcolepsy. Current findings further suggest that an increased shift toward T helper 2 cells, as indicated by the presence of allergic conditions, may modulate the severity of the phenotype in childhood narcolepsy, and reduce the prevalence of cataplexy in these patients. Citation: Aydinoz S, Huang YS, Gozal D, Inocente CO, Franco P, Kheirandish-Gozal L. Allergies and disease severity in childhood

  6. [Narcolepsy as an autoimmune disease].

    PubMed

    Sarkanen, Tomi; Vaarala, Outi; Julkunen, Ilkka; Partinen, Markku

    2015-01-01

    Narcolepsy is a sleep disorder of central origin. Hypocretin deficiency is the essential feature of type 1 narcolepsy. The biological background of type 2 narcolepsy (without cataplexy) is less clear. Infections or other external factors are thought to function as triggers of narcolepsy. After the H1N1 vaccination campaign, the incidence of narcolepsy increased clearly in countries where a vaccine boosted with the AS03 adjuvant was used. According to the current view, the increase of narcolepsy in connection with the pandemic vaccine especially in children and adolescents was associated with the virus component of the vaccine, but the adjuvant may also have boosted the development of autoimmune response.

  7. [Hypocretin system and narcolepsy].

    PubMed

    Arias-Carrión, Oscar

    2009-09-01

    Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) sleep periods. It is now identified as a neurodegenerative disease because there is a massive loss of specific neurons in the brain. These neurons contain the neuropeptides hypocretin-1 and hypocretin-2, which are also known as orexin-A and orexin-B. Cerebrospinal fluid hypocretin-1 measurements are diagnostic for primary narcolepsy. The cause of neural loss could be autoimmune since most patients have the HLA DQB1 0602 allele that predisposes to the disorders. The discovery of hypocretin deficiency is redefining the clinical entity of narcolepsy and offering novel diagnostic procedures. This article reviews the current understanding of narcolepsy and discusses the implications of hypocretin discovery.

  8. Diagnosis and management of pediatric endocrine neoplasms.

    PubMed

    Iqbal, Corey W; Wahoff, David C

    2009-06-01

    To guide the clinician in the diagnostic evaluation of endocrine neoplasms, to distinguish between benign and malignant and determine when surgical referral is indicated. Thyroid nodules are uncommon but malignant in as many as 27% of patients. Fine needle aspiration should be considered in adolescents, in which accuracy is as high as 90%; surgical resection should be undertaken in all preadolescents (<13 years) with a thyroid nodule. Prognosis for most primary thyroid malignancies is favorable. Primary hyperparathyroidism is rare and due to an adenoma in up to 70% of patients. Surgical resection carries a cure rate of 95% with the use of intraoperative parathyroid hormone assays. Adrenal neoplasms cover a wide spectrum of disorder. They are functional in 95% of patients and require a thorough diagnostic evaluation prior to surgical resection. Malignant lesions of the adrenal gland carry a poor prognosis when complete surgical resection cannot be achieved. Carcinoids are rare neuroendocrine neoplasms, primarily of the appendix, associated with carcinoid syndrome in 10% of patients. The indolent course warrants aggressive surgical control. Endocrine neoplasms are unusual in the pediatric population. Their presence should raise concern about a multiple endocrine neoplasia syndrome and appropriate diagnostic and endocrine work-up. Most neoplasms will require surgical resection.

  9. [Importance of questioning and physical examination in pediatric clinical diagnosis].

    PubMed

    Rendón-Macías, M E; Lazcano-Loya, J C

    1996-01-01

    In order to determine the certainty of the nosologic as well as the etiologic diagnosis of a complication that a group of physicians can achieve with the use of the interrogatory and physical examination in solving pediatric cases, a comparative survey was carried out with 36 pediatricians. Three clinical cases were chosen (A, B and C) in three different versions (1 = interrogatory, 2 = interrogatory plus physical examination, and 3 = the same plus clinical laboratory tests). Randomly, the physicians reached a diagnosis in all three cases in any one of its versions. Generally, through interrogatory, 66.6% of the physicians (24/36) reached a nosologic diagnosis, 8.3% (3/26) diagnosed the complication and 41% (15/36) the etiological. Together with the physical examination, the percentages increased to 67.5% (25/ 37), 18.9% (7/37) and 43.2% (16/37), respectively (p < 0.05). In Case A, the main nosologic diagnosis was reached by 71, 90 and 91% of the physicians, V = 1, 2 and 3 (p = ns). In Case B, the main nosologic diagnosis was reached by all of the physicians, and in C, 10, 21 and 90% (p < 0.05) of the physicians, respectively. No differences were found in determining the etiologic diagnosis in versions one and two of the three cases. Differences were found in V3 (p < 0.001). More physicians reached the diagnosis of the complications in Cases A and C. Having previous experience in similar cases allowed for a greater percentage of physicians to reach the main nosologic diagnosis (75%, 18/24 vs. 50%, 6/ 112, p = 0.03). The interrogatory and the physical examinations in pediatrics continue to be a useful tool, allowing for a certain diagnosis in 70% to 100% of the cases of common ambulatory pathology. Previous experience in similar cases is a determining factor in reaching a correct diagnosis.

  10. Narcolepsy: pathophysiology and pharmacology.

    PubMed

    Nishino, Seiji

    2007-01-01

    Narcolepsy, which affects 1 in 2000 people in the general population, is characterized by excessive daytime sleepiness (EDS), cataplexy, and other dissociated manifestations of rapid eye movement sleep (hypnagogic hallucinations and sleep paralysis). The disease is currently treated with amphetamine-like central nervous system stimulants (for EDS) and antidepressants (for cataplexy). Some compounds from other classes, such as modafinil (a non-amphetamine wake-promoting compound for EDS) and sodium oxybate (a short-acting sedative for EDS and cataplexy, administered at night), are also employed. The major pathophysiology of human narcolepsy has recently been revealed by the extension of discoveries of narcolepsy genes in animal models: hypocretin/orexin ligand deficiency has been shown in about 90% of human narcolepsy-cataplexy. This finding led directly to the development of new diagnostic tests (i.e., cerebrospinal fluid hypocretin measures). Hypocretin replacement is also likely to be a new therapeutic option for hypocretin-deficient narcolepsy, but is still not available in humans. In this review, the pharmacologic and pathophysiologic aspects of narcolepsy are discussed.

  11. Treatment Options for Narcolepsy.

    PubMed

    Barateau, Lucie; Lopez, Régis; Dauvilliers, Yves

    2016-05-01

    Narcolepsy type 1 and narcolepsy type 2 are central disorders of hypersomnolence. Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy and is associated with hypocretin-1 deficiency. On the other hand, in narcolepsy type 2, cerebrospinal fluid hypocretin-1 levels are normal and cataplexy absent. Despite major advances in our understanding of narcolepsy mechanisms, its current management is only symptomatic. Treatment options may vary from a single drug that targets several symptoms, or multiple medications that each treats a specific symptom. In recent years, narcolepsy treatment has changed with the widespread use of modafinil/armodafinil for daytime sleepiness, antidepressants (selective serotonin and dual serotonin and noradrenalin reuptake inhibitors) for cataplexy, and sodium oxybate for both symptoms. Other psychostimulants can also be used, such as methylphenidate, pitolisant and rarely amphetamines, as third-line therapy. Importantly, clinically relevant subjective and objective measures of daytime sleepiness are required to monitor the treatment efficacy and to provide guidance on whether the treatment goals are met. Associated symptoms and comorbid conditions, such as hypnagogic/hypnopompic hallucinations, sleep paralysis, disturbed nighttime sleep, unpleasant dreams, REM- and non REM-related parasomnias, depressive symptoms, overweight/obesity, and obstructive sleep apnea, should also be taken into account and managed, if required. In the near future, the efficacy of new wake-promoting drugs, anticataplectic agents, hypocretin replacement therapy and immunotherapy at the early stages of the disease should also be evaluated.

  12. Pediatric cardiac surgery with echocardiographic diagnosis alone.

    PubMed Central

    Sohn, Sejung; Kim, Hae Soon; Han, Jae Jin

    2002-01-01

    The diagnostic accuracy of echocardiography alone and the safety of cardiac surgery using this diagnostic approach were retrospectively assessed in 111 children operated for congenital heart defects (CHD) during a 3.5-yr period ending in October 2001. Preoperative diagnosis was compared with the intraoperative findings obtained by surgical inspection. Perioperative death was defined as death within 30 days postoperatively. Of the patients, 70% were operated on in infancy. Seventy-six percent (84 of 111) underwent surgery after echocardiographic diagnosis alone. A high percentage of patients with patent ductus arteriosus (100%), partial atrioventricular canal (100%), coarctation of the aorta (89%), ventricular septal defect (86%), atrial septal defect (85%), and total anomalous pulmonary venous connection (75%) was operated without prior catheterization. Diagnostic errors occurred in 2.4% (2 of 84) of patients with echocardiography only and in 7.4% of patients with catheterization. No error in either group was related to surgical morbidity or mortality. There were five (6.0%) perioperative deaths in the echocardiography group and two (7.4%) in the catheterization group, with no difference in the mortality between the groups. In conclusion, many patients with CHD can be accurately diagnosed by echocardiography alone, and can safely undergo surgery without catheterization, not increasing the overall risk. PMID:12172039

  13. Narcolepsy and odor: preliminary report.

    PubMed

    Dominguez-Ortega, L; Díaz-Gállego, E; Pozo, F; Cabrera García-Armenter, S; Serrano Comino, M; Dominguez-Sanchez, E

    2013-10-01

    This study has been carried out to test the clinical hypothesis of personal smell as a hint to the diagnosis of narcoleptic patients. Sweat samples from narcoleptic and healthy controls were tested independently by two trained dogs and their positive or negative detection compared to the gold standard diagnosis for narcolepsy. Neither trainer nor dog knew the source of the sample selected or its placement in the search device. Twelve narcoleptic patients, both sexes and various ages, recruited from April 2011 to June 2012 and diagnosed according to standard criteria, through their clinical records and nocturnal polysomnography plus multiple sleep latency test, made up the patient group. The control group was made up of 22 healthy volunteer without sleep disorders, both sexes and various ages. Sweat samples from both patients and controls were collected following the same protocol to avoid contamination, and tested independently by two trained dogs. Eleven narcoleptic were detected positive by the dogs while only three controls. It seems that narcoleptic patients have a distinct typical odor that trained dogs can detect. The development of olfactory test could be a useful method in the screening of narcolepsy while opens a new research area. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  14. Neuroimaging in pediatric leukemia and lymphoma: differential diagnosis.

    PubMed

    Vázquez, Elida; Lucaya, Javier; Castellote, Amparo; Piqueras, Joaquim; Sainz, Pilar; Olivé, Teresa; Sánchez-Toledo, José; Ortega, Juan J

    2002-01-01

    Recent advances in therapy for pediatric hematologic neoplasms have greatly improved the prognosis but have resulted in an increased incidence of associated complications and toxic effects. The main neuroimaging features in pediatric patients with leukemia or lymphoma treated with chemotherapy or radiation therapy were retrospectively reviewed. To simplify the approach and facilitate differential diagnosis, the neuroimaging features have been classified into three main categories: central nervous system manifestations of primary disease, side effects of therapeutic procedures (radiation therapy, chemotherapy, bone marrow transplantation), and complications due to immunosuppression, particularly infections. Manifestations of primary disease include cerebrovascular complications (hemorrhage, cerebral infarction) and central nervous system involvement (infiltration of the meninges, parenchyma, bone marrow, orbit, and spine). Effects of radiation therapy include white matter disease, mineralizing microangiopathy, parenchymal brain volume loss, radiation-induced cryptic vascular malformations, and second neoplasms. Effects of chemotherapy and bone marrow transplantation include hemorrhage, dural venous thrombosis, white matter disease, reversible posterior leukoencephalopathy syndrome, and anterior lumbosacral radiculopathy. Both the underlying malignancy and antineoplastic therapy can cause immunosuppression. Fungi are the most frequent causal microorganisms in immunosuppressed patients with infection. Familiarity with the imaging findings is essential for proper diagnosis of neurologic symptoms in pediatric patients with oncohematologic disease. Copyright RSNA, 2002

  15. Allergies and Disease Severity in Childhood Narcolepsy: Preliminary Findings.

    PubMed

    Aydinoz, Secil; Huang, Yu-Shu; Gozal, David; Inocente, Clara O; Franco, Patricia; Kheirandish-Gozal, Leila

    2015-12-01

    Narcolepsy frequently begins in childhood, and is characterized by excessive daytime sleepiness, with the presence of cataplexy reflecting a more severe phenotype. Narcolepsy may result from genetic predisposition involving deregulation of immune pathways, particularly involving T helper 2 cells (Th2). Increased activation of Th2 cells is usually manifested as allergic conditions such as rhinitis, atopic dermatitis, and asthma. We hypothesized that the presence of allergic conditions indicative of increased Th2 balance may dampen the severity of the phenotype in children with narcolepsy. A retrospective chart review of childhood narcolepsy patients was conducted at three major pediatric sleep centers. Patients were divided into those with narcolepsy without cataplexy (NC-) and narcolepsy with cataplexy (NC+). Demographics, polysomnographic and multiple sleep latency test data, and extraction of information on the presence of allergic diseases such allergic rhinitis, atopic dermatitis, and asthma was performed. There were 468 children identified, with 193 children in NC- group and 275 patients in the NC+ group. Overall, NC+ children were significantly younger, had higher body mass index, and had shorter mean sleep latencies and increased sleep onset rapid eye movement events. The frequency of allergic conditions, particularly asthma and allergic rhinitis, was markedly lower in NC+ (58/275) compared to NC- patients (94/193; P < 0.0001). Involvement of the immune system plays an important role in the pathophysiology of narcolepsy. Current findings further suggest that an increased shift toward T helper 2 cells, as indicated by the presence of allergic conditions, may modulate the severity of the phenotype in childhood narcolepsy, and reduce the prevalence of cataplexy in these patients. © 2015 Associated Professional Sleep Societies, LLC.

  16. Observer agreement in pediatric semi-quantitative vertebral fracture diagnosis

    PubMed Central

    Siminoski, Kerry; Lentle, Brian; Matzinger, Mary-Ann; Shenouda, Nazih; Ward, Leanne M.

    2013-01-01

    Background The Genant semi-quantitative (GSQ) method has been a standard procedure for diagnosis of vertebral fractures in adults, but has only recently been shown to be of clinical utility in pediatrics. Observer agreement using the GSQ method in this age group has not been described. Objective To evaluate observer agreement on vertebral readability and vertebral fracture diagnosis using the GSQ method in pediatric vertebral morphometry. Materials and methods Spine radiographs of 186 children with acute lymphoblastic leukemia were evaluated independently by three radiologists using the same GSQ methodology as in adults. A subset of 100 radiographs was evaluated on two occasions. Results An average of 4.7% of vertebrae were unreadable for the three radiologists. Intraobserver Cohen’s kappa (κ) on readability ranged from 0.434 to 0.648 at the vertebral level and from 0.416 to 0.611 at the patient level, while interobserver κ for readability had a range of 0.330 to 0.504 at the vertebral level and 0.295 to 0.467 at the patient level. Intraobserver κ for the presence of vertebral fracture had a range of 0.529 to 0.726 at the vertebral level and was 0.528 to 0.767 at the patient level. Interobserver κ for fracture at the vertebral level ranged from 0.455 to 0.548 and from 0.433 to 0.486 at the patient level. Conclusion Most κ values for both intra- and interobserver agreement in applying the GSQ method to pediatric spine radiographs were in the moderate to substantial range, comparable to the performance of the technique in adult studies. The GSQ method should be considered for use in pediatric research and clinical practice. PMID:24323185

  17. Delayed diagnosis in pediatric headache: an outpatient Italian survey.

    PubMed

    Colombo, Bruno; Dalla Libera, Dacia; De Feo, Donatella; Pavan, Giulia; Annovazzi, Pietro Osvaldo; Comi, Giancarlo

    2011-09-01

    The aim of this prospective study is to assess the time lapse between the onset of recurring headache and the correct diagnosis in a cohort of pediatric patients attending an Italian children's headache center for the first time. One hundred and one patients and parents, referred to the Pediatric Headache Centre of San Raffaele Hospital in Milan, Italy, underwent a semi-structured interview to ascertain features of headache since onset (clinical and family history, presence of childhood periodic syndromes, previously undergone instrumental exams and specialists' examinations before the correct diagnosis, past and current treatment). All patients were evaluated by expert neurologists and their headache was classified according to the International Classification of Headache Disorders II (2004). The median time delay from the onset of the first episode of recurrent headache to definite diagnosis was 20 months (interquartile range 12 to 36 months). A correlation with younger age and a more delayed headache diagnosis was found (r Spearman = 0.25; P = .039). An association between diagnostic delay and positive family history (median 24 months [12 to 48] vs 12 [6 to 24]; P = .014) or female gender (median 18 months [12 to 42] vs. 12 [5 to 30]; P trend = .070) was also evident. Notably, 76 out of 101 patients referred to our Center received an appropriate diagnosis according to International Classification of Headache Disorders II at the time of our visit only. Of note, up to 21% of this group were previously misdiagnosed (for epilepsy 43%, sinusitis 38%, or other diseases 19%), a fact that contributed to a longer time of clinical assessment (median 39 months) before reaching a correct diagnosis. The other group of 80 patients (79%) did not receive a specific diagnosis and treatment, and were not studied until their symptom became chronic and disabling. Pediatric headache is still under-diagnosed and not adequately considered as a health problem in the

  18. Depressive feelings in children with narcolepsy.

    PubMed

    Inocente, Clara Odilia; Gustin, Marie-Paule; Lavault, Sophie; Guignard-Perret, Anne; Raoux, Aude; Christol, Noemie; Gerard, Daniel; Dauvilliers, Yves; Reimão, Rubens; Bat-Pitault, Flora; Lin, Jian-Sheng; Arnulf, Isabelle; Lecendreux, Michel; Franco, Patricia

    2014-03-01

    We aimed to evaluate depressive feelings and their correlations in children and adolescents with narcolepsy collected in national reference centers for narcolepsy. We compared clinical and sleep characteristics of patients with and without depressive symptoms evaluated on the Children's Depression Inventory (CDI). Our study sample included 88 children (44 boys; 44 de novo patients) with a mean age of 11.9 ± 3.1 years at diagnosis (37.5% were aged ⩽ 10 years). Obesity was found in 59% of the sample and cataplexy was present in 80.7%. The DQB1*0602 allele was positive in 93.5% of our sample. There were 25% of children who had clinically depressive feelings (CDI>16), especially girls older than the age of 10 years. Bivariate associations indicated that depressive feelings were associated with fatigue (48%), hyperactivity (31%), insomnia (16%), and excessive daytime sleepiness (EDS) (14-24%). In the multivariate model adjusted for gender and age, only fatigue explained the variability of the depression score. In our large cohort, high levels of depressive symptoms essentially expressed by fatigue affected 25% of children with narcolepsy. The girls older than 10 years of age were especially vulnerable. The similar prevalence of depressive feelings in treated vs never-treated patients suggests a specific need for diagnosing and managing this symptom in young patients with narcolepsy. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Advances in narcolepsy.

    PubMed

    Cao, Michelle

    2010-05-01

    Narcolepsy with cataplexy is a rare but life-long and challenging disorder. Current insight into the pathophysiology of this condition seems to be autoimmune-mediated postnatal cell death of hypocretin neurons occurring by organ-specific autoimmune targeting with HLA-T-cell receptor interactions. The hypocretin system seems to have an influence on multiple organ systems beyond its wake-promoting mechanisms. The recent availability of cerebrospinal fluid hypocretin-1 analysis has led to definitive diagnostic criteria for narcolepsy with cataplexy. Pharmacologic first-line treatments for excessive daytime sleepiness and cataplexy is sodium oxybate, with modafinil for daytime sleepiness, in adults and children. Other investigative agents and treatment modalities hold promise in future directions for narcolepsy.

  20. Nonconvulsive status epilepticus in pediatric populations: diagnosis and management.

    PubMed

    Galimi, R

    2012-06-01

    The diagnosis and management of nonconvulsive status epilepticus (NCSE) pose special challenges in childhood. NCSE can be defined as a condition of ongoing or intermittent clinical epileptic activity without convulsions, for at least 30 minutes, with electroencephalographic evidence of seizures. NCSE accounts for approximately one-quarter of all cases of status epilepticus. NCSE should be suspected in children with epilepsy who undergo an otherwise inexplicable change in behavior and in children with recent onset change in speech, memory, school performance. NCSE can be observed in acute neurological injuries, specific childhood epilepsy syndromes, individuals with learning difficulties and other neurological conditions. NCSE is not uncommon in pediatric patients with an altered state of consciousness. NCSE in children is thought to be under-recognized. It is a highly heterogeneous clinical condition that is understudied in the pediatric population. Prompt recognition and treatment may be necessary to improve neurological outcome. Based on clinical semiology alone, diagnosis is difficult and requires emergent EEG. Management is often difficult, with highly variable response to treatment. Here I describe the diagnosis and management of NCSE in children.

  1. [Narcolepsy in sleepy obese children. Two case reports].

    PubMed

    Rives-Lange, C; Karsenty, A; Chantereau, H; Oderda, L; Dubern, B; Lecendreux, M; Tounian, P

    2016-06-01

    Narcolepsy is a disabling disorder, characterized by excessive daytime sleepiness, irresistible sleep attacks, and partial or complete cataplexy. Many cases of obesity and precocious puberty have been reported in narcoleptic children, suggesting that the deficiency of hypocretin in narcolepsy could also be implicated in appetite stimulation. We report the observations of two young girls, who were referred for obesity and who developed narcolepsy accompanied by an abrupt weight gain. In both cases, specific drugs promoted wakefulness and overweight stabilization. Narcolepsy has to be suspected in sleepy obese children and not misdiagnosed as obstructive apnea. A nocturnal polysomnography with multiple sleep latency tests should be performed to confirm the diagnosis and begin specific treatment that is effective for sleep disorders and weight gain. Copyright © 2016. Published by Elsevier SAS.

  2. Lucid dreaming in narcolepsy.

    PubMed

    Dodet, Pauline; Chavez, Mario; Leu-Semenescu, Smaranda; Golmard, Jean-Louis; Arnulf, Isabelle

    2015-03-01

    To evaluate the frequency, determinants and sleep characteristics of lucid dreaming in narcolepsy. University hospital sleep disorder unit. Case-control study. Consecutive patients with narcolepsy and healthy controls. Participants were interviewed regarding the frequency and determinants of lucid dreaming. Twelve narcolepsy patients and 5 controls who self-identified as frequent lucid dreamers underwent nighttime and daytime sleep monitoring after being given instructions regarding how to give an eye signal when lucid. Compared to 53 healthy controls, the 53 narcolepsy patients reported more frequent dream recall, nightmares and recurrent dreams. Lucid dreaming was achieved by 77.4% of narcoleptic patients and 49.1% of controls (P < 0.05), with an average of 7.6±11 vs. 0.3±0.8 lucid dreams/ month (P < 0.0001). The frequency of cataplexy, hallucinations, sleep paralysis, dyssomnia, HLA positivity, and the severity of sleepiness were similar in narcolepsy with and without lucid dreaming. Seven of 12 narcoleptic (and 0 non-narcoleptic) lucid dreamers achieved lucid REM sleep across a total of 33 naps, including 14 episodes with eye signal. The delta power in the electrode average, in delta, theta, and alpha powers in C4, and coherences between frontal electrodes were lower in lucid than non-lucid REM sleep in spectral EEG analysis. The duration of REM sleep was longer, the REM sleep onset latency tended to be shorter, and the percentage of atonia tended to be higher in lucid vs. non-lucid REM sleep; the arousal index and REM density and amplitude were unchanged. Narcolepsy is a novel, easy model for studying lucid dreaming. © 2015 Associated Professional Sleep Societies, LLC.

  3. Complex Diagnostic and Treatment Issues in Psychotic Symptoms Associated with Narcolepsy

    PubMed Central

    Ivanenko, Anna

    2009-01-01

    Narcolepsy is an uncommon chronic, neurological disorder characterized by abnormal manifestations of rapid eye movement sleep and perturbations in the sleep-wake cycle. Accurate diagnosis of psychotic symptoms in a person with narcolepsy could be difficult due to side effects of stimulant treatment (e.g., hallucinations) as well as primary symptoms of narcolepsy (e.g., sleep paralysis and hypnagogic and/or hypnapompic hallucinations). Pertinent articles from peer-reviewed journals were identified to help understand the complex phenomenology of psychotic symptoms in patients with narcolepsy. In this ensuing review and discussion, we present an overview of narcolepsy and outline diagnostic and management approaches for psychotic symptoms in patients with narcolepsy. PMID:19724760

  4. Juvenile onset narcolepsy in an individual with Turner syndrome. A case report.

    PubMed

    George, C F; Singh, S M

    1991-06-01

    We describe an 8 year old girl who presented with excessive daytime sleepiness and frequent falling. Following extensive investigations, the diagnosis of both narcolepsy and Turner Syndrome were confirmed. To our knowledge, this is the first report of these two conditions in the same individual. Both conditions are common, but the early expression of narcolepsy is unusual. Although there is a genetic basis for each, the two conditions are not necessarily related since Turner is an X-linked abnormality, while narcolepsy has an autosomal basis. Nonetheless we wonder if the hormonal balance of Turner Syndrome might have some role to play in the early expression of narcolepsy.

  5. Molecular method for the diagnosis of imported pediatric malaria.

    PubMed

    Delhaes Jeanne, L; Berry, A; Dutoit, E; Leclerc, F; Beaudou, J; Leteurtre, S; Camus, D; Benoit-Vical, F

    2010-02-01

    Malaria is a polymorphous disease; it can be life threatening especially for children. We report a case of imported malaria in a boy, illustrating the epidemiological and clinical aspects of severe pediatric malaria. In this case real-time PCR was used to quantify Plasmodium falciparum DNA levels, to monitor the evolution under treatment, and to determine genetic mutations involved in chloroquine resistance. The major epidemiological features of imported malaria, and the difficulty to diagnose childhood severe malaria are described. The contribution of molecular methods for the diagnosis of imported malaria is discussed.

  6. Specimen collection for the diagnosis of pediatric pneumonia.

    PubMed

    Hammitt, Laura L; Murdoch, David R; Scott, J Anthony G; Driscoll, Amanda; Karron, Ruth A; Levine, Orin S; O'Brien, Katherine L

    2012-04-01

    Diagnosing the etiologic agent of pneumonia has an essential role in ensuring the most appropriate and effective therapy for individual patients and is critical to guiding the development of treatment and prevention strategies. However, establishing the etiology of pneumonia remains challenging because of the relative inaccessibility of the infected tissue and the difficulty in obtaining samples without contamination by upper respiratory tract secretions. Here, we review the published and unpublished literature on various specimens available for the diagnosis of pediatric pneumonia. We discuss the advantages and limitations of each specimen, and discuss the rationale for the specimens to be collected for the Pneumonia Etiology Research for Child Health study.

  7. Lucid Dreaming in Narcolepsy

    PubMed Central

    Dodet, Pauline; Chavez, Mario; Leu-Semenescu, Smaranda; Golmard, Jean-Louis; Arnulf, Isabelle

    2015-01-01

    Objective: To evaluate the frequency, determinants and sleep characteristics of lucid dreaming in narcolepsy Settings: University hospital sleep disorder unit Design: Case-control study Participants: Consecutive patients with narcolepsy and healthy controls Methods: Participants were interviewed regarding the frequency and determinants of lucid dreaming. Twelve narcolepsy patients and 5 controls who self-identified as frequent lucid dreamers underwent nighttime and daytime sleep monitoring after being given instructions regarding how to give an eye signal when lucid. Results: Compared to 53 healthy controls, the 53 narcolepsy patients reported more frequent dream recall, nightmares and recurrent dreams. Lucid dreaming was achieved by 77.4% of narcoleptic patients and 49.1% of controls (P < 0.05), with an average of 7.6 ± 11 vs. 0.3 ± 0.8 lucid dreams/month (P < 0.0001). The frequency of cataplexy, hallucinations, sleep paralysis, dyssomnia, HLA positivity, and the severity of sleepiness were similar in narcolepsy with and without lucid dreaming. Seven of 12 narcoleptic (and 0 non-narcoleptic) lucid dreamers achieved lucid REM sleep across a total of 33 naps, including 14 episodes with eye signal. The delta power in the electrode average, in delta, theta, and alpha powers in C4, and coherences between frontal electrodes were lower in lucid than non-lucid REM sleep in spectral EEG analysis. The duration of REM sleep was longer, the REM sleep onset latency tended to be shorter, and the percentage of atonia tended to be higher in lucid vs. non-lucid REM sleep; the arousal index and REM density and amplitude were unchanged. Conclusion: Narcoleptics have a high propensity for lucid dreaming without differing in REM sleep characteristics from people without narcolepsy. This suggests narcolepsy patients may provide useful information in future studies on the nature of lucid dreaming. Citation: Dodet P, Chavez M, Leu-Semenescu S, Golmard JL, Arnulf I. Lucid dreaming in

  8. High Rates of Psychiatric Comorbidity in Narcolepsy: Findings From the Burden of Narcolepsy Disease (BOND) Study of 9,312 Patients in the United States.

    PubMed

    Ruoff, Chad M; Reaven, Nancy L; Funk, Susan E; McGaughey, Karen J; Ohayon, Maurice M; Guilleminault, Christian; Black, Jed

    2017-02-01

    To evaluate psychiatric comorbidity patterns in patients with a narcolepsy diagnosis in the United States. Truven Health Analytics MarketScan Research Databases were accessed to identify individuals ≥ 18 years of age with ≥ 1 ICD-9 diagnosis code(s) for narcolepsy continuously insured between 2006 and 2010 and non-narcolepsy controls matched 5:1 (age, gender, region, payer). Extensive subanalyses were conducted to confirm the validity of narcolepsy definitions. Narcolepsy subjects and controls were compared for frequency of psychiatric comorbid conditions (based on ICD-9 codes/Clinical Classification Software [CCS] level 2 categories) and psychiatric medication use. The final population included 9,312 narcolepsy subjects and 46,559 controls (each group, mean age = 46.1 years; 59% female). All categories of mental illness were significantly more prevalent in patients with narcolepsy versus controls, with the highest excess prevalence noted for CCS 5.8 Mood disorders (37.9% vs 13.8%; odds ratio [OR] = 4.0; 95% CI, 3.8-4.2), CCS 5.8.2 Depressive disorders (35.8% vs 13.0%; OR = 3.9; 95% CI, 3.7-4.1), and CCS 5.2 Anxiety disorders (25.1% vs 11.9%; OR = 2.5; 95% CI, 2.4-2.7). Excess prevalence of anxiety and mood disorders (narcolepsy vs controls) was higher in younger age groups versus older age groups. Psychiatric medication usage was higher in the narcolepsy group versus controls in the following categories: selective serotonin reuptake inhibitors (36% vs 17%), anxiolytic benzodiazepines (34% vs 19%), hypnotics (29% vs 13%), serotonin-norepinephrine reuptake inhibitors (21% vs 6%), and tricyclic antidepressants (13% vs 4%) (all P values < .0001). Narcolepsy is associated with significant comorbid psychiatric illness burden and higher psychiatric medication usage compared with the non-narcolepsy population.

  9. Magnetic resonance urography for diagnosis of pediatric ureteral stricture.

    PubMed

    Arlen, Angela M; Kirsch, Andrew J; Cuda, Scott P; Little, Stephen B; Jones, Richard A; Grattan-Smith, J Damien; Cerwinka, Wolfgang H

    2014-10-01

    Ureteral stricture is a rare cause of hydronephrosis in children and is often misdiagnosed on ultrasound (US) and diuretic renal scintigraphy (DRS), requiring intraoperative diagnosis. We evaluated ureteral strictures diagnosed by magnetic resonance urography (MRU) at our institution. Children with ureteral stricture who underwent MRU were identified. Patient demographics, prior imaging, MRU findings, and management were assessed. The efficacy of MRU in diagnosis of stricture was compared with US and DRS. Patients with ureteropelvic or ureterovesical junction obstruction were excluded. Twenty-eight ureteral strictures diagnosed by MRU between 2003 and 2013 were identified; 22% of strictures were diagnosed by DRS ± US. The mean age at MRU diagnosis was 2.4 years (range 4 weeks-15 years). Hydronephrosis was the most common presentation, accounting for 20 (71%) cases. Other etiologies included pain (3), incontinence (2), and urinary tract infection, cystic kidney, and absent kidney, present in one case each. A mean of 2.7 imaging studies was obtained prior to MRU diagnosis. Twenty-one (75%) ureteral strictures required surgical intervention, with the approach dependent upon location. MRU provides excellent anatomic and functional detail of the collecting system, leading to accurate diagnosis and management of ureteral stricture in children. Copyright © 2014 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  10. Diagnosis of pediatric neuroblastoma by urine cytology: A case report.

    PubMed

    Nishikawa, Shiori; Noguchi, Hiroshi; Tokumitsu, Takako; Ohno, Akinobu; Moriguchi-Goto, Sayaka; Maekawa, Kazunari; Asada, Yujiro; Moritake, Hiroshi; Kinoshita, Mariko; Yamada, Ai; Takamura, Kazunari; Sato, Yuichiro

    2017-10-06

    Neuroblastomas are embryonal tumors arising from the neuronal crest cells of the synaptic nervous system. Findings from aspiration cytology have been reported, but there have been no reports of urine cytology findings. Here, we report a case of pediatric neuroblastoma characterized by urine cytology. A 2-year-old boy presented with abdominal pain, nausea, and loss of appetite. Computed tomography revealed a large tumor in the left suprarenal region with massive infiltration into the kidney. Urinary cytology showed highly cellular clusters composed of small, round, atypical cells with little cytoplasm and high nuclear/cytoplasmic ratio; nuclear molding was also noted in some places. Immunocytochemical staining was positive for synaptophysin and chromogranin A, and neuroblastoma was suggested by urine cytology. A biopsy of the left adrenal tumor later confirmed a diagnosis of poorly differentiated neuroblastoma. Urine cytology may be useful for rapid diagnosis and management of similar cases. © 2017 Wiley Periodicals, Inc.

  11. Narcolepsy: Let the Patient’s Voice Awaken Us!

    PubMed Central

    Flygare, Julie; Parthasarathy, Sairam

    2014-01-01

    This is a “patient-centered” review about narcolepsy that aims to awaken the reader to the narcolepsy condition and to the trials and tribulations of patients with sleep problems in general. Narcolepsy is a neurological disorder with a classic tetrad of symptoms consisting of excessive daytime sleepiness, cataplexy, sleep onset hallucinations, and sleep paralysis. The diagnosis of narcolepsy and other sleep disorders are often overlooked and could be attributed to other medical or even psychiatric conditions with years of missed diagnosis. Implementation of “two sleep-related questions” to the review of systems in the primary care physicians’ office visit may help address the issue of missed diagnosis and allow patients to seek prompt medical attention. Definitive diagnosis can be made by overnight sleep study followed by a nap test, “multiple sleep latency test” (MSLT). There is currently no cure for narcolepsy with the treatments addressing symptoms of excessive daytime sleepiness, cataplexy, and nighttime sleep disruption with stimulants (modafinil, methylphenidate, and amphetamines), anti-cataplexy medications (Serotonin-specific reuptake inhibitors and tricyclic antidepressants) and sedative-hypnotics including sodium oxybate. Narcolepsy, like other sleep disorders, can lead to marked reductions of health-related quality of life and affect patients’ social and work lives deleteriously. While traditional healthcare approaches are focused more on hard biomedical outcomes, a patient-centered approach with novel methods for better sleep assessment of patients, that can bypass the “impossibly crammed” physician office visit, would allow healthcare providers to better detect, diagnose and treat narcolepsy and other such sleep problems. PMID:24931392

  12. Pediatric providers' attitudes and practices regarding concussion diagnosis and management.

    PubMed

    Itriyeva, Khalida; Feinstein, Ronald; Carmine, Linda

    2017-08-25

    Background Concussions, a form of mild traumatic brain injury, are a current "hot topic" in sports and medicine, with current research focusing on diagnosis, treatment, and the long-term effects of repeated concussions on development of chronic traumatic encephalopathy. Concussions represent 8.9% of all high school athletic injuries, and pediatricians see many of these patients in their practices, however evolving guidelines and recommendations have resulted in varying practices among providers. Objective To assess how local pediatricians in New York Chapter 2 of the American Academy of Pediatrics (AAP) diagnose and treat concussion patients, and to evaluate the need for continuing education in this area. Design and methods Survey Monkey™ was used to query providers regarding their diagnosis and treatment of concussion patients. A total of three emails containing a link to the 22 question multiple-choice survey were sent to AAP Chapter 2 members between January 2015 and June 2015. The survey was adapted and modified with permission from one previously used by "Zonfrillo MR, Master CL, Grady MF, Winston FK, Callahan JM, Arbogast KB. Pediatric providers' self-reported knowledge, practices, and attitudes about concussion. Pediatrics. 2012;130:1120-5". Results We received 115 responses from 1436 potential participants to whom the survey link was sent, resulting in an 8% response rate. We excluded subspecialists from our data analysis, resulting in data from 95 primary care pediatricians. Of the PCPs 98.7% reported seeing at least one child or adolescent with a concussion in the previous 12 months and 76.6% reported referring some or all of their concussion patients for ongoing management. The most common reason for referral was "I am not always comfortable with management" and the most common subspecialist referral was to a neurologist. Most providers reported that they did not use any guidelines for management (58.3%) and only 57.4% were familiar with the New York

  13. The Medical and Economic Burden of Narcolepsy: Implications for Managed Care

    PubMed Central

    Thorpy, Michael J.; Hiller, George

    2017-01-01

    Background The neurologic disorder narcolepsy results from dysregulation of the sleep-wake cycle and is primarily characterized by chronic, severely excessive daytime sleepiness and cataplexy, an emotionally induced muscle weakness. The prevalence of narcolepsy is approximately 0.05%, and onset generally occurs during the first 2 decades of life. Narcolepsy is believed to be an autoimmune disorder with destruction of hypocretin-producing neurons in the lateral hypothalamus. Objectives To provide an enhanced understanding of narcolepsy and establish the need for early diagnosis and rapid initiation of effective treatment for patients with narcolepsy. Discussion Narcolepsy reduces daily functioning and is associated with a substantial medical and economic burden, with many patients being on full disability. The annual direct medical costs are approximately 2-fold higher in patients with narcolepsy than in matched controls without this condition ($11,702 vs $5261, respectively; P <.0001). Further contributing to the overall burden is a lack of recognition of the signs and symptoms of narcolepsy and an absence of easily measurable biomarkers, resulting in a diagnostic delay that often exceeds 10 years and may be associated with misdiagnosis and inappropriate resource utilization. Because narcolepsy generally has an onset in childhood or in adolescence, is often misdiagnosed, has no known cure, and requires lifelong treatment, it is an important disease from a managed care perspective. Clinical features, as well as objective testing, should be used to ensure the timely diagnosis and treatment of patients with narcolepsy. Conclusion Policies for the diagnosis and treatment of narcolepsy should be based on the current treatment guidelines, but they should also encourage shared decisions between clinicians and patients to allow for individualized diagnostic and treatment choices, as suggested in best practice recommendations.

  14. Delusional Confusion of Dreaming and Reality in Narcolepsy

    PubMed Central

    Wamsley, Erin; Donjacour, Claire E.H.M.; Scammell, Thomas E.; Lammers, Gert Jan; Stickgold, Robert

    2014-01-01

    Study Objectives: We investigated a generally unappreciated feature of the sleep disorder narcolepsy, in which patients mistake the memory of a dream for a real experience and form sustained delusions about significant events. Design: We interviewed patients with narcolepsy and healthy controls to establish the prevalence of this complaint and identify its predictors. Setting: Academic medical centers in Boston, Massachusetts and Leiden, The Netherlands. Participants: Patients (n = 46) with a diagnosis of narcolepsy with cataplexy, and age-matched healthy healthy controls (n = 41). Interventions: N/A. Measurements and Results: “Dream delusions” were surprisingly common in narcolepsy and were often striking in their severity. As opposed to fleeting hypnagogic and hypnopompic hallucinations of the sleep/wake transition, dream delusions were false memories induced by the experience of a vivid dream, which led to false beliefs that could persist for days or weeks. Conclusions: The delusional confusion of dreamed events with reality is a prominent feature of narcolepsy, and suggests the possibility of source memory deficits in this disorder that have not yet been fully characterized. Citation: Wamsley E; Donjacour CE; Scammell TE; Lammers GJ; Stickgold R. Delusional confusion of dreaming and reality in narcolepsy. SLEEP 2014;37(2):419-422. PMID:24501437

  15. Disrupted Nighttime Sleep in Narcolepsy

    PubMed Central

    Roth, Thomas; Dauvilliers, Yves; Mignot, Emmanuel; Montplaisir, Jacques; Paul, Josh; Swick, Todd; Zee, Phyllis

    2013-01-01

    Study Objectives: Characterize disrupted nighttime sleep (DNS) in narcolepsy, an important symptom of narcolepsy. Methods: A panel of international narcolepsy experts was convened in 2011 to build a consensus characterization of DNS in patients with narcolepsy. A literature search of the Medline (1965 to date), Medline In-Process (latest weeks), Embase (1974 to date), Embase Alert (latest 8 weeks), and Biosis (1965 to date) databases was conducted using the following search terms: narcolepsy and disrupted nighttime sleep, disturbed nighttime sleep, fragmented sleep, consolidated sleep, sleep disruption, and narcolepsy questionnaire. The purpose of the literature search was to identify publications characterizing the nighttime sleep of patients with narcolepsy. The panel reviewed the literature. Nocturnal sleep can also be disturbed by REM sleep abnormalities such as vivid dreaming and REM sleep behavior disorder; however, these were not reviewed in the current paper, as we were evaluating for idiopathic sleep disturbances. Results: The literature reviewed provide a consistent characterization of nighttime sleep in patients with narcolepsy as fragmented, with reports of frequent, brief nightly awakenings with difficulties returning to sleep and associated reports of poor sleep quality. Polysomnographic studies consistently report frequent awakenings/arousals after sleep onset, more stage 1 (S1) sleep, and more frequent shifts to S1 sleep or wake from deeper stages of sleep. The consensus of the International Experts' Panel on Narcolepsy was that DNS can be distressing for patients with narcolepsy and that treatment of DNS warrants consideration. Conclusions: Clinicians involved in the management of patients with narcolepsy should investigate patients' quality of nighttime sleep, give weight and consideration to patient reports of nighttime sleep experience, and consider DNS a target for treatment. Citation: Roth T; Dauvilliers Y; Mignot E; Montplaisir J; Paul J

  16. [Diagnosis of tuberculosis in pediatrics. Consensus document of the Spanish Society of Pediatric Infectology (SEIP) and the Spanish Society of Pediatric Pneumology (SENP)].

    PubMed

    Moreno-Pérez, D; Andrés Martín, A; Altet Gómez, N; Baquero-Artigao, F; Escribano Montaner, A; Gómez-Pastrana Durán, D; González Montero, R; Mellado Peña, M J; Rodrigo-Gonzalo-de-Liria, C; Ruiz Serrano, M J

    2010-09-01

    Tuberculosis is one of the most important health problems worldwide. There are an increased number of cases, including children, due to different reasons in developed countries. The most likely determining cause is immigration coming from high endemic areas. Measures to optimize early and appropriate diagnosis of the different forms of tuberculosis in children are a real priority. Two Societies of the Spanish Pediatric Association (Spanish Society of Pediatric Infectology and Spanish Society of Pediatric Pneumology) have agreed this Consensus Document in order to homogenize diagnostic criteria in pediatric patients.

  17. [Pathological diagnosis of pediatric Burkitt lymphoma involving bone marrow].

    PubMed

    Sun, Qi; Chen, Zhenping; Liu, Enbin; Li, Zhanqi; Yang, Qingying; Sun, Fujun; Ma, Yue; Zhang, Hongju; Zhang, Peihong; Ru, Kun

    2015-02-01

    To investigate pathologic and differential diagnostic features of pediatric Burkitt lymphoma (BL). A total of 20 cases of pediatric BL were retrospectively reviewed for their clinical and pathologic profiles. Bone marrow aspiration specimens were available in all cases and bone marrow biopsies were available for immunohistochemical study in 18 cases. Flow cytometry study was available in 16 cases. MYC translocation by FISH method was performed in 11 cases. Atypical lymphocytes with cytoplasmic vacuoles were found in bone marrow smears in all 20 cases and peripheral blood films in all 19 available cases. The bone marrow biopsies showed infiltration by uniform medium-sized atypical lymphocytes with multiple small nucleoli but without the starry-sky pattern in all 18 cases. Immunohistochemistry showed the following results in all 18 cases: positive for CD20, PAX-5, CD10, CD34 and TdT, but negative for bcl-2 and CD3 with Ki-67 > 95%.Flow cytometry showed CD19+CD20+CD10+FMC7+CD22+TdT-CD3- in 16 cases, including κ+ in 8 cases, λ+ in 7 cases, and κ-λ- in 1 case. MYC gene rearrangement by FISH was observed in 10 of the 11 cases. The histopathology of BL is distinct, including atypical lymphocytes with cytoplasmic vacuoles in bone marrow aspirate, lack of starry-sky patternin bone marrow biopsy. Generally, the diagnosis should be made with a combined immunophenotype and FISH approach. Pediatric BL must be distinguished from DLBCL and B-cell lymphoma, unclassifiable, which has intermediate features between DLBCL and Burkitt lymphoma.

  18. Mediastinitis in pediatric cardiac surgery: Prevention, diagnosis and treatment

    PubMed Central

    Durandy, Yves

    2010-01-01

    In spite of advances in the management of mediastinitis following sternotomy, mediastinitis is still associated with significant morbidity. The prognosis is much better in pediatric surgery compared to adult surgery, but the prolonged hospital stays with intravenous therapy and frequent required dressing changes that occur with several therapeutic approaches are poorly tolerated. Prevention includes nasal decontamination, skin preparation, antibioprophylaxis and air filtration in the operating theater. The expertise of the surgical team is an additional factor that is difficult to assess precisely. Diagnosis is often very simple, being made on the basis of a septic state with wound modification, while retrosternal puncture and CT scan are rarely useful. Treatment of mediastinitis following sternotomy is always a combination of surgical debridement and antibiotic therapy. Continued use of numerous surgical techniques demonstrates that there is no consensus and the best treatment has yet to be determined. However, we suggest that a primary sternal closure is the best surgical option for pediatric patients. We propose a simple technique with high-vacuum Redon’s catheter drainage that allows early mobilization and short term antibiotherapy, which thus decreases physiological and psychological trauma for patients and families. We have demonstrated the efficiency of this technique, which is also cost-effective by decreasing intensive care and hospital stay durations, in a large group of patients. PMID:21179306

  19. UTI: diagnosis and evaluation in symptomatic pediatric patients.

    PubMed

    Heldrich, F J; Barone, M A; Spiegler, E

    2000-08-01

    We retrospectively reviewed data on 260 hospitalized pediatric patients with symptomatic urinary tract infection (UTI). To ascertain the colony-forming units (CFU)/mL compatible with the diagnosis of UTI, a culture from a catheterized urine specimen containing >1,000 CFU/mL was considered diagnostic of UTI and resulted in imaging by renal ultrasound, voiding cystourethrography, and renal nuclear scan with Tc99m dimercaptosuccinic acid (DMSA). A positive DMSA renal scan is indicative of pyelonephritis. We used logistic regression analysis to determine which patient characteristics were predictive of pyelonephritis. We determined that, in hospitalized pediatric patients, the colony count of the positive urine culture, the type of organism grown in culture, and the voiding cystourethrography (VCUG) result (positive or negative for vesicoureteral reflux) did not predict which patients had pyelonephritis. In females, advancing age of the patient and positive renal ultrasound results were predictive of which patients had pyelonephritis when we controlled for other factors. We feel this emphasizes the importance of a thorough evaluation of hospitalized symptomatic patients, including patients with colony counts of 1,000 to 50,000 CFU/mL, to locate the level of infection and plan appropriate therapy.

  20. Prevalence, Clinical Presentation, and Differential Diagnosis of Pediatric Bipolar Disorder

    PubMed Central

    Goldstein, Benjamin I.; Birmaher, Boris

    2016-01-01

    Background Over the past 20 years, the evidence regarding pediatric bipolar disorder (BP) has increased substantially. As a result, recent concerns have focused primarily on prevalence and differential diagnosis. Method Selective review of the literature. Results BP as defined by rigorously applying diagnostic criteria has been observed among children and especially adolescents in numerous countries. In contrast to increasing diagnoses in clinical settings, prevalence in epidemiologic studies has not recently changed. BP-spectrum conditions among youth are highly impairing and confer high risk for conversion to BP-I and BP-II. Compared to adults, youth with BP have more mixed symptoms, more changes in mood polarity, are more often symptomatic and seem to have worse prognosis. The course, clinical characteristics, and comorbidities of BP among children and adolescents are in many ways otherwise similar to those of adults with BP. Nonetheless, many youth with BP receive no treatment and most do not receive BP-specific treatment. Conclusion Despite increased evidence supporting the validity of pediatric BP, discrepancies between clinical and epidemiologic findings suggest that diagnostic misapplication may be common. Simultaneously, low rates of treatment of youth with BP suggest that withholding of BP diagnoses may also be common. Clinicians should apply diagnostic criteria rigorously in order to optimize diagnostic accuracy and ensure appropriate treatment. PMID:22652925

  1. Pediatric bipolar disorder: validity, phenomenology, and recommendations for diagnosis

    PubMed Central

    Youngstrom, Eric A; Birmaher, Boris; Findling, Robert L

    2013-01-01

    Objective To find, review, and critically evaluate evidence pertaining to the phenomenology of pediatric bipolar disorder and its validity as a diagnosis. Methods The present qualitative review summarizes and synthesizes available evidence about the phenomenology of bipolar disorder (BD) in youths, including description of the diagnostic sensitivity and specificity of symptoms, clarification about rates of cycling and mixed states, and discussion about chronic versus episodic presentations of mood dysregulation. The validity of the diagnosis of BD in youths is also evaluated based on traditional criteria including associated demographic characteristics, family environmental features, genetic bases, longitudinal studies of youths at risk of developing BD as well as youths already manifesting symptoms on the bipolar spectrum, treatment studies and pharmacologic dissection, neurobiological findings (including morphological and functional data), and other related laboratory findings. Additional sections review impairment and quality of life, personality and temperamental correlates, the clinical utility of a bipolar diagnosis in youths, and the dimensional versus categorical distinction as it applies to mood disorder in youths. Results A schema for diagnosis of BD in youths is developed, including a review of different operational definitions of `bipolar not otherwise specified.' Principal areas of disagreement appear to include the relative role of elated versus irritable mood in assessment, and also the limits of the extent of the bipolar spectrum – when do definitions become so broad that they are no longer describing `bipolar' cases? Conclusions In spite of these areas of disagreement, considerable evidence has amassed supporting the validity of the bipolar diagnosis in children and adolescents. PMID:18199237

  2. Differential diagnosis and evaluation in pediatric inflammatory demyelinating disorders.

    PubMed

    Rostasy, Kevin; Bajer-Kornek, Barbara; Venkateswaran, Sunita; Hemingway, Cheryl; Tardieu, Marc

    2016-08-30

    Major advances have been made in the clinical and radiologic characterization of children presenting with the different forms of an acquired inflammatory demyelinating syndrome (ADS) such as acute disseminating encephalomyelitis, neuromyelitis optica spectrum disorders, and clinically isolated syndromes. Nevertheless, a proportion of cases that present with similar symptoms are due to a broad spectrum of other inflammatory disorders affecting the white matter, primary CNS tumors, or neurometabolic diseases. The clinician therefore has to be aware of the different forms of ADS, the risk factors for a chronic-relapsing course, and features that indicate an alternative diagnosis. The goal of this article is therefore to provide an outline of a pathway for evaluating pediatric patients with a presumed inflammatory demyelinating disorder and discussing the spectrum of the more common differential diagnoses.

  3. Dante's description of narcolepsy.

    PubMed

    Plazzi, Giuseppe

    2013-11-01

    Sleep, sleepiness, and dreaming are expressed throughout Dante Alighieri's (1265-1321) the Divine Comedy from the start of his journey through the afterlife. In the book, Dante complains that he is "full of sleep," and he experiences sudden wake-dreaming transitions, short and refreshing naps, visions and hallucinations, unconscious behaviors, episodes of muscle weakness, and falls which are always triggered by strong emotions. Taken together these signs are highly reminiscent of narcolepsy, a term coined in 1880 by Gélineau to define a disease consisting of daytime irresistible sleep episodes with remarkable dream mentation, sleep paralysis, hallucinations, and cataplexy (falls triggered by strong emotions). Sleep, sleepiness, and episodes of sudden weakness triggered by emotions are Dante's literary fingerprints from his earliest works, pointing to a lifelong autobiographic trait. In the 19th century, Cesare Lombroso speculated that Dante had epilepsy, as he had suffered from frequent spells and hallucinations. However, the multiple emotionally triggered falls Dante experienced in the Divine Comedy contrast with the epileptic seizure he depicted in one of the damned individuals. It is possible that Dante may have intuitively grasped the main features of narcolepsy, but it also is plausible that Dante's sleep, dreams, hallucinations, and falls are clues to a lifelong pathologic trait and that Dante may have known of or had narcolepsy.

  4. ▼Pitolisant for narcolepsy.

    PubMed

    2017-01-01

    ▼Pitolisant (Wakix-Bioprojet Pharma) is a new treatment for adults with narcolepsy with or without cataplexy. It was licensed for use in the EU in March last year and has orphan drug status.(1) Here, we consider the evidence for pitolisant for the treatment of narcolepsy in adults and how it fits with current management strategies.

  5. Second malignancies in pediatric patients: imaging findings and differential diagnosis.

    PubMed

    Vázquez, Elida; Castellote, Amparo; Piqueras, Joaquim; Ortuno, Pedro; Sánchez-Toledo, José; Nogués, Pere; Lucaya, Javier

    2003-01-01

    Therapeutic advances in the treatment of pediatric neoplasms have improved the prognosis but have also increased the risk of developing rare second malignant neoplasms (SMNs). Primary neoplasms that are often associated with SMNs include lymphoma, retinoblastoma, medulloblastoma, neuroblastoma, and leukemia. The most common SMNs are central nervous system (CNS) tumors, sarcomas, thyroid and parotid gland carcinomas, and leukemia, particularly acute myeloblastic leukemia. Genetic predisposition, chemotherapy, and especially radiation therapy are implicated as pathogenic factors in SMN. All survivors of childhood cancer should have lifelong follow-up, preferably with magnetic resonance imaging, which does not require ionizing radiation and provides greater anatomic detail and resolution in the head and neck region and the CNS. A new or progressive lesion may represent recurrence of the primitive neoplastic process, late radiation injury, or, more infrequently, an SMN. Differential diagnosis can be very difficult, and outcome is often fatal. Treatment protocols should be modified to reduce the risk for SMN without compromising the effectiveness of initial therapy. Clinicians should individualize treatment for patients who are genetically predisposed to SMN. In addition, radiologists should be familiar with the long-term consequences of antineoplastic therapy to facilitate diagnosis and anticipate adverse outcomes.

  6. The Burden of Narcolepsy Disease (BOND) study: health-care utilization and cost findings.

    PubMed

    Black, Jed; Reaven, Nancy L; Funk, Susan E; McGaughey, Karen; Ohayon, Maurice; Guilleminault, Christian; Ruoff, Chad; Mignot, Emmanuel

    2014-05-01

    The aim of this study was to characterize health-care utilization, costs, and productivity in a large population of patients diagnosed with narcolepsy in the United States. This retrospective, observational study using data from the Truven Health Analytics MarketScan Research Databases assessed 5 years of claims data (2006-2010) to compare health-care utilization patterns, productivity, and associated costs among narcolepsy patients (identified by International Classification of Diseases, Ninth Revision (ICD9) narcolepsy diagnosis codes) versus matched controls. A total of 9312 narcolepsy patients (>18 years of age, continuously insured between 2006 and 2010) and 46,559 matched controls were identified. Compared with controls, narcolepsy subjects had approximately twofold higher annual rates of inpatient admissions (0.15 vs. 0.08), emergency department (ED) visits w/o admission (0.34 vs. 0.17), hospital outpatient (OP) visits (2.8 vs. 1.4), other OP services (7.0 vs. 3.2), and physician visits (11.1 vs. 5.6; all p<0.0001). The rate of total annual drug transactions was doubled in narcolepsy versus controls (26.4 vs. 13.3; p<0.0001), including a 337% and 72% higher usage rate of narcolepsy drugs and non-narcolepsy drugs, respectively (both p<0.0001). Mean yearly costs were significantly higher in narcolepsy compared with controls for medical services ($8346 vs. $4147; p<0.0001) and drugs ($3356 vs. $1114; p<0.0001). Narcolepsy was found to be associated with substantial personal and economic burdens, as indicated by significantly higher rates of health-care utilization and medical costs in this large US group of narcolepsy patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Pediatric cancer pathology review from a single institution: Neuropathology expert opinion is essential for accurate diagnosis of pediatric brain tumors.

    PubMed

    Merabi, Zeina; Boulos, Fouad; Santiago, Teresa; Jenkins, Jesse; Abboud, Miguel; Muwakkit, Samar; Tarek, Nidale; Zaatari, Ghazi; Jeha, Sima; El-Solh, Hassan; Saab, Raya

    2017-07-04

    Second pathology review has been reported to improve accuracy in oncologic diagnoses, including pediatric malignancies. We assessed the impact of second review on the diagnosis of pediatric malignancies at a tertiary care referral center in Beirut, Lebanon. Pathology reports of patients treated at the Children's Cancer Institute in Lebanon were retrospectively reviewed for the period 2008-2016 and compared with same samples' diagnoses at St. Jude Children's Research Hospital. Diagnostic disagreements were divided into major, minor, and none based on their effect on diagnosis and/or patient management. Second review was requested for 171 cases, accounting for 19% of all cases during that period. Second opinion was mostly requested for brain tumors (62% of all brain tumor cases) and neuroblastoma for NMYC testing (65% of all neuroblastoma), while hematologic malignancies had the fewest referrals (3% of all hematologic cases). Major disagreements in second review occurred in 20 cases (12% of total), and minor disagreements in 21 cases (12% of total). The largest proportion of major disagreements (71%) occurred in pediatric brain tumors, and novel molecular tests contributed to the diagnosis in 55% of these cases. The availability of a specialized pediatric neuropathologist and a basic panel of relevant molecular testing are essential for appropriate diagnosis of pediatric brain tumors. Centers that do not have the available infrastructure in place can benefit greatly from second review referrals for this challenging subset of tumors. © 2017 Wiley Periodicals, Inc.

  8. Quality of life in children with narcolepsy.

    PubMed

    Inocente, Clara O; Gustin, Marie-Paule; Lavault, Sophie; Guignard-Perret, Anne; Raoux, Aude; Christol, Noemie; Gerard, Daniel; Dauvilliers, Yves; Reimão, Rubens; Bat-Pitault, Flora; Lin, Jian-Sheng; Arnulf, Isabelle; Lecendreux, Michel; Franco, Patricia

    2014-08-01

    To evaluate the health-related quality of life (HRQL) and its correlates in children and adolescents with narcolepsy. We compared the clinical characteristics of control subjects and patients with primary narcolepsy from data collected at the National Reference Centers for Narcolepsy. The cohort included 69 control subjects (29 boys) and 117 patients (65 boys; 59 de novo patients). Cataplexy was present in 81% and DQB1*0602 was positive in 91%. The control children were older (13.5±3.2 vs. 11.6±3.1 years, P<0.001) and less obese (1.4% vs. 60%, P<0.001). Twenty-five percent of the patients and 15.6% of the control subjects had clinically significant depressive feelings on Children's Depression Inventory (CDI≥16) (NS). Fifty-three narcoleptic and 43 control adolescents, 31 narcoleptic children and 23 control children filled out the HRQL questionnaires as well as 83 parents of patients and 60 parents of control subjects. Narcolepsy seriously impacts HRQL in terms of vitality, physical well-being, relations with friends and leisure activities, especially in adolescents. Depression was the factor that most affected HRQL in both narcoleptic and control subjects. For the control subjects and the narcoleptic patients, when the CDI score was entered into the multivariable regression model adjusted for gender and age, no other continuous independent variable could significantly increase the likelihood of the model. When the CDI score increased by 1, the mean HRQL score decreased by 1.7 for narcoleptic patients and 1.5 for control subjects. Apnea-hypopnoea index, diagnosis delay, disease duration, obesity, the presence of cataplexy or treatment had no effects on HRQL. Narcoleptic children and adolescents were at high risk for poor HRQL. Depressive symptoms had a major impact on HRQL. We recommend a more thorough assessment and management of psychological health in this population. © 2014 John Wiley & Sons Ltd.

  9. Diagnosis of Pediatric Appendicitis: Is MR Imaging More Appropriate than CT

    DTIC Science & Technology

    2017-04-30

    More Appropriate than CT? presented at/published to Should Non-Contrast Rapid MRE Evaluation of Clinically Suspected Pediatric Appendicitis Trump ...Appendicitis Trump CT after Equivocal Ultrasound? 6. TITLE OF MA TE RIAL TO BE PUBLISHED OR PRESENTED: Electronic Poster: Diagnosis of Pediatric Appendicitis...MRI Evaluation o f C:Iinically Suspected Pediatric Appendicitis Trump CT after Equivocal Ultrasound? (Ng 181 11c. POSTER (To be demonstrated at

  10. Pediatric generalized anxiety disorder: epidemiology, diagnosis, and management.

    PubMed

    Keeton, Courtney Pierce; Kolos, Amie C; Walkup, John T

    2009-01-01

    Pediatric generalized anxiety disorder (GAD) is characterized by excessive and uncontrollable worry about a variety of events and is accompanied by physical symptoms such as headaches, tension, restlessness, gastrointestinal distress, and heart palpitations. Symptoms impose marked distress and interfere with social, emotional, and educational functioning. GAD occurs in over 10% of children and adolescents, has an average age of onset of 8.5 years, and is more often reported in girls. Common co-occurring conditions include separation anxiety disorder and social phobia. Assessment involves a multi-informant, multi-method approach involving the child, parents, and school teachers. A clinical interview should be conducted to assess for the three primary ways anxiety presents: behaviors, thoughts, and somatic symptoms. Several semi-structured diagnostic interviews are available, and the Anxiety Disorders Interview Schedule is increasingly used. Rating scales completed by the patient, caregivers, and teachers provide useful information for diagnosis and symptom monitoring. Several scales are available to assess patients for the Diagnostic and Statistical Manual of Mental Disorders (4th Edition) GAD diagnosis; however, instruments generally cannot distinguish children with GAD from children with similar anxiety disorders. Both cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy for the treatment of pediatric anxiety disorders including GAD. Evidence suggests that the combination of CBT plus sertraline offers additional benefit compared with either treatment alone. With pharmacotherapy, systematic tracking of treatment-emergent adverse events such as headaches, stomach aches, behavioral activation, worsening symptoms, and emerging suicidal thoughts is important. Recommended starting doses are fluvoxamine 25 mg/day, fluoxetine 10 mg/day, and sertraline 25 mg/day, though lower starting doses are possible. Dosing

  11. Altered Sleep Stage Transitions of REM Sleep: A Novel and Stable Biomarker of Narcolepsy.

    PubMed

    Liu, Yaping; Zhang, Jihui; Lam, Venny; Ho, Crover Kwok Wah; Zhou, Junying; Li, Shirley Xin; Lam, Siu Ping; Yu, Mandy Wai Man; Tang, Xiangdong; Wing, Yun-Kwok

    2015-08-15

    To determine the diagnostic values, longitudinal stability, and HLA association of the sleep stage transitions in narcolepsy. To compare the baseline differences in the sleep stage transition to REM sleep among 35 patients with type 1 narcolepsy, 39 patients with type 2 narcolepsy, 26 unaffected relatives, and 159 non-narcoleptic sleep patient controls, followed by a reassessment at a mean duration of 37.4 months. The highest prevalence of altered transition from stage non-N2/N3 to stage R in multiple sleep latency test (MSLT) and nocturnal polysomnography (NPSG) was found in patients with type 1 narcolepsy (92.0% and 57.1%), followed by patients with type 2 narcolepsy (69.4% and 12.8%), unaffected relatives (46.2% and 0%), and controls (39.3% and 1.3%). Individual sleep variables had varied sensitivity and specificity in diagnosing narcolepsy. By incorporating a combination of sleep variables, the decision tree analysis improved the sensitivity to 94.3% and 82.1% and enhanced specificity to 82.4% and 83% for the diagnosis of type 1 and type 2 narcolepsy, respectively. There was a significant association of DBQ1*0602 with the altered sleep stage transition (OR = 16.0, 95% CI: 1.7-149.8, p = 0.015). The persistence of the altered sleep stage transition in both MSLT and NPSG was high for both type 1 (90.5% and 64.7%) and type 2 narcolepsy (92.3% and 100%), respectively. Altered sleep stage transition is a significant and stable marker of narcolepsy, which suggests a vulnerable wake-sleep dysregulation trait in narcolepsy. Altered sleep stage transition has a significant diagnostic value in the differential diagnosis of hypersomnias, especially when combined with other diagnostic sleep variables in decision tree analysis. © 2015 American Academy of Sleep Medicine.

  12. Quality Measures for the Care of Patients with Narcolepsy

    PubMed Central

    Krahn, Lois E.; Hershner, Shelley; Loeding, Lauren D.; Maski, Kiran P.; Rifkin, Daniel I.; Selim, Bernardo; Watson, Nathaniel F.

    2015-01-01

    The American Academy of Sleep Medicine (AASM) commissioned a Workgroup to develop quality measures for the care of patients with narcolepsy. Following a comprehensive literature search, 306 publications were found addressing quality care or measures. Strength of association was graded between proposed process measures and desired outcomes. Following the AASM process for quality measure development, we identified three outcomes (including one outcome measure) and seven process measures. The first desired outcome was to reduce excessive daytime sleepiness by employing two process measures: quantifying sleepiness and initiating treatment. The second outcome was to improve the accuracy of diagnosis by employing the two process measures: completing both a comprehensive sleep history and an objective sleep assessment. The third outcome was to reduce adverse events through three steps: ensuring treatment follow-up, documenting medical comorbidities, and documenting safety measures counseling. All narcolepsy measures described in this report were developed by the Narcolepsy Quality Measures Work-group and approved by the AASM Quality Measures Task Force and the AASM Board of Directors. The AASM recommends the use of these measures as part of quality improvement programs that will enhance the ability to improve care for patients with narcolepsy. Citation: Krahn LE, Hershner S, Loeding LD, Maski KP, Rifkin DI, Selim B, Watson NF. Quality measures for the care of patients with narcolepsy. J Clin Sleep Med 2015;11(3):335–355. PMID:25700880

  13. Juvenile myoclonic epilepsy and narcolepsy: A series of three cases.

    PubMed

    Joshi, Puja Aggarwal; Poduri, Annapurna; Kothare, Sanjeev V

    2015-10-01

    This paper sets out to demonstrate the coexistence of juvenile myoclonic epilepsy (JME) and narcolepsy that raises the possibility of a shared genetic predisposition to both conditions. The electronic medical records (EMRs) were searched for narcolepsy and JME over 10years. We identified three young adult women diagnosed with JME in their teenage years, with myoclonic, generalized tonic-clonic, and absence seizure semiologies, along with psychiatric comorbidity, well managed on lamotrigine and/or levetiracetam. Our patients were also found to have disturbed sleep preceding the diagnosis of JME by many years, including excessive daytime sleepiness (EDS), fragmented nocturnal sleep, hypnagogic vivid hallucinations, and REM behavior disorder along with daytime cataplexy. They were ultimately diagnosed with coexisting narcolepsy, confirmed by sleep studies and multiple sleep latency testing, along with positive genetic testing for HLA-DQB1*0602 in all three patients. Stimulants, selective serotonin receptor inhibitors, and/or sodium oxybate were used to successfully treat their narcolepsy. The coexistence of JME and narcolepsy has not been well recognized and may be clinically relevant. In addition, it raises the possibility of a shared genetic predisposition to both conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Delusional confusion of dreaming and reality in narcolepsy.

    PubMed

    Wamsley, Erin; Donjacour, Claire E H M; Scammell, Thomas E; Lammers, Gert Jan; Stickgold, Robert

    2014-02-01

    We investigated a generally unappreciated feature of the sleep disorder narcolepsy, in which patients mistake the memory of a dream for a real experience and form sustained delusions about significant events. We interviewed patients with narcolepsy and healthy controls to establish the prevalence of this complaint and identify its predictors. Academic medical centers in Boston, Massachusetts and Leiden, The Netherlands. Patients (n = 46) with a diagnosis of narcolepsy with cataplexy, and age-matched healthy healthy controls (n = 41). N/A. "Dream delusions" were surprisingly common in narcolepsy and were often striking in their severity. As opposed to fleeting hypnagogic and hypnopompic hallucinations of the sleep/wake transition, dream delusions were false memories induced by the experience of a vivid dream, which led to false beliefs that could persist for days or weeks. The delusional confusion of dreamed events with reality is a prominent feature of narcolepsy, and suggests the possibility of source memory deficits in this disorder that have not yet been fully characterized.

  15. Autonomic disturbances in narcolepsy.

    PubMed

    Plazzi, Giuseppe; Moghadam, Keivan Kaveh; Maggi, Leonardo Serra; Donadio, Vincenzo; Vetrugno, Roberto; Liguori, Rocco; Zoccoli, Giovanna; Poli, Francesca; Pizza, Fabio; Pagotto, Uberto; Ferri, Raffaele

    2011-06-01

    Narcolepsy is a clinical condition characterized mainly by excessive sleepiness and cataplexy. Hypnagogic hallucinations and sleep paralysis complete the narcoleptic tetrad; disrupted night sleep, automatic behaviors and weight gain are also usual complaints. Different studies focus on autonomic changes or dysfunctions among narcoleptic patients, such as pupillary abnormalities, fainting spells, erectile dysfunction, night sweats, gastric problems, low body temperature, systemic hypotension, dry mouth, heart palpitations, headache and extremities dysthermia. Even if many studies lack sufficient standardization or their results have not been replicated, a non-secondary involvement of the autonomic nervous system in narcolepsy is strongly suggested, mainly by metabolic and cardiovascular findings. Furthermore, the recent discovery of a high risk for overweight and for metabolic syndrome in narcoleptic patients represents an important warning for clinicians in order to monitor and follow them up for their autonomic functions. We review here studies on autonomic functions and clinical disturbances in narcoleptic patients, trying to shed light on the possible contribute of alterations of the hypocretin system in autonomic pathophysiology.

  16. Diagnosis and Medication Treatment of Pediatric Hypertension: A Retrospective Cohort Study.

    PubMed

    Kaelber, David C; Liu, Weiwei; Ross, Michelle; Localio, A Russell; Leon, Janeen B; Pace, Wilson D; Wasserman, Richard C; Fiks, Alexander G

    2016-12-01

    Pediatric hypertension predisposes children to adult hypertension and early markers of cardiovascular disease. No large-scale studies have examined diagnosis and initial medication management of pediatric hypertension and prehypertension. The objective of this study was to evaluate diagnosis and initial medication management of pediatric hypertension and prehypertension in primary care. Retrospective cohort study aggregating electronic health record data on >1.2 million pediatric patients from 196 ambulatory clinics across 27 states. Demographic, diagnosis, blood pressure (BP), height, weight, and medication prescription data extracted. Main outcome measures include proportion of pediatric patients with ≥3 visits with abnormal BPs, documented hypertension and prehypertension diagnoses, and prescribed antihypertensive medications. Marginal standardization via logistic regression produced adjusted diagnosis rates. Three hundred ninety-eight thousand seventy-nine patients, ages 3 to 18, had ≥3 visits with BP measurements (48.9% girls, 58.6% <10 years old). Of these, 3.3% met criteria for hypertension and 10.1% for prehypertension. Among practices with ≥50 eligible patients, 2813 of 12 138 patients with hypertension (23.2%; 95% confidence interval, 18.2%-28.2%) and 3990 of 38 874 prehypertensive patients (10.2%; 95% confidence interval, 8.2%-12.2%) were diagnosed. Age, weight, height, sex, and number and magnitude of abnormal BPs were associated with diagnosis rates. Of 2813 diagnosed, persistently hypertensive patients, 158 (5.6%) were prescribed antihypertensive medication within 12 months of diagnosis (angiotensin-converting enzyme inhibitors/angiotensin receptive blockers [35%], diuretics [22%], calcium channel blockers [17%], and β-blockers [10%]). Hypertension and prehypertension were infrequently diagnosed among pediatric patients. Guidelines for diagnosis and initial medication management of abnormal BP in pediatric patients are not routinely

  17. Dual Cases of Type 1 Narcolepsy with Schizophrenia and Other Psychotic Disorders

    PubMed Central

    Canellas, Francesca; Lin, Ling; Julià, Maria Rosa; Clemente, Antonio; Vives-Bauza, Cristofol; Ollila, Hanna M.; Hong, Seung Chul; Arboleya, Susana M.; Einen, Mali A.; Faraco, Juliette; Fernandez-Vina, Marcelo; Mignot, Emmanuel

    2014-01-01

    Objective: Cases of narcolepsy in association with psychotic features have been reported but never fully characterized. These patients present diagnostic and treatment challenges and may shed new light on immune associations in schizophrenia. Method: Our case series was gathered at two narcolepsy specialty centers over a 9-year period. A questionnaire was created to improve diagnosis of schizophrenia or another psychotic disorder in patients with narcolepsy. Pathophysiological investigations included full HLA Class I and II typing, testing for known systemic and intracellular/synaptic neuronal antibodies, recently described neuronal surface antibodies, and immunocytochemistry on brain sections to detect new antigens. Results: Ten cases were identified, one with schizoaffective disorder, one with delusional disorder, two with schizophreniform disorder, and 6 with schizophrenia. In all cases, narcolepsy manifested first in childhood or adolescence, followed by psychotic symptoms after a variable interval. These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis. Narcolepsy therapy may have played a role in triggering psychotic symptoms but these did not reverse with changes in narcolepsy medications. Response to antipsychotic treatment was variable. Pathophysiological studies did not reveal any known autoantibodies or unusual brain immunostaining pattern. No strong HLA association outside of HLA DQB1*06:02 was found, although increased DRB3*03 and DPA1*02:01 was notable. Conclusion: Narcolepsy can occur in association with schizophrenia, with significant diagnostic and therapeutic challenges. Dual cases maybe under diagnosed, as onset is unusually early, often in childhood. Narcolepsy and psychosis may share an autoimmune pathology; thus, further investigations in larger samples are warranted. Citation: Canellas F, Lin L, Julià MR, Clemente A, Vives-Bauza C, Ollila HM, Hong

  18. Executive Control of Attention in Narcolepsy

    PubMed Central

    Bayard, Sophie; Croisier Langenier, Muriel; Cochen De Cock, Valérie; Scholz, Sabine; Dauvilliers, Yves

    2012-01-01

    Background Narcolepsy with cataplexy (NC) is a disabling sleep disorder characterized by early loss of hypocretin neurons that project to areas involved in the attention network. We characterized the executive control of attention in drug-free patients with NC to determine whether the executive deficits observed in patients with NC are specific to the disease itself or whether they reflect performance changes due to the severity of excessive daytime sleepiness. Methodology Twenty-two patients with NC compared to 22 patients with narcolepsy without cataplexy (NwC) matched for age, gender, intellectual level, objective daytime sleepiness and number of sleep onset REM periods (SOREMPs) were studied. Thirty-two matched healthy controls were included. All participants underwent a standardized interview, completed questionnaires, and neuropsychological tests. All patients underwent a polysomnography followed by multiple sleep latency tests (MSLT), with neuropsychological evaluation performed the same day between MSLT sessions. Principal Findings Irrespective of diagnosis, patients reported higher self-reported attentional complaints associated with the intensity of depressive symptoms. Patients with NC performed slower and more variably on simple reaction time tasks than patients with NwC, who did not differ from controls. Patients with NC and NwC generally performed slower, reacted more variably, and made more errors than controls on executive functioning tests. Individual profile analyses showed a clear heterogeneity of the severity of executive deficit. This severity was related to objective sleepiness, higher number of SOREMPs on the MSLT, and lower intelligence quotient. The nature and severity of the executive deficits were unrelated to NC and NwC diagnosis. Conclusions We demonstrated that drug-free patients with NC and NwC complained of attention deficit, with altered executive control of attention being explained by the severity of objective sleepiness and

  19. Evidence-based recommendations for the diagnosis and treatment of pediatric acne.

    PubMed

    Eichenfield, Lawrence F; Krakowski, Andrew C; Piggott, Caroline; Del Rosso, James; Baldwin, Hilary; Friedlander, Sheila Fallon; Levy, Moise; Lucky, Anne; Mancini, Anthony J; Orlow, Seth J; Yan, Albert C; Vaux, Keith K; Webster, Guy; Zaenglein, Andrea L; Thiboutot, Diane M

    2013-05-01

    Acne vulgaris is one of the most common skin conditions in children and adolescents. The presentation, differential diagnosis, and association of acne with systemic pathology differs by age of presentation. Current acknowledged guidelines for the diagnosis and management of pediatric acne are lacking, and there are variations in management across the spectrum of primary and specialty care. The American Acne and Rosacea Society convened a panel of pediatric dermatologists, pediatricians, and dermatologists with expertise in acne to develop recommendations for the management of pediatric acne and evidence-based treatment algorithms. Ten major topic areas in the diagnosis and treatment of pediatric acne were identified. A thorough literature search was performed and articles identified, reviewed, and assessed for evidence grading. Each topic area was assigned to 2 expert reviewers who developed and presented summaries and recommendations for critique and editing. Furthermore, the Strength of Recommendation Taxonomy, including ratings for the strength of recommendation for a body of evidence, was used throughout for the consensus recommendations for the evaluation and management of pediatric acne. Practical evidence-based treatment algorithms also were developed. Recommendations were put forth regarding the classification, diagnosis, evaluation, and management of pediatric acne, based on age and pubertal status. Treatment considerations include the use of over-the-counter products, topical benzoyl peroxide, topical retinoids, topical antibiotics, oral antibiotics, hormonal therapy, and isotretinoin. Simplified treatment algorithms and recommendations are presented in detail for adolescent, preadolescent, infantile, and neonatal acne. Other considerations, including psychosocial effects of acne, adherence to treatment regimens, and the role of diet and acne, also are discussed. These expert recommendations by the American Acne and Rosacea Society as reviewed and

  20. [Narcolepsy-cataplexy today].

    PubMed

    Depierreux-Lahaye, F; Fanielle, J; Martin-Lecomte, M; Hans, G; Maquet, P; Poirrier, R

    2014-02-01

    Diagnostic criteria and pathophysiology of narcolepsy-cataplexy have evolved considerably over the last 10 years. The main cause, already mentioned in a previous paper, in the Revue Médicale de Liège (65), in 2002, is based, in human beings, on a destruction of specific cells located in the lateral and posterior part of the hypothalamus (the perifornical nuclei, containing some 70,000 neurons), producing peptides which stimulate the central nervous system; they are called hypocretins or orexins. The role of autoimmunity in their disappearance becomes more evident. The treatment is simplified, but remains symptomatic. It is mainly based on Sodium Oxybate or Gamma-Hydroxybutyrate, syrup, prescribed for the night. The authors report on their own experience in this regard and on future therapeutics more targeted towards the cause of the disease.

  1. Adenotonsillectomy outcomes in children with sleep apnea and narcolepsy.

    PubMed

    Biyani, Sneh; Cunningham, Tina D; Baldassari, Cristina M

    2017-09-01

    To identify improvements in daytime sleepiness following adenotonsillectomy in children with non-severe obstructive sleep apnea and narcolepsy. Case series with chart review over 15 years. Tertiary Children's Hospital. Children between 6 and 17 years of age with narcolepsy that underwent adenotonsillectomy for non-severe obstructive sleep apnea (OSA) were included. Narcolepsy was diagnosed based on clinical assessment and the Multiple Sleep Latency Test (MSLT) results. A standardized instrument, the pediatric Epworth Sleepiness Scale (ESS), was used to assess daytime sleepiness before and after adenotonsillectomy. Nine children with a mean age of 12.1 years were included. The majority of the subjects (78%, n = 7) were African American and six children (66.7%) were obese. Four children (44%) were treated with wake promoting agents during the study. The mean preoperative apnea hypopnea index on polysomnography was 4.89 (SD 1.86), while the mean sleep latency on MSLT was 6.32 min (SD 3.14). The mean preoperative ESS was 16.10 and the postoperative ESS was 10.80 (SD 3.96). There was significant improvement (p = 0.02) in the ESS following adenotonsillectomy with seven children (78%) reporting diminished daytime sleepiness. Children with non-severe OSA and narcolepsy experience significant improvement in daytime sleepiness following adenotonsillectomy. Future studies are needed to determine the incidence and clinical significance of non-severe OSA in children with narcolepsy. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Restless Legs Syndrome -- Self-Tests and Diagnosis

    MedlinePlus

    ... Treatment Jet Lag Overview Symptoms & Self Test Treatment Narcolepsy Overview & Facts Symptoms Self-Tests & Diagnosis Treatment Restless ... Category Insomnias Insomnia Child Insomnia Short Sleeper Hypersomnias Narcolepsy Insufficient Sleep Syndrome Long Sleeper Sleep Breathing Disorders ...

  3. Nocturnal Rapid Eye Movement Sleep Latency for Identifying Patients With Narcolepsy/Hypocretin Deficiency

    PubMed Central

    Andlauer, Olivier; Moore, Hyatt; Jouhier, Laura; Drake, Christopher; Peppard, Paul E.; Han, Fang; Hong, Seung-Chul; Poli, Francesca; Plazzi, Giuseppe; O’Hara, Ruth; Haffen, Emmanuel; Roth, Thomas; Young, Terry; Mignot, Emmanuel

    2014-01-01

    IMPORTANCE Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically. OBJECTIVE To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency. DESIGN, SETTING, AND PARTICIPANTS Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels. MAIN OUTCOME AND MEASURES Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal

  4. Dual cases of type 1 narcolepsy with schizophrenia and other psychotic disorders.

    PubMed

    Canellas, Francesca; Lin, Ling; Julià, Maria Rosa; Clemente, Antonio; Vives-Bauza, Cristofol; Ollila, Hanna M; Hong, Seung Chul; Arboleya, Susana M; Einen, Mali A; Faraco, Juliette; Fernandez-Vina, Marcelo; Mignot, Emmanuel

    2014-09-15

    Cases of narcolepsy in association with psychotic features have been reported but never fully characterized. These patients present diagnostic and treatment challenges and may shed new light on immune associations in schizophrenia. Our case series was gathered at two narcolepsy specialty centers over a 9-year period. A questionnaire was created to improve diagnosis of schizophrenia or another psychotic disorder in patients with narcolepsy. Pathophysiological investigations included full HLA Class I and II typing, testing for known systemic and intracellular/synaptic neuronal antibodies, recently described neuronal surface antibodies, and immunocytochemistry on brain sections to detect new antigens. Ten cases were identified, one with schizoaffective disorder, one with delusional disorder, two with schizophreniform disorder, and 6 with schizophrenia. In all cases, narcolepsy manifested first in childhood or adolescence, followed by psychotic symptoms after a variable interval. These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis. Narcolepsy therapy may have played a role in triggering psychotic symptoms but these did not reverse with changes in narcolepsy medications. Response to antipsychotic treatment was variable. Pathophysiological studies did not reveal any known autoantibodies or unusual brain immunostaining pattern. No strong HLA association outside of HLA DQB1*06:02 was found, although increased DRB3*03 and DPA1*02:01 was notable. Narcolepsy can occur in association with schizophrenia, with significant diagnostic and therapeutic challenges. Dual cases maybe under diagnosed, as onset is unusually early, often in childhood. Narcolepsy and psychosis may share an autoimmune pathology; thus, further investigations in larger samples are warranted. © 2014 American Academy of Sleep Medicine.

  5. A population-based epidemiologic study of adult-onset narcolepsy incidence and associated risk factors, 2004-2013.

    PubMed

    Lee, Rachel U; Radin, Jennifer M

    2016-11-15

    An increase in narcolepsy incidence was noted after the novel pandemic influenza of 2009, leading to further interest in risk factors associated with this disease. However, there is limited data on the epidemiology of narcolepsy, particularly in the adult population. Therefore, we sought to examine narcolepsy incidence rates in the United States and describe associated characteristics. We performed a population based epidemiologic study of active duty military personnel. All outpatient clinics in the continental United States providing care for active duty military between 2004 through 2013 were included utilizing existing databases. Narcolepsy was defined in 3 ways: (1) 2 diagnoses of narcolepsy within 6months of each other, one made by a sleep expert; (2) 2 diagnoses by any provider followed by a narcolepsy prescription within 14days of last visit; and (3) procedure code for a sleep study followed by a narcolepsy diagnosis by a sleep expert within 6months. There were 1675 narcolepsy cases. Overall incidence of narcolepsy trended from 14.6 to 27.3 cases per 100,000 person-years, with an increase starting after 2005-2006 and peaking during the 2011-2012 influenza season. Higher frequencies were seen among females, non-Hispanic blacks, and members living in the south. Narcolepsy incidence rates among active duty military members are higher than previously described. The reason for the steady rise of incidence from 2005 to 2006 through 2011-2012 is unknown; however, these findings require further exploration. We detected risk factors associated with the development of narcolepsy which may aid in future study efforts. Published by Elsevier B.V.

  6. Nocturnal Sleep Dynamics Identify Narcolepsy Type 1

    PubMed Central

    Pizza, Fabio; Vandi, Stefano; Iloti, Martina; Franceschini, Christian; Liguori, Rocco; Mignot, Emmanuel; Plazzi, Giuseppe

    2015-01-01

    Study Objectives: To evaluate the reliability of nocturnal sleep dynamics in the differential diagnosis of central disorders of hypersomnolence. Design: Cross-sectional. Setting: Sleep laboratory. Patients: One hundred seventy-five patients with hypocretin-deficient narcolepsy type 1 (NT1, n = 79), narcolepsy type 2 (NT2, n = 22), idiopathic hypersomnia (IH, n = 22), and “subjective” hypersomnolence (sHS, n = 52). Interventions: None. Methods: Polysomnographic (PSG) work-up included 48 h of continuous PSG recording. From nocturnal PSG conventional sleep macrostructure, occurrence of sleep onset rapid eye movement period (SOREMP), sleep stages distribution, and sleep stage transitions were calculated. Patient groups were compared, and receiver operating characteristic (ROC) curve analysis was used to test the diagnostic utility of nocturnal PSG data to identify NT1. Results: Sleep macrostructure was substantially stable in the 2 nights of each diagnostic group. NT1 and NT2 patients had lower latency to rapid eye movement (REM) sleep, and NT1 patients showed the highest number of awakenings, sleep stage transitions, and more time spent in N1 sleep, as well as most SOREMPs at daytime PSG and at multiple sleep latency test (MSLT) than all other groups. ROC curve analysis showed that nocturnal SOREMP (area under the curve of 0.724 ± 0.041, P < 0.0001), percent of total sleep time spent in N1 (0.896 ± 0.023, P < 0.0001), and the wakefulness-sleep transition index (0.796 ± 0.034, P < 0.0001) had a good sensitivity and specificity profile to identify NT1 sleep, especially when used in combination (0.903 ± 0.023, P < 0.0001), similarly to SOREMP number at continuous daytime PSG (0.899 ± 0.026, P < 0.0001) and at MSLT (0.956 ± 0.015, P < 0.0001). Conclusions: Sleep macrostructure (i.e. SOREMP, N1 timing) including stage transitions reliably identifies hypocretin-deficient narcolepsy type 1 among central disorders of hypersomnolence. Citation: Pizza F, Vandi S

  7. Growing Up with Type 1 Narcolepsy: Its Anthropometric and Endocrine Features

    PubMed Central

    Ponziani, Virginia; Gennari, Monia; Pizza, Fabio; Balsamo, Antonio; Bernardi, Filippo; Plazzi, Giuseppe

    2016-01-01

    Study Objectives: To evaluate the effect of type 1 narcolepsy (NT1) on anthropometric and endocrine features in childhood/adolescence, focusing on patterns and correlates of weight, pubertal development, and growth in treated and untreated patients. Methods: We collected anthropometric (height, weight, body mass index (BMI) z-scores), pubertal, metabolic, and endocrine data from 72 NT1 patients at diagnosis and all available premorbid anthropometric parameters of patients from their pediatric files (n = 30). New measurements at 1-y reassessment in patients undergoing different treatments were compared with baseline data. Results: We detected a high prevalence of overweight (29.2%), obesity (25%), metabolic syndrome (18.8%), and precocious puberty (16.1%), but no signs of linear growth alterations at diagnosis. According to anthropometric records, weight gain started soon after NT1 onset. At 1-y follow-up reassessment, sodium oxybate treatment was associated with a significant BMI z-score reduction (−1.29 ± 0.30, p < 0.0005) after adjusting for baseline age, sex, sleepiness, and BMI. Conclusions: NT1 onset in children/adolescents is associated with rapid weight gain up to overweight/obesity and precocious puberty without affecting growth. In our study, sodium oxybate treatment resulted in a significant weight reduction in NT1 overweight/obese patients at 1-y follow-up. Citation: Ponziani V, Gennari M, Pizza F, Balsamo A, Bernardi F, Plazzi G. Growing up with type 1 narcolepsy: its anthropometric and endocrine features. J Clin Sleep Med 2016;12(12):1649–1657. PMID:27707443

  8. Cultural influences in pediatric cancer from diagnosis to cure/end of life.

    PubMed

    Gray, Wendy N; Szulczewski, Lauren J; Regan, Shilpa M P; Williams, Jaclyn A; Pai, Ahna L H

    2014-01-01

    To review the literature on cultural factors influencing clinical care and family management of pediatric cancer. A literature review including 72 articles related to cultural issues in pediatric cancer was conducted. Information was organized around several clinically driven themes. Cultural factors influenced many aspects of the cancer experience including illness representations, reaction to diagnosis, illness disclosure patterns, complementary and alternative medicine use, management of medical procedures, coping strategies, and end of life issues. Increased awareness of cultural factors is needed to improve clinical care and reduce health disparities. Specific strategies to approach cultural differences are provided to enhance patient and family care from diagnosis to cure/end of life.

  9. Etiopathogenesis and Neurobiology of Narcolepsy: A Review

    PubMed Central

    Kumar, Swarup; Sagili, Haritha

    2014-01-01

    Narcolepsy is a chronic lifelong sleep disorder and it often leaves a debilitating effect on the quality of life of the sufferer. This disorder is characterized by a tetrad of excessive daytime sleepiness, cataplexy (brief loss of muscle tone following strong emotion), hypnogogic hallucinations and sleep paralysis. There are two distinct subgroups of Narcolepsy: Narcolepsy with cataplexy and Narcolepsy without cataplexy. For over 100 years, clinicians have recognised narcolepsy, but only in the last few decades have scientists been able to shed light on the true cause and pathogenesis of narcolepsy. Recent studies have shown that a loss of the hypothalamic neuropeptide Hypocretin/Orexincauses Narcolepsy with cataplexy and that an autoimmune mechanism may be responsible for this loss. Our understanding of the neurophysiologic aspect of narcolepsy has also significantly improved. The basic neural mechanisms behind sleepiness and cataplexy, the two defining symptoms of narcolepsy have started to become clearer. In this review, we have provided a detailed account of the key aspects of etiopathogenesis and neurobiology of narcolepsy, along with a critical appraisal of the more recent and interesting causal associations.We have also looked at the contributions of neuroimaging to the etiopathogenesis of Narcolepsy. PMID:24701532

  10. Pediatric imaging/doppler ultrasound of the chest: Extracardiac diagnosis

    SciTech Connect

    Huhta, J.C.

    1986-01-01

    In this book the author spells out new diagnostic applications in pediatrics for high resolution cross-sectional ultrasonography, and demonstrates the ways in which Doppler techniques complement the cross-sectional method. This reference presents practical, step-by-step methods for non-invasive ultrasound examination of extra-cardiac anatomy and assessment of vascular blood flow.

  11. Commentary: The Diagnosis of Delirium in Pediatric Patients

    ERIC Educational Resources Information Center

    Martini, D. Richard

    2005-01-01

    Pediatric patients seem to be especially vulnerable to toxic, metabolic, or traumatic CNS insults and are at greater risk of delirium with fever regardless of the etiology. Developmental limitations, in the areas of communication and cognition, prevent a thorough evaluation of the young patient for delirium. Only the most severe cases are…

  12. Commentary: The Diagnosis of Delirium in Pediatric Patients

    ERIC Educational Resources Information Center

    Martini, D. Richard

    2005-01-01

    Pediatric patients seem to be especially vulnerable to toxic, metabolic, or traumatic CNS insults and are at greater risk of delirium with fever regardless of the etiology. Developmental limitations, in the areas of communication and cognition, prevent a thorough evaluation of the young patient for delirium. Only the most severe cases are…

  13. Significance of Serum Procalcitonin Levels in Differential Diagnosis of Pediatric Pneumonia.

    PubMed

    Zhu, Feng; Wei, Haiyan; Li, Weihua

    2015-12-01

    The objective of this study was to explore the early diagnosis methods of severe pediatric pneumonia. A total of 65 cases hospitalized in pediatric departments and ICU of our hospital because of severe pneumonia were divided into two groups according to pathogen detection. The groups were as follows: 34 cases of bacterial pneumonia, 32 cases of a non-bacterial pneumonia, and 37 cases of healthy children after physical examination in our hospital as the control group. The peripheral blood was sampled from each of the three groups for procalcitonin (PCT). The pediatric PCT level in peripheral blood of the bacterial pneumonia group was significantly higher than that of non-bacterial pneumonia group and the control group. The statistical differences (each at p < 0.01) and the level of pediatric serum PCT in the bacterial pneumonia group before treatment were statistically different from that in the same group after treatment (p < 0.01), while the level of pediatric serum PCT in non-bacterial pneumonia group before treatment was statistical indifferent from that in the same group after treatment (p > 0.01). PCT level in pediatric peripheral blood is an important diagnostic indicator of bacterial infection and a sensitive indicator of distinction between bacterial pneumonia and the non-bacterial pneumonia, thus being of great significance for clinical and differential diagnosis.

  14. Measurement of narcolepsy symptoms: The Narcolepsy Severity Scale.

    PubMed

    Dauvilliers, Yves; Beziat, Severine; Pesenti, Carole; Lopez, Regis; Barateau, Lucie; Carlander, Bertrand; Luca, Gianina; Tafti, Mehdi; Morin, Charles M; Billiard, Michel; Jaussent, Isabelle

    2017-04-04

    To validate the Narcolepsy Severity Scale (NSS), a brief clinical instrument to evaluate the severity and consequences of symptoms in patients with narcolepsy type 1 (NT1). A 15-item scale to assess the frequency and severity of excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nighttime sleep was developed and validated by sleep experts with patients' feedback. Seventy untreated and 146 treated adult patients with NT1 were evaluated and completed the NSS in a single reference sleep center. The NSS psychometric properties, score changes with treatment, and convergent validity with other clinical parameters were assessed. The NSS showed good psychometric properties with significant item-total score correlations. The factor analysis indicated a 3-factor solution with good reliability, expressed by satisfactory Cronbach α values. The NSS total score temporal stability was good. Significant NSS score differences were observed between untreated and treated patients (dependent sample, 41 patients before and after sleep therapy; independent sample, 29 drug-free and 105 treated patients). Scores were lower in the treated populations (10-point difference between groups), without ceiling effect. Significant correlations were found among NSS total score and daytime sleepiness (Epworth Sleepiness Scale, Mean Sleep Latency Test), depressive symptoms, and health-related quality of life. The NSS can be considered a reliable and valid clinical tool for the quantification of narcolepsy symptoms to monitor and optimize narcolepsy management. © 2017 American Academy of Neurology.

  15. Cultural Influences in Pediatric Cancer: From Diagnosis to Cure/End of Life.

    PubMed

    Gray, Wendy N; Szulczewski, Lauren J; Regan, Shilpa M P; Williams, Jaclyn A; Pai, Ahna L H

    2014-07-10

    To review the literature on cultural factors influencing clinical care and family management of pediatric cancer. A literature review including 72 articles related to cultural issues in pediatric cancer was conducted. Information was organized around several clinically driven themes. Cultural factors influenced many aspects of the cancer experience including illness representations, reaction to diagnosis, illness disclosure patterns, complementary and alternative medicine use, management of medical procedures, coping strategies, and end of life issues. Increased awareness of cultural factors is needed to improve clinical care and reduce health disparities. Specific strategies to approach cultural differences are provided to enhance patient and family care from diagnosis to cure/end of life. © 2014 by Association of Pediatric Hematology/Oncology Nurses.

  16. [Implementation of the unified model of presenting cancer diagnosis in Polish pediatric onco-hematology centers].

    PubMed

    Samardakiewicz, Marzena; Kowalczyk, Jerzy R; Mazurowa, Mieczysława; Budziński, Waldemar; Antonowicz, Małgorzata; Borysławska, Anna; Szweda, Elzbieta; Groth, Anna; Pyka, Małgorzata; Figurska, Martyna; Chybicka, Alicja; Rokicka-Milewska, Roma; Matysiak, Michał; Balwierz, Walentyna; Sońta-Jakimczyk, Danuta; Balcerska, Anna; Wachowiak, Jacek

    2004-01-01

    Presentation of full information related to diagnosis of children with cancer should be one of principles in pediatric oncology. Multidisciplinary approach to each newly diagnosed child and its parents contributes to improving this standard. The Polish Pediatric Leukemia and Lymphoma Group is engaged in these activities since 1998 and it resulted in implementation of several SIOP recommendations in most of Polish pediatric oncohematology centers. The unified model of presentation of diagnosis for a child, parents and family was of an importance and the efforts to introduce it in all cooperating centers was undertaken. Proposed model of informing consists of several steps. Procedure should be individually tailored according to natural history of the disease and characteristics of the family. The purpose of the study was to evaluate the informing procedure in 60 children with newly diagnosed neoplasmatic disease.

  17. Altered Sleep Stage Transitions of REM Sleep: A Novel and Stable Biomarker of Narcolepsy

    PubMed Central

    Liu, Yaping; Zhang, Jihui; Lam, Venny; Ho, Crover Kwok Wah; Zhou, Junying; Li, Shirley Xin; Lam, Siu Ping; Yu, Mandy Wai Man; Tang, Xiangdong; Wing, Yun-Kwok

    2015-01-01

    Objectives: To determine the diagnostic values, longitudinal stability, and HLA association of the sleep stage transitions in narcolepsy. Methods: To compare the baseline differences in the sleep stage transition to REM sleep among 35 patients with type 1 narcolepsy, 39 patients with type 2 narcolepsy, 26 unaffected relatives, and 159 non-narcoleptic sleep patient controls, followed by a reassessment at a mean duration of 37.4 months. Results: The highest prevalence of altered transition from stage non-N2/N3 to stage R in multiple sleep latency test (MSLT) and nocturnal polysomnography (NPSG) was found in patients with type 1 narcolepsy (92.0% and 57.1%), followed by patients with type 2 narcolepsy (69.4% and 12.8%), unaffected relatives (46.2% and 0%), and controls (39.3% and 1.3%). Individual sleep variables had varied sensitivity and specificity in diagnosing narcolepsy. By incorporating a combination of sleep variables, the decision tree analysis improved the sensitivity to 94.3% and 82.1% and enhanced specificity to 82.4% and 83% for the diagnosis of type 1 and type 2 narcolepsy, respectively. There was a significant association of DBQ1*0602 with the altered sleep stage transition (OR = 16.0, 95% CI: 1.7–149.8, p = 0.015). The persistence of the altered sleep stage transition in both MSLT and NPSG was high for both type 1 (90.5% and 64.7%) and type 2 narcolepsy (92.3% and 100%), respectively. Conclusions: Altered sleep stage transition is a significant and stable marker of narcolepsy, which suggests a vulnerable wake-sleep dysregulation trait in narcolepsy. Altered sleep stage transition has a significant diagnostic value in the differential diagnosis of hypersomnias, especially when combined with other diagnostic sleep variables in decision tree analysis. Citation: Liu Y, Zhang J, Lam V, Ho CK, Zhou J, Li SX, Lam SP, Yu MW, Tang X, Wing YK. Altered sleep stage transitions of REM sleep: a novel and stable biomarker of narcolepsy. J Clin Sleep Med 2015

  18. The Diagnosis, Evaluation and Treatment of Acute and Recurrent Pediatric Urinary Tract Infections

    PubMed Central

    Becknell, Brian; Schober, Megan; Korbel, Lindsey; Spencer, John David

    2015-01-01

    Urinary tract infection is one of the most common bacterial infections encountered by pediatricians. Currently, the diagnosis and management of acute urinary tract infection and recurrent urinary tract infection in children remains controversial. Recently published guidelines and large clinical trials have attempted to clarify UTI diagnostic and management strategies. In this manuscript, we review the diagnosis and management of acute and recurrent urinary tract infection in the pediatric population. PMID:25421102

  19. Narcolepsy and influenza A(H1N1) pandemic 2009 vaccination in the United States.

    PubMed

    Duffy, Jonathan; Weintraub, Eric; Vellozzi, Claudia; DeStefano, Frank

    2014-11-11

    To assess the occurrence of narcolepsy after influenza vaccines used in the United States that contained the influenza A(H1N1)pdm09 virus strain. A population-based cohort study in the Vaccine Safety Datalink with an annual population of more than 8.5 million people. All persons younger than 30 years who received a 2009 pandemic or a 2010-2011 seasonal influenza vaccine were identified. Their medical visit history was searched for a first-ever occurrence of an ICD-9 narcolepsy diagnosis code through the end of 2011. Chart review was done to confirm the diagnosis and determine the date of symptom onset. Cases were patients who met the International Classification of Sleep Disorders, 2nd edition, narcolepsy diagnostic criteria. We compared the observed number of cases after vaccination to the number expected to occur by chance alone. The number vaccinated with 2009 pandemic vaccine was 650,995 and with 2010-2011 seasonal vaccine was 870,530. Among these patients, 70 had a first-ever narcolepsy diagnosis code after vaccination, of which 16 had a chart-confirmed incident diagnosis of narcolepsy. None had their symptom onset during the 180 days after receipt of a 2009 pandemic vaccine compared with 6.52 expected, and 2 had onset after a 2010-2011 seasonal vaccine compared with 8.83 expected. Influenza vaccines containing the A(H1N1)pdm09 virus strain used in the United States were not associated with an increased risk of narcolepsy. Vaccination with the influenza A(H1N1)pdm09 vaccine viral antigens does not appear to be sufficient by itself to increase the incidence of narcolepsy in a population. © 2014 American Academy of Neurology.

  20. Going to School with Narcolepsy--Perceptions of Families and Teachers of Children with Narcolepsy

    ERIC Educational Resources Information Center

    Karjalainen, Satu; Nyrhilä, Anna-Maria; Määttä, Kaarina; Uusiautti, Satu

    2014-01-01

    In 2009 and 2010, a large group of Finnish children and adolescents got narcolepsy after the vaccination campaign to prevent swine flu pandemic. A sample of children and adolescents who had gotten narcolepsy after 2009 participated in this study. The purpose of this research was to analyse how narcolepsy that developed from the swine flu…

  1. Going to School with Narcolepsy--Perceptions of Families and Teachers of Children with Narcolepsy

    ERIC Educational Resources Information Center

    Karjalainen, Satu; Nyrhilä, Anna-Maria; Määttä, Kaarina; Uusiautti, Satu

    2014-01-01

    In 2009 and 2010, a large group of Finnish children and adolescents got narcolepsy after the vaccination campaign to prevent swine flu pandemic. A sample of children and adolescents who had gotten narcolepsy after 2009 participated in this study. The purpose of this research was to analyse how narcolepsy that developed from the swine flu…

  2. Frequencies and Associations of Narcolepsy-Related Symptoms: A Cross-Sectional Study

    PubMed Central

    Kim, Lenise Jihe; Coelho, Fernando Morgadinho; Hirotsu, Camila; Araujo, Paula; Bittencourt, Lia; Tufik, Sergio; Andersen, Monica Levy

    2015-01-01

    Objectives: Narcolepsy is a disabling disease with a delayed diagnosis. At least 3 years before the disorder identification, several comorbidities can be observed in patients with narcolepsy. The early recognition of narcolepsy symptoms may improve long-term prognosis of the patients. Thus, we aimed to investigate the prevalence of the symptoms associated with narcolepsy and its social and psychological association in a sample of Sao Paulo city inhabitants. Methods: We performed a cross-sectional evaluation with 1,008 individuals from the Sao Paulo Epidemiologic Sleep Study (EPISONO). Excessive daytime sleepiness (EDS) was assessed by the Epworth Sleepiness Scale. Volunteers were also asked about the occurrence of cataplectic-like, hypnagogic or hypnopompic hallucinations, and sleep paralysis symptoms. The participants underwent a full-night polysomnography and completed questionnaires about psychological, demographic, and quality of life parameters. Results: We observed a prevalence of 39.2% of EDS, 15.0% of cataplectic-like symptom, 9.2% of hypnagogic or hypnopompic hallucinations, and 14.9% of sleep paralysis in Sao Paulo city inhabitants. A frequency of 6.9% was observed when EDS and cataplectic-like symptoms were grouped. The other associations were EDS + hallucinations (4.7%) and EDS + sleep paralysis (7.5%). Symptomatic participants were predominantly women and younger compared with patients without any narcolepsy symptom (n = 451). Narcolepsy symptomatology was also associated with a poor quality of life and symptoms of depression, anxiety, and fatigue. Conclusions: Narcolepsy-related symptoms are associated with poor quality of life and worse psychological parameters. Citation: Kim LJ, Coelho FM, Hirotsu C, Araujo P, Bittencourt L, Tufik S, Andersen ML. Frequencies and associations of narcolepsy-related symptoms: a cross-sectional study. J Clin Sleep Med 2015;11(12):1377–1384. PMID:26235160

  3. Reliability and Effectiveness of Smartphone Technology for the Diagnosis and Treatment Planning of Pediatric Elbow Trauma.

    PubMed

    Paryavi, Ebrahim; Schwartz, Brandon S; Meyer, Carissa L; Herman, Martin J; Abzug, Joshua M

    2016-01-01

    Mobile imaging, such as viewing radiographs as text messages, is increasingly prevalent in clinical settings. The purpose of this study was to determine whether remote diagnosis of pediatric elbow fractures using smartphone technology is reliable. In addition, this study aimed to determine whether the assessment regarding the decision for operative treatment is affected by evaluation of images on a mobile device as opposed to standard picture archiving and communication system (PACS). Standard anteroposterior and lateral radiographs of 50 pediatric elbow trauma cases were evaluated by 2 fellowship-trained pediatric orthopaedic surgeons and 2 senior orthopaedic residents. Raters were asked to classify the case as any of 6 diagnoses: supracondylar humerus, lateral condyle, medial epicondyle, radial neck fracture, positive posterior fat pad sign, or normal pediatric elbow. Raters were asked to choose operative or conservative treatment. After 1 week, photographs of the same images were taken from a standardized distance from a computer monitor with an iPhone 5 camera and transmitted by multimedia messaging to each rater. The same questions were again posed to raters. Interobserver and intraobserver reliabilities were calculated by Cohen κ-statistics with bootstrapped 95% confidence intervals. Intraobserver reliability of classification of injuries on PACS compared with smartphone images was excellent, with an overall κ of 0.91. Treatment decision also demonstrated excellent intraobserver reliability (PACS vs. smartphones) with a κ of 0.86 for all raters. Diagnosis of pediatric elbow injuries can be made equally reliably based on either PACS or transmitted multimedia messaging images taken with an iPhone camera from a computer screen and viewed on a smartphone. Treatment decisions can also be made reliably based on either image modality. Using smartphones to transmit and display radiographs, which is common in current clinical practice, is effective and reliable for

  4. Clinical and polysomnographic course of childhood narcolepsy with cataplexy

    PubMed Central

    Pizza, Fabio; Franceschini, Christian; Peltola, Hanna; Vandi, Stefano; Finotti, Elena; Ingravallo, Francesca; Nobili, Lino; Bruni, Oliviero; Lin, Ling; Edwards, Mark J.; Partinen, Markku; Dauvilliers, Yves; Mignot, Emmanuel; Bhatia, Kailash P.

    2013-01-01

    Our aim was to investigate the natural evolution of cataplexy and polysomnographic features in untreated children with narcolepsy with cataplexy. To this end, clinical, polysomnographic, and cataplexy-video assessments were performed at diagnosis (mean age of 10 ± 3 and disease duration of 1 ± 1 years) and after a median follow-up of 3 years from symptom onset (mean age of 12 ± 4 years) in 21 children with narcolepsy with cataplexy and hypocretin 1 deficiency (tested in 19 subjects). Video assessment was also performed in two control groups matched for age and sex at first evaluation and follow-up and was blindly scored for presence of hypotonic (negative) and active movements. Patients’ data at diagnosis and at follow-up were contrasted, compared with controls, and related with age and disease duration. At diagnosis children with narcolepsy with cataplexy showed an increase of sleep time during the 24 h; at follow-up sleep time and nocturnal sleep latency shortened, in the absence of other polysomnographic or clinical (including body mass index) changes. Hypotonic phenomena and selected facial movements decreased over time and, tested against disease duration and age, appeared as age-dependent. At onset, childhood narcolepsy with cataplexy is characterized by an abrupt increase of total sleep over the 24 h, generalized hypotonia and motor overactivity. With time, the picture of cataplexy evolves into classic presentation (i.e. brief muscle weakness episodes triggered by emotions), whereas total sleep time across the 24 h decreases, returning to more age-appropriate levels. PMID:24142146

  5. Clinical and polysomnographic course of childhood narcolepsy with cataplexy.

    PubMed

    Pizza, Fabio; Franceschini, Christian; Peltola, Hanna; Vandi, Stefano; Finotti, Elena; Ingravallo, Francesca; Nobili, Lino; Bruni, Oliviero; Lin, Ling; Edwards, Mark J; Partinen, Markku; Dauvilliers, Yves; Mignot, Emmanuel; Bhatia, Kailash P; Plazzi, Giuseppe

    2013-12-01

    Our aim was to investigate the natural evolution of cataplexy and polysomnographic features in untreated children with narcolepsy with cataplexy. To this end, clinical, polysomnographic, and cataplexy-video assessments were performed at diagnosis (mean age of 10 ± 3 and disease duration of 1 ± 1 years) and after a median follow-up of 3 years from symptom onset (mean age of 12 ± 4 years) in 21 children with narcolepsy with cataplexy and hypocretin 1 deficiency (tested in 19 subjects). Video assessment was also performed in two control groups matched for age and sex at first evaluation and follow-up and was blindly scored for presence of hypotonic (negative) and active movements. Patients' data at diagnosis and at follow-up were contrasted, compared with controls, and related with age and disease duration. At diagnosis children with narcolepsy with cataplexy showed an increase of sleep time during the 24 h; at follow-up sleep time and nocturnal sleep latency shortened, in the absence of other polysomnographic or clinical (including body mass index) changes. Hypotonic phenomena and selected facial movements decreased over time and, tested against disease duration and age, appeared as age-dependent. At onset, childhood narcolepsy with cataplexy is characterized by an abrupt increase of total sleep over the 24 h, generalized hypotonia and motor overactivity. With time, the picture of cataplexy evolves into classic presentation (i.e., brief muscle weakness episodes triggered by emotions), whereas total sleep time across the 24 h decreases, returning to more age-appropriate levels.

  6. Analysis of clinical value of CT in the diagnosis of pediatric pneumonia and mycoplasma pneumonia.

    PubMed

    Gong, Liang; Zhang, Chong-Lin; Zhen, Qing

    2016-04-01

    Pneumonia is an infectious disease of the lung causing mortality. Mycoplasma pneumonia (MP) is an atypical bacterial pneumonia that damages several organs. Lung computed tomography (CT) has been utilized in its identification. The aim of the present study was to examine the value of computed tomography diagnosis for pediatric MP. The present study prospectively analyzed the clinical and imaging data of 1,280 cases of pediatric MP in the out- and inpatient departments from March, 2010 to March, 2014; analyzed the morphology and distribution of the pneumonic lesion in the lungs; and summarized the value of CT diagnosis for pediatric MP. In the included children, there were 688 cases of lesions in the unilateral lobe, 592 cases of lesions in the bilateral lobes, 1,101 cases of extensive patchy opacity, 496 cases of mottled opacity, 432 cases of increased lung marking, 256 cases of streak opacity, 192 cases of ground-glass opacity, 992 cases of thickened bronchial wall in the lesions, 128 cases of lymphadenopathy in the hilar lymph nodes and mediastinal lymph nodes, and the lung CT showed 32 cases of pulmonary cavity and 144 cases of pleural effusion. In conclusion, the CT signals of pediatric MP had several types with some children exhibiting complicated changes. The child's clinical manifestation and symptoms should thus be considered in the diagnosis to improve the diagnostic rate.

  7. Does Narcolepsy Symptom Severity Vary According to HLA-DQB1*0602 Allele Status?

    PubMed Central

    Watson, Nathaniel F.; Ton, Thanh G.N.; Koepsell, Thomas D.; Gersuk, Vivian H.; Longstreth, W.T.

    2010-01-01

    Study Objectives: To investigate associations between HLA-DQB1*0602 allele status and measures of narcolepsy symptom severity. Design: Cross-sectional study of population-based narcolepsy patients. Setting: King County, Washington. Participants: All prevalent cases (n = 279) of physician-diagnosed narcolepsy ascertained from 2001-2005. Interventions: N/A Measurements: Narcolepsy diagnosis was based on cataplexy status, diagnostic sleep study results, and chart review. The number of HLA-DQB1 alleles was determined from buccal genomic DNA. Symptom severity instruments included the Epworth Sleepiness Scale (ESS), the Ullanlinna Narcolepsy Scale (UNS), age of symptom onset, subjective sleep latency and duration, and various clinical sleep parameters. We used linear regression adjusted for African American race and an extended chi-square test of trend to assess relationships across ordered groups defined by allele number (0, 1, or 2). Results: Narcolepsy patients were 63% female and 82% Caucasian, with a mean age of 47.6 years (SD = 17.1). One hundred forty-one (51%) patients had no DQB1*0602 alleles; 117 (42%) had one; and 21 (7%) had two. In the complete narcolepsy sample after adjustment for African American race, we observed a linear relationship between HLA-DQB1*0602 frequency and sleepiness as defined by the ESS (P < 0.01), narcolepsy severity as defined by UNS (P < 0.001), age of symptom onset (P < 0.05), and sleep latency (P < 0.001). In univariate analyses, HLA-DQB1*0602 frequency was also associated with napping (P < 0.05) and increased car and work accidents or near accidents (both P < 0.01). Habitual sleep duration was not associated with HLA status. These race-adjusted associations remained for the ESS (P < 0.05), UNS (P < 0.01), and sleep latency (P < 0.001) when restricting to narcolepsy with cataplexy. Conclusions: Narcolepsy symptom severity varies in a linear manner according to HLA-DQB1*0602 allele status. These findings support the notion that HLA

  8. A pediatric approach to family history of cardiovascular disease: diagnosis, risk assessment, and management.

    PubMed

    Miller, Erin M; Hinton, Robert B

    2014-02-01

    The medical family history is a comprehensive and dynamic record of illnesses and other pertinent health information among family members. Family history is used to facilitate diagnosis, to identify family members at risk for developing a particular disease, and increasingly to manage disease. This article reviews the application of family history to pediatric cardiovascular disease. As more is learned about the genetic basis of cardiovascular disease, the family history will play an increasingly central role in management. Improved understanding of the causes of pediatric cardiovascular disease promises the opportunity to develop new diagnostic and therapeutic strategies. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Diagnosis and clinical genetics of Cushing syndrome in pediatrics

    PubMed Central

    Stratakis, Constantine A.

    2016-01-01

    SYNOPSIS Endogenous Cushing syndrome (CS) in pediatrics is rare; it may be caused by tumors that produce corticotropin (ACTH) in the pituitary gland (this form of CS is called Cushing disease) or elsewhere (ectopic CS), tumors that produce corticotropin-releasing hormone (CRH) anywhere (mostly neuroendocrine tissues), and finally adrenocortical masses that produce cortisol, such as adrenocortical cancer (ACC) or adenomas, and bilateral adrenocortical hypeprlasia (BAHs). ACC is a very rare cause of CS in children but should be excluded first, especially among younger patients. CS in children is often caused by germline or somatic mutations in an expanding list of genes with implications for the prognosis of the patients and for their families. CS should be early recognized in children; otherwise, it can lead to significant morbidity and mortality. All patients with suspected CS should be referred to specialized clinical centers for work-up; these centers should have access to experienced endocrine and neurological surgeons. PMID:27241967

  10. The impact of spirometry on pediatric asthma diagnosis and treatment.

    PubMed

    Holt, E W; Tan, J; Hosgood, H D

    2006-09-01

    Research has shown that spirometry is underutilized in the clinical setting. This study profiles the use of spirometry in an asthma management program at an inner-city community health clinic. Eligible subjects included 56 children who presented with an acute asthma exacerbation. Physicians recorded patient diagnosis before and after viewing spirometry. Bivariate and multivariate analysis was used to determine associations between symptoms and forced expiratory volume in 1 second (FEV1). Physicians changed 30.4% of patients' treatment plans after viewing spirometry results. Wheezing was significantly associated with FEV1 in bivariate analysis; however, multivariate modeling failed to identify significant relationships. The use of spirometry influenced patient diagnosis and treatment.

  11. Narcolepsy in a hypocretin/orexin-deficient chihuahua.

    PubMed

    Tonokura, M; Fujita, K; Morozumi, M; Yoshida, Y; Kanbayashi, T; Nishino, S

    2003-06-21

    A two-year-old male chihuahua suffered attacks of muscle weakness and immobility, although it had no family history of paroxysmal attacks. No neurological or blood biochemical abnormalities were recorded when it was first examined. The attacks were typically elicited by stimulation, such as feeding, and a case of sporadic narcolepsy-cataplexy was therefore suspected. Treatment orally three times a day with 1 mg/kg imipramine, was effective in reducing the attacks. The concentration of hypocretin-1/orexin A in the dog's cerebrospinal fluid was less than 80 pg/ml (22.5 pmol/litre), compared with normal canine levels of 250 to 350 pg/ml (70.0 to 98.3 pmol/litre), supporting a diagnosis of hypocretin-deficient narcolepsy.

  12. [Topical issues of food allergy diagnosis in pediatric practice].

    PubMed

    Makarova, S G; Namazova-Baranova, L S; Vishneva, E A; Gevorkyan, A K; Alekseeva, A A; Petrovskaya, M I

    2015-01-01

    Food allergy (FA) in children, especially in infancy, is still a significant public health problem. The severity and prognosis of disease progression associated with FA considerably depends on the correct and early diagnostics of this pathology, as well as on the following management of a child. At the same time delayed elimination diet administration, unreasonable or overlong dietary intervention might have become abuse management of a patient and have a negative impact on the development of a child and reduce the quality of life. The article summarizes the current practical approaches to the diagnosis of FA based on evidence-based medicine and adopted European and Russian national consensus documents, as well as on our own experience of management of patients with this pathology. FA diagnosis in a child usually includes clinical laboratory tests and clarification of clinical and anamnestic data. Unfortunately, it is a fact that preference is given to laboratory methods for diagnosis based on specific IgE determination or skin samples. However, the basis for cause-significant allergen identifying is detecting detailed medical history and clinical picture of a disease which still appears to be the most reliable tool for FA diagnosis.

  13. Nocturnal Sleep Dynamics Identify Narcolepsy Type 1.

    PubMed

    Pizza, Fabio; Vandi, Stefano; Iloti, Martina; Franceschini, Christian; Liguori, Rocco; Mignot, Emmanuel; Plazzi, Giuseppe

    2015-08-01

    To evaluate the reliability of nocturnal sleep dynamics in the differential diagnosis of central disorders of hypersomnolence. Cross-sectional. Sleep laboratory. One hundred seventy-five patients with hypocretin-deficient narcolepsy type 1 (NT1, n = 79), narcolepsy type 2 (NT2, n = 22), idiopathic hypersomnia (IH, n = 22), and "subjective" hypersomnolence (sHS, n = 52). None. Polysomnographic (PSG) work-up included 48 h of continuous PSG recording. From nocturnal PSG conventional sleep macrostructure, occurrence of sleep onset rapid eye movement period (SOREMP), sleep stages distribution, and sleep stage transitions were calculated. Patient groups were compared, and receiver operating characteristic (ROC) curve analysis was used to test the diagnostic utility of nocturnal PSG data to identify NT1. Sleep macrostructure was substantially stable in the 2 nights of each diagnostic group. NT1 and NT2 patients had lower latency to rapid eye movement (REM) sleep, and NT1 patients showed the highest number of awakenings, sleep stage transitions, and more time spent in N1 sleep, as well as most SOREMPs at daytime PSG and at multiple sleep latency test (MSLT) than all other groups. ROC curve analysis showed that nocturnal SOREMP (area under the curve of 0.724 ± 0.041, P < 0.0001), percent of total sleep time spent in N1 (0.896 ± 0.023, P < 0.0001), and the wakefulness-sleep transition index (0.796 ± 0.034, P < 0.0001) had a good sensitivity and specificity profile to identify NT1 sleep, especially when used in combination (0.903 ± 0.023, P < 0.0001), similarly to SOREMP number at continuous daytime PSG (0.899 ± 0.026, P < 0.0001) and at MSLT (0.956 ± 0.015, P < 0.0001). Sleep macrostructure (i.e. SOREMP, N1 timing) including stage transitions reliably identifies hypocretin-deficient narcolepsy type 1 among central disorders of hypersomnolence. © 2015 Associated Professional Sleep Societies, LLC.

  14. Canadian pediatric emergency physician knowledge of concussion diagnosis and initial management.

    PubMed

    Zemek, Roger; Eady, Kaylee; Moreau, Katherine; Farion, Ken J; Solomon, Beverly; Weiser, Margaret; Dematteo, Carol

    2015-03-01

    Introduction The diagnosis of concussion is a critical step in the appropriate management of patients following minor head trauma. The authors hypothesized that wide practice variation exists among pediatric emergency medicine physicians in the application of physical and cognitive rest recommendations following an acute concussion. The authors developed a 35-item questionnaire incorporating case vignettes to examine pediatric emergency physician knowledge of concussion diagnosis, understanding of initial management using return-to-play/school/work guidelines, use of existing concussion protocols, and perceived barriers to protocol use. Using a modified Dillman technique, the authors distributed an online survey to members of Pediatric Emergency Research Canada, a national association of pediatric emergency physicians. Of 176 potential participants, 115 (65%) responded to the questionnaire, 89% (95% confidence interval [CI]: 0.81, 0.93) of whom reported having diagnosed 20 or more concussions annually. Although 90% (95% CI: 0.83, 0.94) of respondents adequately diagnosed concussion, only 64% (95% CI: 0.54, 0.72) correctly applied graduated return-to-play guidelines. Cognitive rest recommendations were also frequently limited: 40% (95% CI: 0.31, 0.49) did not recommend school absence, 30% (95% CI: 0.22, 0.39) did not recommend schoolwork reduction, and 35% (95% CI: 0.27, 0.45) did not recommend limiting screen time. Eighty percent (95% CI: 0.72, 0.87) of respondents reported having used guidelines frequently or always to guide clinical decisions regarding concussion. Despite a proficiency in the diagnosis of concussion, pediatric emergency physicians exhibit wide variation in recommending the graduated return to play and cognitive rest following concussion.

  15. Antibody-mediated rejection in pediatric kidney transplantation: pathophysiology, diagnosis, and management.

    PubMed

    Ng, Yolanda W; Singh, Manpreet; Sarwal, Minnie M

    2015-04-01

    Kidney transplant is the preferred treatment of pediatric end-stage renal disease. One of the most challenging aspects of pediatric kidney transplant is the prevention and treatment of antibody-mediated rejection (ABMR), which is one of the main causes of graft dysfunction and early graft loss. Most challenges are similar to those faced in adult kidney transplants; however, factors unique to the pediatric realm include naivety of the immune system and the small number of studies and randomized controlled trials available when considering pharmacological treatment options. Here, we present a case of ABMR in a pediatric patient and a review of the pathophysiology, diagnosis, and management of ABMR. ABMR in pediatric kidney transplant continues to be a frustrating condition to treat because (1) there still remain many unidentified potential antigens leading to ABMR, (2) children and adults are at different stages of their immune system development, and, thus, (3) the full pathophysiology of alloimmunity is still not completely understood, and (4) the efficacy and safety of treatment in adults may not be directly translated to children. As we continue to gain a better understanding towards the precise alloimmune mechanism that drives a particular ABMR, we can also improve pharmacotherapeutic choices. With continued research, they will become more precise in treating a particular mechanism versus using a broad scope of immunosuppression such as steroids. However, there is much more to be uncovered, such as identifying more non-human leukocyte antigens and their role in alloimmunity, determining the exact mechanism of adults achieving complete operational tolerance, and understanding the difference between pediatric and adult transplant recipients. Making strides towards a better understanding of these mechanisms will lead to continued efficacy and safety in treatment of pediatric ABMR.

  16. Increased Lucid Dreaming Frequency in Narcolepsy

    PubMed Central

    Rak, Michael; Beitinger, Pierre; Steiger, Axel; Schredl, Michael; Dresler, Martin

    2015-01-01

    Study Objective: Nightmares are a frequent symptom in narcolepsy. Lucid dreaming, i.e., the phenomenon of becoming aware of the dreaming state during dreaming, has been demonstrated to be of therapeutic value for recurrent nightmares. Data on lucid dreaming in narcolepsy patients, however, is sparse. The aim of this study was to evaluate the frequency of recalled dreams (DF), nightmares (NF), and lucid dreams (LDF) in narcolepsy patients compared to healthy controls. In addition, we explored if dream lucidity provides relief during nightmares in narcolepsy patients. Design: We interviewed patients with narcolepsy and healthy controls. Setting: Telephone interview. Patients: 60 patients diagnosed with narcolepsy (23–82 years, 35 females) and 919 control subjects (14–93 years, 497 females) Interventions: N/A. Measurements and Results: Logistic regression revealed significant (P < 0.001) differences in DF, NF, and LDF between narcolepsy patients and controls after controlling for age and gender, with effect sizes lying in the large range (Cohen's d > 0.8). The differences in NF and LDF between patients and controls stayed significant after controlling for DF. Comparison of 35 narcolepsy patients currently under medication with their former drug-free period revealed significant differences in DF and NF (z < 0.05, signed-rank test) but not LDF (z = 0.8). Irrespective of medication, 70% of narcolepsy patients with experience in lucid dreaming indicated that dream lucidity provides relief during nightmares. Conclusion: Narcolepsy patients experience a markedly higher lucid dreaming frequency compared to controls, and many patients report a positive impact of dream lucidity on the distress experienced from nightmares. Citation: Rak M, Beitinger P, Steiger A, Schredl M, Dresler M. Increased lucid dreaming frequency in narcolepsy. SLEEP 2015;38(5):787–792. PMID:25325481

  17. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia | Office of Cancer Genomics

    Cancer.gov

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden.

  18. Pediatric sleep pharmacology.

    PubMed

    Pelayo, Rafael; Yuen, Kin

    2012-10-01

    This article reviews common sleep disorders in children and pharmacologic options for them. Discussions of pediatric sleep pharmacology typically focus on treatment of insomnia. Although insomnia is a major concern in this population, other conditions of concern in children are presented, such as narcolepsy, parasomnias, restless legs syndrome, and sleep apnea.

  19. Diagnosis and Treatment of Low Back Pain in the Pediatric Population

    PubMed Central

    Taxter, Alysha J.; Chauvin, Nancy A.; Weiss, Pamela F.

    2014-01-01

    Back pain in the pediatric population is a common complaint presenting to sports medicine clinic. There is a wide differential that should be considered, including mechanical, infectious, neoplastic, inflammatory, and amplified musculoskeletal pain. The history, pain quality, and examination are key components to help distinguish the etiologies of the pain and direct further evaluation. Laboratory investigations, including blood counts and inflammatory markers, can provide insight into the diagnosis. The HLA-B27 antigen can be helpful if a spondyloarthropathy is suspected. Imaging as clinically indicated typically begins with radiographs, and the use of MRI, CT, or bone scan can provide additional information. Proper diagnosis of back pain is important because prognosis and treatments are significantly different. This paper will review the pertinent evaluation, differential diagnoses, and treatment of low back pain in the pediatric population. PMID:24565826

  20. Clinical and Neurobiological Aspects of Narcolepsy

    PubMed Central

    Nishino, Seiji

    2007-01-01

    Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy and/or other dissociated manifestations of rapid eye movement (REM) sleep (hypnagogic hallucinations and sleep paralysis). Narcolepsy is currently treated with amphetamine-like central nervous system (CNS) stimulants (for EDS) and antidepressants (for cataplexy). Some other classes of compounds such as modafinil (a non-amphetamine wake-promoting compound for EDS) and gamma-hydroxybutyrate (GHB, a short-acting sedative for EDS/fragmented nighttime sleep and cataplexy) given at night are also employed. The major pathophysiology of human narcolepsy has been recently elucidated based on the discovery of narcolepsy genes in animals. Using forward (i.e., positional cloning in canine narcolepsy) and reverse (i.e., mouse gene knockout) genetics, the genes involved in the pathogenesis of narcolepsy (hypocretin/orexin ligand and its receptor) in animals have been identified. Hypocretins/orexins are novel hypothalamic neuropeptides also involved in various hypothalamic functions such as energy homeostasis and neuroendocrine functions. Mutations in hypocretin-related genes are rare in humans, but hypocretin-ligand deficiency is found in many narcolepsy-cataplexy cases. In this review, the clinical, pathophysiological and pharmacological aspects of narcolepsy are discussed. PMID:17470414

  1. Hoping Is Coping: A Guiding Theoretical Framework for Promoting Coping and Adjustment Following Pediatric Cancer Diagnosis.

    PubMed

    Germann, Julie N; Leonard, David; Stuenzi, Thomas J; Pop, Radu B; Stewart, Sunita M; Leavey, Patrick J

    2015-10-01

    To determine the pattern of resilience and adjustment following pediatric cancer diagnosis and to evaluate hope as a mediator of adjustment. 61 participants with pediatric cancer completed measures of hope, depression, anxiety, and quality of life (QoL) within 4 weeks of cancer diagnosis and every 3 months for 1 year. Participants showed high and increasing levels of hope and QoL, as well as low and decreasing levels of depression and anxiety. Linear mixed-effects regression analyses revealed changes in depression, anxiety, and hope to be significant predictors of changes in QoL. Changes in hope were found to partially mediate the effects of depression and anxiety on QoL. While a variety of interventions are efficacious for treating anxiety and depression, hope theory provides a framework for choosing interventions that may more globally promote children's ability to maintain good functioning, adjustment, well-being, and QoL following cancer diagnosis. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Nanotechnology and Pediatric Cancer: Prevention, Diagnosis and Treatment

    PubMed Central

    Zare-Zardini, H; Amiri, A; Shanbedi, M; Taheri-Kafrani, A; Sadri, Z; Ghanizadeh, F; Neamatzadeh, H; Sheikhpour, R; Keyvani Boroujeni, F; Masoumi Dehshiri, R; Hashemi, A; Aminorroaya, MM; Dehgahnzadeh, MR; Shahriari, Sh

    2015-01-01

    Despite development of new approaches for the treatment of cancer disease, it is the second cause of mortality in world. Annually, 30000 persons die in Iran due to cancer diseases. Eighty percent of cancer patients are children which about 50% children lead to death. Given the high rate of cancer-related death, the new approaches for prevention, control, early diagnosis, and treatment of this disease seem necessary. Investigation of new strategies is the major challenge for scientists at recent century. Nanotechnology as a new scientific field with novel and small compounds utilized different fields over the past ten years especially in medicine. This science has come to the forefront in the areas of medical diagnostics, imaging, and therapeutic scheduls. Therefore, it has the potential applications for cancer detection and therapy. This review will discuss the therapeutic applications of different nano-materials in diagnosis, imaging, and delivery of therapeutic agents for the treatment of cancer with a major focus on their applications for the treatment of cancer and cancer- related diseases in children. The advancements in established nanoparticle technologies such as liposomes, polymer micelles, and functionalization regarding tumor targeting and controlled release strategies as well as drug delivery were discussed. It will also review the blood toxicity of used nanostructures. PMID:26985357

  3. Diagnosis and management of pediatric urinary tract infections.

    PubMed

    Zorc, Joseph J; Kiddoo, Darcie A; Shaw, Kathy N

    2005-04-01

    Urinary tract infection (UTI) is among the most commonly diagnosed bacterial infections of childhood. Although frequently encountered and well researched, diagnosis and management of UTI continue to be a controversial issue with many challenges for the clinician. Prevalence studies have shown that UTI may often be missed on history and physical examination, and the decision to screen for UTI must balance the risk for missed infections with the cost and inconvenience of testing. Interpretation of rapid diagnostic tests and culture is complicated by issues of contamination, false test results, and asymptomatic colonization of the urinary tract with nonpathogenic bacteria. The appropriate treatment of UTI has been controversial and has become more complex with the emergence of resistance to commonly used antibiotics. Finally, the anatomic evaluation and long-term management of a child after a UTI have been based on limited evidence, and newer studies question some of the tenets of prior recommendations. The goal of this review is to provide an up-to-date summary of the literature with particular attention to practical questions about diagnosis and management for the clinician.

  4. Narcolepsy: neural mechanisms of sleepiness and cataplexy

    PubMed Central

    Burgess, C.R.; Scammell, T.E.

    2012-01-01

    Narcolepsy is a common sleep disorder characterized by excessive daytime sleepiness and cataplexy - episodes of muscle weakness triggered by positive emotions. Over the last few years, researchers have discovered that narcolepsy results from a selective loss of neurons in the lateral hypothalamus that produce the orexin/hypocretin neuropeptides. While an autoimmune process is thought to underlie the loss of the orexin neurons this has not yet been conclusively demonstrated. Similarly, it is only partially understood how loss of the orexin neurons results in the various symptoms of narcolepsy. Studies in human patients and animal models of narcolepsy suggest that excessive sleepiness is due to behavioral state instability rather than disruption of sleep homeostasis or circadian rhythms. Cataplexy may result from the inappropriate activation during wakefulness of the pontine circuits that normally generate muscle atonia during REM sleep. This article reviews the clinical features and neurobiology of narcolepsy and outlines important areas in which progress might be achieved. PMID:22956821

  5. Increased lucid dreaming frequency in narcolepsy.

    PubMed

    Rak, Michael; Beitinger, Pierre; Steiger, Axel; Schredl, Michael; Dresler, Martin

    2015-05-01

    Nightmares are a frequent symptom in narcolepsy. Lucid dreaming, i.e., the phenomenon of becoming aware of the dreaming state during dreaming, has been demonstrated to be of therapeutic value for recurrent nightmares. Data on lucid dreaming in narcolepsy patients, however, is sparse. The aim of this study was to evaluate the frequency of recalled dreams (DF), nightmares (NF), and lucid dreams (LDF) in narcolepsy patients compared to healthy controls. In addition, we explored if dream lucidity provides relief during nightmares in narcolepsy patients. We interviewed patients with narcolepsy and healthy controls. Telephone interview. 60 patients diagnosed with narcolepsy (23-82 years, 35 females) and 919 control subjects (14-93 years, 497 females). N/A. Logistic regression revealed significant (P < 0.001) differences in DF, NF, and LDF between narcolepsy patients and controls after controlling for age and gender, with effect sizes lying in the large range (Cohen's d > 0.8). The differences in NF and LDF between patients and controls stayed significant after controlling for DF. Comparison of 35 narcolepsy patients currently under medication with their former drug-free period revealed significant differences in DF and NF (z < 0.05, signed-rank test) but not LDF (z = 0.8). Irrespective of medication, 70% of narcolepsy patients with experience in lucid dreaming indicated that dream lucidity provides relief during nightmares. Narcolepsy patients experience a markedly higher lucid dreaming frequency compared to controls, and many patients report a positive impact of dream lucidity on the distress experienced from nightmares. © 2015 Associated Professional Sleep Societies, LLC.

  6. Fine needle aspiration biopsy: role in diagnosis of pediatric head and neck masses.

    PubMed

    Anne, Samantha; Teot, Lisa A; Mandell, David L

    2008-10-01

    To assess the feasibility and role of fine needle aspiration biopsy (FNAB) as a diagnostic tool in children with neck masses. Retrospective chart review. Tertiary care children's hospital. Consecutive series of 71 children with a head and neck mass who underwent FNAB as the primary diagnostic modality. FNAB was performed and interpreted by a pediatric cytopathologist. Rapid on-site analysis was performed to allow immediate assessment of specimen adequacy and to attain a preliminary diagnosis, after which routine cytologic staining was performed. Flow cytometry was performed on cytological specimens when malignancy was suspected, and open biopsy was performed when the cytologic diagnosis was in question. Technical feasibility of FNAB in children, complications, cytopathological diagnoses, accuracy of rapid on-site analysis, need for subsequent diagnostic evaluations, clinical outcomes and follow-up. Mean age was 8.4 years (S.D. 5.3 years), with mean follow-up of 4.1 months (S.D. 9.6 months). FNAB was performed under general anesthesia in 54 cases (76%). There were no technical complications. On-site rapid interpretation was completed in 55 cases, 18/55 confirmed adequacy of specimen only, 37/55 yielded a preliminary diagnosis, and in 34/37 cases, was same as final cytopathologic result. Overall, FNAB biopsy demonstrated 64 benign lesions, 3 malignant diagnoses, 2 follicular thyroid neoplasms, and 2 non-diagnostic specimens. FNAB was the only pathological test performed in 54 (76%) cases. The most common diagnosis was reactive lymphoid hyperplasia (n = 39), followed by benign granulomatous disease (n = 8). Flow cytometry was performed on 7 specimens (non-diagnostic in 5, negative for malignancy in 2). Of the 15 cases with surgical specimens, 3 revealed a pathologic diagnosis different from initial FNAB. There were no cases in which FNAB missed a malignancy, and there were 2 cases where FNAB suggested malignancy, with benign disease subsequently found on open biopsy

  7. Frequencies and Associations of Narcolepsy-Related Symptoms: A Cross-Sectional Study.

    PubMed

    Kim, Lenise Jihe; Coelho, Fernando Morgadinho; Hirotsu, Camila; Araujo, Paula; Bittencourt, Lia; Tufik, Sergio; Andersen, Monica Levy

    2015-12-15

    Narcolepsy is a disabling disease with a delayed diagnosis. At least 3 years before the disorder identification, several comorbidities can be observed in patients with narcolepsy. The early recognition of narcolepsy symptoms may improve long-term prognosis of the patients. Thus, we aimed to investigate the prevalence of the symptoms associated with narcolepsy and its social and psychological association in a sample of Sao Paulo city inhabitants. We performed a cross-sectional evaluation with 1,008 individuals from the Sao Paulo Epidemiologic Sleep Study (EPISONO). Excessive daytime sleepiness (EDS) was assessed by the Epworth Sleepiness Scale. Volunteers were also asked about the occurrence of cataplectic-like, hypnagogic or hypnopompic hallucinations, and sleep paralysis symptoms. The participants underwent a full-night polysomnography and completed questionnaires about psychological, demographic, and quality of life parameters. We observed a prevalence of 39.2% of EDS, 15.0% of cataplectic-like symptom, 9.2% of hypnagogic or hypnopompic hallucinations, and 14.9% of sleep paralysis in Sao Paulo city inhabitants. A frequency of 6.9% was observed when EDS and cataplectic-like symptoms were grouped. The other associations were EDS + hallucinations (4.7%) and EDS + sleep paralysis (7.5%). Symptomatic participants were predominantly women and younger compared with patients without any narcolepsy symptom (n = 451). Narcolepsy symptomatology was also associated with a poor quality of life and symptoms of depression, anxiety, and fatigue. Narcolepsy-related symptoms are associated with poor quality of life and worse psychological parameters. © 2015 American Academy of Sleep Medicine.

  8. [Cherubism: diagnosis and treatment in the pediatric age].

    PubMed

    Sánchez Burgos, R; Martín Pérez, M; Ramírez Piqueras, M; Gómez García, E; Burgueño García, M

    2012-01-01

    Cherubism is a benign bone dysplasia of childhood, exclusively involving maxillary bones and spontaneous resolving after puberty in different grades. Approximately, 280 cases have been reviewed in the literature. It is an autosomal dominant disorder in which the normal bone is replaced by cellular fibrous and immature bone, resulting in painless symmetrical enlargement of the jaws. Diagnosis is based in clinical and radiological findings, confirmed by histology. Treatment is a controversial issue, and it is recommended surgical management as conservative as possible during the rapid growth phases. An aggressive case of cherubism is reported, diagnosed and followed since early childhood until puberty, with progressive involvement of facial bones developing in a disruption of facial contours and occlusion. The patient is treated by several surgical interventions oriented to minimize the aesthetic impact of the disease being as conservative as possible. The highlights of this case are the great proportion of the lesions, the functional and emotional disturbances brought out by these lesions and the difficulty to choose the most appropriate age and form of treatment.

  9. Homocystinuria: Diagnosis and Neuroimaging Findings of Iranian Pediatric patients.

    PubMed

    Karimzadeh, Parvaneh; Jafari, Narjes; Alai, MohammadReza; Jabbehdari, Sayena; Nejad Biglari, Habibeh

    2015-01-01

    Homocystinuria is a neurometabolic diseases characterized by symptoms include Neurodevelopmental delay, lens dislocation, long limbs and thrombosis. The patients who were diagnosed as homocystinuria marfaniod habits, seizure in the Neurology Department of Mofid Children's Hospital in Tehran, Iran between 2004 and 2014 were included in our study. The disorder was confirmed by clinical andneuroimaging findings along withneurometabolic and genetic assessment fromreference laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 20 patients with homocystinuria. A total of 75% of patients were offspring from consanguineous marriages. A total of 95% of patients had a history of developmental delay and 40% had developmental regression. A total of 75% had seizures from these 45% showed refractory seizures. Seizures among 13 patients werecontrolled with suitable homocystinuria treatment. The patients with homocystinuriawere followed for approximately 10 years and the follow-ups showed that the patients with an early diagnosis and treatment had more favorable clinical responses for growth index, controlled refractory seizures, neurodevelopmental status, and neuroimaging findings. Neuroimaging findings include brain atrophy and/or white matter involvement. According to the results of this study, we suggest that early assessment and detectionplayan important role in the prevention of disease progression and clinical signs. Homocystinuria in patients with a positive family history, developmental delays, or regression, refractory, or recurrent seizures should take precedence over other causes.

  10. Homocystinuria: Diagnosis and Neuroimaging Findings of Iranian Pediatric patients

    PubMed Central

    KARIMZADEH, Parvaneh; JAFARI, Narjes; ALAI, MohammadReza; JABBEHDARI, Sayena; NEJAD BIGLARI, Habibeh

    2015-01-01

    Objective Homocystinuria is a neurometabolic diseases characterized by symptoms include Neurodevelopmental delay, lens dislocation, long limbs and thrombosis. Materials & Methods The patients who were diagnosed as homocystinuria marfaniod habits, seizure in the Neurology Department of Mofid Children’s Hospital in Tehran, Iran between 2004 and 2014 were included in our study. The disorder was confirmed by clinical andneuroimaging findings along withneurometabolic and genetic assessment fromreference laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 20 patients with homocystinuria. Results A total of 75% of patients were offspring from consanguineous marriages. A total of 95% of patients had a history of developmental delay and 40% had developmental regression. A total of 75% had seizures from these 45% showed refractory seizures. Seizures among 13 patients werecontrolled with suitable homocystinuria treatment. The patients with homocystinuriawere followed for approximately 10 years and the follow-ups showed that the patients with an early diagnosis and treatment had more favorable clinical responses for growth index, controlled refractory seizures, neurodevelopmental status, and neuroimaging findings. Neuroimaging findings include brain atrophy and/or white matter involvement. Conclusion According to the results of this study, we suggest that early assessment and detectionplayan important role in the prevention of disease progression and clinical signs. Homocystinuria in patients with a positive family history, developmental delays, or regression, refractory, or recurrent seizures should take precedence over other causes. PMID:25767545

  11. The diagnosis of autism in community pediatric settings: does advanced training facilitate practice change?

    PubMed

    Swanson, Amy R; Warren, Zachary E; Stone, Wendy L; Vehorn, Alison C; Dohrmann, Elizabeth; Humberd, Quentin

    2014-07-01

    The increased prevalence of autism spectrum disorder and documented benefits of early intensive intervention have created a need for flexible systems for determining eligibility for autism-specific services. This study evaluated the effectiveness of a training program designed to enhance autism spectrum disorder identification and assessment within community pediatric settings across the state. Twenty-seven pediatric providers participated in regional trainings across a 3.5-year period. Trainings provided clinicians with strategies for conducting relatively brief within-practice interactive assessments following positive autism spectrum disorder screenings. Program evaluation was measured approximately 1.5 years following training through (a) clinician self-reports of practice change and (b) blind diagnostic verification of a subset of children assessed. Pediatric providers participating in the training reported significant changes in screening and consultation practices following training, with a reported 85% increase in diagnostic identification of children with autism spectrum disorder within their own practice setting. In addition, substantial agreement (86%-93%) was found between pediatrician diagnostic judgments and independent, comprehensive blinded diagnostic evaluations. Collaborative training methods that allow autism spectrum disorder identification within broader community pediatric settings may help translate enhanced screening initiatives into more effective and efficient diagnosis and treatment. © The Author(s) 2013.

  12. Concordance of imaging modalities and cost minimization in the diagnosis of pediatric choledochal cysts

    PubMed Central

    Axt, Jason R.; Crapp, Seth J.; Martin, Colin A.; Crane, Gabriella L.; Lovvorn, Harold N.

    2014-01-01

    Purpose Given evolving imaging technologies, we noted significant variation in the diagnostic evaluation of pediatric choledochal cysts (CDC). To streamline the diagnostic approach to CDC, and minimize associated expenses, we compared typing accuracy and costs of ultrasound (US), intraoperative cholangiography (IOC), and magnetic resonance cholangiopancreatography (MRCP). Methods Records of 30 consecutive pediatric CDC patients were reviewed. Blinded to all clinical data, two pediatric radiologists reviewed all US, MRCPs, and IOCs to type CDCs according to the Todani classification. When compared with pathologic findings, the concordance between and accuracy of each diagnostic test were determined. Inflation-adjusted procedure charges and collections for imaging modalities were analyzed. Results Mean typing accuracy overlapped for US, IOC, and MRCP. Inter-rater reliability was 87 % for US (κ = 0.77), 80 % for IOC (κ = 0.62), and 60 % for MRCP (κ = 0.37). MRCP procedure charges ($1204.69) and collections ($420.85) exceeded IOC and US combined ($264.80 charges, p = 0.0002; $93.40 collections, p = 0.0021). Conclusion Our data support the use of US alone in the diagnosis of pediatric CDC when no intrahepatic biliary ductal dilatation is visualized. However, when dilated intrahepatic ducts are encountered on US, MRCP should be utilized to distinguish a type I from a type IV CDC, which may alter the operative approach. PMID:22526551

  13. Sensitivity and specificity of obesity diagnosis in pediatric ambulatory care in the United States.

    PubMed

    Walsh, Carolyn O; Milliren, Carly E; Feldman, Henry A; Taveras, Elsie M

    2013-09-01

    We examined the sensitivity and specificity of an obesity diagnosis in a nationally representative sample of pediatric outpatient visits. We used the 2005 to 2009 National Ambulatory Medical Care and National Hospital Ambulatory Medical Care surveys. We included visits with children 2 to 18 years, yielding a sample of 48 145 database visits. We determined 3 methods of identifying obesity: documented body mass index (BMI) ≥95th percentile; International Classification of Diseases, Ninth Revision (ICD-9) code; and positive answer to the question, "Does the patient now have obesity?" Using BMI as the gold standard, we calculated the sensitivity and specificity of a clinical obesity diagnosis. Among the 19.5% of children who were obese by BMI, 7.0% had an ICD-9 code and 15.2% had a positive response to questioning. The sensitivity of an obesity diagnosis was 15.4%, and the specificity was 99.2%. The sensitivity of the obesity diagnosis in pediatric ambulatory visits is low. Efforts are needed to increase identification of obese children.

  14. The impact of prenatal diagnosis of congenital heart disease on pediatric cardiology and cardiac surgery.

    PubMed

    Chiappa, Enrico

    2007-01-01

    Since the early 1980s prenatal diagnosis of congenital heart disease (CHD) has progressively impacted on the practice of pediatric cardiology and cardiac surgery. Fetal cardiology today raises special needs in screening programs, training of the involved staff, and allocations of services. Due to the increased detection rate and to the substantial number of terminations, the reduced incidence of CHD at birth can affect the workload of centers of pediatric cardiology and surgery. In utero transportation and competition among centers may change the area of referral in favor of the best centers. Echocardiography is a powerful means to diagnose and to guide lifesaving medical treatment of sustained tachyarrhythmias in the fetus. Prenatal diagnosis not only improves the preoperative conditions in most cases but also postoperative morbidity and mortality in selected types of CHD. Intrauterine transcatheter valvuloplasty in severe outflow obstructive lesions has been disappointing so far and this technique remains investigational, until its benefits are determined by controlled trials. Prenatal diagnosis allows counselling of families which are better prepared for the foreseeable management and outcome of the fetus. These benefits can reduce the risks of litigation for missed ultrasound diagnosis. As increased costs can be expected in institutions dealing with a large number of fetal CHD, the administrators of these institutions should receive protected funds, proportional to their needs.

  15. Prediction of esophageal and gastric histology by macroscopic diagnosis during upper endoscopy in pediatric celiac disease.

    PubMed

    Boschee, Erin D; Yap, Jason Y K; Turner, Justine M

    2017-01-28

    To determine the sensitivity of macroscopic appearance for predicting histological diagnosis at sites other than duodenum in pediatric celiac disease (CD). Endoscopic and histologic findings in pediatric patients undergoing upper endoscopy for first-time diagnosis of CD at Stollery Children's Hospital from 2010-2012 were retrospectively reviewed. Clinical charts from 140 patients were reviewed. Esophageal and gastric biopsies were taken in 54.3% and 77.9% of patients, respectively. Endoscopic appearance was normal in the esophagus and stomach in 75% and 86.2%. Endoscopic esophageal diagnoses were eosinophilic esophagitis (EE) (11.8%), esophagitis (7.9%), glycogenic acanthosis (1.3%) and non-specific abnormalities (3.9%). Endoscopic gastric diagnoses were gastritis (8.3%), pancreatic rest (0.9%), and non-specific abnormalities (4.6%). Histology was normal in 76.3% of esophageal and 87.2% of gastric specimens. Abnormal esophageal histology was EE (10.5%), esophagitis (10.5%), glycogenic acanthosis (1.3%) and non-specific (1.3%). Gastritis was reported in 12.8% of specimens. Sensitivity and specificity of normal endoscopy for predicting normal esophageal histology was 86.2% and 61.1%, and for normal gastric histology was 87.4% and 21.4%. In the absence of macroscopic abnormalities, routine esophageal and gastric biopsy during endoscopy for pediatric CD does not identify major pathologies. These findings have cost and time saving implications for clinical practice.

  16. Screening for psychosocial risk at pediatric cancer diagnosis: the psychosocial assessment tool.

    PubMed

    Kazak, Anne E; Barakat, Lamia P; Ditaranto, Susan; Biros, Daniel; Hwang, Wei-Ting; Beele, David; Kersun, Leslie; Alderfer, Melissa A; Mougianis, Ifigenia; Hocking, Matthew C; Reilly, Anne

    2011-05-01

    To investigate the feasibility of integrating an evidence-based screening tool of psychosocial risk in pediatric cancer care at diagnosis. Parents of children newly diagnosed with cancer received either the Psychosocial Assessment Tool (PAT; n=52) or psychosocial care as usual (n=47; PAU), based on their date of diagnosis and an alternating monthly schedule. Time to completion of the PAT, time to communication of PAT results to clinical care teams, distribution of PAT risk scores, and identification of psychosocial risks in the medical record were examined. Of families receiving the PAT, 88% completed it within 48 hours. PAT was scored and results communicated within 48 hours in 98% of cases. Most families (72%) were classified as Universal risk based on the underlying Pediatric Psychosocial Preventative Health Model, 24% were classified as Targeted risk, and 4% scored in the Clinical range. Significantly more psychosocial risks were recorded in the medical record during PAT intervals than during PAU. An evidence-based psychosocial screener is feasible in pediatric oncology care and is associated with documentation of psychosocial risks in the medical record. Although the majority of families report low levels of psychosocial risk, about one-quarter report problems.

  17. Nightmares in narcolepsy: underinvestigated symptom?

    PubMed

    Pisko, Juraj; Pastorek, Lukas; Buskova, Jitka; Sonka, Karel; Nevsimalova, Sona

    2014-08-01

    Besides main disease symptoms, disturbing dreams are often found in narcoleptics and may contribute to disturbed sleep. Our main goal was to study different types of oneiric activity in narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (N). We have analyzed the medical history of 118 narcoleptics (64 men, 86 with NC, 32 with N, mean age 41.6±15 years). Their most frequent dreams were divided into four groups: (A) low recall/mundane dreams, (B) vivid dreams without disturbing negative emotion, (C) nightmares, (D) reduction of nightmares, possibly by medication. Associations with other features of the disease were statistically analyzed. Nightmares were found in one-third of the patients, proportionally distributed in N and NC groups; not negatively charged vivid dreams appeared more frequently in NC patients (P<0.005). No/mundane dreams occurred with higher prevalence in men (48%) than in women (20%), (P<0.005), without any significant influence of age. Occurrence of nightmares was significantly higher in patients with REM sleep behavior (P<0.05), but lower in patients with obstructive sleep apnea (P<0.005). Polysomnographic correlation of N and NC nightmare groups showed more wakefulness (P<0.05) and higher percentage of NREM1 stage (P<0.05) in NC patients with nightmares. Compared with the general population, nightmares seem to be significantly more prevalent in both NC and N, and they are not sufficiently investigated and treated. The neurobiological basis of narcolepsy and patients' dreaming activities appear to be closely related. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin.

    PubMed

    Morgenthaler, Timothy I; Kapur, Vishesh K; Brown, Terry; Swick, Todd J; Alessi, Cathy; Aurora, R Nisha; Boehlecke, Brian; Chesson, Andrew L; Friedman, Leah; Maganti, Rama; Owens, Judith; Pancer, Jeffrey; Zak, Rochelle

    2007-12-01

    These practice parameters pertain to the treatment of hypersomnias of central origin. They serve as both an update of previous practice parameters for the therapy of narcolepsy and as the first practice parameters to address treatment of other hypersomnias of central origin. They are based on evidence analyzed in the accompanying review paper. The specific disorders addressed by these parameters are narcolepsy (with cataplexy, without cataplexy, due to medical condition and unspecified), idiopathic hypersomnia (with long sleep time and without long sleep time), recurrent hypersomnia and hypersomnia due to medical condition. Successful treatment of hypersomnia of central origin requires an accurate diagnosis, individual tailoring of therapy to produce the fullest possible return of normal function, and regular follow-up to monitor response to treatment. Modafinil, sodium oxybate, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, and selegiline are effective treatments for excessive sleepiness associated with narcolepsy, while tricyclic antidepressants and fluoxetine are effective treatments for cataplexy, sleep paralysis, and hypnagogic hallucinations; but the quality of published clinical evidence supporting them varies. Scheduled naps can be beneficial to combat sleepiness in narcolepsy patients. Based on available evidence, modafinil is an effective therapy for sleepiness due to idiopathic hypersomnia, Parkinson's disease, myotonic dystrophy, and multiple sclerosis. Based on evidence and/or long history of use in the therapy of narcolepsy committee consensus was that modafinil, amphetamine, methamphetamine, dextroamphetamine, and methylphenidate are reasonable options for the therapy of hypersomnias of central origin.

  19. Brain Death in Pediatric Patients in Japan: Diagnosis and Unresolved Issues

    PubMed Central

    ARAKI, Takashi; YOKOTA, Hiroyuki; FUSE, Akira

    2016-01-01

    Brain death (BD) is a physiological state defined as complete and irreversible loss of brain function. Organ transplantation from a patient with BD is controversial in Japan because there are two classifications of BD: legal BD in which the organs can be donated and general BD in which the organs cannot be donated. The significance of BD in the terminal phase remains in the realm of scientific debate. As indicated by the increasing number of organ transplants from brain-dead donors, certain clinical diagnosis for determining BD in adults is becoming established. However, regardless of whether or not organ transplantation is involved, there are many unresolved issues regarding BD in children. Here, we will discuss the historical background of BD determination in children, pediatric emergencies and BD, and unresolved issues related to pediatric BD. PMID:26548741

  20. Syncope In Pediatric Patients: A Practical Approach To Differential Diagnosis And Management In The Emergency Department.

    PubMed

    Fant, Collen; Cohen, Arl

    2017-04-01

    Syncope is a condition that is often seen in the emergency department. Most syncope is benign, but it can be a symptom of a life-threatening condition. While syncope often requires an extensive workup in adults, in the pediatric population, critical questioning and simple, noninvasive testing is usually sufficient to exclude significant or life-threatening causes. For low-risk patients, resource-intensive workups are rarely diagnostic, and add significant cost to medical care. This issue will highlight critical diseases that cause syncope, identify high-risk "red flags," and enable the emergency clinician to develop a cost-effective, minimally invasive algorithm for the diagnosis and treatment of pediatric syncope.

  1. Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications.

    PubMed

    Fonseca, Mariana Bertoldi; Gomes, Francisco Hugo Rodrigues; Valera, Elvis Terci; Pileggi, Gecilmara Salviato; Gonfiantini, Paula Braga; Gonfiantini, Marcela Braga; Ferriani, Virgínia Paes Leme; Carvalho, Luciana Martins de

    2016-12-16

    To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase (LDH) was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition. Copyright © 2016. Published by Elsevier Editora Ltda.

  2. Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications.

    PubMed

    Fonseca, Mariana Bertoldi; Gomes, Francisco Hugo Rodrigues; Valera, Elvis Terci; Pileggi, Gecilmara Salviato; Gonfiantini, Paula Braga; Gonfiantini, Marcela Braga; Ferriani, Virgínia Paes Leme; Carvalho, Luciana Martins de

    To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic. Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer. Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids. The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow-up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition. Copyright © 2017 Elsevier Editora Ltda. All rights reserved.

  3. Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcus: Comparison of Diagnosis and Treatment in the Community and at a Specialty Clinic

    PubMed Central

    Gabbay, Vilma; Coffey, Barbara J.; Babb, James S.; Meyer, Laura; Wachtel, Carly; Anam, Seeba; Rabinovitz, Beth

    2009-01-01

    OBJECTIVES This study aimed to examine whether pediatric autoimmune neuropsychiatric disorders associated with streptococcus were appropriately diagnosed in the community and to determine subsequent rates of unwarranted use of antibiotic treatment for tics and obsessive-compulsive symptoms without the identification of an infection. METHODS The design was a retrospective, cross-sectional, observational study of 176 children and adolescents who were evaluated in a specialty program for tics, Tourette's disorder, and related problems. Previously published diagnostic criteria were used to establish the diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus in our clinic. RESULTS Subjects were significantly less likely to receive a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus at the specialty clinic than in the community. In the community, subjects were significantly more likely to be treated with antibiotics or immunosuppressant medication if they received a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus. Of the 27 subjects with a community diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus who were treated with antibiotics, 22 (82%) were treated without laboratory evidence of an infection; 2 were treated with immunomodulatory medications. CONCLUSIONS Our results support our hypothesis that pediatric autoimmune neuropsychiatric disorders associated with streptococcus are frequently diagnosed in the community without the application of all working diagnostic criteria. This phenomenon has resulted in unwarranted use of antibiotic treatment for tics/obsessive-compulsive disorder without evidence of laboratory infection. PMID:18676543

  4. Narcolepsy Type 1 and Idiopathic Generalized Epilepsy: Diagnostic and Therapeutic Challenges in Dual Cases

    PubMed Central

    Baiardi, Simone; Vandi, Stefano; Pizza, Fabio; Alvisi, Lara; Toscani, Lucia; Zambrelli, Elena; Tinuper, Paolo; Mayer, Geert; Plazzi, Giuseppe

    2015-01-01

    Study Objectives: The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. Methods and Results: Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. Conclusions: Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness. Citation: Baiardi S, Vandi S, Pizza F, Alvisi L, Toscani L, Zambrelli E, Tinuper P, Mayer G, Plazzi G. Narcolepsy type 1 and

  5. Predictors of Hypocretin (Orexin) Deficiency in Narcolepsy Without Cataplexy

    PubMed Central

    Andlauer, Olivier; Moore, Hyatt; Hong, Seung-Chul; Dauvilliers, Yves; Kanbayashi, Takashi; Nishino, Seiji; Han, Fang; Silber, Michael H.; Rico, Tom; Einen, Mali; Kornum, Birgitte R.; Jennum, Poul; Knudsen, Stine; Nevsimalova, Sona; Poli, Francesca; Plazzi, Giuseppe; Mignot, Emmanuel

    2012-01-01

    Study Objectives: To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110–200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1. Setting: University-based sleep clinics and laboratories. Patients: Narcolepsy without cataplexy (n = 171) and control patients (n = 170), all with available CSF hypocretin-1. Design and interventions: Retrospective comparison and receiver operating characteristics curve analysis. Patients were also recontacted to evaluate if they developed cataplexy by survival curve analysis. Measurements and Results: The optimal cutoff of CSF hypocretin-1 for narcolepsy without cataplexy diagnosis was 200 pg/ml rather than 110 pg/ml (sensitivity 33%, specificity 99%). Forty-one patients (24%), all HLA DQB1*06:02 positive, had low concentrations (≤ 110 pg/ml) of CSF hypocretin-1. Patients with low concentrations of hypocretin-1 only differed subjectively from other groups by a higher Epworth Sleepiness Scale score and more frequent sleep paralysis. Compared with patients with normal hypocretin-1 concentration (n = 117, 68%), those with low hypocretin-1 concentration had higher HLA DQB1*06:02 frequencies, were more frequently non-Caucasians (notably African Americans), with lower age of onset, and longer duration of illness. They also had more frequently short rapid-eye movement (REM) sleep latency (≤ 15 min) during polysomnography (64% versus 23%), and shorter sleep latencies (2.7 ± 0.3 versus 4.4 ± 0.2 min) and more sleep-onset REM periods (3.6 ± 0.1 versus 2.9 ± 0.1 min) during the Multiple Sleep Latency Test (MSLT). Patients with intermediate concentrations of CSF hypocretin-1 (n = 13, 8%) had intermediate HLA DQB1*06:02 and polysomnography results, suggesting heterogeneity. Of the 127 patients we were able to recontact, survival analysis showed that almost half (48%) with low concentration of CSF hypocretin-1 had developed

  6. Metastases detected at the time of diagnosis of primary pediatric extremity osteosarcoma at diagnosis: imaging features.

    PubMed

    Kaste, S C; Pratt, C B; Cain, A M; Jones-Wallace, D J; Rao, B N

    1999-10-15

    The authors performed a retrospective study to estimate the incidence rate of metastatic disease at the time of diagnosis of extremity osteosarcoma (OS), to characterize its pattern of presentation, and to identify factors predictive of survival within a cohort of patients with pulmonary metastatic disease at diagnosis. From the institutional solid tumor database, the authors identified all patients diagnosed with extremity OS since CT became available at the study institution (1977). The authors recorded patient demographics, the site of primary disease, the histologic subtype of OS, and the presence of metastases at diagnosis. In those patients with pulmonary metastases at diagnosis, the presence of calcifications, the primary tumor volume, the number of pulmonary lobes with disease, and the number of pulmonary nodules were recorded. Of an evaluable population of 215 patients, 32 (15%) had bone or pulmonary metastases at diagnosis, of whom original imaging from 28 patients was available for review. Osteoblastic histology correlated with lung metastases at diagnosis (P = 0.049). One of the 32 patients had a solitary bone metastasis without lung metastases. Four of 28 patients (14%) with original imaging available had calcifications within the pulmonary nodules. Both the number of nodules and the number of lobes involved were found to be significant predictors of survival (P = 0.0009 and P = 0. 04, respectively); multiple nodules were bilateral in 61% of patients. The rate of incidence of computed tomography detected pulmonary metastases was found to be 14% (31 of 215 patients) at diagnosis and 0.5% (1 of 215 patients) for bone metastases in patients with primary extremity OS. Pulmonary metastases usually are multiple and bilateral and infrequently calcify. The number of nodules and lobes involved are predictors of patient survival. Copyright 1999 American Cancer Society.

  7. Complementary Indicators for Diagnosis of Hepatic Vein Stenosis After Pediatric Living-donor Liver Transplantation.

    PubMed

    Kawano, Y; Mizuta, K; Sanada, Y; Urahashi, T; Ihara, Y; Okada, N; Yamada, N; Sasanuma, H; Sakuma, Y; Taniai, N; Yoshida, H; Kawarasaki, H; Yasuda, Y; Uchida, E

    2016-05-01

    Although hepatic vein stenosis after liver transplantation is a rare complication, the complication rate of 1% to 6% is higher in pediatric living-donor liver transplantation than that in other liver transplantation cases. Diagnosis is very important because this complication can cause hepatic congestion that develops to liver cirrhosis, graft loss, and patient loss. However, this is unlikely in cases where there are no ascites or hypoalbuminemia. Eleven of 167 patients who had undergone pediatric living-donor liver transplantation were identified in the outpatient clinic at Jichi Medical University as having suffered from hepatic vein stenosis, and were enrolled in the study. We conducted a retrospective study in which we reviewed historical patient records to investigate the parameters for diagnosis and examine treatment methods and outcomes. The 11 patients were treated with 16 episodes of balloon dilatation. Three among these received retransplantation and another 2 cases required the placement of a metallic stent at the stenosis. Histological examination revealed severe fibrosis in four of nine patients who had a liver biopsy, with mild fibrosis revealed in the other five grafts. Furthermore, hepatomegaly and splenomegaly diagnosed by computed tomography, elevated levels of hyarulonic acid, and/or a decrease in calcineurin inhibitor clearance were found to be pathognomonic at diagnosis, and tended to improve after treatment. Diagnosis of hepatic vein stenosis after liver transplantation can be difficult, so careful observation is crucial to avoid the risk of acute liver dysfunction. Comprehensive assessment using volumetry of the liver and spleen and monitoring of hyarulonic acid levels and/or calcineurin inhibitor clearance, in addition to some form of imaging examination, is important for diagnosis and evaluation of the effectiveness of therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Missed opportunities for timely diagnosis of pediatric lupus in South Africa: a qualitative study.

    PubMed

    Lewandowski, Laura B; Watt, Melissa H; Schanberg, Laura E; Thielman, Nathan M; Scott, Christiaan

    2017-02-23

    Systemic Lupus Erythematosus (SLE) is a serious multisystem autoimmune disease, which is more aggressive in children and people of African descent. In South Africa, pediatric SLE (pSLE) patients are at high risk for severe disease. Similar to pSLE worldwide, South African children and adolescents with SLE require subspecialized medical care. The aim of this study is to describe the care-seeking experiences of families and examine factors that contribute to delays in the diagnosis of pSLE. Specifically, we sought to identify factors to inform interventions that support the timely referral and diagnosis of pediatric SLE patients in South Africa. In-depth, semi-structured interviews were conducted with 22 caregivers of pSLE patients recruited from two government hospitals in Cape Town, South Africa in 2014. Interviews were audio-recorded, transcribed, and analyzed for themes related to barriers to diagnosis. Six themes were identified and classified as either caregiver or health system barriers to diagnosis. Caregiver barriers included lack of knowledge regarding SLE, financial difficulties, and the social stigma of SLE. Health system barriers were lack of trained staff, a complex medical system, and misdiagnosis. Caregivers reported missed opportunities for diagnosing pSLE in their children. Raising public awareness may improve caregiver awareness and reduce stigma of pSLE. Improving family education at diagnosis holds potential to increase patient-physician trust and mitigate fear. Education modules for primary care providers at initial point of contact with the health care system may improve recognition of early pSLE and facilitate expedited referral to a specialist.

  9. Prevalence of periodical leg movements in patients with narcolepsy in an outpatient facility in São Paulo.

    PubMed

    Pereira, Danielle; Lopes, Eduardo; da Silva Behrens, Nilce Sanny Costa; de Almeida Fonseca, Hassana; Sguillar, Danilo Anunciatto; de Araújo Lima, Taís Figueiredo; Pradella-Hallinan, Marcia; Castro, Juliana; Tufik, Sergio; Santos Coelho, Fernando Morgadinho

    2014-03-01

    Studies have pointed out that approximately 50-60% of narcolepsy patients may demonstrate higher prevalence of periodical leg movements. However, we highlight that the prevalence studies and the effects of periodical leg movements in patients with narcolepsy are limited and with conflicting results. The objective of this study was that of describing and discussing the prevalence of periodical leg movements in patients with narcolepsy in the outpatient facility of diurnal excessive sleepiness of the Federal University of São Paulo, Brazil. We revised 59 files of patients with the clinical and electrophysiological diagnosis of narcolepsy according to the American Academy of Sleep Medicine. Of these 59 cases of patients with narcolepsy, 12 (20.3%) demonstrated periodical leg movements. Thirty five patients (59.3%) had history of cataplexy and 38 patients (64.4%) had the presence of the allele HLA-DQB1⁎0602. There was a higher prevalence of periodical leg movements in patients with cataplexy (p<0.0001) and in patients with the presence of the allele HLA-DQB1⁎0602 (p<0.0001). Our study characterized the higher prevalence of periodical leg movement in patients with narcolepsy, mainly in patients with cataplexy and with the presence of the allele HLA-DQB1⁎0602.

  10. Prevalence of periodical leg movements in patients with narcolepsy in an outpatient facility in São Paulo☆

    PubMed Central

    Pereira, Danielle; Lopes, Eduardo; da Silva Behrens, Nilce Sanny Costa; de Almeida Fonseca, Hassana; Sguillar, Danilo Anunciatto; de Araújo Lima, Taís Figueiredo; Pradella-Hallinan, Marcia; Castro, Juliana; Tufik, Sergio; Santos Coelho, Fernando Morgadinho

    2014-01-01

    Studies have pointed out that approximately 50–60% of narcolepsy patients may demonstrate higher prevalence of periodical leg movements. However, we highlight that the prevalence studies and the effects of periodical leg movements in patients with narcolepsy are limited and with conflicting results. The objective of this study was that of describing and discussing the prevalence of periodical leg movements in patients with narcolepsy in the outpatient facility of diurnal excessive sleepiness of the Federal University of São Paulo, Brazil. We revised 59 files of patients with the clinical and electrophysiological diagnosis of narcolepsy according to the American Academy of Sleep Medicine. Of these 59 cases of patients with narcolepsy, 12 (20.3%) demonstrated periodical leg movements. Thirty five patients (59.3%) had history of cataplexy and 38 patients (64.4%) had the presence of the allele HLA-DQB1⁎0602. There was a higher prevalence of periodical leg movements in patients with cataplexy (p<0.0001) and in patients with the presence of the allele HLA-DQB1⁎0602 (p<0.0001). Our study characterized the higher prevalence of periodical leg movement in patients with narcolepsy, mainly in patients with cataplexy and with the presence of the allele HLA-DQB1⁎0602. PMID:26483906

  11. Polysomnographic and actigraphic characteristics of patients with H1N1-vaccine-related and sporadic narcolepsy.

    PubMed

    Alakuijala, Anniina; Sarkanen, Tomi; Partinen, Markku

    2015-01-01

    After the pandemic H1N1 influenza ASO3-adjuvanted vaccine, Pandemrix©, was used in late 2009 and early 2010, the incidence of narcolepsy increased in many European countries. This incidence mainly increased in children and adolescents and, to a lesser degree, in adults. 125 unmedicated patients, aged 4 to 61 years, were included in this case-series study. Of these, 69 were diagnosed to have an H1N1-vaccine-related narcolepsy and 57 had sporadic narcolepsy. Most of these patients had: an actigraphy recording of 1-2 weeks, polysomnography, a Multiple Sleep Latency Test (MSLT), and cerebrospinal fluid hypocretin-1 concentration analysis. Patients with H1N1-vaccine-related narcolepsy had shorter diagnostic delays, lower periodic leg movement index during sleep, earlier sleep-wake rhythm, and were younger in age at diagnosis, compared with sporadic cases. They also had shorter sleep latency and more sleep onset REM periods in MSLT, but these results were strongly age-dependent. Actigraphy showed quantitatively less sleep and more sleep fragmentation than polysomnography. Regarding polysomnographic and actigraphic characteristics, there were no dramatic deviations between H1N1-vaccine-related and sporadic narcolepsy. Circadian rhythms indicated some interesting new findings with respect to the H1N1-vaccine-related disease. An actigraphy recording of 1-2 weeks is useful when studying the nocturnal aspects of narcolepsy and sleep-wake rhythms of narcoleptic patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Four cases of pediatric deep-seated/subcutaneous pyogenic granuloma: Review of literature and differential diagnosis.

    PubMed

    Putra, Juan; Rymeski, Beth; Merrow, Arnold C; Dasgupta, Roshni; Gupta, Anita

    2017-06-01

    Pyogenic granulomas are benign, reactive, typically superficial vascular lesions that can be idiopathic or arise secondary to trauma, underlying vascular malformations, infections, physiologic or pathologic endocrine changes, and hormone therapy. Deep-seated/subcutaneous pyogenic granulomas (DSPG) are rarely seen in any age group. Pediatric DSPGs can be a clinical and pathologic challenge because these lesions mimic other vascular lesions, including kaposiform hemangioendothelioma, infantile hemangiomas and vascular malformations. Retrospective search of DSPG excised at Cincinnati Children's Hospital Medical center between June 2010 and June 2011 was conducted. Clinical information was obtained from patient charts and histologic slides were retrieved and reviewed. Of the 106 cases of pyogenic granuloma, 4 (3.8%) were diagnosed as DSPG. We report the details of those 4 cases and compare them with the other pediatric DSPG cases reported in the literature. We also review the histologic differential diagnosis of DSPG in pediatric population. Our results suggest that these lesions may not be as rare as inferred by literature, but, rather, underdiagnosed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Diabetes Screening, Diagnosis, and Therapy in Pediatric Patients With Type 2 Diabetes

    PubMed Central

    Rodbard, Helena W.

    2008-01-01

    Abstract and Introduction Abstract The dramatic rise in the incidence and prevalence of type 2 diabetes mellitus in the pediatric and adolescent populations has been associated with the ongoing epidemic of overweight, obesity, insulin resistance, and metabolic syndrome seen in these age groups. Although the majority of pediatric patients diagnosed with diabetes are still classified as having type 1 diabetes, almost 50% of patients with diabetes in the pediatric age range (under 18 years) may have type 2 diabetes. Screening of high-risk patients for diabetes and prediabetes is important. Prompt diagnosis and accurate diabetes classification facilitate appropriate and timely treatment and may reduce the risk for complications. This is especially important in children because lifestyle interventions may be successful and the lifelong risk for complications is greatest. Treatment usually begins with dietary modification, weight loss, and a structured program of physical exercise. Oral antidiabetic agents are added when lifestyle intervention alone fails to maintain glycemic control. Given the natural history of type 2 diabetes, most if not all patients will eventually require insulin therapy. In those requiring insulin, improved glycemic control and reduced frequency of hypoglycemia can be achieved with insulin analogs. It is common to add insulin therapy to existing oral therapy only when oral agents no longer provide adequate glycemic control. Introduction The incidence of type 2 diabetes in children and adolescents has reached epidemic proportions in the United States.[1] Recent reports indicate that as many as 45% of pediatric patients diagnosed with diabetes in the United States have type 2 diabetes.[1] Furthermore, the prevalence of type 2 diabetes may be underestimated due to misclassification of the disease.[2] Prior to the late 1990s, only 1% to 2% of children diagnosed with diabetes mellitus in the United States had type 2 diabetes. Since then, owing to a

  14. Diagnosis and treatment of pediatric nonalcoholic steatohepatitis and the implications for bariatric surgery.

    PubMed

    Pardee, Perrie E; Lavine, Joel E; Schwimmer, Jeffrey B

    2009-08-01

    This review focuses on the diagnosis, risk factors, prevalence, pathogenesis and treatment of pediatric nonalcoholic steatohepatitis (NASH). NASH is a progressive form of nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease in children. The factors that account for differences between children with NASH and children with milder forms of NAFLD are unclear. The diagnosis of NASH requires interpretation of liver histology because no noninvasive markers predict the presence or severity of NASH. There is no proven treatment for NASH. Several clinical trials for NAFLD are in progress; however, clinical trials focusing on NASH are needed. Heightened physician awareness of NAFLD, NASH, and associated risk factors is important to identify and treat affected children.

  15. Diagnosis and Treatment of Pediatric Nonalcoholic Steatohepatitis and the Implications for Bariatric Surgery

    PubMed Central

    Pardee, Perrie E.; Lavine, Joel E.; Schwimmer, Jeffrey B.

    2009-01-01

    This review focuses on the diagnosis, risk factors, prevalence, pathogenesis and treatment of pediatric nonalcoholic steatohepatitis (NASH). NASH is a progressive form of nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease in children. The factors that account for differences between children with NASH versus children with milder forms of NAFLD are unclear. The diagnosis of NASH requires interpretation of liver histology because no noninvasive markers predict the presence or severity of NASH. There is no proven treatment for NASH. Several clinical trials for NAFLD are in progress, however, clinical trials focusing on NASH are needed. Heightened physician awareness of NAFLD, NASH, and associated risk factors is important to identify and treat affected children. PMID:19573756

  16. Pulmonary Tuberculous: Symptoms, diagnosis and treatment. 19-year experience in a third level pediatric hospital

    PubMed Central

    2014-01-01

    Background Pulmonary tuberculosis (PTB) is an infectious disease that involves the lungs and can be lethal in many cases. Tuberculosis (TB) in children represents 5 to 20% of the total TB cases. However, there are few updated information on pediatric TB, reason why the objective of the present study is to know the real situation of PTB in the population of children in terms of its diagnosis and treatment in a third level pediatric hospital. Methods A retrospective study based on a revision of clinical files of patients less than 18 years old diagnosed with PTB from January 1994 to January 2013 at Instituto Nacional de Pediatria, Mexico City was carried out. A probable diagnosis was based on 3 or more of the following: two or more weeks of cough, fever, tuberculin purified protein derivative (PPD) +, previous TB exposure, suggestive chest X-ray, and favorable response to treatment. Definitive diagnosis was based on positive acid-fast bacilli (AFB) or culture. Results In the 19-year period of revision, 87 children were diagnosed with PTB; 57 (65.5%) had bacteriologic confirmation with ZN staining or culture positive (in fact, 22 were ZN and culture positive), and 30 (34.5%) had a probable diagnosis; 14(16.1%) were diagnosed with concomitant disease, while 69/81 were immunized. Median evolution time was 21 days (5–150). Fever was found in 94.3%, cough in 77%, and weight loss in 55.2%. History of contact with TB was established in 41.9%. Chest X-ray showed consolidation in 48.3% and mediastinal lymph node in 47.1%. PPD was positive in 59.2%, while positive AFB was found in 51.7% cases. Culture was positive in 24/79 patients (30.4%), PCR in 20/27 (74.1%). 39 (44.8%) patients were treated with rifampin, isoniazid, and pyrazinamide while 6 (6.9%) received the former drugs plus streptomycin and 42 (48.3%) the former plus ethambutol. There were three deaths. Conclusions PTB in pediatric population represents a diagnostic challenge for the fact that clinical

  17. [Narcolepsy with cataplexy: an autoimmune disease?].

    PubMed

    Jacob, Louis; Dauvilliers, Yves

    2014-12-01

    Narcolepsy type 1 (also named narcolepsy-cataplexy or hypocretin deficiency syndrome) is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy, plus frequently hypnagogic hallucinations, sleep paralysis and nocturnal sleep disturbances. Narcolepsy type 1 is an immune system-associated disease linked with the destruction of 70.000-90.000 hypocretin neurons notably involved in wakefulness. Among narcoleptic patients, 98% are positive for HLA-DQB1*06:02, a HLA class II allele, against 20-25% in general population. Individuals carrying HLA-DQB1*06:02 have an extraordinary risk to develop narcolepsy (odd ratio: 251). Other genes involved in CD4+ T cells and immune system activation as T-cell receptor α are also associated with narcolepsy. The development of the disease is linked with environmental factors such as influenza and streptococcal infections. Narcolepsy type 1 incidence also increased in Europe following the use of Pandemrix, a 2009 H1N1 AS03-adjuvanted vaccine manufactured by GlaxoSmithKline. Interestingly, such increase was not observed with Arepanrix, another vaccine developed by GSK very similar to Pandemrix.

  18. Urine Toxicology Screen in Multiple Sleep Latency Test: The Correlation of Positive Tetrahydrocannabinol, Drug Negative Patients, and Narcolepsy

    PubMed Central

    Dzodzomenyo, Samuel; Stolfi, Adrienne; Splaingard, Deborah; Earley, Elizabeth; Onadeko, Oluwole; Splaingard, Mark

    2015-01-01

    Objective: Drugs can influence results of multiple sleep latency tests (MSLT). We sought to identify the effect of marijuana on MSLT results in pediatric patients evaluated for excessive daytime sleepiness (EDS). Methods: This is a retrospective study of urine drug screens performed the morning before MSLT in 383 patients < 21 years old referred for EDS. MSLT results were divided into those with (1) (−) urine drug screens, (2) urine drug screens (+) for tetrahydrocannabinol (THC) alone or THC plus other drugs, and (3) urine drug screens (+) for drugs other than THC. Groups were compared with Fisher exact tests or one-way ANOVA. Results: 38 (10%) urine drug tests were (+): 14 for THC and 24 for other drugs. Forty-three percent of patients with drug screen (+) for THC had MSLT findings consistent with narcolepsy, 0% consistent with idiopathic hypersomnia, 29% other, and 29% normal. This was statistically different from those with (−) screens (24% narcolepsy, 20% idiopathic hypersomnia, 6% other, 50% normal), and those (+) for drugs other than THC (17% narcolepsy, 33% idiopathic hypersomnia, 4% other, 46% normal (p = 0.01). Six percent (6/93) of patients with MSLT findings consistent with narcolepsy were drug screen (+) for THC; 71% of patients with drug screen (+) for THC had multiple sleep onset REM periods (SOREMS). There were no (+) urine drug screens in patients < 13 years old. Conclusion: Many pediatric patients with (+) urine drug screens for THC met MSLT criteria for narcolepsy or had multiple SOREMs. Drug screening is important in interpreting MSLT findings for children ≥ 13 years. Citation: Dzodzomenyo S, Stolfi A, Splaingard D, Earley E, Onadeko O, Splaingard M. Urine toxicology screen in multiple sleep latency test: the correlation of positive tetrahydrocannabinol, drug negative patients, and narcolepsy. J Clin Sleep Med 2015;11(2):93–99. PMID:25348245

  19. Diagnosis of cardiac disease in pediatric end-stage renal disease

    PubMed Central

    Chavers, Blanche M.; Solid, Craig A.; Sinaiko, Alan; Daniels, Frank X.; Chen, Shu-Cheng; Collins, Allan J.; Frankenfield, Diane L.; Herzog, Charles A.

    2011-01-01

    Background. Cardiac disease is a significant cause of morbidity and mortality in children with end-stage renal disease (ESRD). This study aimed to report the frequency of cardiac disease diagnostic methods used in US pediatric maintenance hemodialysis patients. Methods. A cross-sectional analysis of all US pediatric (ages 0.7–18 years, n = 656) maintenance hemodialysis patients was performed using data from the Centers for Medicare and Medicaid Services ESRD Clinical Performance Measures Project. Clinical and laboratory information was collected in 2001. Results were analysed by age, sex, race, Hispanic ethnicity, dialysis duration, body mass index (BMI), primary ESRD cause and laboratory data. Results. Ninety-two percent of the patients had a cardiovascular risk factor (63% hypertension, 38% anemia, 11% BMI > 94th percentile, 63% serum phosphorus > 5.5 mg/dL and 55% calcium–phosphorus product ≥ 55 mg2/dL2). A diagnosis of cardiac disease was reported in 24% (n = 155) of all patients: left ventricular hypertrophy/enlargement 17%, congestive heart failure/pulmonary edema 8%, cardiomyopathy 2% and decreased left ventricular function 2%. Thirty-one percent of patients were not tested. Of those tested, the diagnostic methods used were chest X-rays in 60%, echocardiograms in 35% and electrocardiograms in 33%; left ventricular hypertrophy/enlargement was diagnosed using echocardiogram (72%), chest X-ray (20%) and electrocardiogram (15%). Conclusions. Although 92% of patients had cardiovascular risk factors, an echocardiography was performed in only one-third of the patients. Our study raises the question of why echocardiography, considered the gold standard for cardiac disease diagnosis, has been infrequently used in pediatric maintenance dialysis patients, a high-risk patient population. PMID:20861193

  20. Prediction of esophageal and gastric histology by macroscopic diagnosis during upper endoscopy in pediatric celiac disease

    PubMed Central

    Boschee, Erin D; Yap, Jason Y K; Turner, Justine M

    2017-01-01

    AIM To determine the sensitivity of macroscopic appearance for predicting histological diagnosis at sites other than duodenum in pediatric celiac disease (CD). METHODS Endoscopic and histologic findings in pediatric patients undergoing upper endoscopy for first-time diagnosis of CD at Stollery Children’s Hospital from 2010-2012 were retrospectively reviewed. RESULTS Clinical charts from 140 patients were reviewed. Esophageal and gastric biopsies were taken in 54.3% and 77.9% of patients, respectively. Endoscopic appearance was normal in the esophagus and stomach in 75% and 86.2%. Endoscopic esophageal diagnoses were eosinophilic esophagitis (EE) (11.8%), esophagitis (7.9%), glycogenic acanthosis (1.3%) and non-specific abnormalities (3.9%). Endoscopic gastric diagnoses were gastritis (8.3%), pancreatic rest (0.9%), and non-specific abnormalities (4.6%). Histology was normal in 76.3% of esophageal and 87.2% of gastric specimens. Abnormal esophageal histology was EE (10.5%), esophagitis (10.5%), glycogenic acanthosis (1.3%) and non-specific (1.3%). Gastritis was reported in 12.8% of specimens. Sensitivity and specificity of normal endoscopy for predicting normal esophageal histology was 86.2% and 61.1%, and for normal gastric histology was 87.4% and 21.4%. CONCLUSION In the absence of macroscopic abnormalities, routine esophageal and gastric biopsy during endoscopy for pediatric CD does not identify major pathologies. These findings have cost and time saving implications for clinical practice. PMID:28216971

  1. Ultrasound-guided core needle biopsy in diagnosis of abdominal and pelvic neoplasm in pediatric patients.

    PubMed

    Wang, Hailing; Li, Fangxuan; Liu, Juntian; Zhang, Sheng

    2014-01-01

    Ultrasound-guided core needle biopsy of abdominal and pelvic masses in adults has gained tremendous popularity. However, the application of the same treatment in children is not as popular because of apprehensions regarding inadequate tissues for the biopsy and accidental puncture of vital organs. Data of the application of ultrasound-guided core needle biopsy in 105 pediatric patients with clinically or ultrasound-diagnosed abdominopelvic masses were reviewed. Diagnostic procedures were conducted in our institution from May 2011 to May 2013. The biopsies were conducted on 86 malignant lesions and 19 benign lesions. 86 malignant tumors comprised neuroblastomas (30 cases), hepatoblastomas (15 cases), nephroblastomas (11 cases), and primitive neuroectodermal tumors/malignant small round cells (6 cases). Among malignant tumor cases, only a pelvic primitive neuroectodermal tumor did not receive a pathological diagnosis. Therefore, the biopsy accuracy was 98.8 % in malignant tumor. However, the biopsies for one neuroblastomas and one malignant small round cell tumor were inadequate for cytogenetic analysis. Therefore, 96.5 % of the malignant tumor patients received complete diagnosis via biopsy. 19 benign tumors comprised mature teratoma (10 cases), hemangioendothelioma (3 cases), paraganglioma (2 cases), and infection (2 cases). The diagnostic accuracy for benign neoplasm was 100 %. Five patients experienced postoperative complications, including pain (2 patients), bleeding from the biopsy site (2 patients), and wound infection (1 patient). Ultrasound-guided core needle biopsy is an efficient, minimally invasive, accurate, and safe diagnostic method that can be applied in the management of abdominal or pelvic mass of pediatric patients.

  2. Pediatrics

    NASA Technical Reports Server (NTRS)

    Spackman, T. J.

    1978-01-01

    The utilization of the Lixiscope in pediatrics was investigated. The types of images that can presently be obtained are discussed along with the problems encountered. Speculative applications for the Lixiscope are also presented.

  3. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia.

    PubMed

    Ma, Xiaotu; Edmonson, Michael; Yergeau, Donald; Muzny, Donna M; Hampton, Oliver A; Rusch, Michael; Song, Guangchun; Easton, John; Harvey, Richard C; Wheeler, David A; Ma, Jing; Doddapaneni, HarshaVardhan; Vadodaria, Bhavin; Wu, Gang; Nagahawatte, Panduka; Carroll, William L; Chen, I-Ming; Gastier-Foster, Julie M; Relling, Mary V; Smith, Malcolm A; Devidas, Meenakshi; Guidry Auvil, Jaime M; Downing, James R; Loh, Mignon L; Willman, Cheryl L; Gerhard, Daniela S; Mullighan, Charles G; Hunger, Stephen P; Zhang, Jinghui

    2015-03-19

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden. Six pathways were frequently mutated, with NT5C2, CREBBP, WHSC1, TP53, USH2A, NRAS and IKZF1 mutations enriched at relapse. Half of the leukaemias had multiple subclonal mutations in a pathway or gene at diagnosis, but mostly with only one, usually minor clone, surviving therapy to acquire additional mutations and become the relapse founder clone. Relapse-specific mutations in NT5C2 were found in nine cases, with mutations in four cases being in descendants of the relapse founder clone. These results provide important insights into the genetic basis of treatment failure in ALL and have implications for the early detection of mutations driving relapse.

  4. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia

    PubMed Central

    Ma, Xiaotu; Edmonson, Michael; Yergeau, Donald; Muzny, Donna M.; Hampton, Oliver A.; Rusch, Michael; Song, Guangchun; Easton, John; Harvey, Richard C.; Wheeler, David A.; Ma, Jing; Doddapaneni, HarshaVardhan; Vadodaria, Bhavin; Wu, Gang; Nagahawatte, Panduka; Carroll, William L.; Chen, I-Ming; Gastier-Foster, Julie M.; Relling, Mary V.; Smith, Malcolm A.; Devidas, Meenakshi; Auvil, Jaime M. Guidry; Downing, James R.; Loh, Mignon L.; Willman, Cheryl L.; Gerhard, Daniela S.; Mullighan, Charles G.; Hunger, Stephen P.; Zhang, Jinghui

    2015-01-01

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden. Six pathways were frequently mutated, with NT5C2, CREBBP, WHSC1, TP53, USH2A, NRAS and IKZF1 mutations enriched at relapse. Half of the leukaemias had multiple subclonal mutations in a pathway or gene at diagnosis, but mostly with only one, usually minor clone, surviving therapy to acquire additional mutations and become the relapse founder clone. Relapse-specific mutations in NT5C2 were found in nine cases, with mutations in four cases being in descendants of the relapse founder clone. These results provide important insights into the genetic basis of treatment failure in ALL and have implications for the early detection of mutations driving relapse. PMID:25790293

  5. High Prevalence of Precocious Puberty and Obesity in Childhood Narcolepsy with Cataplexy

    PubMed Central

    Poli, Francesca; Pizza, Fabio; Mignot, Emmanuel; Ferri, Raffaele; Pagotto, Uberto; Taheri, Shahrad; Finotti, Elena; Bernardi, Filippo; Pirazzoli, Piero; Cicognani, Alessandro; Balsamo, Antonio; Nobili, Lino; Bruni, Oliviero; Plazzi, Giuseppe

    2013-01-01

    Study Objectives: We analyzed the potential predictive factors for precocious puberty, observed in some cases of childhood narcolepsy with cataplexy (NC) and for obesity, a much more common feature of NC, through a systematic assessment of pubertal staging, body mass index (BMI), and metabolic/endocrine biochemical analyses. Design: Cross-sectional on consecutive recruitment. Setting: Hospital sleep center and pediatric unit. Patients: Forty-three children and adolescents with NC versus 52 age-matched obese children as controls. Interventions: N/A. Measurements and Results: Patients underwent clinical interview, polysomnographic recordings, cerebrospinal fluid hypocretin-1 measurement, and human leukocyte antigen typing. Height, weight, arterial blood pressure, and Tanner pubertal stage were evaluated. Plasma lipid and glucose profiles were analyzed. When an altered pubertal development was clinically suspected, plasma concentrations of hypothalamic-pituitary-gonadal axis hormones were determined. Children with NC showed a high prevalence of overweight/obesity (74%) and a higher occurrence of precocious puberty (17%) than obese controls (1.9%). Isolated signs of accelerated pubertal development (thelarche, pubic hair, advanced bone age) were also present (41%). Precocious puberty was significantly predicted by a younger age at first NC symptom onset but not by overweight/obesity or other factors. In addition, overweight/obesity was predicted by younger age at diagnosis; additional predictors were found for overweight/obesity (short disease duration, younger age at weight gain and lower high-density lipoprotein cholesterol), which did not include precocious puberty. NC symptoms, pubertal signs appearance, and body weight gain developed in close temporal sequence. Conclusions: NC occurring during prepubertal age is frequently accompanied by precocious puberty and overweight/obesity, suggesting an extended hypothalamic dysfunction. The severity of these comorbidities

  6. An Algorithmic Approach Using Ultrasonography in the Diagnosis of Pediatric Nasal Bone Fracture.

    PubMed

    Tamada, Ikkei; Mori, Takaaki; Inoue, Nobuaki; Shido, Hirokazu; Aoki, Marie; Nakamura, Yukie; Kamogawa, Ruri

    2017-01-01

    Ultrasonography (US) was recently reported as a reliable modality for diagnosing nasal bone fractures. However, whether US is reliable as a screening tool in the pediatric emergency department (ED) remains unknown. This prospective cohort study had a 2-fold aim: to assess the utility of US in the diagnosis of pediatric nasal bone fracture, and to evaluate the validity of our protocol for managing pediatric nasal bone fractures (Fuchu-Kids algorithm). Among the patients who presented at the ED with facial trauma, those with a suspected nasal bone fracture were enrolled in the study. Patients were treated according to Fuchu-Kids algorithm, and the validity of the protocol using US imaging was evaluated. Among 81 patients who were enrolled during the 1-year study period, 63 patients were able to complete the process described in our protocol for further examination. The diagnostic power of the Fuchu-Kids algorithm had a sensitivity of 91.7%, a specificity of 92.3%, a positive predictive value (PPV) of 88%, and a negative predictive value (NPV) of 94.7%. However, when the performance of US was assessed as a single examination, its sensitivity, specificity, PPV, and NPV were 75%, 92.3%, 85.7%, and 85.7%, respectively. Using our algorithm, the majority of patients with nasal bone fracture were successfully diagnosed and screened out successfully. Repeated US imaging is effective when clinical symptoms persist even if the first US imaging was negative for nasal bone fracture. However, a detailed medical interview and clinical examination are mandatory, regardless of the use of US.

  7. Diagnosis and Treatment of Pediatric Acquired Aplastic Anemia (AAA): an Initial Survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC)

    PubMed Central

    Williams, David A.; Bennett, Carolyn; Bertuch, Alison; Bessler, Monica; Coates, Thomas; Corey, Seth; Dror, Yigal; Huang, James; Lipton, Jeffrey; Olson, Timothy S.; Reiss, Ulrike M.; Rogers, Zora R.; Sieff, Colin; Vlachos, Adrianna; Walkovich, Kelly; Wang, Winfred; Shimamura, Akiko

    2014-01-01

    Background Randomized clinical trials in pediatric aplastic anemia (AA) are rare and data to guide standards of care are scarce. Procedure Eighteen pediatric institutions formed the North American Pediatric Aplastic Anemia Consortium to foster collaborative studies in AA. The initial goal of NAPAAC was to survey the diagnostic studies and therapies utilized in AA. Results Our survey indicates considerable variability among institutions in the diagnosis and treatment of AA. There were areas of general consensus, including the need for a bone marrow evaluation, cytogenetic and specific fluorescent in-situ hybridization assays to establish diagnosis and exclude genetic etiologies with many institutions requiring results prior to initiation of immunosuppressive therapy (IST); uniform referral for hematopoietic stem cell transplantation as first line therapy if an HLA-identical sibling is identified; the use of first-line IST containing horse anti-thymocyte globulin and cyclosporine A (CSA) if an HLA-identical sibling donor is not identified; supportive care measures; and slow taper of CSA after response. Areas of controversy included the need for telomere length results prior to IST, the time after IST initiation defining a treatment failure; use of hematopoietic growth factors; the preferred rescue therapy after failure of IST; the use of specific hemoglobin and platelet levels as triggers for transfusion support; the use of prophylactic antibiotics; and follow-up monitoring after completion of treatment. Conclusions These initial survey results reflect heterogeneity in diagnosis and care amongst pediatric centers and emphasize the need to develop evidence-based diagnosis and treatment approaches in this rare disease. PMID:24285674

  8. Diagnosis and treatment of pediatric acquired aplastic anemia (AAA): an initial survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC).

    PubMed

    Williams, David A; Bennett, Carolyn; Bertuch, Alison; Bessler, Monica; Coates, Thomas; Corey, Seth; Dror, Yigal; Huang, James; Lipton, Jeffrey; Olson, Timothy S; Reiss, Ulrike M; Rogers, Zora R; Sieff, Colin; Vlachos, Adrianna; Walkovich, Kelly; Wang, Winfred; Shimamura, Akiko

    2014-05-01

    Randomized clinical trials in pediatric aplastic anemia (AA) are rare and data to guide standards of care are scarce. Eighteen pediatric institutions formed the North American Pediatric Aplastic Anemia Consortium to foster collaborative studies in AA. The initial goal of NAPAAC was to survey the diagnostic studies and therapies utilized in AA. Our survey indicates considerable variability among institutions in the diagnosis and treatment of AA. There were areas of general consensus, including the need for a bone marrow evaluation, cytogenetic and specific fluorescent in situ hybridization assays to establish diagnosis and exclude genetic etiologies with many institutions requiring results prior to initiation of immunosuppressive therapy (IST); uniform referral for hematopoietic stem cell transplantation as first line therapy if an HLA-identical sibling is identified; the use of first-line IST containing horse anti-thymocyte globulin and cyclosporine A (CSA) if an HLA-identical sibling donor is not identified; supportive care measures; and slow taper of CSA after response. Areas of controversy included the need for telomere length results prior to IST, the time after IST initiation defining a treatment failure; use of hematopoietic growth factors; the preferred rescue therapy after failure of IST; the use of specific hemoglobin and platelet levels as triggers for transfusion support; the use of prophylactic antibiotics; and follow-up monitoring after completion of treatment. These initial survey results reflect heterogeneity in diagnosis and care amongst pediatric centers and emphasize the need to develop evidence-based diagnosis and treatment approaches in this rare disease. © 2013 Wiley Periodicals, Inc.

  9. History of narcolepsy at Stanford University.

    PubMed

    Mignot, Emmanuel J M

    2014-05-01

    Although narcolepsy was first described in the late nineteenth century in Germany and France, much of the research on this disorder has been conducted at Stanford University, starting with Drs. William C. Dement and Christian Guilleminault in the 1970s. The prevalence of narcolepsy was established, and a canine model discovered. Following the finding in Japan that almost all patients with narcolepsy carry a specific HLA subtype, HLA-DR2, Hugh Mac Devitt, F. Carl Grumet, and Larry Steinman initiated immunological studies, but results were generally negative. Using the narcoleptic canines, Dr. Nishino and I established that stimulants increased wakefulness by stimulating dopaminergic transmission while antidepressants suppress cataplexy via adrenergic reuptake inhibition. A linkage study was initiated with Dr. Grumet in 1988, and after 10 years of work, the canine narcolepsy gene was cloned by in 1999 and identified as the hypocretin (orexin) receptor 2. In 1992, studying African Americans, we also found that DQ0602 rather than DR2 was a better marker for narcolepsy across all ethnic groups. In 2000, Dr. Nishino and I, in collaboration with Dr. Lammers in the Netherlands, found that hypocretin 1 levels in the cerebrospinal fluid (CSF) were undetectable in most cases, establishing hypocretin deficiency as the cause of narcolepsy. Pursuing this research, our and Dr. Siegel's group, examining postmortem brains, found that the decreased CSF hypocretin 1 was secondary to the loss the 70,000 neurons producing hypocretin in the hypothalamus. This finding revived the autoimmune hypothesis but attempts at demonstrating immune targeting of hypocretin cells failed until 2013. At this date, Dr. Elisabeth Mellins and I discovered that narcolepsy is characterized by the presence of autoreactive CD4(+) T cells to hypocretin fragments when presented by DQ0602. Following reports that narcolepsy cases were triggered by vaccinations and infections against influenza A 2009 pH1N1, a new

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

    PubMed

    Dauvilliers, Yves; Arnulf, Isabelle; Lecendreux, Michel; Monaca Charley, Christelle; Franco, Patricia; Drouot, Xavier; d'Ortho, Marie-Pia; Launois, Sandrine; Lignot, Séverine; Bourgin, Patrice; Nogues, Béatrice; Rey, Marc; Bayard, Sophie; Scholz, Sabine; Lavault, Sophie; Tubert-Bitter, Pascale; Saussier, Cristel; Pariente, Antoine

    2013-08-01

    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

  11. Spectral Analysis of Polysomnography in Narcolepsy

    PubMed Central

    Yun, Seok Ho; Choi, Ho Dong

    2017-01-01

    Objective This study was conducted to identify differences between people with narcolepsy and the normal control of delta and theta activity using electroencephalogram (EEG) spectrum analysis of nocturnal polysomnography (PSG). Methods Seven narcolepsy patients and seven age-sex matched normal controls underwent PSG and multiple sleep latency tests. Participants' non-rapid eye movement (NREM) sleep EEGs in PSG was analyzed using a Fast Fourier Transform technique. Results While NREM delta activity of people with narcolepsy declined during the first three periods of NREM, there was no change during the 4th period of NREM. The increase in NREM theta activity also lasted until the 3rd period of NREM but did not occur during the 4th period of NREM. In comparing sleep parameters, REM sleep latency in the narcolepsy group was significantly shorter than in controls. Conclusion These results suggest that people with narcolepsy are likely to have a delta and theta activity-related sleep disturbance mechanism in NREM sleep. PMID:28326118

  12. Narcolepsy: current treatment options and future approaches.

    PubMed

    Billiard, Michel

    2008-06-01

    The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy.

  13. Emotion stimulus processing in narcolepsy with cataplexy.

    PubMed

    Susta, Marek; Nemcova, Veronika; Bizik, Gustav; Sonka, Karel

    2017-02-01

    Reported brain abnormalities in anatomy and function in patients with narcolepsy with cataplexy led to a project based on qualitative electroencephalography examination and analysis in an attempt to find a narcolepsy with cataplexy-specific brain-derived pattern, or a sequence of brain locations involved in processing humorous stimuli. Laughter is the trigger of cataplexy in these patients, and the difference between patients and healthy controls during the laughter should therefore be notable. Twenty-six adult patients (14 male, 12 female) suffering from narcolepsy with cataplexy and 10 healthy controls (five male, five female) were examined. The experiment was performed using a 256-channel electroencephalogram and then processed using specialized software built according to the scientific research team's specifications. The software utilizes electroencephalographic data recorded during elevated emotional states in participants to calculate the sequence of brain areas involved in emotion processing using non-linear and linear algorithms. Results show significant differences in activation (pre-laughter) patterns between the patients with narcolepsy and healthy controls, as well as significant similarities within the patients and the controls. Specifically, gyrus orbitalis, rectus and occipitalis inferior are active in healthy controls, while gyrus paracentralis, cingularis and cuneus are activated solely in the patients in response to humorous audio stimulus. There are qualitative electroencephalographic-based patterns clearly discriminating between patients with narcolepsy and healthy controls during laughter processing. © 2016 European Sleep Research Society.

  14. Investigational therapies for the treatment of narcolepsy.

    PubMed

    de Biase, Stefano; Nilo, Annacarmen; Gigli, Gian Luigi; Valente, Mariarosaria

    2017-08-01

    Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. While non-pharmacological treatments are sometimes helpful, more than 90% of narcoleptic patients require a pharmacological treatment. Areas covered: The present review is based on an extensive Internet and PubMed search from 1994 to 2017. It is focused on drugs currently in development for the treatment of narcolepsy. Expert opinion: Currently there is no cure for narcolepsy, with treatment focusing on symptoms control. However, these symptomatic treatments are often unsatisfactory. The research is leading to a better understanding of narcolepsy and its symptoms. New classes of compounds with possible applications in the development of novel stimulant/anticataplectic medications are described. H3 receptor antagonists represent a new therapeutic option for EDS in narcolepsy. JZP-110, with its distinct mechanism of action, would be a new therapeutic option for the treatment of EDS in the coming years. In the future, hypocretin-based therapies and immune-based therapies, could modify the clinical course of the disease. However, more information would be necessary to completely understand the autoimmune process and also how this process can be altered for therapeutic benefits.

  15. Types of pediatric diabetes mellitus defined by anti-islet autoimmunity and random C-peptide at diagnosis

    USDA-ARS?s Scientific Manuscript database

    The objective of this study was to test the hypothesis that anti-islet autoantibody expression and random serum C-peptide obtained at diagnosis define phenotypes of pediatric diabetes with distinct clinical features. We analyzed 607 children aged <19 yr consecutively diagnosed with diabetes after ex...

  16. To CT or not to CT? The influence of computed tomography on the diagnosis of appendicitis in obese pediatric patients

    PubMed Central

    Roy, Haven; Burbridge, Brent

    2015-01-01

    Background Appendicitis is a common pediatric query. However, obesity often results in nondiagnostic ultrasounds and increased likelihood of abdominal computed tomography (CT). Concern regarding radiation exposure led the Canadian Association of Radiologists to recommend foregoing CT when ultrasounds are nondiagnostic and clinical suspicion is high. We evaluated this recommendation by quantifying the influence of CT on the diagnosis of pediatric appendicitis. Methods We performed a 2-year retrospective case series of children presenting with suspected appendicitis. We stratified patients by weight (obese v. nonobese) and pediatric appendicitis score (PAS) and examined how often they received abdominal CT, why they received it, and its influence on diagnosis. Results Of 223 patients (84 obese, 139 nonobese), 54 received CT. Obese patients received CTs more frequently than nonobese patients (29% v. 22%). The most common reason for CT was a nondiagnostic ultrasound (75% in obese, 80% in nonobese patients). Sixty-five percent of CTs obtained after nondiagnostic ultrasounds confirmed the initial diagnosis, but the rates were 80% and 50%, respectively, when only obese and only nonobese patients were considered. Obese patients were 4 times more likely to have a CT confirming their initial appendicitis diagnosis. Conclusion Because obese patients are more likely than nonobese patients to have a CT that confirms appendicitis, when treating an obese pediatric patient with suspected appendicitis and a nondiagnostic ultrasound, surgeons with a high clinical suspicion should strongly consider foregoing CT and proceeding with treatment. PMID:26011850

  17. The role of bronchoscopy in the diagnosis and management of pediatric pulmonary tuberculosis.

    PubMed

    Goussard, Pierre; Gie, Robert

    2014-02-01

    Pulmonary tuberculosis (TB) is the commonest clinical form of childhood TB occurring in approximately 80% of cases. Traditionally, bronchoscopy in pediatric TB suspects was used to collect specimens for mycobacterial culture using especially bronchoalveolar lavage. New data have described the role of bronchoscopy as a more comprehensive instrument for the diagnosis and management of pulmonary TB in children. Flexible bronchoscopy is an important intervention to evaluated airways disease, collect samples for culture, relieve critical threatening airway obstruction and aid in the management of complicated pulmonary TB disease in children. Airway involvement in children suspected of pulmonary TB has been described in 41-63% of cases. The commonest airways involved are bronchus intermedius, left main bronchus and the trachea. Bronchoscopy is safe in children with severe airway obstruction. As bronchoscope images improve, the working channel size increases new applications for bronchoscopy will be developed making them more applicable in small children.

  18. Exploiting molecular biology for diagnosis and targeted management of pediatric low-grade gliomas.

    PubMed

    Garcia, Michael A; Solomon, David A; Haas-Kogan, Daphne A

    2016-06-01

    The majority of brain tumors arising in children are low-grade gliomas. Although historically categorized together as pediatric low-grade gliomas (PLGGs), there is significant histologic and genetic diversity within this group. In general, prognosis for PLGGs is excellent, and limitation of sequelae from tumor and treatment is paramount. Advances in high-throughput genetic sequencing and gene expression profiling are fundamentally changing the way PLGGs are classified and managed. Here, we review the histologic subtypes and highlight how recent advances in elucidating the molecular pathogenesis of these tumors have refined diagnosis and prognostication. Additionally, we discuss how characterizing specific genetic alterations has paved the way for the rational use of targeted therapies that are currently in various phase clinical trials.

  19. Management of pediatric intussusception in general hospitals: diagnosis, treatment, and differences based on age.

    PubMed

    Shekherdimian, Shant; Lee, Steven L

    2011-02-01

    age related differences in the management and outcomes of children with ileocolic intussusception have not been previously published. The purpose of this study is to compare the differences in diagnosis and treatment of pediatric ileocolic intussusception based upon age in general hospitals. a review was made of pediatric patients treated for intussusception at 11 hospitals between 1996 and 2007. The patients were divided into 3 groups based on age: group A: <6 months (n=37), group B: 6 months to 4 years (n=126), group C: >4 years (n=25). Diagnostic modality, operative reports, and hospital records were reviewed. altogether 188 patients were treated for ileocolic intussusception. Contrast enema was performed in 80.3% of the patients. Initial treatment for the patients included contrast enema in 80.3%, immediate operation in 3.2%, and others in 16.5%. Older patients were less likely to undergo a contrast enema (P<0.05) but more likely to be successfully reduced. Patients in group A had the lowest rate of successful reduction (P<0.05). Overall, 3.2% of the patients were taken to the operating room without any diagnostic evaluations, but 65% of the patients ultimately required operative intervention. Patients in groups A and C were more likely to undergo an operation (P<0.05). Rates of bowel resection and length of hospital stay were similar among the three groups. enema reduction for ileocolic intussusception is moderately successful in general hospitals and lower than that reported in children's hospitals. The lowest reduction rate occurs in patients of less than 6 months old and the diagnosis of intussusception in older children is rarely made by contrast enema. There is a higher operative rate in children of less than 6 months or older than 4 years and the rate of intestinal resection is higher than that in children's hospitals.

  20. Variation in the Diagnosis and Management of Appendicitis at Canadian Pediatric Hospitals.

    PubMed

    Thompson, Graham C; Schuh, Suzanne; Gravel, Jocelyn; Reid, Sarah; Fitzpatrick, Eleanor; Turner, Troy; Bhatt, Maala; Beer, Darcy; Blair, Geoffrey; Eccles, Robin; Jones, Sarah; Kilgar, Jennifer; Liston, Natalia; Martin, John; Hagel, Brent; Nettel-Aguirre, Alberto

    2015-07-01

    The objective was to characterize the variations in practice in the diagnosis and management of children admitted to hospitals from Canadian pediatric emergency departments (EDs) with suspected appendicitis, specifically the timing of surgical intervention, ED investigations, and management strategies. Twelve sites participated in this retrospective health record review. Children aged 3 to 17 years admitted to the hospital with suspected appendicitis were eligible. Site-specific demographics, investigations, and interventions performed were recorded and compared. Factors associated with after-hours surgery were determined using generalized estimating equations logistic regression. Of the 619 children meeting eligibility criteria, surgical intervention was performed in 547 (88%). After-hours surgery occurred in 76 of the 547 children, with significant variation across sites (13.9%, 95% confidence interval = 7.1% to 21.6%, p < 0.001). The overall perforation rate was 17.4% (95 of 547), and the negative appendectomy rate was 6.8% (37 of 547), varying across sites (p = 0.004 and p = 0.036, respectively). Use of inflammatory markers (p < 0.001), blood cultures (p < 0.001), ultrasound (p = 0.001), and computed tomography (p = 0.001) also varied by site. ED administration of narcotic analgesia and antibiotics varied across sites (p < 0.001 and p = 0.001, respectively), as did the type of surgical approach (p < 0.001). After-hours triage had a significant inverse association with after-hours surgery (p = 0.014). Across Canadian pediatric EDs, there exists significant variation in the diagnosis and management of children with suspected appendicitis. These results indicate that the best diagnostic and management strategies remain unclear and support the need for future prospective, multicenter studies to identify strategies associated with optimal patient outcomes. © 2015 by the Society for Academic Emergency Medicine.

  1. Narcolepsy Type 1 and Idiopathic Generalized Epilepsy: Diagnostic and Therapeutic Challenges in Dual Cases.

    PubMed

    Baiardi, Simone; Vandi, Stefano; Pizza, Fabio; Alvisi, Lara; Toscani, Lucia; Zambrelli, Elena; Tinuper, Paolo; Mayer, Geert; Plazzi, Giuseppe

    2015-11-15

    The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness. © 2015 American Academy of Sleep Medicine.

  2. Successful treatment of post-traumatic narcolepsy with methylphenidate: a case report.

    PubMed

    Francisco, G E; Ivanhoe, C B

    1996-01-01

    Narcolepsy is a rare sequela of brain injury. We report the case of a 27-yr-old male with post-traumatic narcolepsy who was successfully treated with methylphenidate. This patient sustained moderate brain injury from a motorcycle accident. Subsequently, he manifested the classic tetrad of narcolepsy: cataplexy, excessive daytime sleepiness, sleep paralysis, and hypnogogic hallucinations. There was no premorbid seizure or sleep disorder. There was no family history of sleep disorders. Polysomnography and Multiple Sleep Latency Test confirmed the diagnosis of narcolepsy. Sleep latency (time to sleep onset), rapid eye movement sleep latency (time from sleep onset to rapid eye movement sleep onset), and mean multiple sleep latency were all pathologically shortened (2.5, 66, and 1.2 min, respectively). Twenty-four hour electroencephalographic monitoring and magnetic resonance imaging of the brain were normal, as were serum chemistries. Treatment with caffeine was unsuccessful. He was then started on methylphenidate, 10 mg twice daily, which was increased to 30 mg twice daily over a 4-mo period. Cataplexy and excessive daytime sleepiness started to improve 1 mo after adjustments in methylphenidate dosing. Six months after the initiation of methylphenidate therapy, the patient is completely asymptomatic.

  3. Baclofen for narcolepsy with cataplexy: two cases

    PubMed Central

    Lee, Elliott Kyung; Douglass, Alan Bruce

    2015-01-01

    Narcolepsy is a disabling sleep disorder characterized by daytime hypersomnolence. Those with cataplexy have spells of muscle weakness precipitated by strong emotions, especially laughter or surprise. Cataplexy treatments include antidepressants or a GABA-B agonist, gamma hydroxybutyrate (GHB). GHB is the most effective treatment for cataplexy, but is expensive and can have significant side effects. A recent report of a murine model of narcolepsy-cataplexy suggests R-baclofen has potential efficacy against cataplexy. We report on two narcolepsy patients with multiple daily cataplexy episodes, one of whom had been effectively treated with GHB, but had to discontinue it for unrelated medical reasons. Both subsequently tried baclofen and experienced almost complete resolution of cataplexy. This report suggests baclofen can be an effective treatment for cataplexy in humans and warrants further study. PMID:26251634

  4. The hypocretins and their role in narcolepsy.

    PubMed

    Kroeger, Daniel; de Lecea, Luis

    2009-08-01

    A series of discoveries spanning the last decade have uncovered a new neurotransmitter - hypocretin - and its role in energy metabolism, arousal, and addiction. Also, notably, a lack of hypocretin function has been unequivocally associated with the sleep disorder narcolepsy. Here we review these findings and discuss how they will influence future treatments of narcolepsy and other arousal and hyperarousal disorders. We introduce the concept of the hypocretin peptides and receptors and discuss the neuroanatomy and neurophysiology of the hypocretin system. A gain of function through pharmacolological and optogenetic means is also addressed in the following text, as is the loss of function: specifically narcolepsy in dogs, mice and humans and the challenges currently faced in treatment.

  5. Diagnosis and management of white-coat hypertension in children and adolescents: A Midwest Pediatric Nephrology Consortium study.

    PubMed

    Miyashita, Yosuke; Flynn, Joseph T; Hanevold, Coral D

    2017-09-01

    Although the definition of white-coat hypertension (WCH) in children and adolescents is clearly defined, little is known about how this condition is actually approached clinically. To better understand the contemporary approach to the diagnosis and management of WCH in pediatric patients, the authors surveyed the membership of the Midwest Pediatric Nephrology Consortium. Seventy-four faculty pediatric nephrologists responded to the survey. The survey results demonstrated uniformity in diagnosing WCH, including ambulatory blood pressure monitoring use in 93% of the respondents and a 75% adherence rate according to the 2014 American Heart Association scientific statement on pediatric ambulatory blood pressure monitoring. A total of 85% of respondents would not embark on further diagnostic evaluation once the WCH diagnosis was established, and none would initiate antihypertensive medications. There was a wide variety of practice habits in follow-up of WCH including frequency of office and out-of-office follow-up blood pressure measurements, the setting and timing of physician follow-up, and the role of repeat ambulatory blood pressure monitoring. The results of this survey highlight the need for prospective studies aimed at establishing the optimal approach to pediatric patients with WCH. ©2017 Wiley Periodicals, Inc.

  6. Narcolepsy with Cataplexy Mimicry: The Strange Case of Two Sisters

    PubMed Central

    Pizza, Fabio; Vandi, Stefano; Poli, Francesca; Moghadam, Keivan Kaveh; Franceschini, Christian; Bellucci, Claudia; Cipolli, Carlo; Ingravallo, Francesca; Natalini, Giuliana; Mignot, Emmanuel; Plazzi, Giuseppe

    2013-01-01

    We report on two sisters, 17 and 12 years of age, with clinical features suggesting narcolepsy with cataplexy (NC): daytime sleepiness, spontaneous and emotionally triggered sudden falls to the ground, and overweight/obesity. MSLT showed borderline sleep latency, with 1 and 0 sleep onset REM periods. HLA typing disclosed the DQB1*0602 allele. Video-polygraphy of the spells ruled out NC diagnosis by demonstrating their easy elicitation by suggestion, with wake EEG, electromyo-graphic persistence of muscle tone, and stable presence of tendon reflexes (i.e., pseudo-cataplexy), together with normal cerebrospinal hypocretin-1 levels. Our cases emphasize the need of a clear depiction of cataplexy pattern at the different ages, the usefulness of examining ictal neurophysiology, and collecting all available disease markers in ambiguous cases. Citation: Pizza F; Vandi S; Poli F; Moghadam KK; Fran-ceschini C; Bellucci C; Cipolli C; Ingravallo F; Natalini G; Mignot E; Plazzi G. Narcolepsy with cataplexy mimicry: the strange case of two sisters. J Clin Sleep Med 2013;9(6):611-612. PMID:23772196

  7. Sleep Transitions in Hypocretin-Deficient Narcolepsy

    PubMed Central

    Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

    2013-01-01

    Study Objectives: Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain's sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype. Design: We measured the frequency of transitions in patients with narcolepsy between sleep-wake states and to/from REM and NREM sleep stages. Patients were subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency. Setting: Sleep laboratory studies conducted from 2001-2011. Patients: In total 63 narcolepsy patients were included in the study. Cataplexy was present in 43 of 63 patients and hypocretin-1 deficiency was present in 37 of 57 patients. Measurements and Results: Hypocretin-deficient patients with narcolepsy had a significantly higher frequency of sleep-wake transitions (P = 0.014) and of transitions to/from REM sleep (P = 0.044) than patients with normal levels of hypocretin-1. Patients with cataplexy had a significantly higher frequency of sleep-wake transitions (P = 0.002) than those without cataplexy. A multivariate analysis showed that transitions to/from REM sleep were predicted mainly by hypocretin-1 deficiency (P = 0.011), whereas sleep-wake transitions were predicted mainly by cataplexy (P = 0.001). Conclusions: In human narcolepsy, hypocretin deficiency and cataplexy are both associated with signs of destabilized sleep-wake and REM sleep control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches. Citation: Sorensen GL; Knudsen S; Jennum P. Sleep transitions in hypocretin-deficient narcolepsy. SLEEP 2013;36(8):1173-1177. PMID:23904677

  8. [Workplace accomodations for two workers with narcolepsy].

    PubMed

    Vico Garcerán, Belén; Monzó Salas, Monserrat; Cuenca Esteve, Francisco; Luis Domingo, José

    2013-01-01

    We describe the case of two workers evaluated in our occupational health unit. The first worker was a kitchen aide; the second was a primary care physician. Both had been diagnosed with narcolepsy and had obvious disability.We assessed occupational hazards related to their jobs, analysed their tasks, and performed medical examinations. Afterwards, we offered recommendations to the patients, consisting of avoidance of situations involving a risk of work accidents and improving their sleep habits. Narcolepsy is a rare disorder, but it has important social and occupational consequences. A better understanding of the disease and some work accommodations can help improve the quality of life of affected workers.

  9. Biliary complications after pediatric liver transplantation: Risk factors, diagnosis and management

    PubMed Central

    Feier, Flavia H; da Fonseca, Eduardo A; Seda-Neto, Joao; Chapchap, Paulo

    2015-01-01

    The expanded indications of partial grafts in pediatric liver transplantation have reduced waiting list mortality. However, a higher morbidity is observed, including an increased rate of biliary complications (BCs). Factors such as the type of graft, the preservation methods applied, the donor characteristics, the type of biliary reconstruction, and the number of bile ducts in the liver graft influences the occurrence of these complications. Bile leaks and strictures comprise the majority of post-transplant BCs. Biliary strictures require a high grade of suspicion, and because most children have a bileo-enteric anastomosis, its diagnosis and management rely on percutaneous hepatic cholangiography and percutaneous biliary interventions (PBI). The success rates with PBI range from 70% to 90%. Surgery is reserved for patients who have failed PBI. BCs in children after liver transplantation have a prolonged treatment and are associated with a longer length of stay and higher hospital costs. However, with early diagnosis and aggressive treatment, patient and graft survival are not significantly compromised. PMID:26328028

  10. [The Spanish Society of Pediatric Infectious Diseases Guidelines for the diagnosis and treatment of congenital toxoplasmosis].

    PubMed

    Baquero-Artigao, F; del Castillo Martín, F; Fuentes Corripio, I; Goncé Mellgren, A; Fortuny Guasch, C; de la Calle Fernández-Miranda, M; González-Tomé, M I; Couceiro Gianzo, J A; Neth, O; Ramos Amador, J T

    2013-08-01

    Congenital toxoplasmosis is the result of transplacental fetal infection by Toxoplasma gondii after the primary maternal infection. The severity of the disease depends on the gestational age at transmission. First trimester infections are more severe, but less frequent, than third trimester infections. Acute maternal infection is diagnosed by seroconversion or by the detection of IgM antibodies and a low IgG avidity test. In these cases, spiramycin should be initiated to prevent transmission to the fetus. For identification of fetal infection, polymerase chain reaction (PCR) testing of amniotic fluid after 18 weeks gestation should be performed. If fetal infection is confirmed, the mothers should be treated with pyrimethamine, sulfadiazine and folinic acid. Most infants infected in utero are born with no obvious signs of toxoplasmosis, but up to 80% developed learning and visual disabilities later in life. Neonatal diagnosis with IgM/IgA antibodies or blood/cerebrospinal fluid PCR may be difficult because false-negative results frequently occur. In these cases diagnosis is possible by demonstrating a rise in IgG titers during follow-up or by the detection of antibodies beyond one year of age. Early treatment with pyrimethamine and sulfadiazine may improve the ophthalmologic and neurological outcome. Congenital toxoplasmosis is a preventable disease. Pre-pregnancy screening and appropriate counseling regarding prevention measures in seronegative women may prevent fetal infection. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  11. Utility of Whole Exome Sequencing for Genetic Diagnosis of Previously Undiagnosed Pediatric Neurology Patients.

    PubMed

    Kuperberg, Maya; Lev, Dorit; Blumkin, Lubov; Zerem, Ayelet; Ginsberg, Mira; Linder, Ilan; Carmi, Nirit; Kivity, Sarah; Lerman-Sagie, Tally; Leshinsky-Silver, Esther

    2016-12-01

    Whole exome sequencing enables scanning a large number of genes for relatively low costs. The authors investigate its use for previously undiagnosed pediatric neurological patients. This retrospective cohort study performed whole exome sequencing on 57 patients of "Magen" neurogenetic clinics, with unknown diagnoses despite previous workup. The authors report on clinical features, causative genes, and treatment modifications and provide an analysis of whole exome sequencing utility per primary clinical feature. A causative gene was identified in 49.1% of patients, of which 17 had an autosomal dominant mutation, 9 autosomal recessive, and 2 X-linked. The highest rate of positive diagnosis was found for patients with developmental delay, ataxia, or suspected neuromuscular disease. Whole exome sequencing warranted a definitive change of treatment for 5 patients. Genetic databases were updated accordingly. In conclusion, whole exome sequencing is useful in obtaining a high detection rate for previously undiagnosed disorders. Use of this technique could affect diagnosis, treatment, and prognostics for both patients and relatives.

  12. Validation of Antibody-Based Strategies for Diagnosis of Pediatric Celiac Disease Without Biopsy.

    PubMed

    Wolf, Johannes; Petroff, David; Richter, Thomas; Auth, Marcus K H; Uhlig, Holm H; Laass, Martin W; Lauenstein, Peter; Krahl, Andreas; Händel, Norman; de Laffolie, Jan; Hauer, Almuthe C; Kehler, Thomas; Flemming, Gunter; Schmidt, Frank; Rodrigues, Astor; Hasenclever, Dirk; Mothes, Thomas

    2017-08-01

    A diagnosis of celiac disease is made based on clinical, genetic, serologic, and duodenal morphology features. Recent pediatric guidelines, based largely on retrospective data, propose omitting biopsy analysis for patients with concentrations of IgA against tissue transglutaminase (IgA-TTG) >10-fold the upper limit of normal (ULN) and if further criteria are met. A retrospective study concluded that measurements of IgA-TTG and total IgA, or IgA-TTG and IgG against deamidated gliadin (IgG-DGL) could identify patients with and without celiac disease. Patients were assigned to categories of no celiac disease, celiac disease, or biopsy required, based entirely on antibody assays. We aimed to validate the positive and negative predictive values (PPV and NPV) of these diagnostic procedures. We performed a prospective study of 898 children undergoing duodenal biopsy analysis to confirm or rule out celiac disease at 13 centers in Europe. We compared findings from serologic analysis with findings from biopsy analyses, follow-up data, and diagnoses made by the pediatric gastroenterologists (celiac disease, no celiac disease, or no final diagnosis). Assays to measure IgA-TTG, IgG-DGL, and endomysium antibodies were performed by blinded researchers, and tissue sections were analyzed by local and blinded reference pathologists. We validated 2 procedures for diagnosis: total-IgA and IgA-TTG (the TTG-IgA procedure), as well as IgG-DGL with IgA-TTG (TTG-DGL procedure). Patients were assigned to categories of no celiac disease if all assays found antibody concentrations <1-fold the ULN, or celiac disease if at least 1 assay measured antibody concentrations >10-fold the ULN. All other cases were considered to require biopsy analysis. ULN values were calculated using the cutoff levels suggested by the test kit manufacturers. HLA typing was performed for 449 participants. We used models that considered how specificity values change with prevalence to extrapolate the PPV and NPV to

  13. Urine toxicology screen in multiple sleep latency test: the correlation of positive tetrahydrocannabinol, drug negative patients, and narcolepsy.

    PubMed

    Dzodzomenyo, Samuel; Stolfi, Adrienne; Splaingard, Deborah; Earley, Elizabeth; Onadeko, Oluwole; Splaingard, Mark

    2015-01-15

    Drugs can influence results of multiple sleep latency tests (MSLT). We sought to identify the effect of marijuana on MSLT results in pediatric patients evaluated for excessive daytime sleepiness (EDS). This is a retrospective study of urine drug screens performed the morning before MSLT in 383 patients <21 years old referred for EDS. MSLT results were divided into those with (1) (-) urine drug screens, (2) urine drug screens (+) for tetrahydrocannabinol (THC) alone or THC plus other drugs, and (3) urine drug screens (+) for drugs other than THC. Groups were compared with Fisher exact tests or one-way ANOVA. 38 (10%) urine drug tests were (+): 14 for THC and 24 for other drugs. Forty-three percent of patients with drug screen (+) for THC had MSLT findings consistent with narcolepsy, 0% consistent with idiopathic hypersomnia, 29% other, and 29% normal. This was statistically different from those with (-) screens (24% narcolepsy, 20% idiopathic hypersomnia, 6% other, 50% normal), and those (+) for drugs other than THC (17% narcolepsy, 33% idiopathic hypersomnia, 4% other, 46% normal (p = 0.01). Six percent (6/93) of patients with MSLT findings consistent with narcolepsy were drug screen (+) for THC; 71% of patients with drug screen (+) for THC had multiple sleep onset REM periods (SOREMS). There were no (+) urine drug screens in patients <13 years old. Many pediatric patients with (+) urine drug screens for THC met MSLT criteria for narcolepsy or had multiple SOREMs. Drug screening is important in interpreting MSLT findings for children ≥13 years. © 2014 American Academy of Sleep Medicine.

  14. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome--the French pediatric experience.

    PubMed

    Mialou, Valerie; Philip, Thierry; Kalifa, Chantal; Perol, David; Gentet, Jean-Claude; Marec-Berard, Perrine; Pacquement, Helene; Chastagner, Pascal; Defaschelles, Anne-Sophie; Hartmann, Olivier

    2005-09-01

    The objective of this report was to estimate long-term outcome and prognostic factors in children and adolescents who presented with metastatic osteosarcoma at diagnosis. Patients were treated in six French pediatric oncology centers with surgery and multiagent chemotherapy, mainly with high-dose methotrexate. Their medical records were reviewed retrospectively. The medical records of patients who were treated for metastatic osteosarcoma from 1987 to 2000 were reviewed. Patients were treated with the chemotherapy regimens recommended for nonmetastatic disease in children (the French Society of Pediatric Oncology OS 87 and OS 94 protocols) or, in a few patients, with other chemotherapy regimens. Surgical excision of the primary tumor and, when possible, of all metastatic sites was performed based on a personalized assessment of each patient's situation. Seventy-eight patients age < 20 years were treated. Forty-six patients (59%) had only 1 metastatic site (35 to the lungs and 11 to bone). Twenty-eight patients (36%) achieved a complete remission after combination chemotherapy and surgery. The event-free survival and overall survival rates at 5 years were 14% and 19%, respectively. To date, 14 patients (18%) have remained alive with a median follow-up of 112 months. Pretreatment features associated with a shorter event-free survival in the multivariate analysis were metastasis to at least two organs and high alkaline phosphatase level. Patients with at least 1 of these poor prognostic factors had a 2.6% event-free survival rate at 5 years despite treatment. The survival of patients with metastatic osteosarcoma were treated with conventional chemotherapy and surgery remained very poor. Patients should be classified into different prognostic groups and treated accordingly. New therapeutic approaches are warranted to improve the prognosis for patients with the most severe disease.

  15. Ultrasound based computer-aided-diagnosis of kidneys for pediatric hydronephrosis

    NASA Astrophysics Data System (ADS)

    Cerrolaza, Juan J.; Peters, Craig A.; Martin, Aaron D.; Myers, Emmarie; Safdar, Nabile; Linguraru, Marius G.

    2014-03-01

    Ultrasound is the mainstay of imaging for pediatric hydronephrosis, though its potential as diagnostic tool is limited by its subjective assessment, and lack of correlation with renal function. Therefore, all cases showing signs of hydronephrosis undergo further invasive studies, like diuretic renogram, in order to assess the actual renal function. Under the hypothesis that renal morphology is correlated with renal function, a new ultrasound based computer-aided diagnosis (CAD) tool for pediatric hydronephrosis is presented. From 2D ultrasound, a novel set of morphological features of the renal collecting systems and the parenchyma, is automatically extracted using image analysis techniques. From the original set of features, including size, geometric and curvature descriptors, a subset of ten features are selected as predictive variables, combining a feature selection technique and area under the curve filtering. Using the washout half time (T1/2) as indicative of renal obstruction, two groups are defined. Those cases whose T1/2 is above 30 minutes are considered to be severe, while the rest would be in the safety zone, where diuretic renography could be avoided. Two different classification techniques are evaluated (logistic regression, and support vector machines). Adjusting the probability decision thresholds to operate at the point of maximum sensitivity, i.e., preventing any severe case be misclassified, specificities of 53%, and 75% are achieved, for the logistic regression and the support vector machine classifier, respectively. The proposed CAD system allows to establish a link between non-invasive non-ionizing imaging techniques and renal function, limiting the need for invasive and ionizing diuretic renography.

  16. Body Mass Index-Independent Metabolic Alterations in Narcolepsy with Cataplexy

    PubMed Central

    Poli, Francesca; Plazzi, Giuseppe; Di Dalmazi, Guido; Ribichini, Danilo; Vicennati, Valentina; Pizza, Fabio; Mignot, Emmanuel; Montagna, Pasquale; Pasquali, Renato; Pagotto, Uberto

    2009-01-01

    Study Objectives: To contribute to the anthropometric and metabolic phenotyping of orexin-A–deficient narcoleptic patients, and to explore a possible risk of their developing a metabolic syndrome. Design: We performed a cross-sectional study comparing metabolic alterations in patients with narcolepsy with cataplexy (NC) and patients with idiopathic hypersomnia without long sleep time. Setting: University hospital. Patients: Fourteen patients with narcolepsy with cataplexy and 14 sex and age-matched patients with idiopathic hypersomnia without long sleep time. Interventions: N/A. Measurements and results: Metabolic parameters were evaluated by measuring body mass index (BMI), waist circumference (also with abdominal computed tomography), blood pressure, and daily calorie intake (3-day diary). Chronotypes were assessed through the morningness-eveningness questionnaire. Lumbar puncture for cerebrospinal fluid orexin-A determination and HLA typing were performed. Patients with narcolepsy with cataplexy (all HLA DQB1*0602 positive and with cerebrospinal fluid orexin-A levels < 110 pg/mL) had a higher BMI and BMI-independent metabolic alterations, namely waist circumference, high-density lipoprotein cholesterol, and glucose/insulin ratio (an insulin resistance index), with respect to patients with idiopathic hypersomnia without long sleep time (cerebrospinal fluid orexin-A levels > 300 pg/mL). Despite lower daily food intake, patients with narcolepsy with cataplexy displayed significant alterations in metabolic parameters resulting in a diagnosis of metabolic syndrome in more than half the cases. Conclusions: BMI-independent metabolic alterations and the relative hypophagia of patients with narcolepsy with cataplexy, as compared with patients with idiopathic hypersomnia without long sleep time, suggest that orexin-A influences the etiology of this phenotype. Moreover, considering that these dysmetabolic alterations are present from a young age, a careful metabolic

  17. Diagnostic delay in narcolepsy type 1: combining the patients' and the doctors' perspectives.

    PubMed

    Taddei, Raquel N; Werth, Esther; Poryazova, Rositsa; Baumann, Christian R; Valko, Philipp O

    2016-12-01

    Narcolepsy type 1 is a neurological disorder characterized by a unique syndrome, including the pathognomonic symptom of cataplexy. The diagnosis can be confirmed by objective measures, such as typical findings in the multiple sleep latency test, reduced or undetectable levels of orexin (hypocretin) in the cerebrospinal fluid, and linkage to a specific HLA haplotype. Nevertheless, the mean time that elapses from symptom onset to the correct diagnosis ranges between 10 and 20 years, and the causes and correlates of this delay are poorly understood. Diagnostic delay was assessed on 52 well-defined patients with narcolepsy type 1, evaluating clinical, electrophysiological and neurochemical parameters and the results of a 41-item questionnaire developed to obtain the patients' perspective on various aspects of the diagnostic process. The mean time gap between disease onset and first medical consultation was 3.2 ± 5.1 years; the mean diagnostic delay was 8.9 ± 11.0 years. Prior to correct diagnosis, patients received a wide variety of misdiagnoses. The self-ratings of the patients revealed that the undiagnosed symptoms caused high levels of anxiety and unjustified criticism by family, friends and employers. Multiple regression analysis identified higher cerebrospinal fluid orexin levels (β = 0.311, P = 0.01), and a longer interval between the onset of excessive daytime sleepiness and cataplexy (β = 0.368, P = 0.002) as independent associates of longer diagnostic delay. The diagnostic delay decreased over the last decades (β = -0.672, P < 0.001). In conclusion, delayed diagnosis of narcolepsy type 1 is very common, associated with many adverse consequences, and requires educational efforts to improve awareness on narcolepsy among healthcare providers and the general population. © 2016 European Sleep Research Society.

  18. Occurrence of dermoid cyst in the floor of the mouth: the importance of differential diagnosis in pediatric patients

    PubMed Central

    PURICELLI, Edela; BARREIRO, Bernardo Ottoni Braga; QUEVEDO, Alexandre Silva; PONZONI, Deise

    2017-01-01

    Abstract Lesions in the floor of the mouth can be a challenging diagnosis due to the variety of pathological conditions that might be found in this area. Within a broad range of lesions, attention has to be addressed to those that require specific management, such as a dermoid cyst (DC) and a ranula. Especially in pediatric patients, in whom the failure of diagnosis can postpone the correct treatment and cause sequelae later in life. DC, a developmental anomaly, is managed primarily by surgical resection. On the other hand, ranula is a pseudocyst that may be treated by marsupialization. This article reports a large and painful lesion in the floor of the mouth in a pediatric patient. With a diagnostic hypothesis of ranula, two surgical interventions were performed, but there were recurrences of the lesion. Subsequently, the patient was referred to the Oral and Maxillofacial Surgery Unit for re-evaluation. Computed tomography showed a semi-transparent image suggesting a cystic formation. Another surgical procedure was performed where the lesion was completely removed. Anatomopathological analysis confirmed the diagnosis of DC. The five-year follow-up showed no signs of recurrence. This article indicates that although DC in the floor of the mouth is rare, it should be considered in the differential diagnosis of other diseases in this area. This precaution may be particularly important in the following circumstances: 1) Similar lesions that have different therapeutic approaches and, 2) To prevent future sequelae in pediatric patients. PMID:28678954

  19. Occurrence of dermoid cyst in the floor of the mouth: the importance of differential diagnosis in pediatric patients.

    PubMed

    Puricelli, Edela; Barreiro, Bernardo Ottoni Braga; Quevedo, Alexandre Silva; Ponzoni, Deise

    2017-01-01

    Lesions in the floor of the mouth can be a challenging diagnosis due to the variety of pathological conditions that might be found in this area. Within a broad range of lesions, attention has to be addressed to those that require specific management, such as a dermoid cyst (DC) and a ranula. Especially in pediatric patients, in whom the failure of diagnosis can postpone the correct treatment and cause sequelae later in life. DC, a developmental anomaly, is managed primarily by surgical resection. On the other hand, ranula is a pseudocyst that may be treated by marsupialization. This article reports a large and painful lesion in the floor of the mouth in a pediatric patient. With a diagnostic hypothesis of ranula, two surgical interventions were performed, but there were recurrences of the lesion. Subsequently, the patient was referred to the Oral and Maxillofacial Surgery Unit for re-evaluation. Computed tomography showed a semi-transparent image suggesting a cystic formation. Another surgical procedure was performed where the lesion was completely removed. Anatomopathological analysis confirmed the diagnosis of DC. The five-year follow-up showed no signs of recurrence. This article indicates that although DC in the floor of the mouth is rare, it should be considered in the differential diagnosis of other diseases in this area. This precaution may be particularly important in the following circumstances: 1) Similar lesions that have different therapeutic approaches and, 2) To prevent future sequelae in pediatric patients.

  20. Development of a Pediatric-Specific Clinical Probability Tool for Diagnosis of Venous Thromboembolism: A Feasibility Study

    PubMed Central

    Kerlin, Bryce A.; Stephens, Julie A.; Hogan, Mark J.; Smoyer, William E.; O'Brien, Sarah H.

    2014-01-01

    Background Pediatric venous thromboembolism (VTE) is an increasingly common, difficult to diagnose problem. Clinical probability tools (CPT) for adults estimate VTE likelihood, but are not available for children. We hypothesized that a pediatric-specific CPT is feasible. Methods Radiology reports were utilized to identify children imaged for suspected VTE. Relevant signs, symptoms, and co-morbidity variables, identified from published literature, were extracted from corresponding medical records. Variables associated with pediatric VTE were incorporated into a multivariate logistic regression to create a pilot CPT which was confirmed on a separate cohort. Results 389 subjects meeting inclusion criteria were identified: 91 with VTE and 298 without. Univariate analysis revealed male gender (OR 2.96; p<0.001), asymmetric extremity (OR 1.76; p=0.033), central venous catheter utilization and/or dysfunction (OR 2.51; p<0.001), and cancer (OR 2.35; p=0.014) as VTE predictive variables. Documentation of an alternate diagnosis was inversely related to VTE (OR 0.42; p=0.004). Receiver operating characteristic analysis of the derived CPT demonstrated reasonable ability to discriminate VTE probability in the training cohort (AUC 0.73; p<0.001) and moderate discrimination in a separate validation cohort of 149 children (AUC 0.64; p=0.011). Conclusion A pediatric-specific VTE CPT is feasible, would facilitate early diagnosis, and could lead to improved outcomes. PMID:25518012

  1. Parkinson's disease and narcolepsy-like symptoms.

    PubMed

    Ylikoski, Ari; Martikainen, Kirsti; Sarkanen, Tomi; Partinen, Markku

    2015-04-01

    Various sleep-related problems, for example, insomnia and symptoms of rapid eye movement behavior disorder (RBD), are common in patients with Parkinson's disease (PD). We studied the prevalence of symptoms of narcolepsy (NARC), hallucinations, and RBD and their association with other symptoms. Altogether, 1447 randomly selected patients with PD, aged 43-89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep Questionnaire. Questions on demographics, PD, RBD, and other issues were included. The response rate was 59.0%; of these patients, 73% had answered to all questions that were used in the analyses (N = 623). The occurrence of suspected narcolepsy (Ullanlinna Narcolepsy Scale ≥ 14 and Epworth Sleepiness Scale ≥ 11) was observed in 9.3% of the subjects (PD with NARC), RBD (REM Sleep Behavior Disorder Screening Questionnaire ≥ 6) in 39.2% of all patients with PD, and in 62.1% of those with PD and NARC. In patients with PD, hallucinations before going to bed in the evening occurred in 5.8%, hypnagogic hallucinations in 4.0%, hallucinations during night 8.3%, and hypnopompic hallucinations in 3.2%. Cataplexy symptoms occurred in 43.1% of subjects with PD and NARC. In a logistic regression analysis, PD with NARC was associated with RBD, all types of hallucinations, daytime sleepiness, fatigue, insomnia, and intense dreaming also when adjusted for age, sex, disease duration, and levodopa. Narcolepsy-like symptoms may be present in patients with PD. Symptoms of RBD were associated with symptoms of narcolepsy including symptoms of cataplexy. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Narcolepsy with cataplexy mimicry: the strange case of two sisters.

    PubMed

    Pizza, Fabio; Vandi, Stefano; Poli, Francesca; Moghadam, Keivan Kaveh; Franceschini, Christian; Bellucci, Claudia; Cipolli, Carlo; Ingravallo, Francesca; Natalini, Giuliana; Mignot, Emmanuel; Plazzi, Giuseppe

    2013-06-15

    We report on two sisters, 17 and 12 years of age, with clinical features suggesting narcolepsy with cataplexy (NC): daytime sleepiness, spontaneous and emotionally triggered sudden falls to the ground, and overweight/obesity. MSLT showed borderline sleep latency, with 1 and 0 sleep onset REM periods. HLA typing disclosed the DQB1*0602 allele. Video-polygraphy of the spells ruled out NC diagnosis by demonstrating their easy elicitation by suggestion, with wake EEG, electromyographic persistence of muscle tone, and stable presence of tendon reflexes (i.e., pseudo-cataplexy), together with normal cerebrospinal hypocretin-1 levels. Our cases emphasize the need of a clear depiction of cataplexy pattern at the different ages, the usefulness of examining ictal neurophysiology, and collecting all available disease markers in ambiguous cases.

  3. Hypocretin ligand deficiency in narcolepsy: recent basic and clinical insights.

    PubMed

    Ritchie, Cayde; Okuro, Masashi; Kanbayashi, Takashi; Nishino, Seiji

    2010-05-01

    Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. Both sporadic and familial forms exist in humans. Recently, the major pathophysiology of human narcolepsy was indicated, based on discovery, through animal study, of narcolepsy genes involved in the pathology of hypocretin/orexin ligand and its receptor. Hypocretin ligand deficiency is found in most patients with narcolepsy with cataplexy. This deficiency likely is the result of postnatal cell death of hypocretin neurons, and involvement of autoimmune mechanisms is suggested. Hypocretin deficiency also is found in symptomatic narcolepsy and excessive daytime sleepiness with neurologic conditions, including immune-mediated neurologic disorders. These findings have significant clinical relevance and promote understanding of hypocretin cell death mechanisms. Already, discoveries in humans have led to a new diagnostic test for narcolepsy. Currently, hypocretin replacement therapy has emerged as a promising therapeutic option, and experiments using gene therapy and cell transplantation are in progress.

  4. Diagnosis of Pediatric Hyperthyroidism: Technetium 99 Uptake Versus Thyroid Stimulating Immunoglobulins

    PubMed Central

    Misra, Madhusmita; Levitsky, Lynne L.

    2015-01-01

    Background: Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with 123I or 99Tc (99mTc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with 99mTc uptake for diagnosis of pediatric hyperthyroidism. Methods: We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and 99mTc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. 99mTc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Results: Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI–. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. Conclusion: 99mTc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of 99mTc (two and a half times as much as TSI), it is reasonable to reserve 99mTc uptake assessment for hyperthyroidism of unclear etiology and negative TSI. PMID:25257665

  5. Diagnosis of pediatric colonic volvulus with abdominal radiography: how good are we?

    PubMed

    Marine, Megan B; Cooper, Matthew L; Delaney, Lisa R; Jennings, Samuel Gregory; Rescorla, Frederick J; Karmazyn, Boaz

    2017-04-01

    Colonic volvulus is rare in children and associated with colonic dysmotility. Diagnosis of colonic volvulus on radiographs in these patients can be challenging. The purpose of the study was to identify the accuracy of abdominal radiographs and findings suggestive of colonic volvulus. A retrospective (2003- 2014) study of all children with colonic volvulus proven surgically or endoscopically reviewed their medical charts for underlying disease and clinical presentation as well as their original radiograph reports. Two pediatric radiologists (reader 1 and reader 2) independently reviewed the radiographs. The kappa test was used to evaluate interobserver variability. There were 19 cases of colonic volvulus in 18 patients (11 males) a mean age 14 years. Cecal volvulus was the most common finding at 14/19 cases (74%). Sixteen of 18 (89%) patients had neurological impairment and 10 of 18 (56%) had intestinal dysmotility. The most common presentation was abdominal distension (14/19 [74%]) and pain (11/19 [58%]). Colonic volvulus was diagnosed in only 7/16 (44%) of the abdominal radiographs. The specific finding of a coffee-bean sign was retrospectively observed only by reader 2 in two cases. Absence of rectal gas and focal colonic loop dilation were the most common findings by the readers (average 73.5% and 87%, respectively) with Kappa values of 0.3 and 0.38, respectively. Diagnosis of colonic volvulus in children can be challenging. Radiologists should be alerted to the possibility of colonic volvulus when there is focal colonic loop distention or absent rectal gas.

  6. Risk analysis, diagnosis and management of gastrointestinal mucositis in pediatric cancer patients.

    PubMed

    Kuiken, Nicoline S S; Rings, Edmond H H M; Tissing, Wim J E

    2015-04-01

    Mucositis is a complex inflammatory reaction of the mucous membranes of the alimentary tract upon chemotherapy and radiotherapy treatment in oncology patients. Mucositis can be subdivided in oral and gastrointestinal mucositis (GI mucositis). The damage to the gastrointestinal tract compromises the intestinal function and thereby the nutritional status and the quality of life, and eventually affects survival. The literature on GI mucositis focuses mainly on adults. This review focuses on data available on GI mucositis in pediatric cancer patients. An evaluation of the clinical presentation and consequences of GI mucositis in children is outlined. The review summarizes key issues for clinicians with respect to risk analysis for developing mucositis and the diagnosis of this condition in children. Information on these issues is obtained from clinical trials in children and adults, and from animal models. Diagnostic tools and assessment of severity of GI mucositis in children is elaborated on. Furthermore, the clinical management of the symptoms and consequences of GI mucositis in children, with specific focus on nutritional support, are discussed.

  7. Use of bacterial antigen detection in the diagnosis of pediatric lower respiratory tract infections.

    PubMed

    Ramsey, B W; Marcuse, E K; Foy, H M; Cooney, M K; Allan, I; Brewer, D; Smith, A L

    1986-07-01

    Two immunochemical methods were used to identify Haemophilus influenzae and Streptococcus pneumoniae capsular antigens in the urine and serum of 162 children with acute lower respiratory tract infection. These methods were compared with standard bacterial blood culture. Viral and mycoplasma cultures of respiratory secretions were obtained simultaneously to determine the frequency of antigenuria at the time of nonbacterial acute lower respiratory tract infection. Urine from groups of well children and children with acute otitis media was tested for capsular antigens to determine the incidence of antigenuria. Antigenuria was found in 24% of children 2 months to 18 years of age with acute lower respiratory tract infection compared with a 2% incidence of bacteremia. Antigenuria was found in 4% of asymptomatic children and 16% of children with acute otitis media. One third of children with symptoms of acute lower respiratory tract infection and viral isolates from the oropharynx had bacterial antigenuria. The sixfold increase in frequency of bacterial antigenuria in children at the time of lower respiratory symptoms suggests that bacterial acute lower respiratory tract infection may be more common than identified by traditional culture techniques. Because bacterial antigen may come from other sites such as the middle ear, further studies are needed to determine the role of antigen detection in the diagnosis of pediatric acute lower respiratory tract infection.

  8. Feasibility of confocal endomicroscopy in the diagnosis of pediatric gastrointestinal disorders

    PubMed Central

    Venkatesh, Krishnappa; Cohen, Marta; Evans, Clair; Delaney, Peter; Thomas, Steven; Taylor, Christopher; Abou-Taleb, Ashraf; Kiesslich, Ralf; Thomson, Mike

    2009-01-01

    AIM: To evaluate the feasibility and utility of confocal laser endomicroscopy (CLE) in the description of normal gastrointestinal (GI) mucosa and in the diagnosis of GI disorders in children, in comparison to histology. METHODS: Forty-four patients (19 female) median age 10.9 years (range 0.7-16.6 years) with suspected or known GI pathology underwent esophago-gastro-duodenoscopy (OGD) (n = 36) and/or ileocolonoscopy (IC) (n = 31) with CLE using sodium fluorescein and acriflavine as contrast agents. Histological sections were compared with same site confocal images by two experienced pediatric and GI histopathologists and endoscopists, respectively. RESULTS: Duodenum and ileum were intubated in all but one patient undergoing OGD and IC. The median procedure time was 16.4 min (range 7-25 min) for OGD and 27.9 min (range 15-45 min) for IC. A total of 4798 confocal images were compared with 153 biopsies from the upper GI tract from 36 procedures, and 4661 confocal images were compared with 188 biopsies from the ileocolon from 31 procedures. Confocal images were comparable to conventional histology both in normal and in pathological conditions such as esophagitis, Helicobacter pylori gastritis, celiac disease, inflammatory bowel disease, colonic heterotopia, and graft versus host disease. CONCLUSION: CLE offers the prospect of targeting biopsies to abnormal mucosa, thereby increasing diagnostic yield, reducing the number of biopsies, decreasing the burden on the histopathological services, and reducing costs. PMID:19437560

  9. Hypocretin/orexin and narcolepsy: new basic and clinical insights.

    PubMed

    Nishino, S; Okuro, M; Kotorii, N; Anegawa, E; Ishimaru, Y; Matsumura, M; Kanbayashi, T

    2010-03-01

    Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain-Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for 'narcolepsy with cataplexy' and 'narcolepsy due to medical condition'). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress.

  10. HYPOCRETIN/OREXIN AND NARCOLEPSY NEW BASIC AND CLINICAL INSIGHTS

    PubMed Central

    NISHINO, Seiji; OKURO, Masashi; KOTORII, Nozomu; ANEGAWA, Emiko; ISHIMARU, Yuji; MATSUMURA, Mari; KANBAYASHI, Takashi

    2009-01-01

    Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, and sleep paralysis. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin-ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is likely due to the postnatal cell death of hypocretin neurons. Although tight association between human leukocyte antigen (HLA) association and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proven. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain-Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO) related disorder. These findings likely have significant clinical relevance and for understanding the mechanisms of hypocretin cell death and choice of treatment option. These series of discoveries in humans lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid [CSF] hypocretin-1 levels for narcolepsy with cataplexy and narcolepsy due to medical condition). Since a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress. PMID:19555382

  11. Reduced amygdala activity during aversive conditioning in human narcolepsy.

    PubMed

    Ponz, Aurélie; Khatami, Ramin; Poryazova, Rositsa; Werth, Esther; Boesiger, Peter; Schwartz, Sophie; Bassetti, Claudio L

    2010-03-01

    Narcolepsy with cataplexy is a sleep-wake disorder caused by a loss of hypothalamic hypocretins. Here we assessed the time course of amygdala activation during aversive conditioning in unmedicated patients with narcolepsy. Unlike healthy matched control subjects, narcolepsy patients had no enhancement of amygdala response to conditioned stimuli and no increase in functional coupling between the amygdala and medial prefrontal cortex. These findings suggest that human narcolepsy is accompanied by abnormal emotional learning, and that, in line with animal data, the hypocretin system and the amygdala are involved in this process.

  12. The European Narcolepsy Network (EU-NN) database.

    PubMed

    Khatami, Ramin; Luca, Gianina; Baumann, Christian R; Bassetti, Claudio L; Bruni, Oliviero; Canellas, Francesca; Dauvilliers, Yves; Del Rio-Villegas, Rafael; Feketeova, Eva; Ferri, Raffaele; Geisler, Peter; Högl, Birgit; Jennum, Poul; Kornum, Birgitte R; Lecendreux, Michel; Martins-da-Silva, Antonio; Mathis, Johannes; Mayer, Geert; Paiva, Teresa; Partinen, Markku; Peraita-Adrados, Rosa; Plazzi, Guiseppe; Santamaria, Joan; Sonka, Karel; Riha, Renata; Tafti, Mehdi; Wierzbicka, Aleksandra; Young, Peter; Lammers, Gert Jan; Overeem, Sebastiaan

    2016-06-01

    Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials.

  13. Status cataplecticus as initial presentation of late onset narcolepsy.

    PubMed

    Panda, Samhita

    2014-02-15

    Narcolepsy, one of the important causes of hypersomnia, is an under diagnosed sleep disorder. It has a bimodal age of onset around 15 and 35 years. It is characterized by the tetrad of excessive daytime sleepiness, cataplexy, hypnagogic/ hypnopompic hallucinations, and sleep paralysis. Cataplexy is by far the most predictive feature of narcolepsy. Status cataplecticus is the occurrence of cataplexy repeatedly for hours or days, a rare presentation of narcolepsy. This report describes an elderly gentleman with late onset narcolepsy in the sixth decade of life presenting with initial and chief symptom of status cataplecticus.

  14. [Early diagnosis and comprehensive treatments of post-transplantation lymphoproliferative disorder after pediatric liver transplantation].

    PubMed

    Deng, Zhaohui; Jiang, Lirong; Zhou, Tao; Shen, Conghuan; Chen, Qimin; Xia, Qiang

    2014-08-01

    . EBV infection is the high risk factor for PTLD after liver transplantation. Close clinical surveillance of EBV DNA for pediatric liver transplantation was important for the early diagnosis of PTLD. Reducing doses of immunosuppressive agents and rituximab is the initial therapy for PTLD. A reduction in the dose of tacrolimus is suggested. Operation therapy can also play a role in the management of local complications.

  15. Hypertension Canada's 2017 Guidelines for the Diagnosis, Assessment, Prevention, and Treatment of Pediatric Hypertension.

    PubMed

    Dionne, Janis M; Harris, Kevin C; Benoit, Geneviève; Feber, Janusz; Poirier, Luc; Cloutier, Lyne; Nakhla, Meranda; Rabi, Doreen M; Daskalopoulou, Stella S; Fournier, Anne

    2017-05-01

    After the 2016 guidelines for blood pressure measurement, diagnosis, and investigation of pediatric hypertension, we now present evidence-based guidelines for the prevention and treatment of hypertension in children. These guidelines were developed by Hypertension Canada's Guideline Committee pediatric subgroup after thorough evaluation of the available literature. Included are 10 guidelines specifically addressing health behaviour management, indications for drug therapy in children with hypertension, choice of therapy for children with primary hypertension, and goals of therapy for children with hypertension. Although the pediatric literature is inherently limited by small numbers of participants, fewer trials, and a prolonged latency to the development of vascular outcomes, this report reflects the current and highest level of evidence and provides guidance for primary care practitioners on the management of pediatric hypertension. Studies of therapeutic lifestyle modifications in children are available to guide current management and more antihypertensive drugs have been studied in children since the Food and Drug Administration Modernization Act. Consistent with Hypertension Canada's guideline policy, diagnostic and therapeutic algorithm tools will be developed and the guidelines will be reviewed annually and updated according to new evidence. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  16. Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies.

    PubMed

    Maurovich-Horvat, Eszter; Kemlink, David; Högl, Birgit; Frauscher, Birgit; Ehrmann, Laura; Geisler, Peter; Ettenhuber, Katharina; Mayer, Geert; Peraita-Adrados, Rosa; Calvo, Elena; Lammers, Gert Jan; Van der Heide, Astrid; Ferini-Strambi, Luigi; Plazzi, Giuseppe; Poli, Francesca; Dauvilliers, Yves; Jennum, Poul; Leonthin, Helle; Mathis, Johannes; Wierzbicka, Aleksandra; Puertas, Francisco J; Beitinger, Pierre A; Arnulf, Isabelle; Riha, Renata L; Tormášiová, Maria; Slonková, Jana; Nevšímalová, Sona; Sonka, Karel

    2013-10-01

    In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self-administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P < 0.001) and had a higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More patients with narcolepsy-cataplexy during pregnancy had impaired glucose metabolism and anaemia. Three patients experienced cataplexy during delivery. The rate of caesarean sections was higher in the narcolepsy-cataplexy group compared to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of neonates were within the normal range and did not differ across groups. Neonatal care was affected adversely by symptoms of narcolepsy in 60.1% of those with narcolepsy during pregnancy. This study reports more obstetric complications in patients with narcolepsy-cataplexy during pregnancy; however, these were not severe. This group also had a higher BMI and higher incidence of impaired glucose metabolism during pregnancy. Caesarian section was conducted more frequently in narcolepsy-cataplexy patients, despite cataplexy being a rare event during delivery. Furthermore, symptoms of narcolepsy may render care of the infant more difficult.

  17. Dysautonomia in Narcolepsy: Evidence by Questionnaire Assessment

    PubMed Central

    Klein, Gilles; Vaillant, Michel; Pieri, Vannina; Fink, Gereon R.; Diederich, Nico

    2014-01-01

    Background and Purpose Excessive daytime sleepiness and sudden sleep attacks are the main features of narcolepsy, but rapid-eye-movement sleep behavior disorder (RBD), hyposmia, and depression can also occur. The latter symptoms are nonmotor features in idiopathic Parkinson's disease (IPD). In the present study, IPD-proven diagnostic tools were tested to determine whether they are also applicable in the assessment of narcolepsy. Methods This was a case-control study comparing 15 patients with narcolepsy (PN) and 15 control subjects (CS) using the Scales for Outcomes in Parkinson's Autonomic Test (SCOPA-AUT), Parkinson's Disease Nonmotor Symptoms (PDNMS), University of Pennsylvania Smell Test, Farnsworth-Munsell 100 Hue test, Beck Depression Inventory, and the RBD screening questionnaire. Results Both the PN and CS exhibited mild hyposmia and no deficits in visual tests. Frequent dysautonomia in all domains except sexuality was found for the PN. The total SCOPA-AUT score was higher for the PN (18.47±10.08, mean±SD) than for the CS (4.40±3.09), as was the PDNMS score (10.53±4.78 and 1.80±2.31, respectively). RBD was present in 87% of the PN and 0% of the CS. The PN were more depressed than the CS. The differences between the PN and CS for all of these variables were statistically significant (all p<0.05). Conclusions The results of this study provide evidence for the presence of dysautonomia and confirm the comorbidities of depression and RBD in narcolepsy patients. The spectrum, which is comparable to the nonmotor complex in IPD, suggests wide-ranging, clinically detectable dysfunction beyond the narcoleptic core syndrome. PMID:25324880

  18. Diagnosis and Management of Congenital Coronary Arteriovenous Fistula in the Pediatric Patients Presenting Congestive Heart Failure and Myocardial Ischemia

    PubMed Central

    Chen, Ming

    2009-01-01

    Purpose Four pediatric patients with congenital coronary arteriovenous fistula (CAVF) were reported to remind pediatric practitioners and cardiologists of its diagnosis and management. Materials and Methods Four pediatric patients with congenital CAVF from June 1999 to November 2007 were included in this retrospective study. Study modalities included reviews of patients' profiles of clinical features, chest radiograph, Doppler echocardiography, cardiac catheterization with angiography, myocardial perfusion scan, and computed tomography. Results All 4 patients were symptomatic. The clinical symptoms and signs were feeding problem, continuous murmur, tachycardia, tachypnea, cardiomegaly, and exertional chest pain. Myocardial enzyme was elevated in 1 patient. Echocardiography showed dilatation of the coronary artery in all 4 patients, and traced down its origin in 3 and drainage in 4. The fistulas originated from the right coronary artery in 2 patients and left coronary artery in 2, and were drained into the right ventricle in 2, right atrium in 1, and pulmonary artery in 1. Single left coronary artery was found in 1 patient. The pulmonary-to-systemic blood flow ratios ranged from 1.2 to 2.5. Transcatheter coil occlusion was successfully performed in 4 patients through a coaxial delivery system. The symptoms and signs of congestive heart failure and myocardial ischemia disappeared after the procedure. Conclusion Diagnosis of congenital CAVF could be achieved by appreciation of continuous murmur over area unusual for the ductus, and by scrupulous examination of echocardiography as well as angiography of the coronary artery through which coaxial transcatheter coil occlusion could be performed successfully. PMID:19259355

  19. Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, and Assessment of Risk of Pediatric Hypertension.

    PubMed

    Harris, Kevin C; Benoit, Geneviève; Dionne, Janis; Feber, Janusz; Cloutier, Lyne; Zarnke, Kelly B; Padwal, Raj S; Rabi, Doreen M; Fournier, Anne

    2016-05-01

    We present the inaugural evidence-based Canadian recommendations for the measurement of blood pressure in children and the diagnosis and evaluation of pediatric hypertension. Rates of pediatric hypertension are increasing concomitant with increased rates of childhood obesity. With this, there is growing awareness of the need to measure blood pressure in children. Consequently, the present recommendations have been developed to address an important gap and improve the clinical care of children. For 2016, a total of 15 recommendations are presented. These are categorized in a fashion similar to that of the existing adult recommendations. Specifically, we present recommendations on (1) accurate measurement of blood pressure in children, (2) criteria for diagnosis of hypertension in children, (3) assessment of overall cardiovascular risk in hypertensive children, (4) routine laboratory tests for the investigation of children with hypertension, (5) ambulatory blood pressure measurement in children, and (6) the role of echocardiography. We discuss the rationale for the recommendations and present additional supporting material for the clinician, including tables with standardized techniques for blood pressure measurement and determination of normative blood pressure values for children. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will update the recommendations annually and develop future evidence-based recommendations to guide prevention and treatment of pediatric hypertension. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  20. Utilization of chemical shift MRI in the diagnosis of disorders affecting pediatric bone marrow.

    PubMed

    Winfeld, Matthew; Ahlawat, Shivani; Safdar, Nabile

    2016-09-01

    MRI signal intensity of pediatric bone marrow can be difficult to interpret using conventional methods. Chemical shift imaging (CSI), which can quantitatively assess relative fat content, may improve the ability to accurately diagnose bone marrow abnormalities in children. Consecutive pelvis and extremity MRI at a children's hospital over three months were retrospectively reviewed for inclusion of CSI. Medical records were reviewed for final pathological and/or clinical diagnosis. Cases were classified as normal or abnormal, and if abnormal, subclassified as marrow-replacing or non-marrow-replacing entities. Regions of interest (ROI) were then drawn on corresponding in and out-of-phase sequences over the marrow abnormality or over a metaphysis and epiphysis in normal studies. Relative signal intensity ratio for each case was then calculated to determine the degree of fat content in the ROI. In all, 241 MRI were reviewed and 105 met inclusion criteria. Of these, 61 had normal marrow, 37 had non-marrow-replacing entities (osteomyelitis without abscess n = 17, trauma n = 9, bone infarction n = 8, inflammatory arthropathy n = 3), and 7 had marrow-replacing entities (malignant neoplasm n = 4, bone cyst n = 1, fibrous dysplasia n = 1, and Langerhans cell histiocytosis n = 1). RSIR averages were: normal metaphyseal marrow 0.442 (0.352-0.533), normal epiphyseal marrow 0.632 (0.566-698), non-marrow-replacing diagnoses 0.715 (0.630-0.799), and marrow-replacing diagnoses 1.06 (0.867-1.26). RSIR for marrow-replacing entities proved significantly different from all other groups (p < 0.05). ROC analysis demonstrated an AUC of 0.89 for RSIR in distinguishing marrow-replacing entities. CSI techniques can help to differentiate pathologic processes that replace marrow in children from those that do not.

  1. Point-of-Care Ultrasonography for the Diagnosis of Pediatric Soft Tissue Infection.

    PubMed

    Adams, Cynthia M; Neuman, Mark I; Levy, Jason A

    2016-02-01

    To determine the test characteristics of point-of-care ultrasonography for the identification of a drainable abscess and to compare the test characteristics of ultrasonography with physical examination. In addition, we sought to measure the extent to which ultrasonography impacts clinical management of children with skin and soft tissue infections (SSTIs). We performed a prospective study of children with SSTIs evaluated in a pediatric emergency department. Treating physicians recorded their initial impression of whether a drainable abscess was present based on physical examination. Another physician, blinded to the treating physician's assessment, performed an ultrasound study and conveyed their interpretation and recommendations to the treating physician. Any management change was recorded. An abscess was defined as a lesion from which purulent fluid was expressed during a drainage procedure in the emergency department or during the 2- to 5-day follow-up period. We defined a change in management as correct when the ultrasound diagnosis was discordant from physical examination and matched the ultimate lesion classification. Of 151 SSTIs evaluated among 148 patients, the sensitivity and specificity of point-of-care ultrasonography for the presence of abscess were 96% (95% CI 90%-99%) and 87% (74%-95%), respectively. The sensitivity and specificity of physical examination for the presence of abscess were 84% (75%-90%) and 60% (44%-73%), respectively. For every 4 ultrasound examinations performed, there was 1 correct change in management. Point-of-care ultrasonography demonstrates excellent test characteristics for the identification of skin abscess and has superior test characteristics compared with physical examination alone. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Autosomal dominant cerebellar ataxia deafness and narcolepsy.

    PubMed

    Melberg, A; Hetta, J; Dahl, N; Nennesmo, I; Bengtsson, M; Wibom, R; Grant, C; Gustavson, K H; Lundberg, P O

    1995-12-01

    A new autosomal dominant syndrome in a Swedish pedigree is described. Five patients were affected with cerebellar ataxia and sensorineural deafness. Four of these patients had symptoms of narcolepsy. Optic atrophy, other neurological abnormalities and psychiatric symptoms developed with increasing disease duration. Three patients had non-neurological disease in addition, including diabetes mellitus in two and hypertrophic cardiomyopathy in one. Autopsy with neuropathological examination was performed in one case. Molecular studies focused on the short arm of chromosome 6, including the HLA DR2 locus associated with narcolepsy and the (CAG)n repeat at the spinocerebellar ataxia type 1 (SCA1) locus. Biochemical investigation of muscle biopsy of one case indicated mitochondrial dysfunction with selective decrease in ATP production for substrates that normally give the highest rates. The activity of glutamate dehydrogenase was reduced, indicating a low mitochondrial density. We postulate an autosomal dominant genetic factor responsible for this syndrome. Linkage was excluded to HLA DR2, and a normal sized SCA1 repeat was observed. We conclude that a locus predisposing to ataxia, deafness and narcolepsy exists outside this region of chromosome 6.

  3. Childhood onset inflammatory bowel disease: predictors of delayed diagnosis from the CEDATA German-language pediatric inflammatory bowel disease registry.

    PubMed

    Timmer, Antje; Behrens, Rolf; Buderus, Stephan; Findeisen, Annette; Hauer, Almuthe; Keller, Klaus-Michael; Kliemann, Guido; Lang, Thomas; Lohr, Wolfgang; Rzehak, Peter; Koletzko, Sibylle

    2011-03-01

    To examine predictors of delayed diagnosis of inflammatory bowel disease in children and adolescents. A total of 2,436 patients (age 0-18 years) with Crohn's disease, ulcerative colitis, or unclassified colitis were included from 53 pediatric gastroenterologists. Predictors were examined with the proportional hazards model, presented as hazard ratios (HR) with 95% confidence intervals. HR < 1.0 represent factors associated with late diagnosis. Median time to diagnosis was 4 (2-8) months. Crohn's disease (HR 0.62; 0.56-0.68), and within Crohn's disease, ileal disease (HR 0.77, 95% confidence interval 0.67 to 0.89) were associated with delayed diagnosis. Chances for early diagnosis increased with increasing age (HR 1.07 per year of age; 1.06 to 1.08). There was also an effect by center (HR 0.63, 0.52 to 0.67), but not by sex or country (Austria vs Germany). Growth failure was more common in those cases with delayed diagnosis. There is still concern about delays in the diagnosis of inflammatory bowel disease in the very young and in children with small bowel disease. Inequalities of care by region require further investigation. Copyright © 2011. Published by Mosby, Inc.

  4. Loss of rapid eye movement sleep atonia in patients with REM sleep behavioral disorder, narcolepsy, and isolated loss of REM atonia.

    PubMed

    Khalil, Aytakin; Wright, Mary-Anne; Walker, Matthew C; Eriksson, Sofia H

    2013-10-15

    To compare the amounts of REM sleep without atonia (RSWA) between patients with REM sleep behavior disorder (RBD), "isolated loss of REM atonia," narcolepsy, and control subjects and determine if there were threshold values for the amount of RSWA that differentiate each group from controls. Retrospective analyses of polysomnography (PSG) records were used employing strict quantitative criteria for the measurement of phasic and tonic EMG activity during REM sleep. The PSG recordings of 47 individuals were analyzed (RBD 16, isolated loss of REM atonia 11, narcolepsy 10, control 10). Patients with the diagnosis of isolated loss of REM atonia had significantly lower levels of EMG activity during REM sleep than those with RBD but higher than control subjects. RSWA was higher in narcolepsy than in loss of REM atonia but lower than for RBD patients. Receiver operating characteristic (ROC) curves provided threshold values with high specificity and sensitivity in all patient groups with a cutoff value ≥ 1.22% (100% correctly classified) for phasic and ≥ 3.17% for tonic (92% correctly classified) EMG activity in RBD. Quantification of REM sleep EMG activity can successfully differentiate RBD and isolated loss of REM atonia patients from controls. The consistently increased amount of RSWA in patients with narcolepsy indicates that this can be an additional marker for a diagnosis of narcolepsy. Longitudinal studies of patients with isolated loss of REM atonia are needed to evaluate if these patients are at risk of developing RBD or neurodegenerative disorders.

  5. Evidence for cognitive resource imbalance in adolescents with narcolepsy.

    PubMed

    Witt, Suzanne T; Drissi, Natasha Morales; Tapper, Sofie; Wretman, Anna; Szakács, Attila; Hallböök, Tove; Landtblom, Anne-Marie; Karlsson, Thomas; Lundberg, Peter; Engström, Maria

    2017-03-20

    The study investigated brain activity changes during performance of a verbal working memory task in a population of adolescents with narcolepsy. Seventeen narcolepsy patients and twenty healthy controls performed a verbal working memory task during simultaneous fMRI and EEG acquisition. All subjects also underwent MRS to measure GABA and Glutamate concentrations in the medial prefrontal cortex. Activation levels in the default mode network and left middle frontal gyrus were examined to investigate whether narcolepsy is characterized by an imbalance in cognitive resources. Significantly increased deactivation within the default mode network during task performance was observed for the narcolepsy patients for both the encoding and recognition phases of the task. No evidence for task performance deficits or reduced activation within the left middle frontal gyrus was noted for the narcolepsy patients. Correlation analyses between the spectroscopy and fMRI data indicated that deactivation of the anterior aspect of the default mode in narcolepsy patients correlated more with increased concentrations of Glutamate and decreased concentrations of GABA. In contrast, deactivation in the default mode was correlated with increased concentrations of GABA and decreased concentrations of Glutamate in controls. The results suggested that narcolepsy is not characterized by a deficit in working memory but rather an imbalance of cognitive resources in favor of monitoring and maintaining attention over actual task performance. This points towards dysregulation within the sustained attention system being the origin behind self-reported cognitive difficulties in narcolepsy.

  6. EIF3G is associated with narcolepsy across ethnicities

    PubMed Central

    Holm, Anja; Lin, Ling; Faraco, Juliette; Mostafavi, Sara; Battle, Alexis; Zhu, Xiaowei; Levinson, Douglas F; Han, Fang; Gammeltoft, Steen; Jennum, Poul; Mignot, Emmanuel; Kornum, Birgitte R

    2015-01-01

    Type 1 narcolepsy, an autoimmune disease affecting hypocretin (orexin) neurons, is strongly associated with HLA-DQB1*06:02. Among polymorphisms associated with the disease is single-nucleotide polymorphism rs2305795 (c.*638G>A) located within the P2RY11 gene. P2RY11 is in a region of synteny conserved in mammals and zebrafish containing PPAN, EIF3G and DNMT1 (DNA methyltransferase 1). As mutations in DNMT1 cause a rare dominant form of narcolepsy in association with deafness, cerebellar ataxia and dementia, we questioned whether the association with P2RY11 in sporadic narcolepsy could be secondary to linkage disequilibrium with DNMT1. Based on genome-wide association data from two cohorts of European and Chinese ancestry, we found that the narcolepsy association signal drops sharply between P2RY11/EIF3G and DNMT1, suggesting that the association with narcolepsy does not extend into the DNMT1 gene region. Interestingly, using transethnic mapping, we identified a novel single-nucleotide polymorphism rs3826784 (c.596–260A>G) in the EIF3G gene also associated with narcolepsy. The disease-associated allele increases EIF3G mRNA expression. EIF3G is located in the narcolepsy risk locus and EIF3G expression correlates with PPAN and P2RY11 expression. This suggests shared regulatory mechanisms that might be affected by the polymorphism and are of relevance to narcolepsy. PMID:25669430

  7. Update on the treatment of narcolepsy: clinical efficacy of pitolisant.

    PubMed

    Calik, Michael W

    2017-01-01

    Narcolepsy is a neurological disease that affects 1 in 2,000 individuals and is characterized by excessive daytime sleepiness (EDS). In 60-70% of individuals with narcolepsy, it is also characterized by cataplexy or a sudden loss of muscle tone that is triggered by positive or negative emotions. Narcolepsy decreases the quality of life of the afflicted individuals. Currently used drugs treat EDS alone (modafinil/armodafinil, methylphenidate, and amphetamine), cataplexy alone ("off-label" use of antidepressants), or both EDS and cataplexy (sodium oxybate). These drugs have abuse, tolerability, and adherence issues. A greater diversity of drug options is needed to treat narcolepsy. The small molecule drug, pitolisant, acts as an inverse agonist/antagonist at the H3 receptor, thus increasing histaminergic tone in the wake promoting system of the brain. Pitolisant has been studied in animal models of narcolepsy and used in clinical trials as a treatment for narcolepsy. A comprehensive search of online databases (eg, Medline, PubMed, EMBASE, the Cochrane Library Database, Ovid MEDLINE, Europe PubMed Central, EBSCOhost CINAHL, ProQuest Research Library, Google Scholar, and ClinicalTrials.gov) was performed. Nonrandomized and randomized studies were included. This review focuses on the outcomes of four clinical trials of pitolisant to treat narcolepsy. These four trials show that pitolisant is an effective drug to treat EDS and cataplexy in narcolepsy.

  8. Challenges in the development of therapeutics for narcolepsy.

    PubMed

    Black, Sarah Wurts; Yamanaka, Akihiro; Kilduff, Thomas S

    2015-12-23

    Narcolepsy is a neurological disorder that afflicts 1 in 2000 individuals and is characterized by excessive daytime sleepiness and cataplexy-a sudden loss of muscle tone triggered by positive emotions. Features of narcolepsy include dysregulation of arousal state boundaries as well as autonomic and metabolic disturbances. Disruption of neurotransmission through the hypocretin/orexin (Hcrt) system, usually by degeneration of the HCRT-producing neurons in the posterior hypothalamus, results in narcolepsy. The cause of Hcrt neurodegeneration is unknown but thought to be related to autoimmune processes. Current treatments for narcolepsy are symptomatic, including wake-promoting therapeutics that increase presynaptic dopamine release and anticataplectic agents that activate monoaminergic neurotransmission. Sodium oxybate is the only medication approved by the US Food and Drug Administration that alleviates both sleep/wake disturbances and cataplexy. Development of therapeutics for narcolepsy has been challenged by historical misunderstanding of the disease, its many disparate symptoms and, until recently, its unknown etiology. Animal models have been essential to elucidating the neuropathology underlying narcolepsy. These models have also aided understanding the neurobiology of the Hcrt system, mechanisms of cataplexy, and the pharmacology of narcolepsy medications. Transgenic rodent models will be critical in the development of novel therapeutics for the treatment of narcolepsy, particularly efforts directed to overcome challenges in the development of hypocretin replacement therapy.

  9. Update on the treatment of narcolepsy: clinical efficacy of pitolisant

    PubMed Central

    Calik, Michael W

    2017-01-01

    Narcolepsy is a neurological disease that affects 1 in 2,000 individuals and is characterized by excessive daytime sleepiness (EDS). In 60–70% of individuals with narcolepsy, it is also characterized by cataplexy or a sudden loss of muscle tone that is triggered by positive or negative emotions. Narcolepsy decreases the quality of life of the afflicted individuals. Currently used drugs treat EDS alone (modafinil/armodafinil, methylphenidate, and amphetamine), cataplexy alone (“off-label” use of antidepressants), or both EDS and cataplexy (sodium oxybate). These drugs have abuse, tolerability, and adherence issues. A greater diversity of drug options is needed to treat narcolepsy. The small molecule drug, pitolisant, acts as an inverse agonist/antagonist at the H3 receptor, thus increasing histaminergic tone in the wake promoting system of the brain. Pitolisant has been studied in animal models of narcolepsy and used in clinical trials as a treatment for narcolepsy. A comprehensive search of online databases (eg, Medline, PubMed, EMBASE, the Cochrane Library Database, Ovid MEDLINE, Europe PubMed Central, EBSCOhost CINAHL, ProQuest Research Library, Google Scholar, and ClinicalTrials.gov) was performed. Nonrandomized and randomized studies were included. This review focuses on the outcomes of four clinical trials of pitolisant to treat narcolepsy. These four trials show that pitolisant is an effective drug to treat EDS and cataplexy in narcolepsy. PMID:28490912

  10. Narcolepsy and Orexins: An Example of Progress in Sleep Research

    PubMed Central

    De la Herrán-Arita, Alberto K.; Guerra-Crespo, Magdalena; Drucker-Colín, René

    2011-01-01

    Narcolepsy is a chronic neurodegenerative disease caused by a deficiency of orexin-producing neurons in the lateral hypothalamus. It is clinically characterized by excessive daytime sleepiness and by intrusions into wakefulness of physiological aspects of rapid eye movement sleep such as cataplexy, sleep paralysis, and hypnagogic hallucinations. The major pathophysiology of narcolepsy has been recently described on the bases of the discovery of the neuropeptides named orexins (hypocretins) in 1998; considerable evidence, summarized below, demonstrates that narcolepsy is the result of alterations in the genes involved in the pathology of the orexin ligand or its receptor. Deficient orexin transmission is sufficient to produce narcolepsy, as we describe here, animal models with dysregulated orexin signaling exhibit a narcolepsy-like phenotype. Remarkably, these narcoleptic models have different alterations of the orexinergic circuit, this diversity provide us with the means for making comparison, and have a better understanding of orexin-cell physiology. It is of particular interest that the most remarkable findings regarding this sleep disorder were fortuitous and due to keen observations. Sleep is a highly intricate and regulated state, and narcolepsy is a disorder that still remains as one of the unsolved mysteries in science. Nevertheless, advances and development of technology in neuroscience will provide us with the necessary tools to unravel the narcolepsy puzzle in the near future. Through an evaluation of the scientific literature we traced an updated picture of narcolepsy and orexins in order to provide insight into the means by which neurobiological knowledge is constructed. PMID:21541306

  11. EIF3G is associated with narcolepsy across ethnicities.

    PubMed

    Holm, Anja; Lin, Ling; Faraco, Juliette; Mostafavi, Sara; Battle, Alexis; Zhu, Xiaowei; Levinson, Douglas F; Han, Fang; Gammeltoft, Steen; Jennum, Poul; Mignot, Emmanuel; Kornum, Birgitte R

    2015-11-01

    Type 1 narcolepsy, an autoimmune disease affecting hypocretin (orexin) neurons, is strongly associated with HLA-DQB1*06:02. Among polymorphisms associated with the disease is single-nucleotide polymorphism rs2305795 (c.*638G>A) located within the P2RY11 gene. P2RY11 is in a region of synteny conserved in mammals and zebrafish containing PPAN, EIF3G and DNMT1 (DNA methyltransferase 1). As mutations in DNMT1 cause a rare dominant form of narcolepsy in association with deafness, cerebellar ataxia and dementia, we questioned whether the association with P2RY11 in sporadic narcolepsy could be secondary to linkage disequilibrium with DNMT1. Based on genome-wide association data from two cohorts of European and Chinese ancestry, we found that the narcolepsy association signal drops sharply between P2RY11/EIF3G and DNMT1, suggesting that the association with narcolepsy does not extend into the DNMT1 gene region. Interestingly, using transethnic mapping, we identified a novel single-nucleotide polymorphism rs3826784 (c.596-260A>G) in the EIF3G gene also associated with narcolepsy. The disease-associated allele increases EIF3G mRNA expression. EIF3G is located in the narcolepsy risk locus and EIF3G expression correlates with PPAN and P2RY11 expression. This suggests shared regulatory mechanisms that might be affected by the polymorphism and are of relevance to narcolepsy.

  12. Quality of life among pediatric patients with cancer: Contributions of time since diagnosis and parental chronic stress.

    PubMed

    Hamner, Taralee; Latzman, Robert D; Latzman, Natasha E; Elkin, T David; Majumdar, Suvankar

    2015-07-01

    Pediatric cancer is associated with a host of negative psychosocial consequences; however, outcomes vary extensively suggesting a need to better understand this variation. Empirical research suggests a positive association between time since diagnosis (TSD) and Quality of Life (QoL). In addition to TSD, family stressors have been found to be particularly important in predicting QoL among children. The current study examined parental chronic stress beyond TSD in explanation of QoL functioning among a sample of pediatric patients with cancer. Participants included 43 pediatric patients aged 5-18 years (M(age) = 10.2 ± 3.6) who were undergoing oncological treatment. Parents reported on TSD, child's QoL, and their own chronic stress. TSD was associated with greater physical functioning (r = 0.30, P < 0.05). Parental chronic stress was associated with poorer emotional (r = -0.54, P < 0.01), physical (r = -0.41, P < 0.01), and social functioning (r = -0.44, P < 0.01). Further, hierarchal linear regression analyzes indicated parental chronic stress contributed incrementally beyond TSD in the explanation of physical (β = -0.37, t = -2.58, P < 0.01), emotional (β = -0.47, t = -3.51, P < 0.00), and social functioning (β = -0.38, t = -2.67, P < 0.01). Parental chronic stress is associated with reduced levels of emotional, physical, and social functioning among pediatric patients. Future research is needed to further investigate the process by which chronic stress within the family interferes with adaptive coping among pediatric patients. In addition, clinical services may benefit from increased consideration of family factors, such as parental chronic stress, during oncological treatment. © 2015 Wiley Periodicals, Inc.

  13. Pediatric diabetes consortium type 1 diabetes new onset (NeOn) study: Factors associated with HbA1c levels one year after diagnosis

    USDA-ARS?s Scientific Manuscript database

    To identify determinants of hemoglobin A1c (HbA1c) levels 1 yr after the diagnosis of type 1 diabetes (T1D) in participants in the Pediatric Diabetes Consortium (PDC) T1D New Onset (NeOn) Study. Diabetes-specific as well as socioeconomic factors during the first year following diagnosis were analyze...

  14. AS03 Adjuvanted AH1N1 Vaccine Associated with an Abrupt Increase in the Incidence of Childhood Narcolepsy in Finland

    PubMed Central

    Nohynek, Hanna; Jokinen, Jukka; Partinen, Markku; Vaarala, Outi; Kirjavainen, Turkka; Sundman, Jonas; Himanen, Sari-Leena; Hublin, Christer; Julkunen, Ilkka; Olsén, Päivi; Saarenpää-Heikkilä, Outi; Kilpi, Terhi

    2012-01-01

    Background Narcolepsy is a chronic sleep disorder with strong genetic predisposition causing excessive daytime sleepiness and cataplexy. A sudden increase in childhood narcolepsy was observed in Finland soon after pandemic influenza epidemic and vaccination with ASO3-adjuvanted Pandemrix. No increase was observed in other age groups. Methods Retrospective cohort study. From January 1, 2009 to December 31, 2010 we retrospectively followed the cohort of all children living in Finland and born from January 1991 through December 2005. Vaccination data of the whole population was obtained from primary health care databases. All new cases with assigned ICD-10 code of narcolepsy were identified and the medical records reviewed by two experts to classify the diagnosis of narcolepsy according to the Brighton collaboration criteria. Onset of narcolepsy was defined as the first documented contact to health care because of excessive daytime sleepiness. The primary follow-up period was restricted to August 15, 2010, the day before media attention on post-vaccination narcolepsy started. Findings Vaccination coverage in the cohort was 75%. Of the 67 confirmed cases of narcolepsy, 46 vaccinated and 7 unvaccinated were included in the primary analysis. The incidence of narcolepsy was 9.0 in the vaccinated as compared to 0.7/100,000 person years in the unvaccinated individuals, the rate ratio being 12.7 (95% confidence interval 6.1–30.8). The vaccine-attributable risk of developing narcolepsy was 1∶16,000 vaccinated 4 to 19-year-olds (95% confidence interval 1∶13,000–1∶21,000). Conclusions Pandemrix vaccine contributed to the onset of narcolepsy among those 4 to 19 years old during the pandemic influenza in 2009–2010 in Finland. Further studies are needed to determine whether this observation exists in other populations and to elucidate potential underlying immunological mechanism. The role of the adjuvant in particular warrants further research before drawing

  15. Status Cataplecticus as Initial Presentation of Late Onset Narcolepsy

    PubMed Central

    Panda, Samhita

    2014-01-01

    Narcolepsy, one of the important causes of hypersomnia, is an under diagnosed sleep disorder. It has a bimodal age of onset around 15 and 35 years. It is characterized by the tetrad of excessive daytime sleepiness, cataplexy, hypnagogic/ hypnopompic hallucinations, and sleep paralysis. Cataplexy is by far the most predictive feature of narcolepsy. Status cataplecticus is the occurrence of cataplexy repeatedly for hours or days, a rare presentation of narcolepsy. This report describes an elderly gentleman with late onset narcolepsy in the sixth decade of life presenting with initial and chief symptom of status cataplecticus. Citation: Panda S. Status cataplecticus as initial presentation of late onset narcolepsy. J Clin Sleep Med 2014;10(2):207-209. PMID:24533005

  16. The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions.

    PubMed

    Zeitzer, Jamie M; Nishino, Seiji; Mignot, Emmanuel

    2006-07-01

    Narcolepsy is characterized by excessive daytime sleepiness, cataplexy and other manifestations of dissociated rapid eye movement sleep. Narcolepsy is typically treated with amphetamine-like stimulants (sleepiness) and antidepressants (cataplexy). Newer compounds, such as modafinil (non-amphetamine wake-promoting compound for excessive daytime sleepiness) and sodium oxybate (short-acting sedative for fragmented nighttime sleep, cataplexy, excessive daytime sleepiness), are increasingly used. Recent discoveries indicate that the major pathophysiology of human narcolepsy is the loss of lateral hypothalamic neurons that produce the neuropeptide hypocretin (orexin). Approximately 90% of people diagnosed as having narcolepsy with cataplexy are hypocretin ligand deficient. This has led to the development of new diagnostic tests (cerebrospinal fluid hypocretin-1 measurements). Hypocretin receptor agonists are likely to be ideal therapeutic options for hypocretin-deficient narcolepsy but such compounds are still not available in humans.

  17. The neurochemistry of awakening: findings from sleep disorder narcolepsy.

    PubMed

    Nishino, Seiji; Sagawa, Yohei

    2010-01-01

    Recent progress in our understanding of the pathophysiology of excessive sleepiness (EDS) is particularly indebted to the 1999 discovery of narcolepsy genes (i.e., hypocretin receptor and peptide genes) in animals and the subsequent discovery of hypocretin ligand deficiency in idiopathic cases of human narcolepsy-cataplexy. Hypocretin deficiency is also involved in many cases of symptomatic narcolepsy and EDS. Changes in other neurotransmitter systems (such as monoamines and acetylcholine) previously reported in these conditions are likely to be secondary to the impaired hypocretin neurotransmission; however, these may also mediate the sleep abnormalities seen in hypocretin deficient narcolepsy. The pathophysiology of hypocretin non-deficient narcolepsy is debated. Similarly, the pathophysiology of idiopathic hypersomnia, another defined primary hypersomnia, is largely unknown. This chapter discusses our current understanding of the neurochemistry of EDS, a disease of awakening.

  18. Concomitant loss of dynorphin, NARP, and orexin in narcolepsy

    PubMed Central

    Crocker, Amanda; España, Rodrigo A.; Papadopoulou, Maria; Saper, Clifford B.; Faraco, Juliette; Sakurai, Takeshi; Honda, Makoto; Mignot, Emmanuel; Scammell, Thomas E.

    2008-01-01

    Background Narcolepsy with cataplexy is associated with a loss of orexin/hypocretin. It is speculated that an autoimmune process kills the orexin-producing neurons, but these cells may survive yet fail to produce orexin. Objective To examine whether other markers of the orexin neurons are lost in narcolepsy with cataplexy. Methods We used immunohistochemistry and in situ hybridization to examine the expression of orexin, neuronal activity-regulated pentraxin (NARP), and prodynorphin in hypothalami from five control and two narcoleptic individuals. Results In the control hypothalami, at least 80% of the orexin-producing neurons also contained prodynorphin mRNA and NARP. In the patients with narcolepsy, the number of cells producing these markers was reduced to about 5–10% of normal. Conclusions Narcolepsy with cataplexy is likely caused by a loss of the orexin-producing neurons. In addition, loss of dynorphin and NARP may contribute to the symptoms of narcolepsy. PMID:16247044

  19. Overnight Polysomnography versus Respiratory Polygraphy in the Diagnosis of Pediatric Obstructive Sleep Apnea

    PubMed Central

    Tan, Hui-Leng; Gozal, David; Ramirez, Helena Molero; Bandla, Hari P. R.; Kheirandish-Gozal, Leila

    2014-01-01

    ) when they should have received a trial of anti-inflammatory therapy or been referred for ear, nose, and throat (ENT) review. Sixty percent of patients in group C would have received either a trial of medical treatment to treat mild OSA or no treatment, instead of referral to ENT services or commencement of continuous positive airway pressure. Conclusion: Apnea-hypopnea index (AHI) is underestimated in respiratory polygraphy (RP), and the disparity in AHI-RP and AHI-polysomnography can significantly affect clinical management decisions, particularly in children with mild and moderate obstructive sleep apnea (1 < AHI < 10/h total sleep time). Citation: Tan HL; Gozal D; Ramirez HM; Bandla HPR; Kheirandish-Gozal L. Overnight polysomnography versus respiratory polygraphy in the diagnosis of pediatric obstructive sleep apnea. SLEEP 2014;37(2):255-260. PMID:24497654

  20. Facial expression recognition and emotional regulation in narcolepsy with cataplexy.

    PubMed

    Bayard, Sophie; Croisier Langenier, Muriel; Dauvilliers, Yves

    2013-04-01

    Cataplexy is pathognomonic of narcolepsy with cataplexy, and defined by a transient loss of muscle tone triggered by strong emotions. Recent researches suggest abnormal amygdala function in narcolepsy with cataplexy. Emotion treatment and emotional regulation strategies are complex functions involving cortical and limbic structures, like the amygdala. As the amygdala has been shown to play a role in facial emotion recognition, we tested the hypothesis that patients with narcolepsy with cataplexy would have impaired recognition of facial emotional expressions compared with patients affected with central hypersomnia without cataplexy and healthy controls. We also aimed to determine whether cataplexy modulates emotional regulation strategies. Emotional intensity, arousal and valence ratings on Ekman faces displaying happiness, surprise, fear, anger, disgust, sadness and neutral expressions of 21 drug-free patients with narcolepsy with cataplexy were compared with 23 drug-free sex-, age- and intellectual level-matched adult patients with hypersomnia without cataplexy and 21 healthy controls. All participants underwent polysomnography recording and multiple sleep latency tests, and completed depression, anxiety and emotional regulation questionnaires. Performance of patients with narcolepsy with cataplexy did not differ from patients with hypersomnia without cataplexy or healthy controls on both intensity rating of each emotion on its prototypical label and mean ratings for valence and arousal. Moreover, patients with narcolepsy with cataplexy did not use different emotional regulation strategies. The level of depressive and anxious symptoms in narcolepsy with cataplexy did not differ from the other groups. Our results demonstrate that narcolepsy with cataplexy accurately perceives and discriminates facial emotions, and regulates emotions normally. The absence of alteration of perceived affective valence remains a major clinical interest in narcolepsy with cataplexy

  1. Prospective evaluation of clinical lung ultrasonography in the diagnosis of community-acquired pneumonia in a pediatric emergency department.

    PubMed

    Samson, Frédéric; Gorostiza, Inigo; González, Andrés; Landa, María; Ruiz, Lucía; Grau, Miguel

    2016-08-17

    To evaluate the applicability and utility of point-of-care lung ultrasonography (POCLUS) for the diagnosis of community-acquired pneumonia (CAP) in a pediatric emergency department. A prospective observational study on children with suspected CAP was carried out in a pediatric emergency department from August to December 2014. The evaluation of the chest radiography (CR) by two independent radiologists was considered as a reference standard. POCLUS was performed by pediatricians who were blinded to CR results. Following the WHO criteria, typical CAP was defined as an alveolar consolidation or infiltrate in CR and a visualization of lung consolidation with sonographic air bronchograms in POCLUS. The diagnostic accuracy of POCLUS (sensitivity, specificity, positive, and negative predictive values) was established using CR as a gold standard. We enrolled 200 children with a median age of 29.5 months (interquartile range, 18.5-52.5); 58.1% were males and 42.0% had focal decreased breath sounds and/or crackles. The prevalence of typical CAP according to the radiologist's evaluation was 42.5% (end-point consolidation and/or pleural effusion 56.5%, alveolar infiltrate 43.5%). The sensitivity and specificity of POCLUS were 87.1% [95% confidence interval (CI) 78.0-93.4] and 94.8% (95% CI 89.0-98.1), respectively. The positive and negative predictive values were 92.5% (95% CI 84.4-97.2) and 90.8% (95% CI 84.2-95.3), respectively. POCLUS performed by an emergency pediatrician with a limited experience in ultrasonography enables the diagnosis of pneumonia with high accuracy. POCLUS could become a feasible and promising alternative to CR in the diagnosis of suspected CAP, leading to a relevant decrease in children's exposure to ionizing radiations. Further studies specifically carried out in the pediatric outpatient setting are needed.

  2. Emergency point-of-care ultrasound diagnosis of hematocolpometra and imperforate hymen in the pediatric emergency department.

    PubMed

    Fischer, Jason W; Kwan, Charisse W

    2014-02-01

    A 12-year-old girl presented to the pediatric emergency department with a history of difficulty voiding and was found to have a firm, tender suprapubic mass on examination. Transabdominal emergency point-of-care ultrasound was used at the bedside to diagnose hematocolpometra due to an imperforate hymen. The diagnosis was confirmed by a comprehensive abdominal ultrasound and magnetic resonance imaging in the radiology suite. The patient was discharged on oral contraceptive medication and scheduled for an outpatient surgical hymenectomy following consultation with the gynecology service.

  3. Comparing the accuracy of obstetric sonography and fetal echocardiography during pediatric cardiology consultation in the prenatal diagnosis of congenital heart disease.

    PubMed

    Lai, Carman Wing Sze; Chau, Adolphus Kai Tung; Lee, Chin Peng

    2016-02-01

    The diagnostic accuracy of fetal echocardiogram performed by an obstetrician alone and that performed jointly by an obstetrician and pediatric cardiologist for congenital heart disease were compared. All cases of suspected fetal congenital heart disease (CHD) referred to the Prenatal Diagnostic Clinic at Tsan Yuk Hospital, Hong Kong during 2006-2011 were reviewed. Prenatal fetal echocardiogram findings were compared with postnatal diagnosis. Cases of incorrect prenatal diagnosis with significant difference in prognosis were analyzed qualitatively. One hundred and eleven cases of fetal CHD were analyzed. Complete agreement between prenatal and postnatal diagnosis of CHD was observed in 69.4% of cases by fetal echocardiogram performed by obstetrician and 83.8% by fetal echocardiogram performed during pediatric cardiology consultation (P = 0.001). Collaboration with a pediatric cardiologist also improved detection of ductal-dependent cardiac lesions (77.4% vs. 86%, P = < 0.001). Five cases with an incorrect diagnosis were associated with a different prognosis. Three of the cases involved outflow tract abnormalities with incorrect identification of outflow vessels. Collaboration with a pediatric cardiologist can significantly improve the accuracy of prenatal diagnosis of CHD. In particular, joint consultation is associated with significantly better detection of ductal-dependent lesions. Outflow tract abnormalities remain a diagnostic challenge in prenatal diagnosis. Incorrect identification of outflow tract vessels was the major cause of incorrect diagnosis in our series. © 2015 Japan Society of Obstetrics and Gynecology.

  4. Comparison of pediatric emergency physicians' and surgeons' evaluation and diagnosis of appendicitis.

    PubMed

    Kharbanda, Anupam B; Fishman, Steven J; Bachur, Richard G

    2008-02-01

    To compare the interexaminer reliability and ability to predict appendicitis between pediatric emergency physicians (EPs) and senior surgical residents. The authors conducted a prospective cohort study of children aged 3 to 18 years of age with signs and symptoms suspicious for appendicitis. Patients were initially examined by a pediatric EP attending and then by a consulting senior surgical resident. Physicians reported the presence or absence of specific historical and physical exam findings and predicted the likelihood the patient had appendicitis. Interexaminer reliability of historical and physical exam findings was compared (kappa statistic). Distributions and median probabilities of appendicitis were calculated for pediatric EP and surgeon predictions. The authors evaluated 350 patients with acute abdominal pain. Historical questions revealed slight to very good agreement (kappa statistic range 0.33-0.82) between physician types, whereas physical examination findings exhibited poor to fair agreement (range 0.14-0.48). Physicians predicted similar median probabilities of appendicitis for patients who were ultimately diagnosed with appendicitis (75% vs. 70%; p = 0.73) and patients without appendicitis (25% vs. 30%; p = 0.59). For a subset of patients given a > or = 90% predicted probability of appendicitis, pediatric EPs and senior surgical residents had similar accuracy (80% vs. 79%; p = 0.92). Similarly, among patients with < or = 10% predicted probability, pediatric EPs were correct in 95% and senior surgical residents correct in 94% of patients (p = 0.63). Pediatric EPs and senior surgical residents elicit historical findings from patients with suspected appendicitis with a greater degree of similarity than physical examination findings, which exhibit a wide degree of variability. Pediatric EPs and senior surgical residents do not differ in their ability to clinically predict appendicitis. These findings may be helpful in developing institutional

  5. Disease phenotype at diagnosis in pediatric Crohn's disease: 5-year analyses of the EUROKIDS Registry.

    PubMed

    de Bie, Charlotte I; Paerregaard, Anders; Kolacek, Sanja; Ruemmele, Frank M; Koletzko, Sibylle; Fell, John M E; Escher, Johanna C

    2013-02-01

    It has been speculated that pediatric Crohn's disease (CD) is a distinct disease entity, with probably different disease subtypes. We therefore aimed to accurately phenotype newly diagnosed pediatric CD by using the pediatric modification of the Montreal classification, the Paris classification. Information was collected from the EUROKIDS registry, a prospective, web-based registry of new-onset pediatric IBD patients in 17 European countries and Israel. When a complete diagnostic workup was performed (ileocolonoscopy, upper gastrointestinal [GI] endoscopy, small bowel imaging), CD patients were evaluated for ileocolonic disease extent, esophagogastroduodenal involvement, and jejunal/proximal ileal involvement. Disease behavior and the occurrence of granulomas were also analyzed. In all, 582 pediatric CD patients could be classified according to the Paris classification. Isolated terminal ileal disease (± limited cecal disease) was seen at presentation in 16%, isolated colonic disease in 27%, ileocolonic disease in 53%, and isolated upper GI disease in 4% of patients. In total, 30% had esophagogastroduodenal involvement and 24% jejunal/proximal ileal disease. Patients with L2 disease were less likely to have esophagogastroduodenal involvement or stricturing disease than patients with L1 or L3 disease. Terminal ileal disease and stricturing disease behavior were more common in children diagnosed after 10 years of age than in younger patients. Granulomas were identified in 43% of patients. Accurate phenotyping is essential in pediatric CD, as this affects the management of individual patients. Disease phenotypes differ according to age at disease onset. The Paris classification is a useful tool to capture the variety of phenotypic characteristics of pediatric CD.

  6. Risk of Narcolepsy after AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine in Adults: A Case-Coverage Study in England.

    PubMed

    Stowe, Julia; Andrews, Nicholas; Kosky, Christopher; Dennis, Gary; Eriksson, Sofia; Hall, Andrew; Leschziner, Guy; Reading, Paul; Shneerson, John M; Donegan, Katherine; Miller, Elizabeth

    2016-05-01

    An increased risk of narcolepsy has been observed in children following ASO3-adjuvanted pandemic A/H1N1 2009 (Pandemrix) vaccine. We investigated whether this risk extends to adults in England. Six adult sleep centers in England were visited between November 2012 and February 2014 and vaccination/clinical histories obtained from general practitioners. Suspected narcolepsy cases aged older than 17 y were selected. The risk of narcolepsy following Pandemrix was calculated using cases diagnosed by the time of the center visits and those with a diagnosis by November 30, 2011 after which there was increased awareness of the risk in children. The odds of vaccination in cases and in matched population data were compared using a case-coverage design. Of 1,446 possible cases identified, most had onset before 2009 or were clearly not narcolepsy. Of the 60 remaining cases, 20 were excluded after expert review, leaving 40 cases with narcolepsy; 5 had received Pandemrix between 3 and 18 mo before onset. All the vaccinated cases had cataplexy, two received a diagnosis by November 2011 and two were aged 40 y or older. The odds ratio for vaccination in cases compared to the population was 4.24 (95% confidence interval 1.45-12.38) using all cases and 9.06 (1.90-43.17) using cases with a diagnosis by November 2011, giving an attributable risk of 0.59 cases per 100,000 doses. We found a significantly increased risk of narcolepsy in adults following Pandemrix vaccination in England. The risk was lower than that seen in children using a similar study design. © 2016 Associated Professional Sleep Societies, LLC.

  7. Reliability of Smartphone-Based Instant Messaging Application for Diagnosis, Classification, and Decision-making in Pediatric Orthopedic Trauma.

    PubMed

    Stahl, Ido; Katsman, Alexander; Zaidman, Michael; Keshet, Doron; Sigal, Amit; Eidelman, Mark

    2017-07-11

    Smartphones have the ability to capture and send images, and their use has become common in the emergency setting for transmitting radiographic images with the intent to consult an off-site specialist. Our objective was to evaluate the reliability of smartphone-based instant messaging applications for the evaluation of various pediatric limb traumas, as compared with the standard method of viewing images of a workstation-based picture archiving and communication system (PACS). X-ray images of 73 representative cases of pediatric limb trauma were captured and transmitted to 5 pediatric orthopedic surgeons by the Whatsapp instant messaging application on an iPhone 6 smartphone. Evaluators were asked to diagnose, classify, and determine the course of treatment for each case over their personal smartphones. Following a 4-week interval, revaluation was conducted using the PACS. Intraobserver agreement was calculated for overall agreement and per fracture site. The overall results indicate "near perfect agreement" between interpretations of the radiographs on smartphones compared with computer-based PACS, with κ of 0.84, 0.82, and 0.89 for diagnosis, classification, and treatment planning, respectively. Looking at the results per fracture site, we also found substantial to near perfect agreement. Smartphone-based instant messaging applications are reliable for evaluation of a wide range of pediatric limb fractures. This method of obtaining an expert opinion from the off-site specialist is immediately accessible and inexpensive, making smartphones a powerful tool for doctors in the emergency department, primary care clinics, or remote medical centers, enabling timely and appropriate treatment for the injured child. This method is not a substitution for evaluation of the images in the standard method over computer-based PACS, which should be performed before final decision-making.

  8. Decision Making in Narcolepsy with Cataplexy

    PubMed Central

    Bayard, Sophie; Abril, Beatriz; Yu, Huan; Scholz, Sabine; Carlander, Bertrand; Dauvilliers, Yves

    2011-01-01

    Objectives: To investigate decision-making and addictive behaviors in narcolepsy-cataplexy (NC). NC is caused by the loss of hypothalamic neurons that produce hypocretins. The hypocretin system plays a crucial role in sleep, wakefulness, and energy homeostasis, and is also involved in emotion regulation, reward processing, and addiction. Setting: Academic sleep center. Patients: 23 subject with NC and 23 matched healthy controls. Design: We used the Iowa Gambling Task (IGT) to assess decision making under ambiguity condition based on emotional feedback processing and the Game of Dice Task (GDT) to assess decision making under risk condition. All participants underwent a semi-structured psychiatric interview and completed the Beck Depression Inventory-II and the UPPS Impulsive Behavior Scale. Patients underwent one night of polysomnography followed by an MSLT, with neuropsychological evaluation performed between MSLT sessions. Measurements and Results: NC patients had higher depressive symptoms and showed a significant lack of perseverance. One NC patient had a past history of drug dependence. NC patients also exhibited selective reduced IGT performance and normal performance on the GDT. No clinical or polysomnographic characteristics were associated with increased sensitivity to reward and/or decreased sensitivity to punishment. However, lack of perseverance in NC patients was associated with disadvantageous decision making on the IGT. Conclusion: We demonstrated a lack of perseverance and a selective reduced performance on decision making under ambiguity in NC in contrast to normal decision making under explicit conditions. Patients with narcolepsy-cataplexy may opt for choices with higher immediate emotional valence, regardless of higher future punishment, to compensate for their reduced reactivity to emotional stimuli. Citation: Bayard S; Abril B; Yu H; Scholz S; Carlander B; Dauvilliers Y. Decision making in narcolepsy with cataplexy. SLEEP 2011

  9. Pediatric lymphoma diagnosis: role of FNAC, biopsy, immunohistochemistry and molecular diagnostics.

    PubMed

    Iyer, Venkateswaran K

    2013-09-01

    Peripheral lymphadenopathy in the pediatric age group is screened using fine needle aspiration cytology (FNAC). Cases found to have features suspicious for lymphoma on FNAC need to undergo biopsy with immunohistochemistry for characterization and typing. In pediatric age group, peripheral lymph nodes are common in Hodgkin's lymphoma for which biopsy is needed for subtyping. Distinction of classical Hodgkin's lymphoma of lymphocyte rich type from nodular lymphocyte predominant Hodgkin's lymphoma needs biopsy evaluation and a panel of immunostains. T lymphoblastic lymphomas and Burkitt's lymphoma are the common types of non Hodgkin's lymphoma seen in the pediatric age group. All lymphomas require a biopsy evaluation with immunohistochemistry and analysis of molecular genetic markers for proper characterization and selection of optimal treatment which are discussed in detail in this review.

  10. Disclosure of HIV diagnosis to children: a poorly addressed issue in pediatric HIV care.

    PubMed

    Mengistu, Azene Dessie

    2013-10-01

    As antiretroviral therapy becomes more widely available in developing countries, increasing numbers of HIV infected children are surviving into adolescence and beyond. As they grow older, human immunodeficiency virus (HIV) serostatus disclosure presents a unique challenge to health care workers and care givers of children with HIV/AIDS. Although disclosure is a crucial component of the continuum of pediatric HIV care with proven health benefits, it is poorly addressed in routine clinical practice. The purpose of this paper is to provide a review of researches on disclosure of pediatric HIV infection. The need for practical interventions including a guideline development to support pediatric HIV disclosure which provides children with developmentally appropriate information about the disease is suggested.

  11. Pharmacological management of narcolepsy with and without cataplexy.

    PubMed

    Kallweit, Ulf; Bassetti, Claudio L

    2017-06-01

    Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered: This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies. First- and second-line options are discussed as well as combination therapies. In addition, treatment options for frequent coexisting co-morbidities and different phenotypes of narcolepsy are presented. Finally, this review considers potential future management strategies. Non-pharmacological approaches are important in the management of narcolepsy but will not be covered in this review. Expert opinion: Concise evaluation of symptoms and type of narcolepsy, coexisting co-morbidities and patients´ distinct needs is mandatory in order to identify a suitable, individual pharmacological treatment. First-line options include Modafinil/Armodafinil (for excessive daytime sleepiness, EDS), Sodium Oxybate (for EDS and/with cataplexy), Pitolisant (for EDS and cataplexy) and Venlafaxine (for cataplexy (off-label) and co-morbid depression). New symptomatic and causal treatment most probably will be completed by hypocretin-replacement and immune-modifying strategies.

  12. A consensus definition of cataplexy in mouse models of narcolepsy.

    PubMed

    Scammell, Thomas E; Willie, Jon T; Guilleminault, Christian; Siegel, Jerome M

    2009-01-01

    People with narcolepsy often have episodes of cataplexy, brief periods of muscle weakness triggered by strong emotions. Many researchers are now studying mouse models of narcolepsy, but definitions of cataplexy-like behavior in mice differ across labs. To establish a common language, the International Working Group on Rodent Models of Narcolepsy reviewed the literature on cataplexy in people with narcolepsy and in dog and mouse models of narcolepsy and then developed a consensus definition of murine cataplexy. The group concluded that murine cataplexy is an abrupt episode of nuchal atonia lasting at least 10 seconds. In addition, theta activity dominates the EEG during the episode, and video recordings document immobility. To distinguish a cataplexy episode from REM sleep after a brief awakening, at least 40 seconds of wakefulness must precede the episode. Bouts of cataplexy fitting this definition are common in mice with disrupted orexin/hypocretin signaling, but these events almost never occur in wild type mice. It remains unclear whether murine cataplexy is triggered by strong emotions or whether mice remain conscious during the episodes as in people with narcolepsy. This working definition provides helpful insights into murine cataplexy and should allow objective and accurate comparisons of cataplexy in future studies using mouse models of narcolepsy.

  13. Clinical evaluation of a 2K x 2K workstation for primary diagnosis in pediatric radiology

    NASA Astrophysics Data System (ADS)

    Razavi, Mahmood; Sayre, James W.; Simons, Margaret A.; Hamedaninia, Azar; Boechat, Maria I.; Hall, Theodore R.; Kangarloo, Hooshang; Taira, Ricky K.; Chuang, Keh-Shih; Kashifian, Payam

    1991-07-01

    Preliminary results of a large-scale ROC study evaluating the diagnostic performance of digital hardcopy film and 2K X 2K softcopy display for pediatric chest radiographs are presented. The pediatric disease categories studied were pneumothorax, linear atelectasis, air bronchograms, and interstitial disease. Digital images were obtained directly from a computed radiography system. Results from the readings of 239 chest radiographs by 4 radiologists show no significant difference between viewing images on film and softcopy display for the disease categories pneumothorax and air bronchograms. A slight performance edge for softcopy was seen for the disease categories of interstitial disease and linear atelectasis.

  14. A rare case of splenic pseudoaneurysm in pediatric splenic blunt trauma patient: Review of diagnosis and management

    PubMed Central

    Zhu, Roger Chen; Kurbatov, Vadim; Leung, Patricia; Sugiyama, Gainosuke; Roudnitsky, Valery

    2015-01-01

    Introduction Splenic pseudoaneurysms (SPA) are a rare but serious sequela of blunt traumatic injury to the spleen. Management of adult blunt splenic trauma is well-studied, however, in children, the management is much less well-defined. Presentation of case A 15 year-old male presented with severe abdominal pain of acute onset after sustaining injury to his left side while playing football. FAST was positive for free fluid in the abdomen. Initial abdomen CT demonstrated a grade III/IV left splenic laceration with moderate to large hemoperitoneum with no active extravasation or injury to the splenic vessels noted. A follow-up CT angiography of the abdomen demonstrated a splenic hypervascular structure suspicious for a small pseudoaneurysm. Splenic arteriogram which demonstrated multiple pseudoaneurysms arising from the second order splenic artery branches which was angioembolized and treated. Discussion & conclusion Questions still remain regarding the timing of repeat imaging for diagnosis of SPA following non-operative blunt splenic trauma, which patients should be imaged, and how to manage SPA upon diagnosis. More clinical study and basic science research is warranted to study the disease process of SPA in pediatric patient. We believe that our proposed management algorithm timely detect formation of delayed SPA formation and addresses the possible fatal disease course of pediatric SPA. PMID:26117449

  15. Localized Loss of Hypocretin (Orexin) Cells in Narcolepsy Without Cataplexy

    PubMed Central

    Thannickal, Thomas C.; Nienhuis, Robert; Siegel, Jerome M.

    2009-01-01

    Study Objectives: Narcolepsy with cataplexy is characterized by a loss of approximately 90% of hypocretin (Hcrt) neurons. However, more than a quarter of narcoleptics do not have cataplexy and have normal levels of hypocretin in their cerebrospinal fluid, raising the possibility that their disease is caused by unrelated abnormalities. In this study we examined hypocretin pathology in narcolepsy without cataplexy. Design: We examined postmortem brain samples, including the hypothalamus of 5 narcolepsy with cataplexy patients; one narcolepsy without cataplexy patient whose complete hypothalamus was available (patient 1); one narcolepsy without cataplexy patient with anterior hypothalamus available (patient 2); and 6 normal brains. The hypothalamic tissue was immunostained for Hcrt-1, melanin-concentrating hormone (MCH), and glial fibrillary acidic protein (GFAP). Measurements and Results: Neither of the narcolepsy without cataplexy patients had a loss of Hcrt axons in the anterior hypothalamus. The narcolepsy without cataplexy patient whose entire brain was available for study had an overall loss of 33% of hypocretin cells compared to normals, with maximal cell loss in the posterior hypothalamus. We found elevated levels of gliosis with GFAP staining, with levels increased in the posterior hypothalamic nucleus by (295%), paraventricular (211%), periventricular (123%), arcuate (126%), and lateral (72%) hypothalamic nuclei, but not in the anterior, dorsomedial, or dorsal hypothalamus. There was no reduction in the number of MCH neurons in either patient. Conclusions: Narcolepsy without cataplexy can be caused by a partial loss of hypocretin cells. Citation: Thannickal TC; Nienhuis R; Siegel JM. Localized loss of hypocretin (orexin) cells in narcolepsy without cataplexy. SLEEP 2009;32(8):993-998. PMID:19725250

  16. [Pediatric bipolar disorder - case report of a bipolar patient with disease onset in childhood and adolescence: implications for diagnosis and therapy].

    PubMed

    Lackner, N; Birner, A; Bengesser, S A; Reininghaus, B; Kapfhammer, H P; Reininghaus, E

    2014-11-01

    In recent years, intense controversies have evolved about the existence and exact diagnostic criteria of pediatric bipolar affective disorder. The present study aims to discuss pediatric bipolar affective disorder based on the current literature focussing on the diagnostic prospects. Based on a case study, a process of bipolar disorder developed in childhood is depicted exemplarily. Because of the high comorbidity and overlapping symptoms of paediatric bipolar affective disorder and other psychiatric disorders, the major impact of the differential diagnosis has to be stressed. An early diagnosis and the treatment possibilities are discussed.

  17. Hypocretin/orexin, sleep and narcolepsy.

    PubMed

    Hungs, M; Mignot, E

    2001-05-01

    The discovery that hypocretins are involved in narcolepsy, a disorder associated with excessive daytime sleepiness, cataplexy and unusually rapid transitions to rapid-eye-movement sleep, opens a new field of investigation in the area of sleep control physiology. Hypocretin-1 and -2 (also called orexin-A and -B) are newly discovered neuropeptides processed from a common precursor, preprohypocretin. Hypocretin-containing cells are located exclusively in the lateral hypothalamus, with widespread projections to the entire neuroaxis. Two known receptors, Hcrtr1 and Hcrtr2, have been reported. The functional significance of the hypocretin system is rapidly emerging in both animals and humans. Hypocretin abnormalities cause narcolepsy in dogs, human and mice. The role of the hypocretin system in normal sleep regulation is more uncertain. We believe hypocretin cells drive cholinergic and monoaminergic activity across the sleep cycle. Input from the suprachiasmatic nucleus to hypocretin-containing neurons may explain the occurrence of clock-dependent alertness. Other functions are suggested by pharmacological and neurochemical experiments. These include regulation of food intake, neuroendocrine function, autonomic nervous system activity and energy balance.

  18. Cognitive behavioral treatment for narcolepsy: can it complement pharmacotherapy?

    PubMed Central

    Marín Agudelo, Hernán Andrés; Jiménez Correa, Ulises; Carlos Sierra, Juan; Pandi-Perumal, Seithikurippu R.; Schenck, Carlos H.

    2014-01-01

    Sleep medicine in general and psychology in particular have recently developed cognitive behavioral treatment for narcolepsy (CBT-N). Despite a growing interest in this topic, most studies since 2007 have reviewed CBT applications for other sleep disorders. Currently, 6 reviews have been published on narcolepsy, with an expert consensus being reached that CBT represented an important adjunctive treatment for the disease. The current paper reviews the need for CBT applications for narcolepsy by generalizing the application of multicomponent treatments and performing studies that extrapolate the results obtained from multicenter studies. Nineteen studies were found in which the need-for-treatment guidelines identified the use of CBT for narcolepsy. Three additional studies were identified that evaluated the effectiveness of cognitive behavioral measures and multicomponent treatments for which treatment protocols have been proposed. PMID:26483898

  19. Narcolepsy and psychiatry: an evolving association of increasing interest.

    PubMed

    Fortuyn, H A Droogleever; Mulders, P C; Renier, W O; Buitelaar, J K; Overeem, S

    2011-08-01

    Gélineau originally described narcolepsy as a disease with an organic cause. However, the disorder had undeniable emotional triggers and psychiatric-like expressions, and soon a psychiatric etiology of narcolepsy became a seriously considered option. In fact, the psychiatric view dominated scientific thinking for a long time, not necessarily to the benefit of patients. When hypocretin (orexin) defects were proven to be the cause of narcolepsy Gélineau's original disease model was shown to be right. However, the psychiatric symptoms of the disease were not forgotten afterwards, but gained a different significance: as psychiatric expressions of a brain disease. These symptoms, such as anxiety and eating disorders, can be highly debilitating and warrant clinical attention. Here, we describe the role of psychiatry in the history of narcolepsy, showing their evolving association. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Post Tick-Borne Encephalitis Virus Vaccination Narcolepsy with Cataplexy

    PubMed Central

    Hidalgo, Hildegard; Kallweit, Ulf; Mathis, Johannes; Bassetti, Claudio L.

    2016-01-01

    Study Objectives: Narcolepsy with cataplexy (NC) is a chronic neurological disorder thought to result from an altered immune response based on a genetic predisposition coupled with environmental factors. Pandemrix vaccination has been reported to increase the risk of narcolepsy. We aimed at identifying other vaccines associated with the onset of narcolepsy. Methods: Case series and retrospective database study. Results: We identified four cases of NC following a tick-borne encephalitis (TBE) vaccination with FSME Immun. Additional four cases could be detected in the database of the Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines in Germany. Conclusions: Our findings implicate TBE vaccination as a potential additional environmental factor for the development of NC and add additional evidence for an immunological mechanism in the pathogenesis of the disease. Citation: Hidalgo H, Kallweit U, Mathis J, Bassetti CL. Post tick-borne encephalitis virus vaccination narcolepsy with cataplexy. SLEEP 2016;39(10):1811–1814. PMID:27397572

  1. Assessing narcolepsy with cataplexy in children and adolescents: development of a cataplexy diary and the ESS-CHAD

    PubMed Central

    Wang, Y Grace; Benmedjahed, Khadra; Lambert, Jérémy; Evans, Christopher J; Hwang, Steve; Black, Jed; Johns, Murray W

    2017-01-01

    Objective The aim of this study was to qualitatively evaluate concepts for incorporation into a daily diary to capture cataplexy frequency and to assess the content validity of the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD) in pediatric patients with narcolepsy. Patients and methods Face-to-face concept elicitation and cognitive interviews were conducted with children (7–9 years; n=13) and adolescents (10–17 years; n=16) who have narcolepsy with cataplexy, and their parents/caregivers. Results Similarities and differences were noted between narcolepsy concepts described by children and their parents/caregivers, suggesting some different but complementary perspectives; parents may not recognize cataplexy symptoms/triggers as well as children, but parents have greater recognition of the circumstances of falling asleep. Cataplexy diary modifications included changes in definitions and examples of cataplexy, using child-friendly terminology, adding a quantitative question to determine daily frequency, and standardizing the questionnaire for evening administration with self-completion by the child. Modifications were made to ESS-CHAD for child-friendly wording and to ensure that items reflect activities (eating, watching TV/video) and environments (school, bus/car transport) in which children are likely to participate. Two ESS-CHAD versions were proposed: one with a 1-month recall period, for general use, and the other with a recall period of “since your last study visit,” for research, which could be shorter or longer than 1 month (as short as 1 week). Conclusion The cataplexy diary and ESS-CHAD were modified for the assessment of children and adolescents. Further psychometric validation is recommended. These measures are being used in a Phase III, placebo-controlled clinical trial of sodium oxybate in children and adolescents with narcolepsy. PMID:28860883

  2. Primary liver tumors in pediatric patients: proper imaging technique for diagnosis and staging.

    PubMed

    Rozell, Joseph M; Catanzano, Tara; Polansky, Stanley M; Rakita, Dmitry; Fox, Lindsay

    2014-08-01

    Liver tumors in children are rare and comprise a diverse set of both benign and malignant lesions, most of which are not clinically detected until they are large and often difficult to resect. Technological advances in diagnostic imaging have greatly influenced the surgical planning of these lesions and ultimately the clinical outcome. The intent of this article is to present an imaging algorithm for the effective and efficient workup of liver tumors in pediatric patients. This includes the appropriate timing and use of various imaging modalities, such as conventional radiographs, ultrasound, computed tomography, and magnetic resonance imaging. This article also addresses the use of sedation, intravenous contrast agents, and the benefits and limitations of specific imaging modalities. An overview of the radiologic and pathologic findings in common liver lesions in pediatric patients, as well as individual case examples demonstrating the use of the proposed workup algorithm, is provided.

  3. Pediatric migraine variants: a review of epidemiology, diagnosis, treatment, and outcome.

    PubMed

    Lagman-Bartolome, Ana Marissa; Lay, Christine

    2015-06-01

    Pediatric migraine variants, previously known as childhood periodic syndromes, migraine equivalents, or migraine precursors, are a group of periodic or paroxysmal disorders occurring in patients who also have migraine with or without aura, or who have an increased likelihood of developing migraine. They have common key clinical features including periodic or paroxysmal character, normal neurological examination between attacks, family history of migraine, and clinical evolution to classic types of migraine. This article aims to review the pathophysiology, evaluation, and management of the pediatric migraine variants including abdominal migraine, benign paroxysmal vertigo, cyclic vomiting syndrome, and benign paroxysmal torticollis as well as the episodic syndromes that may lead to migraine, infantile colic, alternating hemiplegia of childhood, and vestibular migraine.

  4. Diagnosis versus dialogue: oral testimony and the study of pediatric pain.

    PubMed

    Nutkiewicz, Michael

    2008-01-01

    Through the perspectives of the children, this essay examines the communication between pediatric pain patients and their doctors. Based upon the oral history responses of thirty-two patients with chronic pain present for evaluation at the Pediatric Pain Clinic at UCLA, oral testimony was employed to uncover a wide range of topics related to a child's experience with pain such as family dynamics, how and when pain became a life-changing factor, coping strategies, and external sources that contribute to the child's understanding of pain. Most important, children were encouraged to explain what it was like to be in pain, not only to describe symptoms but also to share their dreams and hopes, their fears and uncertainties -- as well as the place of pain in their world.

  5. Insufficient non-REM sleep intensity in narcolepsy-cataplexy.

    PubMed

    Khatami, Ramin; Landolt, Hans-Peter; Achermann, Peter; Rétey, Julia V; Werth, Esther; Mathis, Johannes; Bassetti, Claudio L

    2007-08-01

    To compare electroencephalogram (EEG) dynamics during nocturnal sleep in patients with narcolepsy-cataplexy and healthy controls. Fragmented nocturnal sleep is a prominent feature and contributes to excessive daytime sleepiness in narcolepsy-cataplexy. Only 3 studies have addressed changes in homeostatic sleep regulation as a possible mechanism underlying nocturnal sleep fragmentation in narcolepsy-cataplexy. Baseline sleep of 11 drug-naive patients with narcolepsy-cataplexy (19-37 years) and 11 matched controls (18-41 years) was polysomnographically recorded. The EEG was subjected to spectral analysis. None, baseline condition. All patients with narcolepsy-cataplexy but no control subjects showed a sleep-onset rapid eye movement (REM) episode. Non-REM (NREM)-REM sleep cycles were longer in patients with narcolepsy-cataplexy than in controls (P = 0.04). Mean slow-wave activity declined in both groups across the first 3 NREM sleep episodes (P<0.001). The rate of decline, however, appeared to be steeper in patients with narcolepsy-cataplexy (time constant: narcolepsy-cataplexy 51.1 +/- 23.8 minutes [mean +/- SEM], 95% confidence interval [CI]: 33.4-108.8 minutes) than in controls (169.4 +/- 81.5 minutes, 95% CI: 110.9-357.6 minutes) as concluded from nonoverlapping 95% confidence interval of the time constants. The steeper decline of SWA in narcolepsy-cataplexy compared to controls was related to an impaired build-up of slow-wave activity in the second cycle. Sleep in the second cycle was interrupted in patients with narcolepsy-cataplexy, when compared with controls, by an increased number (P = 0.01) and longer duration (P = 0.01) of short wake episodes. Insufficient NREM sleep intensity is associated with nonconsolidated nocturnal sleep in narcolepsy-cataplexy. The inability to consolidate sleep manifests itself when NREM sleep intensity has decayed below a certain level and is reflected in an altered time course of slow-wave activity across NREM sleep episodes.

  6. At the bottom of the differential diagnosis list: unusual causes of pediatric hypertension.

    PubMed

    Grinsell, Matthew M; Norwood, Victoria F

    2009-11-01

    Hypertension affects 1-5% of children and adolescents, and the incidence has been increasing in association with obesity. However, secondary causes of hypertension such as renal parenchymal diseases, congenital abnormalities and renovascular disorders still remain the leading cause of pediatric hypertension, particularly in children under 12 years old. Other less common causes of hypertension in children and adolescents, including immobilization, burns, illicit and prescription drugs, dietary supplements, genetic disorders, and tumors will be addressed in this review.

  7. Pediatric sudden sensorineural hearing loss: Etiology, diagnosis and treatment in 20 children.

    PubMed

    Dedhia, Kavita; Chi, David H

    2016-09-01

    1. To report our experience in children with sudden-onset sensorineural hearing loss (SSNHL). 2. To describe the etiology and management of children with SSNHL. Retrospective review of 20 children with SSNHL, from 2000 to 2013 at a tertiary pediatric facility. Patients had the following inclusion criteria: history of normal hearing, hearing loss occurring in less than 3 days, and audiogram documentation. The average age of patients presenting with SSNHL is 11 years 3 months (22months-18years). Only 6 (30%) children presented prior to 2 weeks. Tinnitus (55%) was the most common associated symptoms followed by otalgia (25%), and vertigo (20%). Eight patients had bilateral hearing loss, 6 only right and 6 only left. Hearing loss severity ranged from profound (45%) being most common to mild. Etiology was unknown (30%), viral (25%), anatomic abnormality (25%), Meniere's disease (5%), autoimmune (5%), perilymphatic fistula (5%), and suppurative labyrinthitis (5%). Eight patients had initial treatment with oral steroids of which 50% had improvement on audiograms. Two patients underwent intratympanic injections, both showed improvement. Of the 12 patients with no treatment, only 1 had improved hearing. The true incidence of pediatric SSNHL is not well established in our literature. Unique aspects of pediatric SSNHL are delayed presentation and higher percent of anatomic findings. In our study 70% presented more than 2 weeks after experiencing symptoms. Anatomic abnormalities are in 40% of patients. Hearing improvement occurred in 50% of children treated with oral steroids. Intratympanic steroid treatment is another option but may have practical limitation in the pediatric population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Toxic-Metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management and Future Research

    PubMed Central

    Husain, Sohail Z.; Morinville, Veronique; Pohl, John; Abu-El-Haija, Maisam; Bellin, Melena D.; Freedman, Steve; Hegyi, Peter; Heyman, Melvin B; Himes, Ryan; Ooi, Chee Y.; Schwarzenberg, Sarah Jane; Usatin, Danielle; Uc, Aliye

    2016-01-01

    Objectives Pancreatitis in children can result from metabolic and toxic risk factors, but the evidence linking these factors is sparse. We review the evidence for association or causality of these risk factors in pancreatitis, discuss management strategies and their rationale. Methods We conducted a review of the pediatric pancreatitis literature with respect to the following risk factors: (a) hyperlipidemia, (b) hypercalcemia, (c) chronic renal failure, (d) smoking exposure, (e) alcohol, and (f) medications. Areas of additional research were identified. Results Hypertriglyceridemia of 1000 mg/dl or greater poses an absolute risk for pancreatitis; persistent elevations of calcium are predisposing. Further research is necessary to determine whether end stage renal disease leads to increased pancreatitis in children similar to adults. It is unknown whether cigarette smoking exposure, which clearly increases risk in adults, also increases risk in children. The role of alcohol in pediatric pancreatitis, whether direct or modifying, needs to be elucidated. The evidence supporting most cases of medication-induced pancreatitis is poor. Drug structure, improper handling of drug by host, and by-stander status may be implicated. Other pancreatitis risk factors must be sought in all cases. Conclusions The quality of evidence supporting causative role of various toxic and metabolic factors in pediatric pancreatitis is variable. Careful phenotyping is essential, including search for other etiologic risk factors. Directed therapy includes correction/ removal of any agent identified, and general supportive measures. Further research is necessary to improve our understanding of these pancreatitis risk factors in children. PMID:26594832

  9. Rotational thromboelastometry in the diagnosis of coagulopathy in major pediatric surgical operations.

    PubMed

    Sangkhathat, Surasak; Suwannarat, Daryth; Boonpipattanapong, Teeranut; Sangthong, Burapat

    2015-11-01

    To examine the correlation between rotational thromboelastometry (ROTEM) and coagulopathy after major pediatric surgical operations. From November 2013 until April 2015, pediatric cases who underwent major noncardiac surgeries and met the coagulopathy-risk criteria were reviewed for postoperative clinically significant coagulopathy (CSC). Two ROTEM studies, EXTEM and INTEM, were performed at the immediately postoperatively without the results being taken into any clinical decision making. Seventy-seven operations on 73 patients were included in this analysis. CSC occurred following 24 operations (32%) with a significantly higher incidence when a patient had a higher coagulopathy risk. On univariate analysis, evidence of diffuse bleeding in the operative field and massive bleeding were the 2 parameters with the strongest association with CSC. INTEM and EXTEM had specificities in diagnosing CSC of 75.5% and 94.3%, respectively. When each individual EXTEM and INTEM item was analyzed against CSC using ROC analysis, clot forming time (CFT) gave the largest under the curve area. The cut-off CFTs that gave the highest sensitivity and specificity in this study were 120seconds for EXTEM and 100seconds for INTEM. Postoperative coagulopathy is a risk that should always be considered in pediatric surgical operations. Thromboelastometry can be a hemostatic test providing high predictive value for this condition. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Delayed Diagnosis of Cushing's Disease in a Pediatric Patient due to Apparent Remission from Spontaneous Apoplexy.

    PubMed

    Rahman, Sara H; Chittibonia, Prashant; Quezado, Martha; Patronas, Nicholas; Stratakis, Constantine A; Lodish, Maya B

    2016-12-01

    We report here a pediatric patient whose Cushing's Disease was diagnosed late because of her cyclical presentation, presumably due to subclinical pituitary apoplexy. Starting at age 8, she presented with observable signs of Cushing's but was not clinically assessed for Cushing's Syndrome until the age of 15. Initial tests at age 15 were consistent with Cushing's Disease, however, the patient presented with spontaneous remission of hypercortisolemia just a few short months later. Her cushingoid features never subsided, and at age 17, her MRI showed a partially empty sella; this finding of an empty sella contributed evidence to our suspicion of asymptomatic apoplexy, especially since the patient never reported an episode of acute headache. Pituitary apoplexy in corticotroph adenomas is very uncommon, but even more rare in microadenomas, making this case very unusual. Lost to follow-up, she was not reevaluated for Cushing's Disease until age 25, and her laboratory tests were consistent with an adrenocorticotrophic-dependent pituitary tumor; Pituitary magnetic resonance imaging revealed a 9 mm X 6 mm X 8 mm mass projecting on the superior aspect of pituitary and abutting the wall of the right cavernous sinus. The patient had a transsphenoidal surgery to remove the microadenoma and is planned to undergo radiation therapy. To the best of our knowledge, this is the first report of subclinical apoplexy of a microadenoma in a pediatric patient with Cushing's Disease. It brings to light the importance of long term follow up for pediatric patients presenting with clinical symptoms of Cushing's Syndrome.

  11. Systematic tracking of dysregulated modules identifies disrupted pathways in narcolepsy

    PubMed Central

    Liu, Zhenhua; Zhao, Jiali; Tan, Yinyin; Tang, Minglu; Li, Guanzhen

    2015-01-01

    Objective: The objective of this work is to identify disrupted pathways in narcolepsy according to systematically tracking the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. Here, we performed systematic identification and comparison of modules across normal and narcolepsy conditions by integrating PPI and gene-expression data. Methods: Firstly, normal and narcolepsy PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, modules in PPI network were explored by clique-merging algorithm and we identified altered modules using a maximum weight bipartite matching and in non-increasing order. Finally, pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test to illuminate the biological pathways in narcolepsy. Results: Our analyses revealed that 235 altered modules were identified by comparing modules in normal and narcolepsy PPI network. Pathway functional enrichment analysis of disrupted module genes showed 59 disrupted pathways within threshold P < 0.001. The most significant five disrupted pathways were: oxidative phosphorylation, T cell receptor signaling pathway, cell cycle, Alzheimer’s disease and focal adhesion. Conclusions: We successfully identified disrupted pathways and these pathways might be potential biological processes for treatment and etiology mechanism in narcolepsy. PMID:26309600

  12. The clinical spectrum of narcolepsy and idiopathic hypersomnia.

    PubMed

    Aldrich, M S

    1996-02-01

    To better define the clinical spectra of narcolepsy and idiopathic hypersomnia, we retrospectively compared clinical and polygraphic findings and questionnaire results in groups of subjects with narcolepsy with or without cataplexy, idiopathic hypersomnia, insufficient sleep syndrome, mild sleep apnea, and excessive daytime sleepiness not otherwise specified. Sleep paralysis and sleep-related hallucinations were most frequent in narcolepsy-cataplexy, but their frequency did not differ between narcolepsy without cataplexy and idiopathic hypersomnia. Mean durations of nocturnal sleep, daytime naps, and morning grogginess were not increased in idiopathic hypersomnia compared with other groups. Among subjects without cataplexy, symptoms of sleep paralysis and sleep-related hallucinations were equally common in subjects with and without frequent sleep-onset REM periods. These findings suggest that the occurrence of these symptoms in subjects without classical narcolepsy-cataplexy is a function of factors other than a propensity for early onset of REM sleep and indicate a need to reevaluate diagnostic criteria for narcolepsy and idiopathic hypersomnia.

  13. Functional involvement of cerebral cortex in human narcolepsy.

    PubMed

    Oliviero, A; Della Marca, G; Tonali, P A; Pilato, F; Saturno, E; Dileone, M; Versace, V; Mennuni, G; Di Lazzaro, V

    2005-01-01

    The pathophysiology of human narcolepsy is still poorly understood. The hypoactivity of some neurotransmitter systems has been hypothesised on the basis of the canine model. To determine whether narcolepsy is associated with changes in excitability of the cerebral cortex, we assessed the excitability of the motor cortex with transcranial magnetic stimulation (TMS) in 13 patients with narcolepsy and in 12 control subjects. We used several TMS paradigms that can provide information on the excitability of the motor cortex. Resting and active motor thresholds were higher in narcoleptic patients than in controls and intracortical inhibition was more pronounced in narcoleptic patients. No changes in the other evaluated measures were detected. These results are consistent with an impaired balance between excitatory and inhibitory intracortical circuits in narcolepsy that leads to cortical hypoexcitability. We hypothesise that the deficiency of the excitatory hypocretin/orexin-neurotransmitter-system in narcolepsy is reflected in changes of cortical excitability since circuits originating in the lateral hypothalamus and in the basal forebrain project widely to the neocortex, including motor cortex. This abnormal excitability of cortical networks could be the physiological correlate of excessive daytime sleepiness and it could be the substrate for allowing dissociated states of wakefulness and sleep to emerge suddenly while patients are awake, which constitute the symptoms of narcolepsy.

  14. Differential diagnosis of pediatric tumors of the nasal cavity and paranasal sinuses: a 45-year multi-institutional review.

    PubMed

    Holsinger, F Christopher; Hafemeister, Adam C; Hicks, M John; Sulek, Marcelle; Huh, Winston W; Friedman, Ellen M

    2010-11-01

    We conducted a retrospective case-series review to identify the various diagnoses of neoplasms of the nasal cavity and paranasal sinuses in a pediatric population. Our study group was made up of 54 children-23 boys and 31 girls, aged 8 months to 16 years (mean: 9 yr). All patients had been diagnosed with a tumor of the nasal cavity or paranasal sinuses between Jan. 1, 1955, and Dec. 31, 1999, at one of four university-based, tertiary care referral centers. We compiled data on tumoral characteristics (location, size, and histopathology), morbidity and mortality, and rates of recurrence. Lesions included adnexal neoplasm, ameloblastic fibro-odontoma, basal cell carcinoma, benign fibrous histiocytoma, blue nevus, chondrosarcoma, compound nevus, epithelioma adenoides cysticum, esthesioneuroblastoma, Ewing sarcoma, fibrosarcoma, giant cell granuloma, granulocytic sarcoma, hemangioma, hemangiopericytoma, Langerhans cell histiocytosis, lymphangioma, lymphoma, melanoma, neuroblastoma, neurofibroma, ossifying osteofibroma, osteochondroma, osteosarcoma, port wine stain, rhabdomyosarcoma, Spitz nevus, and xanthogranuloma. To the best of our knowledge, this is the largest such study of its kind to date. We believe that the large size of this study and the data on disease incidence will allow clinicians to be better informed of the differential diagnosis of neoplasms of the nasal cavity and paranasal sinuses in the pediatric population.

  15. Early results of pediatric appendicitis after adoption of diagnosis-related group-based payment system in South Korea

    PubMed Central

    Moon, Suk-Bae

    2015-01-01

    Purpose As an alternative to the existing fee-for-service (FFS) system, a diagnosis-related group (DRG)-based payment system has been suggested. The aim of this study was to investigate the early results of pediatric appendicitis treatment under the DRG system, focusing on health care expenditure and quality of health care services. Patients and methods The medical records of 60 patients, 30 patients before (FFS group), and 30 patients after adoption of the DRG system (DRG), were reviewed retrospectively. Results Mean hospital stay was shortened, but the complication and readmission rates did not worsen in the DRG. Overall health care expenditure and self-payment decreased from Korean Won (KRW) 2,499,935 and KRW 985,540, respectively, in the FFS group to KRW 2,386,552 and KRW 492,920, respectively, in the DRG. The insurer’s payment increased from KRW 1,514,395 in the FFS group to KRW 1,893,632 in the DRG. For patients in the DRG, calculation by the DRG system yielded greater overall expenditure (KRW 2,020,209 vs KRW 2,386,552) but lower self-payment (KRW 577,803 vs KRW 492,920) than calculation by the FFS system. Conclusion The DRG system worked well in pediatric patients with acute appendicitis in terms of cost-effectiveness over the short term. The gradual burden on the national health insurance fund should be taken into consideration. PMID:26648734

  16. Procalcitonin as the biomarker of inflammation in diagnosis of appendicitis in pediatric patients and prevention of unnecessary appendectomies.

    PubMed

    Chandel, Vishal; Batt, Sajjid Hussain; Bhat, Mohammad Younis; Kawoosa, Nadeem Ulnazeer; Yousuf, Adfar; Zargar, Babar Rashid

    2011-04-01

    Numerous diseases mimic appendicitis, and it is often difficult to rule it out on the basis of clinical presentation. Concentration of procalcitonin selectively increases in inflammatory conditions and determination of its level can help in the diagnosis of acute appendicitis. A prospective, single centre based observational study carried out at our tertiary care institute. Twenty eight patients were admitted with preliminary diagnosis of acute appendicitis. The control group involved around 12 healthy children. Serum Procalcitonin concentration was measured in all patients using the 'Immunoluminometric Method' (LUMI- Test PCT), besides carrying out clinical examination and other investigations. The serums PCT comes out to be a better diagnostic test than serum CRP measurement as serum PCT was able to differentiate patients who came with abdominal pain but were having normal appendix from the patients who were actual cases of acute appendicitis. In patients with histologically confirmed acute appendicitis the level of PCT was above the normal value of 0.5 ng/ml in most cases. The analysis of procalcitonin in different groups of patients showed the serum procalcitonin test having high sensitivity of 95.65% and a specificity of about 100% on the basis of histopathological diagnosis of the removed appendix taking as the standard. The serum procalcitonin test when combined with reliable clinical signs and symptoms is an excellent diagnostic marker of the disease and should be done in the patients of pediatric appendicitis so that proper handling of the patient can be done and we can prevent unnecessary appendectomies.

  17. Is the Diagnosis of Physical Abuse Changed when Child Protective Services Consults a Child Abuse Pediatrics Subspecialty Group as a Second Opinion?

    ERIC Educational Resources Information Center

    Anderst, James; Kellogg, Nancy; Jung, Inkyung

    2009-01-01

    Objectives: To characterize the changes regarding the diagnosis of physical abuse provided to Child Protective Services (CPS) when CPS asks a Child Abuse Pediatrics (CAP) specialty group for a second opinion and works in concert with that CAP group. Methods: Subjects were reported to CPS for suspected physical abuse and were first evaluated by a…

  18. Cerebral salt wasting syndrome following brain injury in three pediatric patients: suggestions for rapid diagnosis and therapy.

    PubMed

    Berkenbosch, John W; Lentz, Christopher W; Jimenez, David F; Tobias, Joseph D

    2002-02-01

    The association between hyponatremia and intracranial pathology has been well described. When accompanied by natriuresis, hyponatremia has most commonly been attributed to inappropriate secretion of antidiuretic hormone. However, there is growing evidence to suggest that many of these patients may actually have cerebral mediated salt losses, a disorder referred to as the cerebral salt wasting syndrome (CSWS). While this syndrome has been reasonably well described in adults, data regarding CSWS in pediatric-aged patients remains sparse. Since fluid management of these disorders is different, it is important that the clinician be able to rapidly differentiate between them. We report three cases of CSWS in acutely brain-injured children and comment on the role that early quantitation of urine volume and urine sodium concentration had in rapidly establishing the correct diagnosis.

  19. Narrating narcolepsy--centering a side effect.

    PubMed

    Lundgren, Britta

    2015-01-01

    The mass-vaccination with Pandemrix was the most important preventive measure in Sweden during the A(H1N1) influenza pandemic of 2009-2010, and covered 60% of the population. From 2010, an increased incidence of the neurological disease narcolepsy was reported, and an association with Pandemrix was affirmed for more than 200 children and young adults. The parental experience of this side effect provided a starting point for a collectively shaped critical narrative to be acted out in public, but also personalized narratives of continual learning about the disease and its consequences. This didactic functionality resulted in active meaning-making practices about how to handle the aftermath--using dark humor, cognitive tricks, and making themselves and their children's bodies both objects and subjects of knowledge. Using material from interviews with parents, this mixing of knowledge work and political work, and the potential for reflective consciousness, is discussed.

  20. Is narcolepsy a classical autoimmune disease?

    PubMed

    Arango, María-Teresa; Kivity, Shaye; Shoenfeld, Yehuda

    2015-02-01

    Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness. It is caused by the loss of orexin producing neurons in the lateral hypothalamus. Current evidences suggest an autoimmune mediated process causing the specific loss of orexin neurons. The high association of the disease with the HLA DQB1*06:02, as well as the link with environmental factors and are important clues supporting this theory. Recently, the association between the occurrence of the disease and vaccination campaign after the 2009 H1N1 pandemic highlighted the importance to increase the knowledge in the Pandora box of the vaccines. This review discusses the last finding regarding the pathogenesis of the disease and its relationship with the H1N1 vaccines.

  1. Decision making in narcolepsy with cataplexy.

    PubMed

    Bayard, Sophie; Abril, Beatriz; Yu, Huan; Scholz, Sabine; Carlander, Bertrand; Dauvilliers, Yves

    2011-01-01

    To investigate decision-making and addictive behaviors in narcolepsy-cataplexy (NC). NC is caused by the loss of hypothalamic neurons that produce hypocretins. The hypocretin system plays a crucial role in sleep, wakefulness, and energy homeostasis, and is also involved in emotion regulation, reward processing, and addiction. Academic sleep center. 23 subject with NC and 23 matched healthy controls. We used the Iowa Gambling Task (IGT) to assess decision making under ambiguity condition based on emotional feedback processing and the Game of Dice Task (GDT) to assess decision making under risk condition. All participants underwent a semi-structured psychiatric interview and completed the Beck Depression Inventory-II and the UPPS Impulsive Behavior Scale. Patients underwent one night of polysomnography followed by an MSLT, with neuropsychological evaluation performed between MSLT sessions. NC patients had higher depressive symptoms and showed a significant lack of perseverance. One NC patient had a past history of drug dependence. NC patients also exhibited selective reduced IGT performance and normal performance on the GDT. No clinical or polysomnographic characteristics were associated with increased sensitivity to reward and/or decreased sensitivity to punishment. However, lack of perseverance in NC patients was associated with disadvantageous decision making on the IGT. We demonstrated a lack of perseverance and a selective reduced performance on decision making under ambiguity in NC in contrast to normal decision making under explicit conditions. Patients with narcolepsy-cataplexy may opt for choices with higher immediate emotional valence, regardless of higher future punishment, to compensate for their reduced reactivity to emotional stimuli.

  2. Diagnosis features of pediatric Gaucher disease patients in the era of enzymatic therapy, a national-base study from the Spanish Registry of Gaucher Disease.

    PubMed

    Andrade-Campos, Marcio; Alfonso, Pilar; Irun, Pilar; Armstrong, Judith; Calvo, Carmen; Dalmau, Jaime; Domingo, Maria-Rosario; Barbera, Jose-Luis; Cano, Horacio; Fernandez-Galán, Maria-Angeles; Franco, Rafael; Gracia, Inmaculada; Gracia-Antequera, Miguel; Ibañez, Angela; Lendinez, Francisco; Madruga, Marcos; Martin-Hernández, Elena; O'Callaghan, Maria Del Mar; Del Soto, Alberto Pérez; Del Prado, Yolanda Ruiz; Sancho-Val, Ignacio; Sanjurjo, Pablo; Pocovi, Miguel; Giraldo, Pilar

    2017-05-03

    The enzymatic replacement therapy (ERT) availability for Gaucher disease (GD) has changed the landscape of the disease, several countries have screening programs. These actions have promoted the early diagnosis and avoided many complications in pediatric patients. In Spain ERT has been available since 1993 and 386 patients have been included in the Spanish Registry of Gaucher Disease (SpRGD). The aim of this study is to analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. To analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. A review of data in SpRGD from patients' diagnosed before 18 years old was performed. The cohort was split according the year of diagnosis (≤1994, cohort A; ≥1995, cohort B). A total of 98 pediatric patients were included, GD1: 80, GD3: 18; mean age: 7.2 (0.17-16.5) years, 58 (59.2%) males and 40 (40.8%) females. Forty-five were diagnosed ≤ 1994 and 53 ≥ 1995. Genotype: N370S/N370S: 2 (2.0%), N370S/L444P: 27 (27.5%), N370S/other: 47 (48%), L444P/L444P: 7 (7.1%), L444P/D409H: 2 (2.0%), L444P/other: 3 (6.2%), other/other: 10 (10.2%). The mean age at diagnosis was earlier in patients diagnosed after 1995 (p < 0.001) and different between the subtypes, GD1: 8.2 (0.2-16.5) years and GD3: 2.8 (0.17-10.2) years (p < 0.001). There were more severe patients in the group diagnosed before 1994 (p = 0.045) carrying L444P (2), D409H (2), G377S (1), G195W (1) or the recombinant mutation. The patients' diagnosed ≤1994 showed worse cytopenias, higher chance of bone vascular complications at diagnosis and previous spleen removal. The patients started ERT at a median time after diagnosis of 5.2 years [cohort A] and 1.6 years [cohort B] (p < 0.001). The early diagnosis of Gaucher disease in the era of ERT availability has permitted to reduce the incidence of

  3. Pediatric diabetes consortium T1D New Onset (NeOn) study: clinical outcomes during the first year following diagnosis.

    PubMed

    Cengiz, Eda; Connor, Crystal G; Ruedy, Katrina J; Beck, Roy W; Kollman, Craig; Klingensmith, Georgeanna J; Tamborlane, William V; Lee, Joyce M; Haller, Michael J

    2014-06-01

    There have been few prospective, multicenter studies investigating the natural history of type 1 diabetes (T1D) from the time of diagnosis. The objective of this report from the Pediatric Diabetes Consortium (PDC) T1D New Onset (NeOn) study was to assess the natural history and clinical outcomes in children during the first year after diagnosis of T1D. Clinical measures from the first year following diagnosis were analyzed for 857 participants (mean age 9.1 yr, 51% female, 66% non-Hispanic White) not participating in an intervention study who had a HbA1c result at 12 months. Mean HbA1c ± SD was 102 ± 25 mmol/mol (11.4 ± 2.3%) at diagnosis, 55 ± 12 mmol/mol (7.2 ± 1.1%) at 3 months, 56 ± 15 mmol/mol (7.3 ± 1.3%) at 6 months and 62 ± 16 mmol/mol (7.8 ± 1.5%) at 12 months from diagnosis. A severe hypoglycemic (SH) event occurred in 31 (4%) participants (44 events, 5.2 events per 100 person-years). Diabetic ketoacidosis (DKA) not including diagnosis occurred in 10 (1%) participants (13 events, 1.5 events per 100 person-years). After onset of T1D, mean HbA1c reaches its nadir at 3-6 months with a gradual increase through 12 months. SH and DKA are uncommon but still occur during the first year with T1D. Data from large cohorts, such as the PDC T1D NeOn study, provide important insights into the course of T1D during the first year following diagnosis, which will help to inform the development of models to target future interventions. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. [Pediatric lymphomas diagnosis after needle biopsy in Abidjan: value of cytology versus MYC translocation examination].

    PubMed

    Yao, Gnangoran Victor; Toutain, Jérôme; Enoh, Jacob; Tre-Yavo, Mireille; Dachary, Dominique; Couitchere, Line; Koffi, Kouakou Emmanuel; Doukoure, Brahima; Ando, Joseph; De Mascarel, Antoine; Merlio, Jean-Philippe

    2012-02-01

    In Africa, lymphomas are widely represented by pediatric Burkitt lymphomas. In Abidjan, cytology performed after needle biopsy may be an examination of choice for pediatric lymphomas because of its low cost. We evaluated the value of this cytological examination in comparison with MYC rearrangement assessment. A cytological examination was performed after needle biopsy of masses suspected for lymphoma. The reliability of this cytological examination was assessed versus a cytogenetic technique of fluorescence in situ hybridization with a probe targeting locus 8q24 (MYC) which is recurrently rearranged in Burkitt lymphomas. Thirty-four patients were enrolled in this study. The median age was 8 years old. The main locations of the suspicious masses were maxillofacial and abdominal. Thirty cytological examinations identified cytological aspects of Burkitt lymphoma. Among these cases, the cytogenetic technique identified 24 cytogenetic rearrangements compatible with a translocation involving MYC as described in Burkitt lymphoma. Six cytological examinations identified cytological aspects of Burkitt lymphoma without MYC translocation. Two cytological examinations were not compatible with Burkitt lymphoma and a normal MYC status was observed. Two cytological examinations were technically not contributive. The cytological examination showed good performance, notably with excellent sensitivity. The cytological examinations compatible with a Burkitt lymphoma without MYC translocation (6/30=20.0%) could be explained by the absence of translocation involving locus 8q24 (MYC) in some endemic Burkitt lymphomas. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  5. Clinical effectiveness in the diagnosis and acute management of pediatric nephrolithiasis.

    PubMed

    Van Batavia, Jason P; Tasian, Gregory E

    2016-12-01

    The incidence of pediatric nephrolithiasis has risen over the past few decades leading to a growing public health burden. Children and adolescents represent a unique patient population secondary to their higher risks from radiation exposure as compared to adults, high risk of recurrence, and longer follow up time given their longer life expectancies. Ultrasound imaging is the first-line modality for diagnosing suspected nephrolithiasis in children. Although data is limited, the best evidence based medicine supports the use of alpha-blockers as first-line MET in children, especially when stones are small and in a more distal ureteral location. Surgical management of pediatric nephrolithiasis is similar to that in adults with ESWL and URS first-line for smaller stones and PCNL reserved for larger renal stone burden. Clinical effectiveness in minimizing risks in children and adolescents with nephrolithiasis centers around ED pathways that limit CT imaging, strict guidance to ALARA principles or use of US during surgical procedures, and education of both patients and families on the risks of repeat ionizing radiation exposures during follow up and acute colic events. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  6. NASPGHAN Clinical Report: Surveillance, Diagnosis, and Prevention of Infectious Diseases in Pediatric Patients With Inflammatory Bowel Disease Receiving Tumor Necrosis Factor-α Inhibitors.

    PubMed

    Ardura, Monica I; Toussi, Sima S; Siegel, Jane D; Lu, Ying; Bousvaros, Athos; Crandall, Wallace

    2016-07-01

    Children and adolescents with inflammatory bowel disease (IBD) receiving therapy with tumor necrosis factor α inhibitors (anti-TNFα) pose a unique challenge to health care providers in regard to the associated risk of infection. Published experience in adult populations with distinct autoinflammatory and autoimmune diseases treated with anti-TNFα therapies demonstrates an increased risk of serious infections with intracellular bacteria, mycobacteria, fungi, and some viruses; however, there is a paucity of robust pediatric data. With a rising incidence of pediatric IBD and increasing use of biologic therapies, heightened knowledge and awareness of infections in this population is important for primary care pediatricians, pediatric gastroenterologists, and infectious disease (ID) physicians. This clinical report is the result of a consensus review performed by pediatric ID and gastroenterology physicians detailing relevant published literature regarding infections in pediatric patients with IBD receiving anti-TNFα therapies. The objective of this document is to provide comprehensive information for prevention, surveillance, and diagnosis of infections based on current knowledge, until additional pediatric data are available to inform evidence-based recommendations.

  7. [Diagnosis and treatment of pediatric subglottic stenosis: experience in a tertiary care center].

    PubMed

    Botto, Hugo Alberto; Pérez, Cinthia Giselle; Cocciaglia, Alejandro; Nieto, Mary; Rodríguez, Hugo Aníbal

    2015-08-01

    Subglottic stenosis is among the most common causes of airway obstruction in children, 90% of which resulting from endotracheal intubation. The diagnosis is based on the patient's clinical, radiologic evaluation, flexible laryngoscopy and rigid airway endoscopy under general anesthesia. It must be suspected in children with respiratory distress after extubation. The therapeutic approach depends on the severity of the subglottic stenosis and the patient's symptoms. We describe our experience with the subglottic stenosis etiologies, diagnosis, treatment and outcome of patients with this condition.

  8. Sleeping Beauty in the Classroom: What Do Teachers Know about Narcolepsy?

    ERIC Educational Resources Information Center

    Cosgrove, Maryellen S.

    2002-01-01

    Investigated teachers' awareness of narcolepsy and the accuracy of their knowledge. Found educators uninformed about narcolepsy and how to accommodate narcoleptic students. Recommended that teachers be aware of narcolepsy's symptoms, plan variety and movement into students' lessons, and allow students to redo assignments if a sleep attack…

  9. Sleeping Beauty in the Classroom: What Do Teachers Know about Narcolepsy?

    ERIC Educational Resources Information Center

    Cosgrove, Maryellen S.

    2002-01-01

    Investigated teachers' awareness of narcolepsy and the accuracy of their knowledge. Found educators uninformed about narcolepsy and how to accommodate narcoleptic students. Recommended that teachers be aware of narcolepsy's symptoms, plan variety and movement into students' lessons, and allow students to redo assignments if a sleep attack…

  10. Psychosocial Profile and Quality of Life in Children With Type 1 Narcolepsy: A Case-Control Study

    PubMed Central

    Rocca, Francesca Letizia; Finotti, Elena; Pizza, Fabio; Ingravallo, Francesca; Gatta, Michela; Bruni, Oliviero; Plazzi, Giuseppe

    2016-01-01

    Study Objectives: To investigate behavioral aspects and quality of life in children and adolescents with type 1 narcolepsy (NT1). Methods: We performed a case-control study comparing 29 patients with NT1 versus sex- and age-matched patients with idiopathic epilepsy (n = 39) and healthy controls (n = 39). Behavior and quality of life were evaluated by self-administered questionnaires (Child Behavior Checklist, Pediatric Quality of Life Inventory). Patient groups were contrasted and scale results were correlated with clinical and polysomnographic parameters, and cerebrospinal fluid hypocretin-1 levels. Results: Young patients with NT1 showed increased internalizing problems associated with aggressive behavior. Emotional profile in patients with NT1 positively correlated with age at onset, diagnostic delay, and subjective sleepiness, whereas treatment and disease duration were associated with fewer behavioral problems (attention problems, aggressive behavior, and attention deficit/hyperactivity disorder). Psychosocial health domains of pediatric NT1 were worse than in healthy controls, whereas the physical health domains were comparable. Conclusions: Young NT1 patients show a discrete pattern of altered behavioral, thought, and mood profile in comparison with healthy controls and with idiopathic epilepsy patients thus suggesting a direct link with sleepiness. Further studies investigating behavior in patients with idiopathic hypersomnia or type 2 narcolepsy are needed to disentangle the role of REM sleep dysfunction and hypocretin deficiency in psychiatric disorders. Symptoms of withdrawal, depression, somatic complaints, thought problems, and aggressiveness were common, NT1 children perceived lower school competencies than healthy children, and their parents also reported worse psychosocial health. Our data suggest that early effective treatment and disease self-awareness should be promoted in NT1 children for their positive effect on behavior and psychosocial health

  11. Genetic association, seasonal infections and autoimmune basis of narcolepsy.

    PubMed

    Singh, Abinav Kumar; Mahlios, Josh; Mignot, Emmanuel

    2013-06-01

    In recent years, a growing number of potential autoimmune disorders affecting neurons in the central nervous system have been identified, including narcolepsy. Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone), hypnagogic hallucinations, and abnormalities of Rapid Eye Movement sleep. Narcolepsy is generally a sporadic disorder and is caused by the loss of hypocretin (orexin)-producing neurons in the hypothalamus region of the brain. Studies have established that more than 90% of patients have a genetic association with HLA DQB1*06:02. Genome-wide association analysis shows a strong association between narcolepsy and polymorphisms in the TCRα locus and weaker associations within TNFSF4 (also called OX40L), Cathepsin H and the P2RY11-DNMT1 (purinergic receptor subtype P2Y11 to DNMT1, a DNA methytransferase) loci, suggesting an autoimmune basis. Mutations in DNMT1 have also been reported to cause narcolepsy in association with a complex neurological syndrome, suggesting the importance of DNA methylation in the pathology. More recently, narcolepsy was identified in association with seasonal streptococcus, H1N1 infections and following AS03-adjuvanted pH1N1 influenza vaccination in Northern Europe. Potential immunological pathways responsible for the loss of hypocretin producing neurons in these cases may be molecular mimicry or bystander activation. Specific autoantibodies or T cells cross-reactive with hypocretin neurons have not yet been identified, however, thus narcolepsy does not meet Witebsky's criteria for an autoimmune disease. As the brain is not an easily accessible organ, mechanisms of disease initiation and progression remain a challenge to researchers.

  12. Genetic association, seasonal infections and autoimmune basis of narcolepsy

    PubMed Central

    Singh, Abinav Kumar; Mahlios, Josh; Mignot, Emmanuel

    2014-01-01

    In recent years, a growing number of potential autoimmune disorders affecting neurons in the central nervous system have been identified, including narcolepsy. Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness with irresistible sleep attacks, cataplexy (sudden bilateral loss of muscle tone), hypnagogic hallucinations, and abnormalities of Rapid Eye Movement sleep. Narcolepsy is generally a sporadic disorder and is caused by the loss of hypocretin (orexin)-producing neurons in the hypothalamus region of the brain. Studies have established that more than 90% of patients have a genetic association with HLA DQB1*06:02. Genome-wide association analysis shows a strong association between narcolepsy and polymorphisms in the TCRα locus and weaker associations within TNFSF4 (also called OX40L), Cathepsin H and the P2RY11-DNMT1 (purinergic receptor subtype P2Y11 to DNMT1, a DNA methytransferase) loci, suggesting an autoimmune basis. Mutations in DNMT1 have also been reported to cause narcolepsy in association with a complex neurological syndrome, suggesting the importance of DNA methylation in the pathology. More recently, narcolepsy was identified in association with seasonal streptococcus, H1N1 infections and following AS03-adjuvanted pH1N1 influenza vaccination in Northern Europe. Potential immunological pathways responsible for the loss of hypocretin producing neurons in these cases may be molecular mimicry or bystander activation. Specific autoantibodies or T cells cross-reactive with hypocretin neurons have not yet been identified, however, thus narcolepsy does not meet Witebsky’s criteria for an autoimmune disease. As the brain is not an easily accessible organ, mechanisms of disease initiation and progression remain a challenge to researchers. PMID:23497937

  13. Screening and counseling associated with obesity diagnosis in a national survey of ambulatory pediatric visits.

    PubMed

    Cook, Stephen; Weitzman, Michael; Auinger, Peggy; Barlow, Sarah E

    2005-07-01

    To examine clinician-reported diagnosis of obesity and frequency of blood pressure assessment and diet and exercise counseling during ambulatory visits made by children and adolescents. The National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey 1997 to 2000 were combined for visits to clinicians of 2- to 18-year-olds. Well-child visits (WCVs) were examined for frequencies of obesity diagnosis, blood pressure screening, and diet and exercise counseling in relation to patient and clinician characteristics. Multivariate models examined the relationship of patient and visit characteristics with diet and exercise counseling. Of the 32 930 ambulatory visits made by 2- to 18-year-olds in 1997-2000, obesity was diagnosed at 0.78% of all visits and 0.93% of WCVs. Blood pressure assessment was reported in 61.1% of WCVs with obesity diagnosis compared with 43.9% of WCVs without obesity diagnosis. WCVs with obesity diagnosis had higher diet counseling rates (88.4% vs 35.7%) and higher exercise counseling rates (69.2% vs 18.6%). Diet counseling was reported for 88.4% and exercise counseling was reported for 69.2% of visits with an obesity diagnosis compared with 35.7% and 18.6% during WCVs without a diagnosis of obesity. In multivariate analyses, factors associated with diet counseling at WCVs were diagnosis of obesity (odds ratio [OR]: 12.9; 95% confidence interval [CI]: 3.0-55.3), being seen by pediatricians (OR: 2.5; 95% CI: 1.6-3.9), 2- to 5-year-olds compared with 12- to 18-year-olds (OR: 0.7; 95% CI: 0.5-1.0), and self-pay compared with private insurance visits (OR: 0.6; 95% CI: 0.4-0.9). Associations with exercise counseling were similar to those for diet counseling, but exercise counseling occurred less frequently in visits by black youths compared with white youths (OR: 0.5; 95% CI: 0.3-0.8). Clinicians may overlook obesity during WCVs. Programs to increase obesity diagnosis could improve diet and exercise counseling rates, but

  14. Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP).

    PubMed

    Barone, Angelica; Lucarelli, Annunziata; Onofrillo, Daniela; Verzegnassi, Federico; Bonanomi, Sonia; Cesaro, Simone; Fioredda, Francesca; Iori, Anna Paola; Ladogana, Saverio; Locasciulli, Anna; Longoni, Daniela; Lanciotti, Marina; Macaluso, Alessandra; Mandaglio, Rosalba; Marra, Nicoletta; Martire, Baldo; Maruzzi, Matteo; Menna, Giuseppe; Notarangelo, Lucia Dora; Palazzi, Giovanni; Pillon, Marta; Ramenghi, Ugo; Russo, Giovanna; Svahn, Johanna; Timeus, Fabio; Tucci, Fabio; Cugno, Chiara; Zecca, Marco; Farruggia, Piero; Dufour, Carlo; Saracco, Paola

    2015-06-01

    Acquired aplastic anemia (AA) is a rare heterogeneous disease characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3/million inhabitants/year, in Europe, but higher in East Asia. Survival in severe aplastic anemia (SAA) has markedly improved in the past 2 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive and biologic drugs, and supportive care. In SAA hematopoietic stem cell transplant (HSCT) from a matched sibling donor (MSD) is the treatment of choice. If a MSD is not available, the options include immunosuppressive therapy (IST) or unrelated donor HSCT. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary, evidence-based document issued by a group of pediatric hematologists was discussed, modified and approved during a series of "Consensus Conferences" according to procedures previously validated by the AIEOP Board. The guidelines highlight the importance of referring pediatric patients with AA to pediatric centers with long experience in diagnosis, differential diagnosis, management, supportive care and follow-up of AA.

  15. Variations in Mental Health Diagnosis and Prescribing Across Pediatric Primary Care Practices

    PubMed Central

    Mayne, Stephanie L.; Ross, Michelle E.; Song, Lihai; McCarn, Banita; Steffes, Jennifer; Liu, Weiwei; Margolis, Benyamin; Azuine, Romuladus; Gotlieb, Edward; Grundmeier, Robert W.; Leslie, Laurel K.; Localio, Russell; Wasserman, Richard

    2016-01-01

    BACKGROUND: Primary care pediatricians increasingly care for children’s mental health problems, but little is known about practice-level variation in diagnosis and psychotropic medication prescribing practices. METHODS: This retrospective review of electronic heath records from 43 US primary care practices included children aged 4 to 18 years with ≥1 office visit from January 1, 2009, to June 30, 2014. We examined variability in diagnosis and psychotropic prescribing across practices using logistic regression with practice fixed effects and evaluated associations of the availability of colocated or community-based mental health providers or the proportion of children in foster care with diagnosis and prescribing using generalized linear mixed models. RESULTS: Among 294 748 children, 40 932 (15%) received a mental health diagnosis and 39 695 (14%) were prescribed psychotropic medication. Attention deficit/hyperactivity disorder was most commonly diagnosed (1%–16% per practice). The proportion of children receiving any psychotropic medication (4%-26%) and the proportion receiving ≥2 medication classes (1%-12%) varied across practices. Prescribing of specific medication classes also varied (stimulants, 3%–18%; antidepressants, 1%–12%; α-agonists, 0%–8%; second-generation antipsychotics, 0%–5%). Variability was partially explained by community availability of psychiatrists (significantly higher odds of a diagnosis or prescription when not available) but not by colocation of mental health professionals or percentage of children in foster care. CONCLUSIONS: The prevalence of mental health diagnosis and psychotropic medication prescribing varies substantially across practices and is only partially explained by psychiatrist availability. Research is needed to better define the causes of variable practice-level diagnosis and prescribing and implications for child mental health outcomes. PMID:27244791

  16. Prenatal diagnosis and the pediatric surgeon: the impact of prenatal consultation on perinatal management.

    PubMed

    Crombleholme, T M; D'Alton, M; Cendron, M; Alman, B; Goldberg, M D; Klauber, G T; Cohen, A; Heilman, C; Lewis, M; Harris, B H

    1996-01-01

    Pediatric surgeons are increasingly called on by obstetrical colleagues to counsel parents about the implications of a prenatal ultrasound finding. Our understanding of the natural history of many prenatally diagnosed surgical conditions has grown significantly in recent years. Whether prenatal surgical consultation can influence perinatal course had not been investigated. During an 21-month period, 12,865 prenatal ultrasound studies were performed on a total of 4,551 patients, and 221 prenatal surgical consultations were obtained through a newly established fetal treatment program at a tertiary care prenatal diagnostic center. To evaluate the impact of prenatal pediatric surgical consultation on perinatal course, the authors reviewed changes in management including termination of pregnancy, in utero intervention, and altered site, mode, or timing of delivery. Two hundred twenty-one fetuses were referred for consultation; their 234 congenital anomalies included genitourinary (36%), thoracic (16%), intraabdominal (14.5%), abdominal wall (10.6%), neurological (9%), skeletal (6%), and head and neck (2.5%) defects; 2.5% had tumors and 2.5% were twin pregnancies. Pregnancy was terminated in 9.5% of cases, because of patient request, chromosomal abnormality, or dismal prognosis. In 3.6%, the decision to terminate was changed as a result of consultation. Site of delivery was changed as a result of consultation in 37% to facilitate postnatal evaluation and initiate immediate treatment. Mode of delivery was changed in 6.8% to prevent dystocia, hemorrhage into a tumor, as in sacrococcygeal teratoma, or to provide an emergency airway, as in cervical teratoma. The timing of delivery was changed in 4.5% to avoid further damage to fetal organs in cases of obstructive uropathy, gastroschisis, sacrococcygeal teratoma with high-output failure, and hydrocephalus. Five percent (11) underwent treatment in utero for fetal hydrothorax, obstructive uropathy, twin-twin transfusion

  17. Preoperative multiple endocrine neoplasia type 1 diagnosis improves the surgical outcomes of pediatric patients with primary hyperparathyroidism.

    PubMed

    Romero Arenas, Minerva A; Morris, Lilah F; Rich, Thereasa A; Cote, Gilbert J; Grubbs, Elizabeth G; Waguespack, Steven G; Perrier, Nancy D

    2014-04-01

    Primary hyperparathyroidism (PHPT) is uncommon in children. The surgical management of PHPT in children has evolved over the past two decades. A retrospective study of patients who underwent parathyroidectomy for PHPT diagnosed at age < 18 years and managed at a tertiary referral center for endocrine and familial disorders. Thirty-eight patients met eligibility criteria (1981-2012). Median age at PHPT diagnosis was 15 years. Two-thirds of patients were symptomatic (68%, n=26), most commonly from nephrolithiasis. Twenty-six (68%) patients underwent a standard cervical exploration while 32% underwent a focused unilateral parathyroidectomy. Multiple endocrine neoplasia type 1 (MEN1) was diagnosed preoperatively in 22/26 patients. Patients with a preoperative diagnosis of MEN1 were more likely to undergo a complete initial operation (≥ 3 gland parathyroidectomy with transcervical thymectomy, 13/22, 59% vs. 0/4, 0%; P=0.03) and less likely to have recurrent disease (10/22, 45% vs. 3/4, 75%; P<0.001) during follow up than patients diagnosed postoperatively. Children with PHPT should raise suspicion for MEN1. Preoperative MEN1 evaluation helped guide the extent of initial parathyroidectomy and was associated with lower rates of recurrence in sporadic and familial PHPT in pediatric patients. Management should occur at a high volume center with experienced clinicians and genetic counseling services. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Effect of sodium oxybate on disrupted nighttime sleep in patients with narcolepsy.

    PubMed

    Roth, Thomas; Dauvilliers, Yves; Guinta, Diane; Alvarez-Horine, Sarah; Dynin, Efim; Black, Jed

    2016-11-03

    This post hoc analysis evaluated the dose-related effects of sodium oxybate on sleep continuity and nocturnal sleep quality in patients with narcolepsy-cataplexy. Polysomnography data, including shifts to Stage N1/Wake, were from a randomized, placebo-controlled trial of sodium oxybate. Patients were ≥16 years old with a diagnosis of narcolepsy including symptoms of cataplexy and excessive daytime sleepiness. Treatment was for 8 weeks with placebo or sodium oxybate 4.5, 6 or 9 g administered as two equally divided nightly doses. Relative to baseline, significant dose-dependent reductions in the number of shifts per hour from Stages N2/3/rapid eye movement and Stages N2/3 to Stage N1/Wake were observed at week 8 with sodium oxybate (P < 0.05); sodium oxybate 6- and 9-g doses also resulted in similar reductions in shifts per hour of rapid eye movement to Stage N1/Wake (both P < 0.05). Across all shift categories, the shift reductions with sodium oxybate 9 g were significantly greater than those observed with placebo (P < 0.05). Improvements from baseline in reported sleep quality were significantly greater with sodium oxybate 4.5 and 9 g at week 8 (P < 0.05). Correlations between change from baseline in number of shifts per hour to Stage N1/Wake and cataplexy frequency, patient-reported nocturnal sleep quality, and excessive daytime sleepiness assessed using the Epworth Sleepiness Scale were numerically highest for the sodium oxybate 9-g dose across all sleep stage shift categories. In these patients with narcolepsy, sodium oxybate showed improvements in the sleep continuity and nocturnal sleep quality that are characteristic of disrupted nighttime sleep (ClinicalTrials.gov identifier NCT00049803).

  19. [Is diagnosis of persistent pediatric hearing loss still made too late?].

    PubMed

    Finckh-Krämer, U; Spormann-Lagodzinski, M E; Nubel, K; Hess, M; Gross, M

    1998-06-01

    Since 1994, the German Registry for hearing Loss in Children has registered data of 1500 children and by now can present results concerning the age at diagnosis of permanent hearing loss in children in Germany. The mean age at diagnosis is still very high. There is a strong correlation between age at diagnosis and degree of hearing loss, i.e., severe and profound hearing loss, is diagnosed distinctly earlier than mild and moderate hearing loss. On average, mild hearing loss is diagnosed with 6.2 years, moderate h.l. with 4.4 years, severe hearing loss with 2.5 years and profound hearing loss with 1.9 years. This corresponds with the results of regional German studies. At least regionally, in other European countries the age at diagnosis is known to be distinctly lower. In 36% of the children registered in Germany the delay between first suspicion and diagnosis of permanent hearing loss is 1 year or more.

  20. Utility of peripheral blood immunophenotyping by flow cytometry in the diagnosis of pediatric acute leukemia.

    PubMed

    Metrock, Laura K; Summers, Ryan J; Park, Sunita; Gillespie, Scott; Castellino, Sharon; Lew, Glen; Keller, Frank G

    2017-10-01

    Childhood acute leukemia is traditionally diagnosed from a bone marrow aspirate (BMA). New-onset acute leukemia patients do not always have visible circulating blasts in the peripheral blood (PB) at diagnosis. While the role of bone marrow flow cytometry for the diagnosis of acute leukemia is well established, the utility of PB flow cytometry (PBFC) is unknown. We performed a single-institution retrospective analysis to compare PBFC versus BMA in establishing or excluding a diagnosis of childhood acute leukemia. We retrospectively identified 485 PBFC samples with concurrent BMA from 2008 to 2013. Results of four-color flow cytometry for immunophenotypic characterization of leukemic versus nonclonal disease were characterized. Sensitivity and specificity were calculated among patients without a known diagnosis or prior therapy. Among 485 samples eligible for analysis, 120 had negative PBFC and BMA, 359 had positive PBFC and BMA, 3 had negative PBFC and positive BMA, and 3 had positive PBFC and negative BMA. There were small but significant differences in sensitivity (100 vs. 93.8%; P = 0.002) and positive predictive value (100 vs. 93.8%; P = 0.002) favoring BMA over PBFC among those demonstrating absence of circulating morphologic blasts. PBFC has high sensitivity and specificity for the diagnosis of childhood acute leukemia. The predictive value of PBFC remains high for patients without visible circulating blasts and may enhance the diagnostic process for determining the indications for marrow testing. © 2017 Wiley Periodicals, Inc.

  1. The role of US in finding intussusception and alternative diagnosis: a report of 100 pediatric cases.

    PubMed

    Ja Lim, Kyoung; Lee, Kwanseop; Yoon, Dae Young; Moon, Jin Hee; Lee, Hyun; Kim, Min-Jeong; Kim, Sam Soo

    2015-02-01

    The clinical diagnosis of intussusception remains challenging, because many children with intussusception may present with non-specific signs and symptoms, which overlap with other conditions. Therefore imaging, in particular ultrasonography (US), plays a significant role in the management of these patients. To evaluate how US can contribute to the diagnosis in clinically suspected intussusception and finding alternative diagnosis. We retrospectively reviewed reports of US examinations and medical records of 100 patients (51 boys, 49 girls; mean age, 23.0 ± 12.1 months) who underwent abdominal US for clinically suspected intussusception. Each US study was assessed for the presence or absence of intussusception and for a possible alternative diagnosis in cases interpreted as negative for intussusception. Thirty-seven patients had US findings consistent with intussusception, which was confirmed by air enema. In seven patients, US studies were normal. Alternative diagnoses were identified by US for each of the remaining 56 patients, including ileocolitis (n = 20), terminal ileitis (n = 18), mesenteric lymphadenitis (n = 13), choledochal cyst (n = 1), accessory spleen torsion (n = 1), small bowel ileus (n = 1), midgut volvulus with bowel ischemia (n = 1), and hydronephrosis (n = 1). With the high sensitivity and specificity of this study we conclude that US is valuable in detecting intussusception and finding the alternative diagnosis. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  2. Risk of Narcolepsy after AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine in Adults: A Case-Coverage Study in England

    PubMed Central

    Stowe, Julia; Andrews, Nicholas; Kosky, Christopher; Dennis, Gary; Eriksson, Sofia; Hall, Andrew; Leschziner, Guy; Reading, Paul; Shneerson, John M.; Donegan, Katherine; Miller, Elizabeth

    2016-01-01

    Study Objectives: An increased risk of narcolepsy has been observed in children following ASO3-adjuvanted pandemic A/H1N1 2009 (Pandemrix) vaccine. We investigated whether this risk extends to adults in England. Methods: Six adult sleep centers in England were visited between November 2012 and February 2014 and vaccination/clinical histories obtained from general practitioners. Suspected narcolepsy cases aged older than 17 y were selected. The risk of narcolepsy following Pandemrix was calculated using cases diagnosed by the time of the center visits and those with a diagnosis by November 30, 2011 after which there was increased awareness of the risk in children. The odds of vaccination in cases and in matched population data were compared using a case-coverage design. Results: Of 1,446 possible cases identified, most had onset before 2009 or were clearly not narcolepsy. Of the 60 remaining cases, 20 were excluded after expert review, leaving 40 cases with narcolepsy; 5 had received Pandemrix between 3 and 18 mo before onset. All the vaccinated cases had cataplexy, two received a diagnosis by November 2011 and two were aged 40 y or older. The odds ratio for vaccination in cases compared to the population was 4.24 (95% confidence interval 1.45–12.38) using all cases and 9.06 (1.90–43.17) using cases with a diagnosis by November 2011, giving an attributable risk of 0.59 cases per 100,000 doses. Conclusions: We found a significantly increased risk of narcolepsy in adults following Pandemrix vaccination in England. The risk was lower than that seen in children using a similar study design. Citation: Stowe J, Andrews N, Kosky C, Dennis G, Eriksson S, Hall A, Leschziner G, Reading P, Shneerson JM, Donegan K, Miller E. Risk of narcolepsy after AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine in adults: a case-coverage study in England. SLEEP 2016;39(5):1051–1057. PMID:26856903

  3. Pediatric feeding and eating disorders: current state of diagnosis and treatment.

    PubMed

    Kelly, Nichole R; Shank, Lisa M; Bakalar, Jennifer L; Tanofsky-Kraff, Marian

    2014-05-01

    The Diagnostic and Statistical Manual of Mental Disorders now recognizes six primary feeding and eating disorders including pica, rumination disorder, avoidant/restrictive food intake disorder, anorexia nervosa, bulimia nervosa and binge-eating disorder. Guided by research from the past 3 years, the current review outlines diagnostic criteria for each disorder, their clinical correlates and treatment options. Recent modifications to diagnostic criteria will likely help to improve treatment outcomes and prognosis. Nevertheless, several concerns remain regarding the validity of current diagnostic criteria for youth, including the clinical relevance of the size and frequency of binge eating episodes. Additionally, the lack of randomized controlled trials has led to an overreliance on data from quasi-experimental studies, case series and single case studies that impede development of strong clinical recommendations for treating feeding and eating disorders. Recommendations for future research include identifying empirically supported treatments and prevention programs focused on early markers of pediatric feeding and eating concerns.

  4. ANTERIOR CRUCIATE LIGAMENT INJURY DIAGNOSIS AND MANAGEMENT IN A PEDIATRIC PATIENT: A CASE REPORT

    PubMed Central

    Duby, Cherie

    2012-01-01

    The management of the skeletally immature athlete sustaining injury to the anterior cruciate ligament and other knee structures provides multiple challenges for both the treating clinicians and parents of the injured child. The diagnostic process and subsequent decision making present additional complexities because of the developmental anatomy and the potential for disturbance of normal growth patterns by some surgical interventions. In the following case report, the course to appropriate management of a young athlete is detailed, including the contributions of imaging results. The reconstructive options available to orthopedic surgeons and the patient's post‐operative progression are also briefly discussed. Rehabilitation practitioners require an understanding of the unique issues present when providing care for pediatric and adolescent athletes with knee injuries in order to assist in optimal decision making in the phases during which they are involved. Level of Evidence: 5 (Single Case Report) PMID:23316431

  5. Pediatric Headaches.

    PubMed

    Slover, Robin; Kent, Sheryl

    2015-08-01

    Pediatric headaches are common, and many may never require intervention by a health care provider. However, migraines can become more difficult to treat, especially if they become chronic daily headaches. Pediatric headache is a subjective and unique experience that requires attention to both psychological and physiologic components in diagnosis and treatment. A biopsychosocial, multidisciplinary approach, including both medication management and psychological treatment, is considered essential for effective management.

  6. The Trypomastigote Small Surface Antigen from Trypanosoma cruzi improves treatment evaluation and diagnosis in pediatric Chagas disease.

    PubMed

    Balouz, Virginia; Melli, Luciano J; Volcovich, Romina; Moscatelli, Guillermo; Moroni, Samanta; González, Nicolás; Ballering, Griselda; Bisio, Margarita; Ciocchini, Andrés; Buscaglia, Carlos A; Altcheh, Jaime

    2017-10-04

    Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. Assessment of parasitological cure upon treatment with available drugs relies on achieving consistent negative results in conventional parasitological and serological tests, which may take years to assess. Here, we evaluated the use of a recombinant T. cruzi antigen termed TSSA as an early serological marker of drug efficacy in T. cruzi-infected children. A cohort of 78 pediatric patients born to T. cruzi-infected mothers was included in this study. Solely 39 of them were infected with T. cruzi, and were immediately treated with trypanocidal drugs. Serological responses against TSSA were evaluated in infected and non-infected populations during the follow-up period using an in-house ELISA test, and compared to conventional serological methods. Anti-TSSA antibody titers decreased significantly faster than anti-whole parasite antibodies detected by conventional serology in both T. cruzi-infected patients undergoing effective treatment and in those not infected. This differential kinetics allowed a significant reduction in the required follow-up periods to evaluate therapeutic responses or to rule out maternal-fetal transmission, respectively. Finally, we present the case of a congenitally-infected patient with atypical course, in which TSSA provided an early marker for T. cruzi infection. In conclusion, we showed that TSSA was efficacious both for rapid assessment of treatment efficiency and for early negative diagnosis in infants at risk of congenital T. cruzi infection. Based upon these findings we propose the inclusion of TSSA for refining the post-therapeutic cure criterion and other diagnostic needs in pediatric Chagas disease. Copyright © 2017 American Society for Microbiology.

  7. Integrated imaging using MRI and 123I metaiodobenzylguanidine scintigraphy to improve sensitivity and specificity in the diagnosis of pediatric neuroblastoma.

    PubMed

    Pfluger, Thomas; Schmied, Christoph; Porn, Ute; Leinsinger, Gerda; Vollmar, Christian; Dresel, Stefan; Schmid, Irene; Hahn, Klaus

    2003-10-01

    The objectives of this study were to compare MRI and iodine-123 ((123)I) metaiodobenzylguanidine (MIBG) scintigraphy in the detection of neuroblastoma lesions in pediatric patients and to assess the additional value of combined imaging. Fifty MRI and 50 (123)I MIBG examinations (mean interval, 6.4 days) were analyzed retrospectively with regard to suspected or proven neuroblastoma lesions (n = 193) in 28 patients. MRI and MIBG scans were reviewed by two independent observers each. Separate and combined analyses of MRI and MIBG scintigraphy were compared with clinical and histologic findings. With regard to the diagnosis of neuroblastoma lesion, MIBG scintigraphy, MRI, and combined analysis showed a sensitivity of 69%, 86%, and 99% and a specificity of 85%, 77%, and 95%, respectively. On MRI, 15 false-positive findings were recorded: posttherapeutic reactive changes (n = 10), benign adrenal tumors (n = 3), and enlarged lymph nodes (n = 2). On MIBG scintigraphy, 10 false-positive findings occurred: ganglioneuromas (n = 2), benign liver tumors (n = 2), and physiologic uptake (n = 6). Thirteen neuroblastoma metastases and two residual masses under treatment with chemotherapy were judged to be false-negative findings on MRI. Two primary or residual neuroblastomas and one orbital metastasis were misinterpreted as Wilms' tumor, reactive changes after surgery, and rhabdomyosarcoma on MRI. Thirty-two bone metastases, six other neuroblastoma metastases, and one adrenal neuroblastoma showed no MIBG uptake. On combined imaging, one false-negative (bone metastasis) and three false-positive (two ganglioneuromas and one pheochromocytoma) findings remained. In the assessment of neuroblastoma lesions in pediatric patients, MRI showed a higher sensitivity and MIBG scintigraphy a higher specificity. However, integrated imaging showed an increase in both sensitivity and specificity.

  8. Feasibility study of the diagnosis and monitoring of cystic fibrosis in pediatric patients using stationary digital chest tomosynthesis

    NASA Astrophysics Data System (ADS)

    Potuzko, Marci; Shan, Jing; Pearce, Caleb; Lee, Yueh Z.; Lu, Jianping; Zhou, Otto

    2015-03-01

    Digital chest tomosynthesis (DCT) is a 3D imaging modality which has been shown to approach the diagnostic capability of CT, but uses only one-tenth the radiation dose of CT. One limitation of current commercial DCT is the mechanical motion of the x-ray source which prolongs image acquisition time and introduces motion blurring in images. By using a carbon nanotube (CNT) x-ray source array, we have developed a stationary digital chest tomosynthesis (s- DCT) system which can acquire tomosynthesis images without mechanical motion, thus enhancing the image quality. The low dose and high quality 3D image makes the s-DCT system a viable imaging tool for monitoring cystic fibrosis (CF) patients. The low dose is especially important in pediatric patients who are both more radiosensitive and have a longer lifespan for radiation symptoms to develop. The purpose of this research is to evaluate the feasibility of using s-DCT as a faster, lower dose means for diagnosis and monitoring of CF in pediatric patients. We have created an imaging phantom by injecting a gelatinous mucus substitute into porcine lungs and imaging the lungs from within an anthropomorphic hollow chest phantom in order to mimic the human conditions of a CF patient in the laboratory setting. We have found that our s-DCT images show evidence of mucus plugging in the lungs and provide a clear picture of the airways in the lung, allowing for the possibility of using s- DCT to supplement or replace CT as the imaging modality for CF patients.

  9. Pediatric reference intervals for plasma free and total metanephrines established with a parametric approach: relevance to the diagnosis of neuroblastoma.

    PubMed

    Franscini, Laura Crosazzo; Vazquez-Montes, Maria; Buclin, Thierry; Perera, Rafael; Dunand, Marielle; Grouzmann, Eric; Beck-Popovic, Maja

    2015-04-01

    Urine catecholamines, vanillylmandelic, and homovanillic acid are recognized biomarkers for the diagnosis and follow-up of neuroblastoma. Plasma free (f) and total (t) normetanephrine (NMN), metanephrine (MN) and methoxytyramine (MT) could represent a convenient alternative to those urine markers. The primary objective of this study was to establish pediatric centile charts for plasma metanephrines. Secondarily, we explored their diagnostic performance in 10 patients with neuroblastoma. We recruited 191 children (69 females) free of neuroendocrine disease to establish reference intervals for plasma metanephrines, reported as centile curves for a given age and sex based on a parametric method using fractional polynomials models. Urine markers and plasma metanephrines were measured in 10 children with neuroblastoma at diagnosis. Plasma total metanephrines were measured by HPLC with coulometric detection and plasma free metanephrines by tandem LC-MS. We observed a significant age-dependence for tNMN, fNMN, and fMN, and a gender and age-dependence for tMN, fNMN, and fMN. Free MT was below the lower limit of quantification in 94% of the children. All patients with neuroblastoma at diagnosis were above the 97.5th percentile for tMT, tNMN, fNMN, and fMT, whereas their fMN and tMN were mostly within the normal range. As expected, urine assays were inconstantly predictive of the disease. A continuous model incorporating all data for a given analyte represents an appealing alternative to arbitrary partitioning of reference intervals across age categories. Plasma metanephrines are promising biomarkers for neuroblastoma, and their performances need to be confirmed in a prospective study on a large cohort of patients. © 2015 Wiley Periodicals, Inc.

  10. [Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (i): Epidemiology and diagnosis. Congenital tuberculosis].

    PubMed

    Baquero-Artigao, F; Mellado Peña, M J; Del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L

    2015-10-01

    Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is recommended in case of symptoms of TB disease, close contact with a patient with infectious TB, or high risk of developing active disease. The new interferon gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women with positive TST and no known risk factors for TB, and in those immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis is difficult due to the non-specific symptoms, the increased frequency of extrapulmonary disease, the delay in radiological examinations, and the high rate of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or through airborne transmission after delivery (postnatal TB). Congenital TB is extremely rare and does not cause fetal malformations. It may be evident at birth, although it usually presents after the second week of life. In newborns with no family history of TB, the disease should be considered in cases of miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic meningitis with hypoglycorrhachia, especially in those born to immigrants from high TB-burden countries. TST is usually negative, and IGRAs have lower sensitivity than in older children. However, the yield of acid-fast smear and culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable early diagnosis and detection of drug resistance mutations. There is a substantial risk of disseminated disease and death. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  11. Mechanistic insights into influenza vaccine-associated narcolepsy

    PubMed Central

    Ahmed, S. Sohail; Steinman, Lawrence

    2016-01-01

    ABSTRACT We previously reported an increased frequency of antibodies to hypocretin (HCRT) receptor 2 in sera obtained from narcoleptic patients who received the European AS03-adjuvanted vaccine Pandemrix (GlaxoSmithKline Biologicals, s.a.) for the global influenza A H1N1 pandemic in 2009 [A(H1N1)pdm09]. These antibodies cross-reacted with a particular fragment of influenza nucleoprotein (NP) – one of the proteins naturally contained in the virus used to make seasonal influenza vaccine and pandemic influenza vaccines. The purpose of this commentary is to provide additional insights and interpretations of the findings and share additional data not presented in the original paper to help the reader appreciate the key messages of that publication. First, a brief background to narcolepsy and vaccine-induced narcolepsy will be provided. Then, additional insights and clarification will be provided on the following topics: 1) the critical difference identified in the adjuvanted A(H1N1)pdm09 vaccines, 2) the contributing factor likely for the discordant association of narcolepsy between the AS03-adjuvanted pandemic vaccines Pandemrix and Arepanrix (GlaxoSmithKline Biologicals, s.a.), 3) the significance of detecting HCRT receptor 2 (HCRTr2) antibodies in some Finnish control subjects, 4) the approach used for the detection of HCRTr2 antibodies in vaccine-associated narcolepsy, and 5) the plausibility of the proposed mechanism involving HCRTr2 modulation in vaccine-associated narcolepsy. PMID:27031682

  12. Mechanistic insights into influenza vaccine-associated narcolepsy.

    PubMed

    Ahmed, S Sohail; Steinman, Lawrence

    2016-12-01

    We previously reported an increased frequency of antibodies to hypocretin (HCRT) receptor 2 in sera obtained from narcoleptic patients who received the European AS03-adjuvanted vaccine Pandemrix (GlaxoSmithKline Biologicals, s.a.) for the global influenza A H1N1 pandemic in 2009 [A(H1N1)pdm09]. These antibodies cross-reacted with a particular fragment of influenza nucleoprotein (NP) - one of the proteins naturally contained in the virus used to make seasonal influenza vaccine and pandemic influenza vaccines. The purpose of this commentary is to provide additional insights and interpretations of the findings and share additional data not presented in the original paper to help the reader appreciate the key messages of that publication. First, a brief background to narcolepsy and vaccine-induced narcolepsy will be provided. Then, additional insights and clarification will be provided on the following topics: 1) the critical difference identified in the adjuvanted A(H1N1)pdm09 vaccines, 2) the contributing factor likely for the discordant association of narcolepsy between the AS03-adjuvanted pandemic vaccines Pandemrix and Arepanrix (GlaxoSmithKline Biologicals, s.a.), 3) the significance of detecting HCRT receptor 2 (HCRTr2) antibodies in some Finnish control subjects, 4) the approach used for the detection of HCRTr2 antibodies in vaccine-associated narcolepsy, and 5) the plausibility of the proposed mechanism involving HCRTr2 modulation in vaccine-associated narcolepsy.

  13. Orexin neurons suppress narcolepsy via 2 distinct efferent pathways

    PubMed Central

    Hasegawa, Emi; Yanagisawa, Masashi; Sakurai, Takeshi; Mieda, Michihiro

    2014-01-01

    The loss of orexin neurons in humans is associated with the sleep disorder narcolepsy, which is characterized by excessive daytime sleepiness and cataplexy. Mice lacking orexin peptides, orexin neurons, or orexin receptors recapitulate human narcolepsy phenotypes, further highlighting a critical role for orexin signaling in the maintenance of wakefulness. Despite the known role of orexin neurons in narcolepsy, the precise neural mechanisms downstream of these neurons remain unknown. We found that targeted restoration of orexin receptor expression in the dorsal raphe (DR) and in the locus coeruleus (LC) of mice lacking orexin receptors inhibited cataplexy-like episodes and pathological fragmentation of wakefulness (i.e., sleepiness), respectively. The suppression of cataplexy-like episodes correlated with the number of serotonergic neurons restored with orexin receptor expression in the DR, while the consolidation of fragmented wakefulness correlated with the number of noradrenergic neurons restored in the LC. Furthermore, pharmacogenetic activation of these neurons using designer receptor exclusively activated by designer drug (DREADD) technology ameliorated narcolepsy in mice lacking orexin neurons. These results suggest that DR serotonergic and LC noradrenergic neurons play differential roles in orexin neuron–dependent regulation of sleep/wakefulness and highlight a pharmacogenetic approach for the amelioration of narcolepsy. PMID:24382351

  14. Clinical and practical considerations in the pharmacologic management of narcolepsy.

    PubMed

    Thorpy, Michael J; Dauvilliers, Yves

    2015-01-01

    Despite published treatment recommendations and the availability of approved and off-label pharmacologic therapies for narcolepsy, the clinical management of this incurable, chronic neurologic disorder remains challenging. While treatment is generally symptomatically driven, decisions regarding which drug(s) to use need to take into account a variety of factors that may affect adherence, efficacy, and tolerability. Type 1 narcolepsy (predominantly excessive daytime sleepiness with cataplexy) or type 2 narcolepsy (excessive daytime sleepiness without cataplexy) may drive treatment decisions, with consideration given either to a single drug that targets multiple symptoms or to multiple drugs that each treat a specific symptom. Other drug-related characteristics that affect drug choice are dosing regimens, tolerability, and potential drug-drug interactions. Additionally, the patient should be an active participant in treatment decisions, and the main symptomatic complaints, treatment goals, psychosocial setting, and use of lifestyle substances (ie, alcohol, nicotine, caffeine, and cannabis) need to be discussed with respect to treatment decisions. Although there is a lack of narcolepsy-specific instruments for monitoring therapeutic effects, clinically relevant subjective and objective measures of daytime sleepiness (eg, Epworth Sleepiness Scale and Maintenance of Wakefulness Test) can be used to provide guidance on whether treatment goals are being met. These considerations are discussed with the objective of providing clinically relevant recommendations for making treatment decisions that can enhance the effective management of patients with narcolepsy.

  15. Pediatric Necrotizing Fasciitis: Restitutio Ad Integrum after Early Diagnosis and Aggressive Surgical Treatment

    PubMed Central

    Lemaréchal, Angela; Zundel, Sabine; Szavay, Philipp

    2016-01-01

    Necrotizing fasciitis (NF) is a severe, life-threatening infectious condition. Diagnosis is difficult due to unspecific symptoms yet crucial for favorable outcomes. We report a case of a 1 year old, previously healthy boy, where early suspicion of NF led to prompt aggressive therapy and consecutive restitutio ad integrum. PMID:28035291

  16. A Novel de novo Exon 21 DNMT1 Mutation Causes Cerebellar Ataxia, Deafness, and Narcolepsy in a Brazilian Patient

    PubMed Central

    Pedroso, José Luiz; Povoas Barsottini, Orlando Graziani; Lin, Ling; Melberg, Atle; Oliveira, Acary S. B.; Mignot, Emmanuel

    2013-01-01

    Study Objectives: Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is caused by DNMT1 mutations. Diagnosing the syndrome can be difficult, as all clinical features may not be present at onset, HLA-DQB1*06:02 is often negative, and sporadic cases occur. We report on clinical and genetic findings in a 31-year-old woman with cerebellar ataxia, deafness, and narcolepsy, and discuss diagnostic challenges. Design: Clinical and genetic investigation in a patient and family members. Setting: Ataxia clinic, São Paulo, Brazil. Patients or Participants: One patient and her family members. Interventions: N/A. Measurements and Results: Narcolepsy was supported by polysomnographic and multiple sleep latency testing. HLA-DQB1*06:02 was positive. CSF hypocretin-1 was 191 pg/mL (normal values > 200 pg/mL). Mild brain atrophy was observed on MRI, with cerebellar involvement. The patient, her asymptomatic mother, and 3 siblings gave blood samples for genetic analysis. DNMT1 exons 20 and 21 were sequenced. Haplotyping of polymorphic markers surrounding the mutation was performed. The proband had a novel DNMT1 mutation in exon 21, p.Cys596Arg, c.1786T > C. All 4 parental haplotypes could be characterized in asymptomatic siblings without the mutation, indicating that the mutation is de novo in the patient. Conclusions: The Brazilian patient reported here further adds to the worldwide distribution of ADCA-DN. The mutation is novel, and illustrates a sporadic case with de novo mutation. We believe that many more cases with this syndrome are likely to be diagnosed in the near future, mandating knowledge of this condition and consideration of the diagnosis. Citation: Pedroso JL; Barsottini OGP; Lin L; Melberg A; Oliveira ASB; Mignot E. A novel de novo exon 21 DNMT1 mutation causes cerebellar ataxia, deafness, and narcolepsy in a Brazilian patient. SLEEP 2013;36(8):1257-1259. PMID:23904686

  17. Comorbidity of Narcolepsy Type 1 With Autoimmune Diseases and Other Immunopathological Disorders: A Case-Control Study

    PubMed Central

    Martinez-Orozco, Francisco Javier; Vicario, Jose Luis; De Andres, Clara; Fernandez-Arquero, Miguel; Peraita-Adrados, Rosa

    2016-01-01

    Background Several evidences suggest that autoimmune diseases (ADs) tend to co-occur in an individual and within the same family. Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a selective loss of hypocretin-producing neurons due to a mechanism of neural destruction that indicates an autoimmune pathogenesis, although no evidence is available. We report on the comorbidity of ADs and other immunopathological diseases (including allergy diseases) in narcolepsy. Methods We studied 158 Caucasian NT1 patients (60.7% male; mean age 49.4 ± 19.7 years), in whom the diagnosis was confirmed by polysomnography followed by a multiple sleep latency test, or by hypocretin-1 levels measurements. Results Thirty out of 158 patients (18.99%; 53.3% female; 29 sporadic and one familial cases) had one or more immunopathological diseases associated. A control group of 151 subjects were matched by gender and age with the narcolepsy patients. Results demonstrated that there was a higher frequency of ADs in our series of narcolepsy patients compared to the sample of general population (odds ratio: 3.17; 95% confidence interval: 1.01 - 10.07; P = 0.040). A temporal relationship with the age at onset of the diseases was found. Conclusions Cataplexy was significantly more severe in NT1 patients with immunopathological diseases, and immunopathological diseases are a risk factor for severe forms of cataplexy in our series (odds ratio: 23.6; 95% confidence interval: 5.5 - 100.1). PMID:27298657

  18. Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease.

    PubMed

    Marzuillo, Pierluigi; Grandone, Anna; Perrone, Laura; Miraglia Del Giudice, Emanuele

    2015-06-07

    In the last years childhood obesity has reached epidemic diffusion with about 200 million school-age children worldwide being overweight or obese. Simultaneously, also the prevalence of obesity comorbidities has been increased and the non-alcoholic fatty liver disease (NAFLD) has become the most common form of liver disease in childhood. Also if there are some not-invasive diagnostic possibilities, the diagnostic gold standard is represented by hepatic biopsy giving to the clinicians the possibility to both diagnose the NAFLD and evaluate its progression to fibrosis or cirrhosis with greater certainty than other techniques. The use of liver biopsy in clinical practice causes debate among health care providers. Most patients with NAFLD have a good prognosis and, therefore, the risks of a liver biopsy seem to outweigh the clinical benefits. It represents an impractical screening procedure because it is both expensive and invasive and, moreover, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies because histological lesions of non-alcoholic steatohepatitis are unevenly distributed throughout the liver parenchyma. The liver biopsy limitations have led the clinicians to use, also if highly imperfect, non-invasive methods to diagnose and stage NAFLD. In this editorial the main diagnostic controversies in pediatric NAFLD are examined.

  19. Controversy in the diagnosis of pediatric non-alcoholic fatty liver disease

    PubMed Central

    Marzuillo, Pierluigi; Grandone, Anna; Perrone, Laura; Miraglia del Giudice, Emanuele

    2015-01-01

    In the last years childhood obesity has reached epidemic diffusion with about 200 million school-age children worldwide being overweight or obese. Simultaneously, also the prevalence of obesity comorbidities has been increased and the non-alcoholic fatty liver disease (NAFLD) has become the most common form of liver disease in childhood. Also if there are some not-invasive diagnostic possibilities, the diagnostic gold standard is represented by hepatic biopsy giving to the clinicians the possibility to both diagnose the NAFLD and evaluate its progression to fibrosis or cirrhosis with greater certainty than other techniques. The use of liver biopsy in clinical practice causes debate among health care providers. Most patients with NAFLD have a good prognosis and, therefore, the risks of a liver biopsy seem to outweigh the clinical benefits. It represents an impractical screening procedure because it is both expensive and invasive and, moreover, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies because histological lesions of non-alcoholic steatohepatitis are unevenly distributed throughout the liver parenchyma. The liver biopsy limitations have led the clinicians to use, also if highly imperfect, non-invasive methods to diagnose and stage NAFLD. In this editorial the main diagnostic controversies in pediatric NAFLD are examined. PMID:26074683

  20. The diagnosis and care of transsexual children and adolescents: a pediatric endocrinologists' perspective.

    PubMed

    Houk, Christopher P; Lee, Peter A

    2006-02-01

    The normally developed child whose gender identity and anatomic sex disagree is referred to as a transgendered child, or as used subsequently in this text, a transsexual. The ramifications of this disagreement include a high risk of psychiatric conflict and maladjustment, for both the individuals themselves and their families. Despite the efforts of researchers to systematically study this group of children, many fundamental questions remain. In many respects, those lingering questions are shared by patients with physical intersex who have been cared for by pediatric endocrinologists. In intersex and transsexual patients, the medical community, although sincerely interested, remains wary to intervene in ways that may lead to further inconsistency between anatomic sex and adult gender identity. A perspective on the problems of differentiating permanent from transient gender identity, some thoughts on the most appropriate management of the transsexual child/adolescent as well as remaining questions are discussed. Both the flexible and therefore potentially misleading gender identity in children and the medical communities' pledge to first do no harm (primum non nocere) have regrettably fostered disharmony between gender disordered patients, their families, and the practitioners who want to help them.

  1. Pediatric seatbelt injuries: diagnosis and treatment of lumbar flexion-distraction injuries.

    PubMed

    Greenwald, T A; Mann, D C

    1994-11-01

    Motor vehicle accidents are the major cause of flexion-distraction injuries of the thoracolumbar spine. In a retrospective review, we present the results of operative treatment for six pediatric patients who sustained such injuries while wearing seatbelts. There were three purely ligamentous injuries, two bony injuries (Chance fractures), and one combination injury. There were also concomitant neurological and intra-abdominal injuries. Of note is that two patients had either their spinal or abdominal injury missed on initial evaluation. All patients were treated surgically with open reduction and internal fixation. At average follow up of 2 years, all patients had a full range of motion with no back pain. Five had returned to their preinjury activity levels, while the sixth patient was paraplegic from his injury but was able to ambulate at home with crutches and knee-ankle-foot orthoses. We recommend operative reduction and two-level fusion of these injuries when (1) instability is apparent in either a purely ligamentous injury or an overtly unstable fracture-pattern, (2) significant kyphosis is present which cannot be reduced or maintained in a cast, or (3) there is associated neurological or intra-abdominal injury.

  2. Etiological diagnosis of bilateral, sensorineural hearing impairment in a pediatric Greek population.

    PubMed

    Riga, M; Psarommatis, I; Lyra, Ch; Douniadakis, D; Tsakanikos, M; Neou, P; Apostolopoulos, N

    2005-04-01

    Early diagnosis, evaluation and treatment of childhood deafness are essential for a child's normal growth. Etiological diagnosis of hearing loss makes prevention, family scheduling and more effective therapy feasible goals. Etiological assessment of sensorineural deafness still remains difficult although recently with the progress of genetics it has become more efficient. In this retrospective study, the etiology of bilateral, sensorineural hearing loss with indication for hearing aids has been studied in 153 hearing impaired children. Etiological diagnosis was based on family and patient record, physical, audiological and laboratory examinations. Among the 94 children who completed the diagnostic protocol etiological groups revealed the following distribution: non-hereditary acquired hearing impairment was present in 36 children (38%) and hereditary was present in 44 (47%) children. The etiology remained unknown in 14 (15%) children. Non-syndromic autosomal dominant type accounted for 13 (29% of hereditary hearing loss) children, non-syndromic autosomal recessive type for 21 (48%) children and syndromic deafness for 10 (23%) children. Modern diagnostic methods, such as genetic testing, help diminish the number of cases with hearing impairment of unknown etiology, for the benefit of children who receive early and appropriate medical, audiologic, genetic and educational counseling based on the etiology of their hearing loss.

  3. Pediatric otolaryngology, molecular diagnosis of hereditary hearing loss: next-generation sequencing approach.

    PubMed

    Jasper, Kayla M; Jamshidi, Aria; Reilly, Brian K

    2015-12-01

    Sensorineural hearing loss (SNHL) is the most common sensory birth defect. The purpose of this article is to review the advances in next-generation sequencing (NGS) and molecular diagnosis of hereditary hearing loss. Early diagnosis and detection of SNHL is critical for the development of appropriate speech and language, as neuroplasticity peaks in the first few years of life. There has been increased accuracy of NGS genetic testing, which has helped created a paradigm shift in the diagnosis of hearing loss. The diagnostic yield of genetic testing now approaches that of radiographic imaging; however, there remains a difference in cost and time delay. With the introduction of comprehensive genetic panels, 23-129 genes can be sequenced from the same blood sample. Diagnostic genetic testing of SNHL in the past has been confined to a few genes through Sanger sequencing. The advent of NGS allows for development of comprehensive genetic panels, which test for up to 129 genes while improving the accuracy and efficiency of testing. This type of testing may become more common as the costs decrease and more genes are discovered.

  4. Post Tick-Borne Encephalitis Virus Vaccination Narcolepsy with Cataplexy.

    PubMed

    Hidalgo, Hildegard; Kallweit, Ulf; Mathis, Johannes; Bassetti, Claudio L

    2016-10-01

    Narcolepsy with cataplexy (NC) is a chronic neurological disorder thought to result from an altered immune response based on a genetic predisposition coupled with environmental factors. Pandemrix vaccination has been reported to increase the risk of narcolepsy. We aimed at identifying other vaccines associated with the onset of narcolepsy. Case series and retrospective database study. We identified four cases of NC following a tick-borne encephalitis (TBE) vaccination with FSME Immun. Additional four cases could be detected in the database of the Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines in Germany. Our findings implicate TBE vaccination as a potential additional environmental factor for the development of NC and add additional evidence for an immunological mechanism in the pathogenesis of the disease.

  5. Pandemrix™ and narcolepsy: A critical appraisal of the observational studies

    PubMed Central

    Verstraeten, Thomas; Cohet, Catherine; Dos Santos, Gaël; Ferreira, Germano LC; Bollaerts, Kaatje; Bauchau, Vincent; Shinde, Vivek

    2016-01-01

    A link between Pandemrix™ (AS03-adjuvanted H1N1 pandemic influenza vaccine, GSK Vaccines, Belgium) and narcolepsy was first suspected in 2010 in Sweden and Finland following a number of reports in children and adolescents. Initial scepticism about the reported association faded as additional countries reported similar findings, leading several regulatory authorities to restrict the use of Pandemrix™. The authors acknowledge that currently available data suggest an increased risk of narcolepsy following vaccination with Pandemrix™; however, from an epidemiologist's perspective, significant methodological limitations of the studies have not been fully addressed and raise questions about the reported risk estimates. We review the most important biases and confounders that potentially occurred in 12 European studies of the observed association between Pandemrix™ and narcolepsy, and call for further analyses and debate. PMID:26379011

  6. Pandemrix™ and narcolepsy: A critical appraisal of the observational studies.

    PubMed

    Verstraeten, Thomas; Cohet, Catherine; Dos Santos, Gaël; Ferreira, Germano Lc; Bollaerts, Kaatje; Bauchau, Vincent; Shinde, Vivek

    2016-01-01

    A link between Pandemrix™ (AS03-adjuvanted H1N1 pandemic influenza vaccine, GSK Vaccines, Belgium) and narcolepsy was first suspected in 2010 in Sweden and Finland following a number of reports in children and adolescents. Initial scepticism about the reported association faded as additional countries reported similar findings, leading several regulatory authorities to restrict the use of Pandemrix™. The authors acknowledge that currently available data suggest an increased risk of narcolepsy following vaccination with Pandemrix™; however, from an epidemiologist's perspective, significant methodological limitations of the studies have not been fully addressed and raise questions about the reported risk estimates. We review the most important biases and confounders that potentially occurred in 12 European studies of the observed association between Pandemrix™ and narcolepsy, and call for further analyses and debate.

  7. Alopecia areata and narcolepsy: a tale of obscure autoimmunity.

    PubMed

    Nigam, Gaurav; Pathak, Charu; Riaz, Muhammad

    2016-04-08

    Alopecia areata is an autoimmune dermatological disorder characterised by loss of hair in one or more discrete patches over the scalp. It has been linked to multiple disorders having an autoimmune origin. Like many autoimmune disorders it tends to be more common in females. To date, only five cases have been reported where alopecia has been associated with narcolepsy. Male gender is less commonly affected by alopecia areata. No case of alopecia areata in males has been associated with narcolepsy to the best of our knowledge. The current case represents the first ever-reported case of alopecia areata in a male patient with narcolepsy type 1. This coexistence is most likely the manifestation of a common underlying pathoimmunological mechanism that has not been completely understood, rather than a random association.

  8. Whole-Proteome Peptide Microarrays for Profiling Autoantibody Repertoires within Multiple Sclerosis and Narcolepsy.

    PubMed

    Zandian, Arash; Forsström, Björn; Häggmark-Månberg, Anna; Schwenk, Jochen M; Uhlén, Mathias; Nilsson, Peter; Ayoglu, Burcu

    2017-02-09

    The underlying molecular mechanisms of autoimmune diseases are poorly understood. To unravel the autoimmune processes across diseases, comprehensive and unbiased analyses of proteins targets recognized by the adaptive immune system are needed. Here we present an approach starting from high-density peptide arrays to characterize autoantibody repertoires and to identify new autoantigens. A set of ten plasma and serum samples from subjects with multiple sclerosis, narcolepsy, and without any disease diagnosis were profiled on a peptide array representing the whole proteome, hosting 2.2 million 12-mer peptides with a six amino acid lateral shift. On the basis of the IgG reactivities found on these whole-proteome peptide microarrays, a set of 23 samples was then studied on a targeted array with 174 000 12-mer peptides of single amino acid lateral shift. Finally, verification of IgG reactivities was conducted with a larger sample set (n = 448) using the bead-based peptide microarrays. The presented workflow employed three different peptide microarray formats to discover and resolve the epitopes of human autoantibodies and revealed two potentially new autoantigens: MAP3K7 in multiple sclerosis and NRXN1 in narcolepsy. The presented strategy provides insights into antibody repertoire reactivity at a peptide level and may accelerate the discovery and validation of autoantigens in human diseases.

  9. Absence of NMDA receptor antibodies in the rare association between Type 1 Narcolepsy and Psychosis

    PubMed Central

    Dauvilliers, Y.; Gaig, C.; Barateau, L.; Graus, F.; Iranzo, A.; Lopez, R.; Santamaria, J.

    2016-01-01

    Frequency and mechanisms underlying the association between narcolepsy type 1 (NT1) and psychosis remain unclear with potential role for a common immune pathway. We estimated the frequency of psychosis and its characteristics in NT1 at two European sleep centers (France, n = 381; Spain, n = 161) and measured IgG autoantibodies that recognize the GluN1 subunit of the NMDAR in 9 patients with NT1 with psychosis, and 25 NT1 patients without psychosis. Ten NT1 patients (6 in France, 4 in Spain) were diagnosed with comorbid psychosis, a frequency of 1.8%. One patient reported psychotic symptoms few months before narcolepsy onset, two patients few months after onset, and one patient one year after onset but after modafinil introduction. The six remaining patients reported long delays between NT1 and psychosis onset. Half the patients, mostly male adults, reported onset or worsening of psychotic symptoms after medication. We found no IgG antibodies to NR1/NR2B heteromers of the NMDARs in patients with NT1 with or without psychosis. To conclude, psychosis is rare in NT1, with limited evidence for a key impact of stimulants, and no association with anti-NMDAR antibodies. However, dramatic NT1 and schizophrenia exists especially in early onset NT1, which may lead to inappropriate diagnosis and management. PMID:27143278

  10. Current and emerging options for the drug treatment of narcolepsy.

    PubMed

    De la Herrán-Arita, Alberto K; García-García, Fabio

    2013-11-01

    Narcolepsy/hypocretin deficiency (now called type 1 narcolepsy) is a lifelong neurologic disorder with well-established diagnostic criteria and etiology. Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness (EDS) and symptoms of dissociated rapid eye movement sleep such as cataplexy (sudden loss of muscle tone), hypnagogic hallucinations (sensory events that occur at the transition from wakefulness to sleep), sleep paralysis (inability to perform movements upon wakening or sleep onset), and nocturnal sleep disruption. As these symptoms are often disabling, most patients need life-long treatment. The treatment of narcolepsy is well defined, and, traditionally, amphetamine-like stimulants (i.e., dopaminergic release enhancers) have been used for clinical management to improve EDS and sleep attacks, whereas tricyclic antidepressants have been used as anticataplectics. However, treatments have evolved to better-tolerated compounds such as modafinil or armodafinil (for EDS) and adrenergic/serotonergic selective reuptake inhibitors (as anticataplectics). In addition, night-time administration of a short-acting sedative, c-hydroxybutyrate (sodium oxybate), has been used for the treatment for EDS and cataplexy. These therapies are almost always needed in combination with non-pharmacologic treatments (i.e., behavioral modification). A series of new drugs is currently being tested in animal models and in humans. These include a wide variety of hypocretin agonists, melanin- concentrating hormone receptor antagonists, antigenspecific immunopharmacology, and histamine H3 receptor antagonists/inverse agonists (e.g., pitolisant), which have been proposed for specific therapeutic applications, including the treatment of Alzheimer's disease, attention-deficit hyperactivity disorder, epilepsy, and more recently, narcolepsy. Even though current treatment is strictly symptomatic, based on the present state of knowledge of the pathophysiology of

  11. Neurometabolic Diagnosis in Children who referred as Neurodevelopmental Delay (A Practical Criteria, in Iranian Pediatric Patients)

    PubMed Central

    KARIMZADEH, Parvaneh; JAFARI, Narjes; NEJAD BIGLARI, Habibeh; JABBEHDARI, Sayena; KHAYAT ZADEH, Simin; AHMAD ABADI, Farzad; LOTFI, Azra

    2016-01-01

    Objective We aimed to investigate the clinical and para clinical manifestations of neuro metabolic disorders, in patients who presented by neuro developmental delay in their neuro developmental milestones. Materials & Methods The patients diagnosed as neuro developmental delay and regression with or without seizure at the Neurology Department of Mofid Children Hospital in Tehran, Iran between 2004 and 2014 were included in our study. These patients diagnosed as neuro developmental delay by pediatric neurologists in view of diagnostic /screening neuro developmental assessment tests. The patients who completed our inclusion criteria as neuro metabolic disorders were evaluated in terms of metabolic and genetic study in referral lab. Results Overall, 213 patients with neurometabolic disorders were diagnosed. 54.3% of patients were male. The average age of patients was 41 +-46.1 months. 71.4% of parent’s patients had consanguinity of marriages. Eighty seven percent of patients had developmental delay (or/and) regression. 55.5% of them had different type of seizures. Overall, 213 patients with 34 different neurometabolic disorders were diagnosed and classified in the 7 sub classes, consisting of: 1- organic acidemia and aminoacidopathy (122 patients), 2-storage disease (37 patients) 3- eukodystrophy (27 patients), other classes consisted: lipid oxidation disorders, urea cycle disorders, progressive myoclonic epilepsy; and peroxizomal disorders (27 patients). Conclusion In patients with developmental delay or regression, with or without seizure, abnormal neurologic exam along with positive family history of similar disorder or relative parents, abnormal brain imaging with specific patterns, neurometabolic disorders should be considered as one of the important treatable diseases PMID:27375759

  12. Treatment of Narcolepsy and other Hypersomnias of Central Origin

    PubMed Central

    Wise, Merrill S.; Arand, Donna L.; Auger, R. Robert; Brooks, Stephen N.; Watson, Nathaniel F.

    2007-01-01

    Objective: The purpose of this paper is to summarize current knowledge about treatment of narcolepsy and other hypersomnias of central origin. Methods: The task force performed a systematic and comprehensive review of the relevant literature and graded the evidence using the Oxford grading system. This paper discusses the strengths and limitations of the available evidence regarding treatment of these conditions, and summarizes key information about safety of these medications. Our findings provide the foundation for development of evidence-based practice parameters on this topic by the Standards of Practice Committee of the American Academy of Sleep Medicine. Results: The majority of recent papers in this field provide information about use of modafinil or sodium oxybate for treatment of sleepiness associated with narcolepsy. Several large randomized, placebo-controlled studies indicate that modafinil and sodium oxybate are effective for treatment of hypersomnia due to narcolepsy. We identified no studies that report direct comparison of these newer medications versus traditional stimulants, or that indicate what proportion of patients treated initially with these medications require transition to traditional stimulants or to combination therapy to achieve adequate alertness. As with the traditional stimulants, modafinil and sodium oxybate provide, at best, only moderate improvement in alertness rather than full restoration of alertness in patients with narcolepsy. Several large randomized placebo-controlled studies demonstrate that sodium oxybate is effective for treatment of cataplexy associated with narcolepsy, and earlier studies provide limited data to support the effectiveness of fluoxetine and tricyclic antidepressants for treatment of cataplexy. Our findings indicate that very few reports provide information regarding treatment of special populations such as children, older adults, and pregnant or breastfeeding women. The available literature provides a

  13. Use of the 2010 McDonald criteria can facilitate early diagnosis of pediatric multiple sclerosis in a predominantly black cohort.

    PubMed

    Williams, Mitchel T; Tapos, Daniela O; Juhász, Csaba

    2014-12-01

    Pediatric-onset multiple sclerosis represents around 3-5% of all patients with multiple sclerosis. Both the 2005 and 2010 McDonald criteria for multiple sclerosis have been suggested for the possible use in pediatric-onset multiple sclerosis. Modifications incorporated into the 2010 criteria enabled the fulfillment of dissemination in time to be met with the initial magnetic resonance imaging. The present study was designed to compare the diagnostic sensitivity of these criteria at initial presentation, the time to fulfilling them, and secondary effects of ethnicity in pediatric-onset multiple sclerosis. Twenty-five children with clinically definite multiple sclerosis (mean age, 14.6 ± 3.1 years; 15 girls) from a single center between 2005 and 2012 were analyzed using both the 2005 and 2010 McDonald criteria based on initial clinical presentation and neuroimaging findings comparing diagnostic sensitivity, time interval to meet diagnosis, and ethnicity. Initial multiple sclerosis diagnosis rates applying the 2005 McDonald criteria were 32% compared with 92% for the 2010 criteria (P = 0.0003). The mean time after initial signs until the 2005 and 2010 McDonald criteria for multiple sclerosis were met was 5.0 vs 0.7 months, respectively (P = 0.001). Time to diagnosis using the 2010 criteria was shorter in black children than the European white (P = 0.005). The 2010 McDonald criteria are an appropriate tool for the timely diagnosis of pediatric multiple sclerosis, especially in black children, potentially allowing an earlier initiation of disease-modifying therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Utilizing ultrasonography in the diagnosis of pediatric fibroepithelial polyps causing ureteropelvic junction obstruction.

    PubMed

    Wang, Xiao Man; Jia, Li Qun; Wang, Yu; Wang, Ning

    2012-09-01

    Fibroepithelial polyps are a rare cause of ureteropelvic junction (UPJ) obstruction in children. Preoperative US diagnosis of fibroepithelial polyps is infrequently reported, with intravenous pylogram and retrograde pyelography being most commonly used for diagnosis. To recommend the most accurate process for diagnosing this disease in children by assessing a modified ultrasonographic procedure for the diagnosis of fibroepithelial polyps. A retrospective review of US and IVP imaging studies performed in surgically and histologically confirmed cases of fibroepithelial polyps in children. Each child was asked to drink as much water as possible 30 min before the US testing. For US, the renal pelvis, UPJ and the proximal ureter were inspected for an echogenic mass resulting in hydronephrosis. For IVP studies, abdominal plain films were performed at 7, 15 and 30 min following contrast injection. Thirty-five children, 34 boys and 1 girl, had confirmed fibroepithelial polyps. The children ranged in age from 3 to 14 years (mean age 9 years). Clinical presentation included intermittent vague abdominal pain (100%) and/or hematuria (9.7%) for a period ranging from 1 month to 5 years. Of the 35 children (37 polyps), 21 (23 polyps) were correctly diagnosed preoperatively with US, establishing a 62.2% (23/37) US accuracy rate. Twenty polyps were seen on the left, three on the right and two children had bilateral polyps. The masses were all mildly echogenic with defined edges. Eight children (9 polyps) had an IVP consistent with fibroepithelial polyps giving IVP an accuracy rate of 24.3% (9/37). US is an effective screening tool for identifying fibroepithelial polyps causing UPJ obstruction in children.

  15. Glassy droplet inclusions within the cytoplasm of Kupffer cells: A novel ultrastructural feature for the diagnosis of pediatric autoimmune hepatitis.

    PubMed

    Lotowska, Joanna Maria; Sobaniec-Lotowska, Maria Elzbieta; Daniluk, Urszula; Lebensztejn, Dariusz Marek

    2017-08-01

    Since Kupffer cells/macrophages (KCs/MPs) may be involved in the pathogenesis of autoimmune hepatitis (AIH), this pioneer study was undertaken to evaluate KCs/MPs in pediatric AIH in transmission-electron microscope. Ultrastructural analyses were performed using liver biopsies from 14 children with clinicopathologically diagnosed AIH. In all AIH children, ultrastructural findings revealed changes in the cells lining sinusoidal vessels, especially KCs/MPs and endothelial cells. KCs/MPs showed increased phagocytic activity and damaged mitochondria, frequently with accompanying intense fibrosis. In 10/14 AIH patients, the cytoplasm of sinusoidal KCs/MPs contained characteristic glassy droplet inclusions. They were round, sharply circumscribed, and contained homogeneous material and distinct translucent fields. Their ultrastructure was identical with the Russel bodies of plasma cells, which were also found in liver biopsies in the same patients. Ultrastructural identification of characteristic cytoplasmic droplets with glassy appearance in KCs/MPs, never before described in AIH, provides a useful novel morphological feature in the diagnosis of this disease. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  16. DAX-1 Expression in Pediatric Rhabdomyosarcomas: Another Immunohistochemical Marker Useful in the Diagnosis of Translocation Positive Alveolar Rhabdomyosarcoma

    PubMed Central

    Virgone, Calogero; Lalli, Enzo; Bisogno, Gianni; Lazzari, Elena; Roma, Josep; Zin, Angelica; Poli, Elena; Cecchetto, Giovanni; Dall’Igna, Patrizia; Alaggio, Rita

    2015-01-01

    Objectives The aim of this study was to investigate the expression of DAX-1 in a series of pediatric rhabdomyosarcomas (RMS) with known translocation and compare it to Ap2β, known to be selectively expressed in ARMS. Design We revised a series of 71 alveolar rhabdomyosarcomas (ARMS), enrolled in the Italian Protocols RMS 79 and 96, and 23 embryonal rhabdomyosarcomas (ERMS) as controls. Before investigating Ap2β and DAX-1, ARMS were reviewed and reclassified as 48 ARMS and 23 non-ARMS. Results Translocation positive ARMS showed a characteristic Ap2β/DAX-1+ staining pattern in 78% of cases, while 76% of classic ERMS were negative for both. Ap2β alone was positive in 3.9% of RMS lacking translocation, whereas DAX-1 alone was positive in 25.4%. Conversely, 9% and 6% of translocation positive ARMS were positive only for DAX-1 or Ap2β, respectively. The 23 non-ARMS shared the same phenotype as ERMS but had a higher frequency of DAX-1 expression. Conclusions DAX-1 is less specific than Ap2β, however it is a sensitive marker for translocation positive ARMS and can be helpful in their diagnosis if used in combination with Ap2β. PMID:26168243

  17. [Siblings with pediatric hearing loss. Data on age at diagnosis and degree of hearing loss].

    PubMed

    Finckh-Krämer, U; Spormann-Lagodzinski, M E; Gross, M

    2001-03-01

    The Deutsches Zentralregister für kindliche Hörstörungen (DZH = German Registry for Hearing Loss in Children) has so far (30.6.2000) entered data records of 4,027 permanently hearing impaired children. These records include data on a total of 151 pairs of siblings. In seven cases a third sibling was registered. An analysis of the data of siblings with different dates of birth shows that the diagnosis for older siblings was delayed 2 years on average compared to the younger siblings (mean 23.6 months, 95% confidence interval 19.3-27.8 months). The degree of hearing loss, which crucially determines the average age at which a child is diagnosed, correlates statistically significantly with pairs of siblings, so that misleading results can be almost totally avoided. In 11 of 17 cases of twins and triplets, the diagnosis was pronounced simultaneously for both siblings; in the remaining 6 cases, one sibling was diagnosed later. It has become apparent that younger siblings of hearing-impaired children profit from the concomitant routine diagnostic investigation of siblings of hearing-impaired children nowadays common in many institutions, but avoidable delays nevertheless still occur, as shown by the data for twins and triplets. Since in approximately 18% of the registered children with one or more siblings one of the brothers or sisters is likewise hearing-impaired, consistent family investigation is recommended.

  18. The Diagnosis and Management of Attention-Deficit/Hyperactivity Disorder in Pediatric Patients

    PubMed Central

    Adesman, Andrew R.

    2001-01-01

    Attention-deficit/hyperactivity disorder (ADHD), characterized by developmentally inappropriate inattentiveness, impulsivity, and hyperactivity, is the most common and thoroughly researched neuropsychiatric disorder affecting children and adolescents. The diagnosis of ADHD requires a comprehensive clinical assessment including a detailed patient history, clinical interview and observation, and a thorough physical examination. A variety of other disorders can masquerade as ADHD or coexist with the disorder. The clinician must recognize environmental influences that may affect the severity of symptoms exhibited in the child or adolescent with ADHD. Clinically, treatment with a stimulant can be expected to result in an immediate, often dramatic, improvement in the core symptoms of ADHD. Studies published over the past 20 years indicate that the symptoms of ADHD, which were originally thought to diminish as a child matured, may persist into adolescence and adulthood. This article is a review of the most recent recommendations and clinical data regarding the diagnosis and management of ADHD in children and adolescents to assist with appropriate and prudent clinical decision making. PMID:15014618

  19. [Ultrasound diagnosis of nephrologic and urologic diseases in pediatrics. Report on 1000 patients].

    PubMed

    Maurer, G

    1985-01-04

    Urological conditions of infancy and childhood account for the largest single disease group requiring either surgical or medical intervention. This makes early detection and classification of abnormalities mandatory. This study presents an analysis of the results of ultrasonic screening in 1000 patients. Ultrasonic examination was readily instituted even in children with uncharacteristic symptoms for the early detection of abnormalities. Most cases of kidney and upper urinary tract abnormalities were diagnosable by ultrasound examination alone, whereby the characteristic pathoanatomical pattern of the lesion was seen. Lower urinary tract abnormalities were also detected with high accuracy. However, in most patients radiographic investigations were necessary for further classification. Sonography was also of great value in the initial investigation of acute renal failure; in patients with non-specific clinical and laboratory findings ultrasonography often presented the key to the diagnosis. Ultrasound also proved extremely useful in the follow up of patients with kidney and urinary tract disease. Based on the ultrasonic examination of 1000 patients it is shown that sonography is a most helpful and reliable method for the diagnosis or exclusion of kidney and/or urinary tract disease in paediatric patients of any age.

  20. Limitations of urease test in diagnosis of pediatric Helicobacter pylori infection

    PubMed Central

    Seo, Ji-Hyun; Park, Ji Sook; Rhee, Kwang Ho; Youn, Hee-Shang

    2015-01-01

    The diagnosis of Helicobacter pylori (H. pylori) infection is usually based on the results of urease test and histology. The urease test known as a simple and cheap method does not need special skills to perform or to read the result. The time needed for the test to turn positive depends on the concentration of bacteria, and the accuracy is up to the density of H. pylori density in the biopsy sample, which is generally lower in children than adolescents and adults. Therefore, there are debates about the sensitivity of the urease test in children. The reason for lower sensitivity of the urease test in children was not identified, but might be related to the low density and patchy distribution of bacteria. In this review, we discuss the limitations of the urease test in children according to age, histology, number of biopsy samples, and biopsy site. In children under 5 years old, the differences in positivity rate when the urease test used one or three biopsy samples, and samples from the antrum or the gastric body, were larger than those in children aged 5-15 years. Thus, three or more biopsy samples from both the antrum and body would improve the sensitivity of H. pylori infection diagnosis in children under 5 years old. PMID:26566487

  1. Ectopic cervical thymus as a rare cause of pediatric neck mass: the role of ultrasound and MRI in the diagnosis. Case report.

    PubMed

    Ozel, Alper; Akdur, Pinar Ozdemır; Celebi, Irfan; Karasu, Rabia; Yilmaz, Banu; Basak, Muzaffer

    2015-06-01

    Ectopic cervical thymus (ECT) is an uncommon cause for cervical mass in the pediatric age group. Ultrasound and magnetic resonance imaging findings of the mass (located along the thymic descent pathway along the thymopharyngeal tract and has identical echostructure and signal intensities to the native thymus in the superior mediastinum) would lead to the diagnosis. The diagnosis is confirmed by fine needle aspiration biopsy or histopathology after resection. The management of ECT is a conservative follow up, except in symptomatic cases with tracheal compression and histologically confirmed neoplasia where surgery is indicated. We present the case of ECT presenting as a left upper neck mass in a 12 year old girl.

  2. Autoimmune hemolytic anemia in systemic lupus erythematosus at diagnosis: differences between pediatric and adult patients.

    PubMed

    Gormezano, N W S; Kern, D; Pereira, O L; Esteves, G C X; Sallum, A M E; Aikawa, N E; Pereira, R M R; Silva, C A; Bonfá, E

    2017-04-01

    Objective To determine the overall prevalence of autoimmune hemolytic anemia (AIHA), and to compare clinical and laboratory features in a large population of children and adult lupus patients at diagnosis. Methods This retrospective study evaluated the medical charts of 336 childhood-onset systemic lupus erythematosus (cSLE) and 1830 adult SLE (aSLE) patients followed in the same tertiary hospital. Demographic data, clinical features and disease activity were recorded. AIHA was defined according to the presence of anemia (hemoglobin <10 g/dL) and evidence of hemolysis (reticulocytosis and positive direct antiglobulin test (DAT)/Coombs test) at SLE diagnosis. Evans syndrome (ES) was defined by the combination of immune thrombocytopenia (platelet count <100,000/mm(3)) and AIHA. Results The frequency of AIHA at diagnosis was significantly higher in cSLE patients compared to aSLE (49/336 (14%) vs 49/1830 (3%), p = 0.0001), with similar frequency of ES (3/336 (0.9%) vs 10/1830 (0.5%), p = 0.438). The median of hemoglobin levels was reduced in cSLE vs aSLE patients (8.3 (2.2-10) vs 9.5 (6.6-10) g/dL, p = 0.002) with a higher frequency of multiple hemorrhagic manifestations (41% vs 7%, p = 0.041) and erythrocyte transfusion due to bleeding (24% vs 5%, p = 0.025). cSLE patients also had more often constitutional involvement (84% vs 31%, p < 0.001), fever (65% vs 26%, p < 0.001), weight loss > 2 kg (39% vs 6%, p < 0.001), reticuloendothelial manifestations (48% vs 8%, p < 0.001), hepatomegaly (25% vs 2%, p < 0.001) and splenomegaly (21% vs 2%, p = 0.004). Other major organ involvements were common but with similar frequencies in cSLE and aSLE ( p > 0.05). Median systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) was comparable in cSLE and aSLE (p = 0.161). Conclusions We identified that AIHA was not a common condition in cSLE and aSLE, with distinct features characterized by a higher prevalence

  3. Pediatric restless legs syndrome and periodic limb movement disorder: parent-child pairs.

    PubMed

    Picchietti, Daniel L; Rajendran, Ramji R; Wilson, Michael P; Picchietti, Matthew A

    2009-09-01

    Although recent publications have reported the occurrence of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in children and adolescents, the literature is relatively limited. The goals of this retrospective study were to (1) apply the recent International Classification of Sleep Disorders 2nd edition (ICSD-2) diagnostic criteria for RLS and PLMD in pediatric cases where periodic limb movements in sleep (PLMS) 5 per hour were found; (2) review parental history of RLS; and (3) further define the clinical characteristics of RLS and PLMD in a pediatric subgroup where each child had a parent with clinically assessed RLS. This was a retrospective analysis of consecutive polysomnograms (PSGs) with PLMS >5 per hour in patients 19 years of age from a single pediatric sleep/neurology practice over 11 years. Excluded were cases with sleep apnea, narcolepsy, or medication that might induce or aggravate PLMS or RLS. ICSD-2 diagnostic criteria for definite RLS and PLMD were applied to the pediatric cases, and parental history for RLS was assessed. A subset of cases was included for detailed review if the child or adolescent had RLS or PLMD and a biological parent met RLS criteria and had a formal sleep evaluation. There were 204 cases that met the initial inclusion criteria. A positive parental history of RLS was found in 53% of pediatric RLS cases and in 52% of pediatric PLMD cases. A subset of 37 children or adolescents and 36 biological parents, from 33 different families, met full inclusion criteria and are presented in detail. Of these 37, 10 had a diagnosis of RLS and 27 a diagnosis of PLMD. Over this same period of time, PLMS >5 per hour were found in 74% of pediatric definite RLS cases assessed by PSG. This case series adds to the growing literature describing RLS and PLMD in children and adolescents using recently revised diagnostic criteria. The similar prevalence of parental RLS in both pediatric RLS and pediatric PLMD cases suggests a close

  4. Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study.

    PubMed

    Harris, M B; Gieser, P; Goorin, A M; Ayala, A; Shochat, S J; Ferguson, W S; Holbrook, T; Link, M P

    1998-11-01

    To estimate the duration of survival (S) of patients with metastatic osteosarcoma (MOS) at diagnosis treated with a multiagent, ifosfamide-containing chemotherapeutic and surgical regimen and to evaluate the toxicity of this regimen. Thirty patients aged younger than 30 years received two courses of ifosfamide followed by surgery on the primary tumor and metastatic sites. Patients then received a postsurgical multiagent chemotherapeutic regimen that consisted of high-dose methotrexate (HDMTX), ifosfamide, doxorubicin, and cisplatin. The 5-year event-free survival (EFS) rate was 46.7% (95% confidence interval [CI]; 28.5 to 64.9) and 5-year S rate was 53.3% (95% CI; 35.1 to 71.5). Three patients with bone metastases and one patient with lymph node metastases died. Twenty-six patients presented with pulmonary metastatic nodules only. Eight of these patients had at least eight nodules at diagnosis and had an estimated 5-year EFS rate of 25.0% compared with 66.7% for the 18 patients with less than eight nodules (P=.06). Fourteen patients presented with bilateral lung metastases and had a 5-year EFS rate of 35.7% compared with the 12 patients who presented with unilateral involvement and had a 5-year EFS rate of 75.0% (P=.03). The hematopoietic toxicity experienced by the patients during the entire regimen was relatively mild. Seven patients had renal toxicity characterized by hypophosphatemia and/or hypokalemia. This ifosfamide-containing regimen is tolerable and effective in the treatment of patients with osteosarcoma (OS) who present with lung metastases. However, better regimens are required for this group of patients.

  5. Diagnostic Value of Ceruloplasmin in the Diagnosis of Pediatric Wilson's Disease

    PubMed Central

    Kim, Jung Ah; Kim, Hyun Jin; Cho, Jin Min; Lee, Beom Hee; Kim, Gu-Hwan; Choi, Jin-Ho; Kim, Kyung Mo; Yoo, Han-Wook

    2015-01-01

    Purpose Measurement of serum ceruloplasmin level is the first step in screening for Wilson's disease (WD). Despite the rarity of WD in the general population, ceruloplasmin levels are routinely measured through hepatitis screening in both adults and children. Herein, we evaluated the diagnostic value of ceruloplasmin for the diagnosis of WD among children with hepatitis. Methods We retrospectively reviewed data on serum ceruloplasmin levels measured as a serologic marker for patients with hepatitis at Asan Medical Center (Seoul, Korea) between from January 2004 to November 2013. The diagnosis of WD was confirmed by the identification of pathogenic variants in the ATP7B gene. To determine the diagnostic accuracy of ceruloplasmin, receiver operation characteristic (ROC) curves were constructed and the area under curve (AUC) were calculated. Results Measurements of serum ceruloplasmin were performed in 2,834 children who had hepatitis. Among these, 181 (6.4%) children were diagnosed with WD. The sensitivity, specificity, and accuracy of a ceruloplasmin level of <20 mg/dL in the discrimination of WD were 93.4%, 84.2%, and 84.8%, respectively. In this study, 418 (14.7%) false-positive cases and 12 (0.4%) false-negative cases were noted. Using a ROC curve, a ceruloplasmin level of ≤16.6 mg/dL showed the highest AUC value (0.956) with a sensitivity of 91.2%, a specificity of 94.9%, and an accuracy of 94.7%. Conclusion The measurement of serum ceruloplasmin was frequently used for the screening of WD in children, despite a low positive rate. The diagnostic value of ceruloplasmin may be strengthened by adopting a new lower cut-off level. PMID:26473139

  6. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease.

    PubMed

    Husby, S; Koletzko, S; Korponay-Szabó, I R; Mearin, M L; Phillips, A; Shamir, R; Troncone, R; Giersiepen, K; Branski, D; Catassi, C; Lelgeman, M; Mäki, M; Ribes-Koninckx, C; Ventura, A; Zimmer, K P

    2012-01-01

    Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the autoantigen in CD, tissue transglutaminase, has been identified; the perception of CD has changed from that of a rather uncommon enteropathy to a common multiorgan disease strongly dependent on the haplotypes human leukocyte antigen (HLA)-DQ2 and HLA-DQ8; and CD-specific antibody tests have improved. A panel of 17 experts defined CD and developed new diagnostic criteria based on the Delphi process. Two groups of patients were defined with different diagnostic approaches to diagnose CD: children with symptoms suggestive of CD (group 1) and asymptomatic children at increased risk for CD (group 2). The 2004 National Institutes of Health/Agency for Healthcare Research and Quality report and a systematic literature search on antibody tests for CD in paediatric patients covering the years 2004 to 2009 was the basis for the evidence-based recommendations on CD-specific antibody testing. In group 1, the diagnosis of CD is based on symptoms, positive serology, and histology that is consistent with CD. If immunoglobulin A anti-tissue transglutaminase type 2 antibody titers are high (>10 times the upper limit of normal), then the option is to diagnose CD without duodenal biopsies by applying a strict protocol with further laboratory tests. In group 2, the diagnosis of CD is based on positive serology and histology. HLA-DQ2 and HLA-DQ8 testing is valuable because CD is unlikely if both haplotypes are negative. The aim of the new guidelines was to achieve a high diagnostic accuracy and to reduce the burden for patients and their families. The performance of these guidelines in clinical practice should be evaluated prospectively.

  7. Pediatric RIFLE for acute kidney injury diagnosis and prognosis for children undergoing cardiac surgery: a single-center prospective observational study.

    PubMed

    Ricci, Zaccaria; Di Nardo, Matteo; Iacoella, Claudia; Netto, Roberta; Picca, Stefano; Cogo, Paola

    2013-08-01

    This study evaluated the performance of the pediatric RIFLE (pRIFLE) score for acute kidney injury (AKI) diagnosis and prognosis after pediatric cardiac surgery. It was a single-center prospective observational study developed in a pediatric cardiac intensive care unit (pCICU) of a tertiary children's hospital. The study enrolled 160 consecutive children younger than 1 year with congenital heart diseases and undergoing cardiac surgery with cardiopulmonary bypass. Of the 160 children, 50 (31 %) were neonates, and 20 (12 %) had a univentricular heart. Palliative surgery was performed for 53 patients (33 %). A diagnosis of AKI was determined for 90 patients (56 %), and 68 (42 %) of these patients achieved an "R" level of AKI severity, 17 patients (10 %) an "I" level, and 5 patients (3 %) an "F" level. Longer cross-clamp times (p = 0.045), a higher inotropic score (p = 0.02), and a higher Risk-Adjusted Classification for Congenital Heart Surgery score (p = 0.048) but not age (p = 0.27) correlated significantly with pRIFLE class severity. Patients classified with a higher pRIFLE score required a greater number of mechanical ventilation days (p = 0.03) and a longer pCICU stay (p = 0.045). Renal replacement therapy (RRT) was needed for 13 patients (8.1 %), with two patients receiving continuous hemofiltration, and 11 patients receiving peritoneal dialysis. At the start of dialysis, the distribution of RRT patients differed significantly within pRIFLE classes (p = 0.015). All deceased patients were classified as pRIFLE "I" or "F" (p = 0.0001). The findings showed that pRIFLE is easily and feasibly applied for pediatric patients with congenital heart disease. The pRIFLE classification showed that AKI incidence in pediatric cardiac surgery infants is high and associated with poorer outcomes.

  8. p24 antigen rapid test for diagnosis of acute pediatric HIV infection.

    PubMed

    Parpia, Zaheer A; Elghanian, Robert; Nabatiyan, Arman; Hardie, Diana R; Kelso, David M

    2010-12-01

    Currently, the majority of HIV-infected infants are found within limited-resource settings, where inadequate screening for HIV due to the lack of access to simple and affordable point-of-care tests impedes implementation of antiretroviral therapy. Here we report development of a low-cost dipstick p24 antigen assay using a visual readout format that can facilitate the diagnosis of HIV for infants in resource-poor conditions. A heat shock methodology was developed to optimize disruption of immune complexes present in the plasma of infected infants. The analytical sensitivity of the assay using recombinant p24 antigen is 50 pg/mL (2 pM) with whole virus detection as low as 42.5k RNA copies per milliliter plasma. In a blinded study comprising 51 archived infant samples from the Women and Infants Transmission Study, our assay demonstrated an overall sensitivity and specificity of 90% and 100%, respectively. In field evaluations of 389 fresh samples from South African infants, a sensitivity of 95% and specificity of 99% was achieved. The assay is simple to perform, requires minimal plasma volume (25 μL), and yields a result in less than 40 minutes making it ideal for implementation in resource-limited settings.

  9. [Costs of appendicitis treatment by diagnosis-related groups in a third-level pediatric hospital].

    PubMed

    Tlacuilo-Parra, Alberto; Hernández-Hernández, Araceli; Venegas-Dávalos, Martha; Gutiérrez-Hermosillo, Violeta; Guevara-Gutiérrez, Elizabeth; Ambriz-González, Gabriela

    2014-01-01

    Diagnosis-related groups (DRGs) are widely used in Europe. They allow performing comparisons in hospitals and incurrent hospital payment systems, defining the payment categories. We undertook this study to classify children who underwent appendectomy according to DRGs. Cross-sectional study. Comorbidities, length of hospitalization, histopathologic classification, and DRG classifications were analyzed. We included 313 patients, 62% males, with an average age of 8 ± 3 years; 91% were referred by another hospital and 67% were treated at night. Average length of hospitalization was 4 ± 3 days. There were comorbidities in 8% and surgical complications in 11%. According to histopathology, appendicitis was edematous (11%), suppurative (36%), gangrenous (22%), perforated (29%), and abscessed (2%). At discharge, 97% of the patients were healthy. Total cost for DRG 343 was $10,470,173.00 (Mexican pesos), DRG 342 was $1,227,592.00 and DRG 340 was $511,521.00. The global amount was $12,209,286.00 (Mexican pesos). The unitary cost for treatment of appendectomy for DRG 343 was $37,935.00, for DRG 342 was $49,103.00 and for DRG 340 was $42,626.00 (Mexican pesos). Because 88% of the cases of appendicitis were uncomplicated, this amount of money could be spent to treat these patients in a second-level hospital, using reimbursement 343 without generating additional expenses.

  10. Current controversies in diagnosis, management, and prevention of congenital cytomegalovirus: updates for the pediatric practitioner.

    PubMed

    Harrison, Gail J

    2015-05-01

    Congenital cytomegalovirus (CMV) infection has been called "the elephant in our living room" because it is a major public health problem that for decades has been unrecognized and unaddressed. Congenital CMV infection is a common cause of sensorineural hearing loss, vision loss, neurodevelopment disabilities, liver disease, and growth failure. Diagnostic tests are now widely available to identify newborns with congenital CMV infection, congenitally infected newborns now can be easily assessed for evidence of organ involvement, and there are now antiviral treatments and other interventions available to improve the outcome in children with congenital CMV disease. A licensed vaccine to prevent CMV infection is not yet available; however, a "CMV knowledge vaccine," composed of "an ounce of CMV awareness and three simple precautions" and that is endorsed by the Centers for Disease Control and Prevention is available for pregnant women who wish to reduce their contact with potentially CMV-infected secretions and therefore reduce their risk of acquiring CMV during pregnancy. Medical experts in the field of congenital CMV have been called upon for a consensus statement for diagnosis and treatment, and nonprofit organizations of families affected by congenital CMV from around the world have formed a collaborative coalition to facilitate the spread of CMV knowledge and awareness.

  11. Orthodontic extrusion: diagnosis and treatment with CBCT in a pediatric patient.

    PubMed

    Bahadure, Rakesh N; Thosar, Nilima; Khubchandani, Monika

    2013-07-01

    Traumatic injury to a primary tooth can affect the underlying permanent tooth germ, and may result in a malformed, hypoplastic crown or root. The degree and nature of malformation depends on the injury. Most trauma cases can be diagnosed using conventional 2-dimensional radiographs, but some cases may benefit from more advanced 3-dimensional imaging such as cone-beam computed tomography (CBCT). This report describes the use of CBCT in the diagnosis and treatment planning of a case in which a 10-year-old girl reported with an impacted, recessed central incisor. The tooth was deformed due to trauma at an early age. Conventional 2-dimensional occlusal and periapical radiographs seemed to indicate that the root had almost completely resorbed. This implied that the optimal treatment plan would be the extraction of the central incisor and, later, the placement of an implant with a crown or bridge. However, a 3-dimensional CBCT radiographic examination showed that the tooth root was long and had enough of a crown-to-root ratio to anchor the tooth. The CBCT examination compelled the treating dentists to maintain the central incisor by orthodontically extruding the tooth and then rebuilding it with a bonded composite restoration.

  12. Optic neuritis in pediatric population: a review in current tendencies of diagnosis and management.

    PubMed

    Pérez-Cambrodí, Rafael José; Gómez-Hurtado Cubillana, Aránzazu; Merino-Suárez, María L; Piñero-Llorens, David P; Laria-Ochaita, Carlos

    2014-01-01

    Optic neuritis is an inflammation of the optic nerve and may be related to different systemic conditions. The clinical presentation of this pathology usually includes sudden loss of visual acuity (VA) which may be unilateral or bilateral, visual field restriction, pain with eye movements, dyschromatopsia, a relative afferent pupillary defect and optic disk swelling. Optic neuritis in children has specific clinical features and a better prognosis than in adulthood. Although usually appears an underlying viral disease, the main concern for practitioners is the relationship of optic neuritis with multiple sclerosis. In addition to the classical techniques as magnetic resonance imaging (MRI), current tendencies of diagnosis for eye practitioners include new imaging devices as optical coherence tomography (OCT), useful to show a thinning of the retinal fibers layer (RFL) after the inflammatory episode. Regarding the management of these patients, short-term intravenous steroid dosages seem to be the best option to treat acute attacks characterized by a very poor bilateral VA. Copyright © 2013 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

  13. Positive Effects of Massage Therapy on a Patient with Narcolepsy

    PubMed Central

    Hill, Robyn; Baskwill, Amanda

    2013-01-01

    Purpose The purpose of this case report was to investigate the effects of massage therapy on the sleep patterns of a woman with narcolepsy. Participant The 23-year-old woman’s primary symptoms included excessive daytime sleepiness and periodic leg movements (PLM), which were associated with her diagnoses of both narcolepsy and cataplexy. Intervention Five 45-minute massage therapy treatments were administered over a five-week period. The patient’s sleep patterns were recorded each week before the treatment. A final measurement was recorded in the sixth week. The sleep patterns were monitored using the Leeds Sleep Evaluation Questionnaire, which included ten visual analogue scales. Results The results of this case report included an improvement in getting to sleep by 148%, an improvement in quality of sleep by 1100%, an improvement in awake following sleep by 121%, and an improvement in behaviour following wakening by 28% using the Leeds Sleep Evaluation Questionnaire. Conclusion This case report suggests that massage therapy had a positive effect on this patient with narcolepsy. Further research is needed to investigate the effects of massage therapy on narcolepsy and sleep patterns. PMID:23730398

  14. Narcolepsy with long sleep time: a specific entity?

    PubMed

    Vernet, Cyrille; Arnulf, Isabelle

    2009-09-01

    The classical narcolepsy patient reports intense feelings of sleepiness (with/out cataplexy), normal or disrupted nighttime sleep, and takes short and restorative naps. However, with long-term monitoring, we identified some narcoleptics resembling patients with idiopathic hypersomnia. To isolate and describe a new subtype of narcolepsy with long sleep time). University Hospital Controlled, prospective cohort Out of 160 narcoleptics newly diagnosed within the past 3 years, 29 (18%) had a long sleep time (more than 11 h/24 h). We compared narcoleptics with (n = 23) and without (n = 29) long sleep time to 25 hypersomniacs with long sleep time and 20 healthy subjects. Patients and controls underwent face-to face interviews, questionnaires, human leukocyte antigen (HLA) genotype, an overnight polysomnography, multiple sleep latency tests, and 24-h ad libitum sleep monitoring. Narcoleptics with long sleep time had a similar disease course and similar frequencies of cataplexy, sleep paralysis, hallucinations, multiple sleep onset in REM periods, short mean sleep latencies, and HLA DQB1*0602 positivity as narcoleptics with normal sleep time did. However, they had longer sleep time during 24 h, and higher sleep efficiency, lower Epworth Sleepiness Scale scores, and reported their naps were more often unrefreshing. Only 3/23 had core narcolepsy (HLA and cataplexy positive). The subgroup of narcoleptics with a long sleep time comprises 18% of narcoleptics. Their symptoms combine the disabilities of both narcolepsy (severe sleepiness) and idiopathic hypersomnia (long sleep time and unrefreshing naps). Thus, they may constitute a group with multiple arousal system dysfunctions.

  15. Hypocretin (orexin) biology and the pathophysiology of narcolepsy with cataplexy.

    PubMed

    Liblau, Roland S; Vassalli, Anne; Seifinejad, Ali; Tafti, Mehdi

    2015-03-01

    The discovery of hypocretins (orexins) and their causal implication in narcolepsy is the most important advance in sleep research and sleep medicine since the discovery of rapid eye movement sleep. Narcolepsy with cataplexy is caused by hypocretin deficiency owing to destruction of most of the hypocretin-producing neurons in the hypothalamus. Ablation of hypocretin or hypocretin receptors also leads to narcolepsy phenotypes in animal models. Although the exact mechanism of hypocretin deficiency is unknown, evidence from the past 20 years strongly favours an immune-mediated or autoimmune attack, targeting specifically hypocretin neurons in genetically predisposed individuals. These neurons form an extensive network of projections throughout the brain and show activity linked to motivational behaviours. The hypothesis that a targeted immune-mediated or autoimmune attack causes the specific degeneration of hypocretin neurons arose mainly through the discovery of genetic associations, first with the HLA-DQB1*06:02 allele and then with the T-cell receptor α locus. Guided by these genetic findings and now awaiting experimental testing are models of the possible immune mechanisms by which a specific and localised brain cell population could become targeted by T-cell subsets. Great hopes for the identification of new targets for therapeutic intervention in narcolepsy also reside in the development of patient-derived induced pluripotent stem cell systems.

  16. Validation of the new diagnosis grouping system for pediatric emergency department visits using the International Classification of Diseases, 10th Revision.

    PubMed

    Lee, Jin Hee; Hong, Ki Jeong; Kim, Do Kyun; Kwak, Young Ho; Jang, Hye Young; Kim, Hahn Bom; Noh, Hyun; Park, Jungho; Song, Bongkyu; Jung, Jae Yun

    2013-12-01

    A clinically sensible diagnosis grouping system (DGS) is needed for describing pediatric emergency diagnoses for research, medical resource preparedness, and making national policy for pediatric emergency medical care. The Pediatric Emergency Care Applied Research Network (PECARN) developed the DGS successfully. We developed the modified PECARN DGS based on the different pediatric population of South Korea and validated the system to obtain the accurate and comparable epidemiologic data of pediatric emergent conditions of the selected population. The data source used to develop and validate the modified PECARN DGS was the National Emergency Department Information System of South Korea, which was coded by the International Classification of Diseases, 10th Revision (ICD-10) code system. To develop the modified DGS based on ICD-10 code, we matched the selected ICD-10 codes with those of the PECARN DGS by the General Equivalence Mappings (GEMs). After converting ICD-10 codes to ICD-9 codes by GEMs, we matched ICD-9 codes into PECARN DGS categories using the matrix developed by PECARN group. Lastly, we conducted the expert panel survey using Delphi method for the remaining diagnosis codes that were not matched. A total of 1879 ICD-10 codes were used in development of the modified DGS. After 1078 (57.4%) of 1879 ICD-10 codes were assigned to the modified DGS by GEM and PECARN conversion tools, investigators assigned each of the remaining 801 codes (42.6%) to DGS subgroups by 2 rounds of electronic Delphi surveys. And we assigned the remaining 29 codes (4%) into the modified DGS at the second expert consensus meeting. The modified DGS accounts for 98.7% and 95.2% of diagnoses of the 2008 and 2009 National Emergency Department Information System data set. This modified DGS also exhibited strong construct validity using the concepts of age, sex, site of care, and seasons. This also reflected the 2009 outbreak of H1N1 influenza in Korea. We developed and validated clinically

  17. Diagnosis, comorbidities, and management of restless legs syndrome.

    PubMed

    Becker, Philip M; Novak, Marta

    2014-08-01

    This narrative review describes the differential diagnosis of restless legs syndrome, and provides an overview of the evidence for the associations between RLS and potential comorbidities. Secondary causes of RLS and the characteristics of pediatric RLS are also discussed. Finally, management strategies for RLS are summarized. The review began with a comprehensive PubMed search for 'restless legs syndrome/Willis-Ekbom disease' in combination with the following: anxiety, arthritis, attention-deficit hyperactivity disorder, cardiac, cardiovascular disease, comorbidities, depression, end-stage renal disease, erectile dysfunction, fibromyalgia, insomnia, kidney disease, liver disease, migraine, mood disorder, multiple sclerosis, narcolepsy, neuropathy, obesity, pain, Parkinson's disease, polyneuropathy, pregnancy, psychiatric disorder, sleep disorder, somatoform pain disorder, and uremia. Additional papers were identified by reviewing the reference lists of retrieved publications. Although clinical diagnosis of RLS can be straightforward, diagnostic challenges may arise when patients present with comorbid conditions. Comorbidities of RLS include insomnia, depressive and anxiety disorders, and pain disorders. Differential diagnosis is particularly important, as some of the medications used to treat insomnia and depression may exacerbate RLS symptoms. Appropriate diagnosis and management of RLS symptoms may benefit patient well-being and, in some cases, may lessen comorbid disease burden. Therefore, it is important that physicians are aware of the presence of RLS when treating patients with conditions that commonly co-occur with the disorder.

  18. Evaluation of polygenic risks for narcolepsy and essential hypersomnia.

    PubMed

    Yamasaki, Maria; Miyagawa, Taku; Toyoda, Hiromi; Khor, Seik-Soon; Liu, Xiaoxi; Kuwabara, Hitoshi; Kano, Yukiko; Shimada, Takafumi; Sugiyama, Toshiro; Nishida, Hisami; Sugaya, Nagisa; Tochigi, Mamoru; Otowa, Takeshi; Okazaki, Yuji; Kaiya, Hisanobu; Kawamura, Yoshiya; Miyashita, Akinori; Kuwano, Ryozo; Kasai, Kiyoto; Tanii, Hisashi; Sasaki, Tsukasa; Honda, Yutaka; Honda, Makoto; Tokunaga, Katsushi

    2016-10-01

    In humans, narcolepsy is a sleep disorder that is characterized by sleepiness, cataplexy and rapid eye movement (REM) sleep abnormalities. Essential hypersomnia (EHS) is another type of sleep disorder that is characterized by excessive daytime sleepiness without cataplexy. A human leukocyte antigen (HLA) class II allele, HLA-DQB1*06:02, is a major genetic factor for narcolepsy. Almost all narcoleptic patients are carriers of this HLA allele, while 30-50% of EHS patients and 12% of all healthy individuals in Japan carry this allele. The pathogenesis of narcolepsy and EHS is thought to be partially shared. To evaluate the contribution of common single-nucleotide polymorphisms (SNPs) to narcolepsy onset and to assess the common genetic background of narcolepsy and EHS, we conducted a polygenic analysis that included 393 narcoleptic patients, 38 EHS patients with HLA-DQB1*06:02, 119 EHS patients without HLA-DQB1*06:02 and 1582 healthy individuals. We also included 376 individuals with panic disorder and 213 individuals with autism to confirm whether the results were biased. Polygenic risks in narcolepsy were estimated to explain 58.1% (PHLA-DQB1*06:02=2.30 × 10(-48), Pwhole genome without HLA-DQB1*06:02=6.73 × 10(-2)) including HLA-DQB1*06:02 effects and 1.3% (Pwhole genome without HLA-DQB1*06:02=2.43 × 10(-2)) excluding HLA-DQB1*06:02 effects. The results also indicated that small-effect SNPs contributed to the development of narcolepsy. Reported susceptibility SNPs for narcolepsy in the Japanese population, CPT1B (carnitine palmitoyltransferase 1B), TRA@ (T-cell receptor alpha) and P2RY11 (purinergic receptor P2Y, G-protein coupled, 11), were found to explain 0.8% of narcolepsy onset (Pwhole genome without HLA-DQB1*06:02=9.74 × 10(-2)). EHS patients with HLA-DQB1*06:02 were estimated to have higher shared genetic background to narcoleptic patients than EHS patients without HLA-DQB1*06:02 even when the effects of HLA-DQB1*06:02 were excluded (EHS with HLA-DQB1

  19. Clinical and genetic diagnosis of familial hypertrophic cardiomyopathy: Results in pediatric cardiology.

    PubMed

    Cardoso, Bárbara; Gomes, Inês; Loureiro, Petra; Trigo, Conceição; Ferreira Pinto, Fátima

    2017-03-01

    Hypertrophic cardiomyopathy (HCM) is most often of autosomal dominant inheritance with incomplete penetrance and variable expression. The main purpose of family screening is to identify relatives with unrecognized HCM and to monitor those at risk for disease, in order to minimize complications and to assess risk of sudden cardiac death. The ESC and ACCF/AHA guidelines on the diagnosis and management of HCM recommend the screening of child relatives from the age of 10-12 years. We studied the outcome of clinical screening and genetic testing of child probands and relatives (<18 years of age) from families with HCM and assessed the age-related penetrance of HCM during the follow-up of these young relatives. Twenty patients from ten families were included between 2004 and 2013, consisting of three probands and 17 first-degree relatives (80% male; median age 10 years). Fourteen child relatives were mutation carriers (70%; median age eight years). Seven (50%) of the 14 mutation carriers were diagnosed with HCM at initial assessment. At-risk child relatives were defined as those with a positive mutation but a negative phenotype at enrollment. After 3.5±0.8 years of follow-up, two of the phenotype-negative mutation carriers developed HCM at 10 and 15 years of age (28% penetrance rate). The penetrance of HCM in phenotype-negative child relatives was 28% after 3.5 years of follow-up. This underlines the need for long-term monitoring of mutation carriers irrespective of the presence of a positive phenotype. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Narcolepsy with Long Sleep Time: A Specific Entity?

    PubMed Central

    Vernet, Cyrille; Arnulf, Isabelle

    2009-01-01

    Background: The classical narcolepsy patient reports intense feelings of sleepiness (with/out cataplexy), normal or disrupted nighttime sleep, and takes short and restorative naps. However, with long-term monitoring, we identified some narcoleptics resembling patients with idiopathic hypersomnia. Objective: To isolate and describe a new subtype of narcolepsy with long sleep time). Setting: University Hospital Design: Controlled, prospective cohort Participants: Out of 160 narcoleptics newly diagnosed within the past 3 years, 29 (18%) had a long sleep time (more than 11 h/24 h). We compared narcoleptics with (n = 23) and without (n = 29) long sleep time to 25 hypersomniacs with long sleep time and 20 healthy subjects. Intervention: Patients and controls underwent face-to face interviews, questionnaires, human leukocyte antigen (HLA) genotype, an overnight polysomnography, multiple sleep latency tests, and 24-h ad libitum sleep monitoring. Results: Narcoleptics with long sleep time had a similar disease course and similar frequencies of cataplexy, sleep paralysis, hallucinations, multiple sleep onset in REM periods, short mean sleep latencies, and HLA DQB1*0602 positivity as narcoleptics with normal sleep time did. However, they had longer sleep time during 24 h, and higher sleep efficiency, lower Epworth Sleepiness Scale scores, and reported their naps were more often unrefreshing. Only 3/23 had core narcolepsy (HLA and cataplexy positive). Conclusions: The subgroup of narcoleptics with a long sleep time comprises 18% of narcoleptics. Their symptoms combine the disabilities of both narcolepsy (severe sleepiness) and idiopathic hypersomnia (long sleep time and unrefreshing naps). Thus, they may constitute a group with multiple arousal system dysfunctions. Citation: Vernet C; Arnulf I. Narcolepsy with long sleep time: a specific entity? SLEEP 2009;32(9):1229-1235. PMID:19750928

  1. Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution.

    PubMed

    Lin, Wei-Xia; Zeng, Han-Shi; Zhang, Zhan-Hui; Mao, Man; Zheng, Qi-Qi; Zhao, Shu-Tao; Cheng, Ying; Chen, Feng-Ping; Wen, Wang-Rong; Song, Yuan-Zong

    2016-07-11

    Citrin deficiency (CD) is a Mendelian disease due to biallelic mutations of SLC25A13 gene. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major pediatric CD phenotype, and its definite diagnosis relies on SLC25A13 genetic analysis. China is a vast country with a huge population, but the SLC25A13 genotypic features of CD patients in our country remains far from being well clarified. Via sophisticated molecular analysis, this study diagnosed 154 new CD patients in mainland China and identified 9 novel deleterious SLC25A13 mutations, i.e. c.103A > G, [c.329 - 154_c.468 + 2352del2646; c.468 + 2392_c.468 + 2393ins23], c.493C > T, c.755 - 1G > C, c.845_c.848 + 1delG, c.933_c.933 + 1insGCAG, c.1381G > T, c.1452 + 1G > A and c.1706_1707delTA. Among the 274 CD patients diagnosed by our group thus far, 41 SLC25A13 mutations/variations were detected. The 7 mutations c.775C > T, c.851_854del4, c.1078C > T, IVS11 + 1G > A, c.1364G > T, c.1399C > T and IVS16ins3kb demonstrated significantly different geographic distribution. Among the total 53 identified genotypes, only c.851_854del4/c.851_854del4 and c.851_854del4/c.1399C > T presented different geographic distribution. The northern population had a higher level of SLC25A13 allelic heterogeneity than those in the south. These findings enriched the SLC25A13 mutation spectrum and brought new insights into the geographic distribution of the variations and genotypes, providing reliable evidences for NICCD definite diagnosis and for the determination of relevant molecular targets in different Chinese areas.

  2. High-dimensional single-cell analysis reveals the immune signature of narcolepsy.

    PubMed

    Hartmann, Felix J; Bernard-Valnet, Raphaël; Quériault, Clémence; Mrdjen, Dunja; Weber, Lukas M; Galli, Edoardo; Krieg, Carsten; Robinson, Mark D; Nguyen, Xuan-Hung; Dauvilliers, Yves; Liblau, Roland S; Becher, Burkhard

    2016-11-14

    Narcolepsy type 1 is a devastating neurological sleep disorder resulting from the destruction of orexin-producing neurons in the central nervous system (CNS). Despite its striking association with the HLA-DQB1*06:02 allele, the autoimmune etiology of narcolepsy has remained largely hypothetical. Here, we compared peripheral mononucleated cells from narcolepsy patients with HLA-DQB1*06:02-matched healthy controls using high-dimensional mass cytometry in combination with algorithm-guided data analysis. Narcolepsy patients displayed multifaceted immune activation in CD4(+) and CD8(+) T cells dominated by elevated levels of B cell-supporting cytokines. Additionally, T cells from narcolepsy patients showed increased production of the proinflammatory cytokines IL-2 and TNF. Although it remains to be established whether these changes are primary to an autoimmune process in narcolepsy or secondary to orexin deficiency, these findings are indicative of inflammatory processes in the pathogenesis of this enigmatic disease. © 2016 Hartmann et al.

  3. High-dimensional single-cell analysis reveals the immune signature of narcolepsy

    PubMed Central

    Quériault, Clémence; Krieg, Carsten; Nguyen, Xuan-Hung

    2016-01-01

    Narcolepsy type 1 is a devastating neurological sleep disorder resulting from the destruction of orexin-producing neurons in the central nervous system (CNS). Despite its striking association with the HLA-DQB1*06:02 allele, the autoimmune etiology of narcolepsy has remained largely hypothetical. Here, we compared peripheral mononucleated cells from narcolepsy patients with HLA-DQB1*06:02-matched healthy controls using high-dimensional mass cytometry in combination with algorithm-guided data analysis. Narcolepsy patients displayed multifaceted immune activation in CD4+ and CD8+ T cells dominated by elevated levels of B cell–supporting cytokines. Additionally, T cells from narcolepsy patients showed increased production of the proinflammatory cytokines IL-2 and TNF. Although it remains to be established whether these changes are primary to an autoimmune process in narcolepsy or secondary to orexin deficiency, these findings are indicative of inflammatory processes in the pathogenesis of this enigmatic disease. PMID:27821550

  4. Adolescent and Pediatric Brain Tumors

    MedlinePlus

    ... Children Pediatric Brain Tumor Diagnosis Family Impact Late Effects After Treatment Returning to School Pediatric Caregiver Resource Center About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials ...

  5. Hallucinations in narcolepsy with and without cataplexy: contrasts with Parkinson's disease.

    PubMed

    Leu-Semenescu, Smaranda; De Cock, Valerie Cochen; Le Masson, Valerie Dauriac; Debs, Rachel; Lavault, Sophie; Roze, Emmanuel; Vidailhet, Marie; Arnulf, Isabelle

    2011-05-01

    Narcolepsy and Parkinson's disease (PD) are associated with hallucinations, excessive daytime sleepiness, REM sleep behavior disorder (RBD), as well as complete (narcolepsy with cataplexy) vs. partial (PD, narcolepsy without cataplexy) hypocretin-1 deficiency. To compare the hallucinations associated with narcolepsy to those of PD. One hundred patients with narcolepsy (with and without cataplexy) and 100 patients with PD were consecutively interviewed about their hallucinations (frequency, phenomenology, insight into unreality and association with sleep) as well as their risk factors. Hallucinations occurred more frequently and with more motor and multimodal aspects in narcolepsy with cataplexy (59%) than in narcolepsy without cataplexy (28%) and PD (26%). Compared to PD, the hallucinations in narcolepsy were less frequently of the passage/presence type (passage: brief visions of a person or animal passing sideways; presence: perception that a living character or an animal is behind or near the subject, without the subject actually seeing, hearing or touching it), more frequently auditory and more often associated with sleep. However, in 40% of the patients with narcolepsy and 54% of the patients with PD, the hallucinations occurred while the patients were wide awake. Patients with cataplexy had reduced immediate insight into the unreality of their hallucinations compared to patients with PD, but the delusions were exceptional (2%), transient and based on hallucinations in both groups. The risk factors for hallucinations were sleep paralysis and RBD in narcolepsy and motor disability and sleepiness in PD. The multimodal, dreamlike aspect of hallucinations in narcolepsy with cataplexy could transiently impair the patients' insight. The high frequency of these hallucinations (compared to those in narcolepsy without cataplexy or PD) suggests that complete (more than partial) hypocretin-1 deficiency promotes hallucinations. Copyright © 2011 Elsevier B.V. All rights

  6. Health-Related Stigma as a Determinant of Functioning in Young Adults with Narcolepsy

    PubMed Central

    Kapella, Mary C.; Berger, Barbara E.; Vern, Boris A.; Vispute, Sachin; Prasad, Bharati; Carley, David W.

    2015-01-01

    Symptoms of narcolepsy tend to arise during adolescence or young adulthood, a formative time in human development during which people are usually completing their education and launching a career. Little is known about the impact of narcolepsy on the social aspects of health-related quality of life in young adults. The purpose of this study was to examine relationships between health-related stigma, mood (anxiety and depression) and daytime functioning in young adults with narcolepsy compared to those without narcolepsy. Young adults (age 18–35) with narcolepsy (N = 122) and without narcolepsy (N = 93) were mailed a packet that included questionnaires and a self-addressed postage paid envelope. The questionnaire included demographic information and a composite of instruments including the SF 36, Functional Outcomes of Sleep Questionnaire (FOSQ), Fife Stigma Scale (FSS), Epworth Sleepiness Scale (ESS) and Hospital Anxiety and Depression Scale (HADS). Variable associations were assessed using descriptive statistics, ANOVA, Mann-Whitney U Test, correlations, stepwise multiple regression and path analysis. Young adults with narcolepsy perceived significantly more stigma and lower mood and health-related quality of life than young adults without narcolepsy (p<0.01). Health-related stigma was directly and indirectly associated with lower functioning through depressed mood. Fifty-two percent of the variance in functioning was explained by the final model in the young adults with narcolepsy. Health-related stigma in young adults with narcolepsy is at a level consistent with other chronic medical illnesses. Health-related stigma may be an important determinant of functioning in young adults with narcolepsy. Future work is indicated toward further characterizing stigma and developing interventions that address various domains of stigma in people with narcolepsy. PMID:25898361

  7. Health-related stigma as a determinant of functioning in young adults with narcolepsy.

    PubMed

    Kapella, Mary C; Berger, Barbara E; Vern, Boris A; Vispute, Sachin; Prasad, Bharati; Carley, David W

    2015-01-01

    Symptoms of narcolepsy tend to arise during adolescence or young adulthood, a formative time in human development during which people are usually completing their education and launching a career. Little is known about the impact of narcolepsy on the social aspects of health-related quality of life in young adults. The purpose of this study was to examine relationships between health-related stigma, mood (anxiety and depression) and daytime functioning in young adults with narcolepsy compared to those without narcolepsy. Young adults (age 18-35) with narcolepsy (N = 122) and without narcolepsy (N = 93) were mailed a packet that included questionnaires and a self-addressed postage paid envelope. The questionnaire included demographic information and a composite of instruments including the SF 36, Functional Outcomes of Sleep Questionnaire (FOSQ), Fife Stigma Scale (FSS), Epworth Sleepiness Scale (ESS) and Hospital Anxiety and Depression Scale (HADS). Variable associations were assessed using descriptive statistics, ANOVA, Mann-Whitney U Test, correlations, stepwise multiple regression and path analysis. Young adults with narcolepsy perceived significantly more stigma and lower mood and health-related quality of life than young adults without narcolepsy (p<0.01). Health-related stigma was directly and indirectly associated with lower functioning through depressed mood. Fifty-two percent of the variance in functioning was explained by the final model in the young adults with narcolepsy. Health-related stigma in young adults with narcolepsy is at a level consistent with other chronic medical illnesses. Health-related stigma may be an important determinant of functioning in young adults with narcolepsy. Future work is indicated toward further characterizing stigma and developing interventions that address various domains of stigma in people with narcolepsy.

  8. Unmet needs of patients with narcolepsy: perspectives on emerging treatment options

    PubMed Central

    Wozniak, Dariusz R; Quinnell, Timothy G

    2015-01-01

    The treatment options currently available for narcolepsy are often unsatisfactory due to suboptimal efficacy, troublesome side effects, development of drug tolerance, and inconvenience. Our understanding of the neurobiology of narcolepsy has greatly improved over the last decade. This knowledge has not yet translated into additional therapeutic options for patients, but progress is being made. Some compounds, such as histaminergic H3 receptor antagonists, may prove useful in symptom control of narcolepsy. The prospect of finding a cure still seems distant, but hypocretin replacement therapy offers some promise. In this narrative review, we describe these developments and others which may yield more effective narcolepsy treatments in the future. PMID:26045680

  9. Polymorphisms in the vicinity of the hypocretin/orexin are not associated with human narcolepsy.

    PubMed

    Hungs, M; Lin, L; Okun, M; Mignot, E

    2001-11-27

    Human narcolepsy/cataplexy is associated with reduced hypocretin (orexin) transmission. A common preprophypocretin (HCRT) polymorphism (-909C/T) was identified and tested in 502 subjects (105 trio families, 80 Caucasian narcolepsy cases, and 107 Caucasian control subjects). This polymorphism was not associated with the disease. The promoter and 5' untranslated (5'URT) regions of the HCRT gene (-320 to +21 from ATG) were also sequenced in 281 subjects. None of the subjects carried -22T, a rare 5'UTR polymorphism previously reported to be associated with narcolepsy. The HCRT locus is not a major narcolepsy susceptibility locus.

  10. Disrupted Sleep in Narcolepsy: Exploring the Integrity of Galanin Neurons in the Ventrolateral Preoptic Area.

    PubMed

    Gavrilov, Yury V; Ellison, Brian A; Yamamoto, Mihoko; Reddy, Hasini; Haybaeck, Johannes; Mignot, Emmanuel; Baumann, Christian R; Scammell, Thomas E; Valko, Philipp O

    2016-05-01

    To examine the integrity of sleep-promoting neurons of the ventrolateral preoptic nucleus (VLPO) in postmortem brains of narcolepsy type 1 patients. Postmortem examination of five narcolepsy and eight control brains. VLPO galanin neuron count did not differ between narcolepsy patients (11,151 ± 3,656) and controls (13,526 ± 9,544). A normal number of galanin-immunoreactive VLPO neurons in narcolepsy type 1 brains at autopsy suggests that VLPO cell loss is an unlikely explanation for the sleep fragmentation that often accompanies the disease. © 2016 Associated Professional Sleep Societies, LLC.

  11. Pediatric rosacea.

    PubMed

    Kellen, Roselyn; Silverberg, Nanette B

    2016-07-01

    Because rosacea is uncommon in the pediatric population, care must be taken to exclude other papulopustular disorders. Children can present with vascular, papulopustular, and/or ocular findings. Importantly, ocular symptoms can appear before the cutaneous symptoms of rosacea, leading to misdiagnosis. Rosacea is a clinical diagnosis, but histopathologic examination typically reveals dilated vessels, perivascular lymphohistiocytic infiltrates in the upper dermis, elastosis, and disorganization of the upper dermal connective tissue. Treatment involves avoiding known triggers and utilizing topical and/or systemic therapies. Although treatment can control flares, pediatric rosacea often persists into adulthood.

  12. Genomic profiling of pediatric acute myeloid leukemia reveals a changing mutational landscape from disease diagnosis to relapse | Office of Cancer Genomics

    Cancer.gov

    The genomic and clinical information used to develop and implement therapeutic approaches for AML originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident and may signify the need to age-stratify treatment regimens. The NCI/COG TARGET-AML initiative employed whole exome capture sequencing (WXS) to interrogate the genomic landscape of matched trios representing specimens collected upon diagnosis, remission, and relapse from 20 cases of de novo childhood AML.

  13. Pediatric dermatology.

    PubMed

    Baruch, K

    1986-07-01

    Dr. Baruch presents some of the most common pediatric lower extremity skin conditions seen in clinical practice. The conditions that he discusses appear to be relatively easy to diagnose in the early stages; however, some of them, such as contact dermatitis and atopic dermatitis, may be hard to distinguish from one another. I have to admit that I have never seen lichen planus in the pediatric age group; I will need to keep looking. I agree with Dr. Baruch that classification of lesions into either the primary and secondary groups will aid in diagnosis and treatment. It also seems that the ever-present verrucae is the most common pediatric condition seen in our office, and we have taken similar steps in treating this condition with blunt dissection with excellent results.

  14. Pediatric photosensitivity.

    PubMed

    Grossberg, Anna L

    2012-08-01

    Photosensitivity is a rarely encountered problem in the pediatric population. It may be caused by a diverse group of primary, idiopathic photosensitivity conditions, or may reflect photoexacerbation of an existing dermatosis. In addition, there are several genodermatoses, metabolic disorders, and connective tissue disorders that can present with photosensitivity, usually in addition to other extracutaneous clinical and laboratory findings. It is important that both dermatologic and pediatric practitioners be able to recognize the various causes of photosensitivity, as well as be familiar with the associated stigmata and necessary workup, if needed, of each particular disorder. This review offers an approach to the pediatric patient who presents with photosensitivity, with emphasis on arriving at the proper diagnosis, necessary evaluations, and management strategies. © 2012 John Wiley & Sons A/S.

  15. The role of hypocretins (orexins) in sleep regulation and narcolepsy.

    PubMed

    Taheri, Shahrad; Zeitzer, Jamie M; Mignot, Emmanuel

    2002-01-01

    The hypocretins (orexins) are two novel neuropeptides (Hcrt-1 and Hcrt-2), derived from the same precursor gene, that are synthesized by neurons located exclusively in the lateral, posterior, and perifornical hypothalamus. Hypocretin-containing neurons have widespread projections throughout the CNS with particularly dense excitatory projections to monoaminergic centers such as the noradrenergic locus coeruleus, histaminergic tuberomammillary nucleus, serotoninergic raphe nucleus, and dopaminergic ventral tegmental area. The hypocretins were originally believed to be primarily important in the regulation of appetite; however, a major function emerging from research on these neuropeptides is the regulation of sleep and wakefulness. Deficiency in hypocretin neurotransmission results in the sleep disorder narcolepsy in mice, dogs, and humans. The hypocretins are also uniquely positioned to link sleep, appetite, and neuroendocrine control. The aim of this review is to describe and discuss the current knowledge regarding the hypocretin neurotransmitter system in narcolepsy and normal sleep.

  16. The Safety of Adjuvanted Vaccines Revisited: Vaccine-Induced Narcolepsy.

    PubMed

    Ahmed, S Sohail; Montomoli, Emanuele; Pasini, Franco Laghi; Steinman, Lawrence

    2016-01-01

    Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1) pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed "black box" attitude towards all vaccines. The focus of this review article is to revisit this "black box" using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine.

  17. GABAB Agonism Promotes Sleep and Reduces Cataplexy in Murine Narcolepsy

    PubMed Central

    Black, Sarah Wurts; Morairty, Stephen R.; Chen, Tsui-Ming; Leung, Andrew K.; Wisor, Jonathan P.

    2014-01-01

    γ-Hydroxybutyrate (GHB) is an approved therapeutic for the excessive sleepiness and sudden loss of muscle tone (cataplexy) characteristic of narcolepsy. The mechanism of action for these therapeutic effects is hypothesized to be GABAB receptor dependent. We evaluated the effects of chronic administration of GHB and the GABAB agonist R-baclofen (R-BAC) on arousal state and cataplexy in two models of narcolepsy: orexin/ataxin-3 (Atax) and orexin/tTA; TetO diphtheria toxin mice (DTA). Mice were implanted for EEG/EMG monitoring and dosed with GHB (150 mg/kg), R-BAC (2.8 mg/kg), or vehicle (VEH) bid for 15 d–a treatment paradigm designed to model the twice nightly GHB dosing regimen used by human narcoleptics. In both models, R-BAC increased NREM sleep time, intensity, and consolidation during the light period; wake bout duration increased and cataplexy decreased during the subsequent dark period. GHB did not increase NREM sleep consolidation or duration, although NREM delta power increased in the first hour after dosing. Cataplexy decreased from baseline in 57 and 86% of mice after GHB and R-BAC, respectively, whereas cataplexy increased in 79% of the mice after VEH. At the doses tested, R-BAC suppressed cataplexy to a greater extent than GHB. These results suggest utility of R-BAC-based therapeutics for narcolepsy. PMID:24806675

  18. Exploring the presence of narcolepsy in patients with schizophrenia.

    PubMed

    Sansa, Gemma; Gavaldà, Alba; Gaig, Carles; Monreal, José; Ercilla, Guadalupe; Casamitjana, Roser; Ribera, Gisela; Iranzo, Alex; Santamaria, Joan

    2016-06-01

    There are several case reports of patients with narcolepsy and schizophrenia, but a systematic examination of the association of both disorders has not been done. The aim of this work is to assess the frequency of narcolepsy with cataplexy in a large consecutive series of adult patients with schizophrenia and schizoaffective disorder. We screened 366 consecutive patients with schizophrenia or schizoaffective disorder with a sleep questionnaire and the Epworth Sleepines scale (ESS) exploring narcoleptiform symptoms. Those who screened positive were assessed by a sleep specialist, and offered an HLA determination. CSF hypocretin-1 determination was proposed to those who were HLA DQB1*06:02 positive. On the screening questionnaire, 17 patients had an ESS score ≥11 without cataplexy, 15 had cataplexy-like symptoms with an ESS score < 11, and four had an ESS score ≥11 plus cataplexy-like symptoms. Of those, 24 patients were evaluated by a sleep specialist. Five of these 24 were HLA DQB1*06:02 positive, and three of these five subjects underwent lumbar puncture showing normal hypocretin-1 levels. Our results suggest that narcolepsy with cataplexy is not an unrecognized disease in adult patients with schizophrenia or schizoaffective disorder.

  19. Manipulation of skin temperature improves nocturnal sleep in narcolepsy.

    PubMed

    Fronczek, R; Raymann, R J E M; Overeem, S; Romeijn, N; van Dijk, J G; Lammers, G J; Van Someren, E J W

    2008-12-01

    Besides excessive daytime sleepiness, disturbed nocturnal sleep is a major complaint of patients with narcolepsy. Previously, alterations in skin temperature regulation in narcoleptic patients have been shown to be related to increased sleepiness. This study tests the hypothesis that direct control of nocturnal skin temperature might be applied to improve the disturbed sleep of narcoleptic patients. Participants were eight patients (five males) diagnosed as having narcolepsy with cataplexy according to the ICSD-2 criteria, mean (SD) age 28.6 (6.4) years, range 18-35 years. During two nights, sleep was recorded polysomnographically while proximal and distal skin temperature were manipulated using a comfortable thermosuit that induced skin temperature to cycle slowly with an amplitude of only 0.4 degrees C within the comfortable range normally observed during sleep. Logistic regression was used to evaluate the effect of skin temperature manipulation on the probability of occurrence of different sleep stages and nocturnal wakefulness. Proximal skin warming significantly suppressed wakefulness and enhanced slow wave sleep (SWS). In contrast, distal skin warming enhanced wakefulness and stage 1 sleep at the cost of SWS and REM sleep. The optimal combination of proximal skin warming and distal skin cooling led to a 160% increase in SWS, a 50% increase in REM sleep and a 68% decrease in wakefulness, compared with the least beneficial combination of proximal skin cooling and distal skin warming. Subtle skin temperature manipulations under controlled conditions significantly improved the typical nocturnal sleep problems in narcolepsy.

  20. An autoantibody in narcolepsy disrupts colonic migrating motor complexes.

    PubMed

    Jackson, Michael W; Reed, Joanne H; Smith, Anthony J F; Gordon, Tom P

    2008-12-03

    Despite strong circumstantial evidence for the autoimmune hypothesis of narcolepsy, conventional immunological methods have failed to detect an autoantibody. This study investigated the real-time effects of narcoleptic immunoglobulins on a spontaneous colonic migrating motor complex (CMMC) preparation. IgG from patients with narcolepsy with cataplexy or healthy controls was added directly to isolated mouse colons undergoing CMMC activity to test for autoantibodies that disrupt colonic motility. The effect of immunoglobulins prepared for clinical intravenous treatment (IVIg) on autoantibody-mediated colonic disruption was also assessed. Narcoleptic IgGs markedly reduced the frequency of CMMCs or irreversibly abolished them. Abrogation of CMMCs was followed by an increase in the resting tension of the colon preparation and appearance of atropine-sensitive phasic smooth muscle contractions. IVIg partially neutralized the inhibitory effect of narcoleptic IgG on the CMMCs. The dramatic effect of narcoleptic IgG on CMMC generation is consistent with an autoantibody-mediated disruption of enteric neural pathways. The ex vivo whole-organ approach allows real-time examination of the physiological effects of the narcoleptic autoantibody and offers a new avenue for exploring the autoimmune basis of narcolepsy. The neutralizing effect of IVIg on the autoantibody provides a rationale for the reported clinical improvement in cataplexy when IVIg are given at disease onset.

  1. Pediatric vasculitis.

    PubMed

    Barut, Kenan; Sahin, Sezgin; Kasapcopur, Ozgur

    2016-01-01

    The aim of this review is to define childhood vasculitis and to highlight new causative factors and treatment modalities under the guidance of recently published studies. Childhood vasculitis is difficult to diagnose because of the wide variation in the symptoms and signs. New nomenclature and classification criteria were proposed for the diagnosis of pediatric vasculitis. Recently, progress has been made toward understanding the genetic susceptibility to pediatric vasculitis as it was in other diseases. Various radiological techniques provide great opportunities in establishing the diagnosis of pediatric vasculitis. Mild central nervous system disease can accompany Henoch-Schonlein purpura and can go unnoticed. Antineutrophilic cytoplasmic antibody-associated vasculitis is rare in children. Increased severity of the disease, subglottic stenosis, and renal disease are described more frequently among children. Biological therapies are used with success in children as in adults. Future studies, whose aims are to evaluate treatment responses, prognosis and to design guidelines for activity, and damage index of vasculitis for children are required. Henoch-Schonlein purpura and Kawasaki disease are the most frequent vasculitides of children. Experience from adult studies for treatment and prognosis are usually used because of low incidence of other vasculitides in children. Multicenter studies of pediatric vasculitis should be conducted to detail treatment responses and prognosis in children.

  2. Localization and diagnosis framework for pediatric cataracts based on slit-lamp images using deep features of a convolutional neural network

    PubMed Central

    Zhang, Kai; Long, Erping; Cui, Jiangtao; Zhu, Mingmin; An, Yingying; Zhang, Jia; Liu, Zhenzhen; Lin, Zhuoling; Li, Xiaoyan; Chen, Jingjing; Cao, Qianzhong; Li, Jing; Wu, Xiaohang; Wang, Dongni

    2017-01-01

    Slit-lamp images play an essential role for diagnosis of pediatric cataracts. We present a computer vision-based framework for the automatic localization and diagnosis of slit-lamp images by identifying the lens region of interest (ROI) and employing a deep learning convolutional neural network (CNN). First, three grading degrees for slit-lamp images are proposed in conjunction with three leading ophthalmologists. The lens ROI is located in an automated manner in the original image using two successive applications of Candy detection and the Hough transform, which are cropped, resized to a fixed size and used to form pediatric cataract datasets. These datasets are fed into the CNN to extract high-level features and implement automatic classification and grading. To demonstrate the performance and effectiveness of the deep features extracted in the CNN, we investigate the features combined with support vector machine (SVM) and softmax classifier and compare these with the traditional representative methods. The qualitative and quantitative experimental results demonstrate that our proposed method offers exceptional mean accuracy, sensitivity and specificity: classification (97.07%, 97.28%, and 96.83%) and a three-degree grading area (89.02%, 86.63%, and 90.75%), density (92.68%, 91.05%, and 93.94%) and location (89.28%, 82.70%, and 93.08%). Finally, we developed and deployed a potential automatic diagnostic software for ophthalmologists and patients in clinical applications to implement the validated model. PMID:28306716

  3. Localization and diagnosis framework for pediatric cataracts based on slit-lamp images using deep features of a convolutional neural network.

    PubMed

    Liu, Xiyang; Jiang, Jiewei; Zhang, Kai; Long, Erping; Cui, Jiangtao; Zhu, Mingmin; An, Yingying; Zhang, Jia; Liu, Zhenzhen; Lin, Zhuoling; Li, Xiaoyan; Chen, Jingjing; Cao, Qianzhong; Li, Jing; Wu, Xiaohang; Wang, Dongni; Lin, Haotian

    2017-01-01

    Slit-lamp images play an essential role for diagnosis of pediatric cataracts. We present a computer vision-based framework for the automatic localization and diagnosis of slit-lamp images by identifying the lens region of interest (ROI) and employing a deep learning convolutional neural network (CNN). First, three grading degrees for slit-lamp images are proposed in conjunction with three leading ophthalmologists. The lens ROI is located in an automated manner in the original image using two successive applications of Candy detection and the Hough transform, which are cropped, resized to a fixed size and used to form pediatric cataract datasets. These datasets are fed into the CNN to extract high-level features and implement automatic classification and grading. To demonstrate the performance and effectiveness of the deep features extracted in the CNN, we investigate the features combined with support vector machine (SVM) and softmax classifier and compare these with the traditional representative methods. The qualitative and quantitative experimental results demonstrate that our proposed method offers exceptional mean accuracy, sensitivity and specificity: classification (97.07%, 97.28%, and 96.83%) and a three-degree grading area (89.02%, 86.63%, and 90.75%), density (92.68%, 91.05%, and 93.94%) and location (89.28%, 82.70%, and 93.08%). Finally, we developed and deployed a potential automatic diagnostic software for ophthalmologists and patients in clinical applications to implement the validated model.

  4. Complex Movement Disorders at Disease Onset in Childhood Narcolepsy with Cataplexy

    ERIC Educational Resources Information Center

    Plazzi, Giuseppe; Pizza, Fabio; Palaia, Vincenzo; Franceschini, Christian; Poli, Francesca; Moghadam, Keivan K.; Cortelli, Pietro; Nobili, Lino; Bruni, Oliviero; Dauvilliers, Yves; Lin, Ling; Edwards, Mark J.; Mignot, Emmanuel; Bhatia, Kailash P.

    2011-01-01

    Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of…

  5. Complex Movement Disorders at Disease Onset in Childhood Narcolepsy with Cataplexy

    ERIC Educational Resources Information Center

    Plazzi, Giuseppe; Pizza, Fabio; Palaia, Vincenzo; Franceschini, Christian; Poli, Francesca; Moghadam, Keivan K.; Cortelli, Pietro; Nobili, Lino; Bruni, Oliviero; Dauvilliers, Yves; Lin, Ling; Edwards, Mark J.; Mignot, Emmanuel; Bhatia, Kailash P.

    2011-01-01

    Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of…

  6. Pediatric sialendoscopy.

    PubMed

    Bruch, Jean M; Setlur, Jennifer

    2012-01-01

    Sialendoscopy was introduced in the early 1990s as a minimally invasive alternative to standard methods for diagnosis and treatment of inflammatory and obstructive salivary gland disease. The technique was pioneered in adults; however, advances in instrumentation have allowed this to be adapted to the smaller salivary ductal anatomy found in the pediatric population. In this chapter, the technique of sialendoscopy for parotid and submandibular glands is described.

  7. Disrupted Sleep in Narcolepsy: Exploring the Integrity of Galanin Neurons in the Ventrolateral Preoptic Area

    PubMed Central

    Gavrilov, Yury V.; Ellison, Brian A.; Yamamoto, Mihoko; Reddy, Hasini; Haybaeck, Johannes; Mignot, Emmanuel; Baumann, Christian R.; Scammell, Thomas E.; Valko, Philipp O.

    2016-01-01

    Study Objectives: To examine the integrity of sleep-promoting neurons of the ventrolateral preoptic nucleus (VLPO) in postmortem brains of narcolepsy type 1 patients. Methods: Postmortem examination of five narcolepsy and eight control brains. Results: VLPO galanin neuron count did not differ between narcolepsy patients (11,151 ± 3,656) and controls (13,526 ± 9,544). Conclusions: A normal number of galanin-immunoreactive VLPO neurons in narcolepsy type 1 brains at autopsy suggests that VLPO cell loss is an unlikely explanation for the sleep fragmentation that often accompanies the disease. Citation: Gavrilov YV, Ellison BA, Yamamoto M, Reddy H, Haybaeck J, Mignot E, Baumann CR, Scammell TE, Valko PO. Disrupted sleep in narcolepsy: exploring the integrity of galanin neurons in the ventrolateral preoptic area. SLEEP 2016;39(5):1059–1062. PMID:26951397

  8. Narcolepsy with cataplexy in a child with Charcot-Marie-Tooth disease. Case Report.

    PubMed

    Zheng, Feixia; Wang, Shuang

    2016-09-01

    We report an 8-year-old boy diagnosed with both CMT1 and narcolepsy, which were not reported simultaneously presenting in one person. The boy presented with a history of increased suddenly falling frequency and excessive daytime sleepiness for 3 months. CMT1 was diagnosed by electrophysiology and genetic testing. Narcolepsy had not been diagnosed until the frequently falling caused by sudden and transient episodes of legs weakness triggered by emotion was found. Multiple sleep latency test showed multiple sleep onset REM periods with reduced sleep latency. When CMT1 and narcolepsy were coexist in an individual, the latter might be overlooked. Cataplexy caused by narcolepsy might be disregard as distal muscle weakness of CMT1. The daytime sleepiness might also be ignored. Therefore, we recommend that patients with sleep disorders should be queried about the symptoms of narcolepsy.

  9. Diagnosis of an Intraventricular Cyst Using Point-of-Care Cranial Ultrasound in the Pediatric Emergency Department.

    PubMed

    Doctor, Kaynan; Cohen, Joanna S

    2017-03-01

    A 2-month-old previously healthy male infant presents with 2 days of unusual eye movements and increased fatigue. During evaluation in the pediatric emergency department, point-of-care cranial ultrasound identified a cyst-like mass. Subsequent magnetic resonance imaging confirmed the presence of a cyst within the third ventricle causing obstructive hydrocephalus.

  10. Fear of harm, a possible phenotype of pediatric bipolar disorder: a dimensional approach to diagnosis for genotyping psychiatric syndromes.

    PubMed

    Papolos, Demitri; Mattis, Steven; Golshan, Shahrokh; Molay, Francine

    2009-11-01

    In a prior concordance study of affected sibling pairs with a community diagnosis of pediatric bipolar disorder (PBD) a behavioral phenotype termed Fear of Harm (FOH) was found to have one of the strongest concordance coefficients (rho) between probands and siblings, and the widest contrasts between the rho-estimates for the proband/sibling vs. proband/comparison pairs [Papolos, D., Hennen, J., Cockerham, M.S, Lachman, H., 2007]. A strategy for identifying phenotypic subtypes: concordance of symptom dimensions between sibling pairs who met screening criteria for a genetic linkage study of childhood-onset bipolar disorder using the Child Bipolar Questionnaire (CBQ) was employed. J. Affect. Disord. 99, 27-36.]. We used the Child Bipolar Questionnaire (OUT) (CBQ) to further elucidate this behavioral phenotype of PBD. We hypothesized that selective factors including parent reported symptoms of mania and depression, would be distinguishing features of impairment between groups defined by 1) the magnitude of their score on a continuous measure of FOH, and 2) the high FOH group would have significantly greater levels of severity on course of illness variables. These measures included earlier age of onset of first psychiatric symptoms, first hospitalization, and frequency of psychiatric hospitalizations, as well as, degree of social impairment as determined by exposure to the juvenile justice system and school performance problems. The sample was comprised of children with community diagnoses of bipolar disorder or at risk for the illness based on enriched family history with multiple first degree relatives diagnosed with BPD (N=5335). Included were all subjects who had >40 positively endorsed CBQ symptom items at frequencies of very often, almost always, and always. This group was divided randomly into two groups, the exploratory group (N=2668) and the hypothesis testing (study) group (N=2666). The exploratory group was used for the development of hypotheses and the study

  11. Cerebrospinal fluid and serum cytokine profiles in narcolepsy with cataplexy: a case-control study.

    PubMed

    Dauvilliers, Yves; Jaussent, Isabelle; Lecendreux, Michel; Scholz, Sabine; Bayard, Sophie; Cristol, Jean Paul; Blain, Hubert; Dupuy, Anne-Marie

    2014-03-01

    Recent advances in the identification of susceptibility genes and environmental exposures provide strong support that narcolepsy-cataplexy is an immune-mediated disease. Only few serum cytokine studies with controversial results were performed in narcolepsy and none in the cerebrospinal fluid. We measured a panel of 12 cytokines by a proteomic approach in the serum of 35 patients with narcolepsy-cataplexy compared to 156 healthy controls, and in the cerebrospinal fluid of 34 patients with narcolepsy-cataplexy compared to 17 non-narcoleptic patients; and analyzed the effect of age, duration and severity of disease on the cytokine levels. After multiple adjustments we reported lower serum IL-2, IL-8, TNF-α, MCP-1 and EGF levels, and a tendency for higher IL-4 level in narcolepsy compared to controls. Significant differences were only found for IL-4 in cerebrospinal fluid, being higher in narcolepsy. Positive correlations were found in serum between IL-4, daytime sleepiness, and cataplexy frequency. The expression of some pro-inflammatory cytokines (MCP-1, VEGF, EGF, IL2, IL-1β, IFN-γ) in either serum or CSF was negatively correlated with disease severity and duration. No correlation was found for any specific cytokine in 18 of the patients with narcolepsy with peripheral and central samples collected the same day. Significant decreased pro/anti-inflammatory cytokine profiles were found at peripheral and central levels in narcolepsy, together with a T helper 2/Th1 serum cytokine secretion imbalance. To conclude, we showed some evidence for alterations in the cytokine profile in patients with narcolepsy-cataplexy compared to controls at peripheral and central levels, with the potential role of IL-4 and significant Th1/2 imbalance in the pathophysiology of narcolepsy.

  12. Etiological diagnosis of bloodstream infections through a multiplex real-time polymerase chain reaction test in pediatric patients: a case series from a tertiary Italian hospital.

    PubMed

    Calitri, Carmelina; Denina, Marco; Scolfaro, Carlo; Garazzino, Silvia; Licciardi, Francesco; Burdino, Elisa; Allice, Tiziano; Carraro, Francesca; De Intinis, Gianfranco; Ghisetti, Valeria; Tovo, Pier-Angelo

    2015-02-01

    The outcome of bloodstream infections (BSIs) is strongly related to microbiological diagnosis. Several factors may reduce blood culture (BC) diagnostic yield in pediatric BSIs, making the application of molecular methods quite promising. Multiplex real-time polymerase chain reaction (PCR) tests (the LightCycler Septifast Test MGRADE by Roche Diagnostics--LC-SF) performed in the tertiary centre of Regina Margherita Children's Hospital (Turin, Italy) over a 3-year period were retrospectively evaluated. Results of the LC-SF test were compared with those of BC (Automated Bact/Alert 3D, Biomerieux) collected at a close time point. 545 LC-SF tests were collected from 289 patients (183 males, median age 6.8 years, interquartile range (IQR) = 2.7-13.1); 163 had congenital or acquired immunodeficiency. In 515 cases (94.5%) the LC-SF test was performed with ongoing empirical antimicrobial therapy. Etiological definition was achieved in 111 BSI cases (20.4%). Both LC-SF and BC identified the responsible pathogen in 39 episodes. The LC-SF test alone gave a positive result in 29 septic episodes; BC alone permitted the etiological diagnosis in 43 episodes, but isolates were not included in the LC-SF master list in 10 cases. A 26% increase in bacterial identification chances due to the LC-SF test was documented. Cohen's kappa test indicated a moderate strength of agreement (0.49) between LC-SF tests and BCs closely collected. BC remains the gold standard for the etiological diagnosis of BSIs, but PCR methods proved to be a valuable adjunctive diagnostic tool in pediatric BSIs, especially in children receiving empirical chemotherapy.

  13. The epidemiology of anemia in pediatric inflammatory bowel disease: prevalence and associated factors at diagnosis and follow-up and the impact of exclusive enteral nutrition.

    PubMed

    Gerasimidis, Konstantinos; Barclay, Andrew; Papangelou, Alexandros; Missiou, Despoina; Buchanan, Elaine; Tracey, Cardigan; Tayler, Rachel; Russell, Richard K; Edwards, Christine A; McGrogan, Paraic

    2013-10-01

    Anemia is poorly studied in pediatric inflammatory bowel disease. This study explored the epidemiology and associated factors of anemia at diagnosis, after 1 year, and during treatment with exclusive enteral nutrition (EEN). Three cohorts were included: (1) a representative population of newly diagnosed inflammatory bowel disease children (n = 184); (2) patients currently receiving care with data available at diagnosis (n = 179) and after 1 year (n = 139); and (3) 84 children treated with EEN. At diagnosis, 72% were anemic. Abnormal inflammatory markers were more common in Crohn's disease with severe anemia (severe versus no anemia [%]: raised C-reactive protein; 89% versus 48%; suboptimal albumin; 97% versus 29%; P < 0.002). Anemic children with Crohn's disease had shorter diagnosis delay and lower BMI than nonanemic patients (severe versus mild versus no anemia, median [interquartile range]; diagnosis delay [months]: 3 [3.9] versus 6 [10] versus 8 [18], P < 0.001; BMI z score [SD]: -1.4 [1.4] versus -1.3 [1.5] versus -0.2 [1.4], P = 0.003). Extensive colitis was associated with severe anemia in ulcerative colitis. The proportion of severely anemic patients decreased from 34% to 9% and mild anemia doubled at 1 year. After EEN, severe anemia decreased (32% to 9%; P < 0.001) and the hemoglobin concentration increased by 0.75 g/dL. This was observed only after 8 weeks of treatment. Disease improvement and low hemoglobin at EEN initiation but not weight gain were associated with hemoglobin improvement. Anemia is high at diagnosis and follow-up and should receive more attention from the clinical team; however, the focus should remain suppression of inflammatory process in active disease.

  14. Impact of cytokine in type 1 narcolepsy: Role of pandemic H1N1 vaccination ?

    PubMed

    Lecendreux, Michel; Libri, Valentina; Jaussent, Isabelle; Mottez, Estelle; Lopez, Régis; Lavault, Sophie; Regnault, Armelle; Arnulf, Isabelle; Dauvilliers, Yves

    2015-06-01

    Recent advances in the identification of susceptibility genes and environmental exposures (pandemic influenza 2009 vaccination) provide strong support that narcolepsy type 1 is an immune-mediated disease. Considering the limited knowledge regarding the immune mechanisms involved in narcolepsy whether related to flu vaccination or not and the recent progresses in cytokine measurement technology, we assessed 30 cytokines, chemokines and growth factors using the Luminex technology in either peripheral (serum) or central (CSF) compartments in a large population of 90 children and adult patients with narcolepsy type 1 in comparison to 58 non-hypocretin deficient hypersomniacs and 41 healthy controls. Furthermore, we compared their levels in patients with narcolepsy whether exposed to pandemic flu vaccine or not, and analyzed the effect of age, duration of disease and symptom severity. Comparison for sera biomarkers between narcolepsy (n = 84, 54 males, median age: 15.5 years old) and healthy controls (n = 41, 13 males, median age: 20 years old) revealed an increased stimulation of the immune system with high release of several pro- and anti-inflammatory serum cytokines and growth factors with interferon-γ, CCL11, epidermal growth factor, and interleukin-2 receptor being independently associated with narcolepsy. Increased levels of interferon-γ, CCL11, and interleukin-12 were found when close to narcolepsy onset. After several adjustments, only one CSF biomarker differed between narcolepsy (n = 44, 26 males, median age: 15 years old) and non-hypocretin deficient hypersomnias (n = 57, 24 males, median age: 36 years old) with higher CCL 3 levels found in narcolepsy. Comparison for sera biomarkers between patients with narcolepsy who developed the disease post-pandemic flu vaccination (n = 36) to those without vaccination (n = 48) revealed an increased stimulation of the immune system with high release of three cytokines, regulated upon activation normal T-cell expressed

  15. Treatment paradigms for cataplexy in narcolepsy: past, present, and future

    PubMed Central

    Swick, Todd J

    2015-01-01

    Cataplexy is defined as episodes of sudden loss of voluntary muscle tone triggered by emotions generally lasting <2 minutes. Cataplexy is most commonly associated with and considered pathognomonic for narcolepsy, a sleep disorder affecting ~0.05% of the general population. Knowledge of the pathophysiology of cataplexy has advanced through study of canine, murine, and human models. It is now generally considered that loss of signaling by hypothalamic hypocretin/orexin-producing neurons plays a key role in the development of cataplexy. Although the cause of hypocretin/orexin neuron loss in narcolepsy with cataplexy is unknown, an autoimmune etiology is widely hypothesized. Despite these advances, a literature review shows that treatment of cataplexy remains limited. Multiple classes of antidepressants have been commonly used off-label for cataplexy in narcolepsy and are suggested for this use in expert consensus guidelines based on traditional practice, case reports, and small trials. However, systematic research evidence supporting antidepressants for cataplexy is lacking. The single pharmacotherapy indicated for cataplexy and the guideline-recommended first-line treatment in Europe and the US is sodium oxybate, the sodium salt of gamma-hydroxybutyrate. Clinical trial evidence of its efficacy and safety in cataplexy is robust, and it is hypothesized that its therapeutic effects may occur through gamma-aminobutyric acid receptor type B-mediated effects at noradrenergic, dopaminergic, and thalamocortical neurons. Additional possible mechanisms for cataplexy therapy suggested by preliminary research include antagonism of the histamine H3 autoreceptor with pitolisant and intravenous immunoglobulin therapy for amelioration of the presumed autoimmune-mediated hypocretin/orexin cell loss. Further research and development of therapeutic approaches to cataplexy are needed. PMID:26715865

  16. Treatment paradigms for cataplexy in narcolepsy: past, present, and future.

    PubMed

    Swick, Todd J

    2015-01-01

    Cataplexy is defined as episodes of sudden loss of voluntary muscle tone triggered by emotions generally lasting <2 minutes. Cataplexy is most commonly associated with and considered pathognomonic for narcolepsy, a sleep disorder affecting ~0.05% of the general population. Knowledge of the pathophysiology of cataplexy has advanced through study of canine, murine, and human models. It is now generally considered that loss of signaling by hypothalamic hypocretin/orexin-producing neurons plays a key role in the development of cataplexy. Although the cause of hypocretin/orexin neuron loss in narcolepsy with cataplexy is unknown, an autoimmune etiology is widely hypothesized. Despite these advances, a literature review shows that treatment of cataplexy remains limited. Multiple classes of antidepressants have been commonly used off-label for cataplexy in narcolepsy and are suggested for this use in expert consensus guidelines based on traditional practice, case reports, and small trials. However, systematic research evidence supporting antidepressants for cataplexy is lacking. The single pharmacotherapy indicated for cataplexy and the guideline-recommended first-line treatment in Europe and the US is sodium oxybate, the sodium salt of gamma-hydroxybutyrate. Clinical trial evidence of its efficacy and safety in cataplexy is robust, and it is hypothesized that its therapeutic effects may occur through gamma-aminobutyric acid receptor type B-mediated effects at noradrenergic, dopaminergic, and thalamocortical neurons. Additional possible mechanisms for cataplexy therapy suggested by preliminary research include antagonism of the histamine H3 autoreceptor with pitolisant and intravenous immunoglobulin therapy for amelioration of the presumed autoimmune-mediated hypocretin/orexin cell loss. Further research and development of therapeutic approaches to cataplexy are needed.

  17. [Changes of sleep architecture in patients with narcolepsy].

    PubMed

    Li, Jing; Xu, Yan; Dong, Xiao-Song; Han, Xu; He, Zhong-Ming; Lü, Yun-Hui; Wang, Li; He, Quan-Ying; Han, Fang

    2007-03-06

    To investigate the sleep architectures of patients with narcolepsy. 38 drug-naive narcoleptic patients, 25 males and 13 females, aged 21 +/- 6.5, and 44 age-, sex ratio-, and BMI-matched normal persons underwent polysomnography (PSG) and multiple sleep latency test (MSLT) during one night sleep. Conventional visual scoring of the polysomnograms was performed according to the international. The sleep latency of the patients was 5.6 min, however, 30 patients (79%) complained of fragmented nocturnal sleep and difficulty to fall asleep again. The sleep efficiency of the narcoleptics was 81.7% +/- 12.5%, significantly lower than that of the normal persons (87.1% +/- 7.9%, P = 0.029). The non-rapid eye movement (NREM) I sleep accounted for (21.5 +/- 12.2)% in the patients, a proportion significantly higher than that of the normal persons [(10.3 +/- 6.3)%, P = 0.000]). The AHI of the patients was 0.6 +/- 1.3 times/h, not significantly different from that of the normal persons (0.5 +/- 1.1 times/h). Although the rapid eye movement (REM) period and eye movement density of the narcoleptics were significantly increased, their REM period duration was not significantly different from that of the normal subjects (17.7% +/- 6.9% vs 18.9% +/- 5.5%, P = 0.23), probably due to the interruption of REM sleep by more frequent arousals in narcoleptics. PSG did not show significant periodic leg movements in these 2 groups. One of the important symptoms of narcolepsy, night sleep disturbance may contribute to the pathological sleepiness of narcolepsy during daytime.

  18. Central Disorders of Hypersomnolence: Focus on the Narcolepsies and Idiopathic Hypersomnia.

    PubMed

    Khan, Zeeshan; Trotti, Lynn Marie

    2015-07-01

    The central disorders of hypersomnolence are characterized by severe daytime sleepiness, which is present despite normal quality and timing of nocturnal sleep. Recent reclassification distinguishes three main subtypes: narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia (IH), which are the focus of this review. Narcolepsy type 1 results from loss of hypothalamic hypocretin neurons, while the pathophysiology underlying narcolepsy type 2 and IH remains to be fully elucidated. Treatment of all three disorders focuses on the management of sleepiness, with additional treatment of cataplexy in those patients with narcolepsy type 1. Sleepiness can be treated with modafinil/armodafinil or sympathomimetic CNS stimulants, which have been shown to be beneficial in randomized controlled trials of narcolepsy and, quite recently, IH. In those patients with narcolepsy type 1, sodium oxybate is effective for the treatment of both sleepiness and cataplexy. Despite these treatments, there remains a subset of hypersomnolent patients with persistent sleepiness, in whom alternate therapies are needed. Emerging treatments for sleepiness include histamine H3 antagonists (eg, pitolisant) and possibly negative allosteric modulators of the gamma-aminobutyric acid-A receptor (eg, clarithromycin and flumazenil).

  19. Emerging drugs for common conditions of sleepiness: obstructive sleep apnea and narcolepsy.

    PubMed

    Sullivan, Shannon S; Guilleminault, Christian

    2015-01-01

    Obstructive sleep apnea (OSA) and narcolepsy are sleep disorders associated with high prevalence and high symptomatic burden including prominent sleepiness, daytime dysfunction and poor nocturnal sleep. Both have elevated risk of poor health outcomes. Current therapies are often underutilized, cumbersome, costly or associated with residual symptoms. This review covers current available therapies for OSA and narcolepsy as well as discusses areas for potential drug development, and agents in the therapeutic pipeline, including the cannabinoid dronabinol (OSA), the histamine inverse agonist/ antagonist pitolisant (narcolepsy), and stimulants with uncertain and/or multiple activities such as JZP-110 and JZP-386 (narcolepsy, possibly OSA). Finally it addresses new approaches and uses for therapies currently on the market such as the carbonic anhydrase inhibitor acetazolamide (OSA). Both OSA and narcolepsy are conditions of sleepiness for which lifelong treatments are likely to be required. In OSA, while continuous positive airway pressure will likely remain the gold standard therapy for the foreseeable future, there is plenty of room for integrating phenotypes and variants of OSA into therapeutic strategies to lead to better, more personalized disease modification. In narcolepsy, unlike OSA, drug therapy is the current mainstay of treatment. Advances using novel mechanisms to treat targeted symptoms such as sleepiness and/or novel agents that can treat more than one symptom of narcolepsy, hold promise. However, cost, convenience and side effects remain challenges.

  20. Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy.

    PubMed

    Dauvilliers, Yves; Jennum, Poul; Plazzi, Giuseppe

    2013-08-01

    Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with neurodegenerative disorders including Parkinsonisms, but is also reported in narcolepsy in up to 60% of patients. RBD in patients with narcolepsy is, however, a distinct phenotype with respect to other RBD patients and characterized also by absence of gender predominance, elementary rather than complex movements, less violent behavior and earlier age at onset of motor events, and strong association to narcolepsy with cataplexy/hypocretin deficiency. Patients with narcolepsy often present dissociated sleep features including RSWA, increased density of phasic chin EMG and frequent shift from REM to NREM sleep, with or without associated clinical RBD. Most patients with narcolepsy with cataplexy lack the hypocretin neurons in the lateral hypothalamus. Tonic and phasic motor activities in REM sleep and dream-enacting behavior are mostly reported in presence of cataplexy. Narcolepsy without cataplexy is a condition rarely associated with hypocretin deficiency. We proposed that hypocretin neurons are centrally involved in motor control during wakefulness and sleep in humans, and that hypocretin deficiency causes a functional defect in the motor control involved in the development of cataplexy during wakefulness and RBD/RSWA/phasic motor activity during REM sleep.

  1. Disorders of Excessive Daytime Sleepiness Including Narcolepsy and Idiopathic Hypersomnia.

    PubMed

    Berkowski, Joseph Andrew; Shelgikar, Anita Valanju

    2016-09-01

    Central disorders of hypersomnolence are rare conditions with a poorly understood pathophysiology, making the identification and management challenging for sleep clinicians. Clinical history is essential for ruling out secondary causes of hypersomnolence and distinguishing among diagnoses. Current diagnostic criteria rely heavily on the polysomnogram and multiple sleep latency test. The current focus of treatment of hypersomnolence is on drugs that promote alertness. Additionally, in the case of narcolepsy type 1, medication management addresses control of cataplexy, the hallmark symptom of this disorder. Elucidation of pathophysiology of these disorders in the future will be essential to better categorization and management.

  2. Effectiveness of a staged US and CT protocol for the diagnosis of pediatric appendicitis: reducing radiation exposure in the age of ALARA.

    PubMed

    Krishnamoorthi, Rajesh; Ramarajan, Naresh; Wang, Nancy E; Newman, Beverley; Rubesova, Erika; Mueller, Claudia M; Barth, Richard A

    2011-04-01

    To evaluate the effectiveness of a staged ultrasonography (US) and computed tomography (CT) imaging protocol for the accurate diagnosis of suspected appendicitis in children and the opportunity for reducing the number of CT examinations and associated radiation exposure. This retrospective study was compliant with HIPAA, and a waiver of informed consent was approved by the institutional review board. This study is a review of all imaging studies obtained in children suspected of having appendicitis between 2003 and 2008 at a suburban pediatric emergency department. A multidisciplinary staged US and CT imaging protocol for the diagnosis of appendicitis was implemented in 2003. In the staged protocol, US was performed first in patients suspected of having appendicitis; follow-up CT was recommended when US findings were equivocal. Of 1228 pediatric patients who presented to the emergency department for suspected appendicitis, 631 (287 boys, 344 girls; age range, 2 months to 18 years; median age, 10 years) were compliant with the imaging pathway. The sensitivity, specificity, negative appendectomy rate (number of appendectomies with normal pathologic findings divided by the number of surgeries performed for suspected appendicitis), missed appendicitis rate, and number of CT examinations avoided by using the staged protocol were analyzed. The sensitivity and specificity of the staged protocol were 98.6% and 90.6%, respectively. The negative appendectomy rate was 8.1% (19 of 235 patients), and the missed appendicitis rate was less than 0.5% (one of 631 patients). CT was avoided in 333 of the 631 patients (53%) in whom the protocol was followed and in whom the US findings were definitive. A staged US and CT imaging protocol in which US is performed first in children suspected of having acute appendicitis is highly accurate and offers the opportunity to substantially reduce radiation. © RSNA, 2011.

  3. Plasma obestatin and autonomic function are altered in orexin-deficient narcolepsy, but ghrelin is unchanged.

    PubMed

    Huda, M S B; Mani, H; Durham, B H; Dovey, T M; Halford, J C G; Aditya, B S; Pinkney, J H; Wilding, J P; Hart, I K

    2013-06-01

    Narcolepsy-cataplexy is characterised by orexin deficiency, sleep disturbance, obesity and dysautonomia. Ghrelin and obestatin affect both energy intake and sleep. Our aim was to investigate ghrelin, obestatin and metabolic/autonomic function in narcolepsy-cataplexy. Eight narcolepsy-cataplexy patients (seven CSF orexin-deficient) and eight matched controls were studied. The subjects had a fixed energy meal with serial blood samples and measurement of heart rate variability (HRV). Fasting plasma obestatin was more than threefold higher in narcolepsy subjects (narcolepsy 89.6 ± 16 pg/ml vs. control 24.9 ± 3 pg/ml, p < 0.001). There was no change in HRV total power, but post-prandial low-frequency (LF) power and high-frequency (HF) power were lower in the narcolepsy group [area under the curve (AUC): HF power narcolepsy 1.4 × 10(5) ± 0.2 × 10(5) vs. control 3.3 × 10(5) ± 0.6 × 10(5 )ms(2)/h, p < 0.001]. On multiple regression analyses, the only significant predictor of plasma obestatin was HF power, which was inversely correlated with obestatin (β = -0.65 R (2) = 38 %, p = 0.009). Fasting and post-prandial plasma ghrelin were similar in both groups (narcolepsy 589.5 ± 88 pg/ml vs. control 686.9 ± 81 pg/ml, p = 0.5; post-prandial AUC-narcolepsy 161.3 ± 22 ng/ml/min vs. control 188.6 ± 62 ng/ml/min, p = 0.4). Only the narcolepsy group had significant suppression of plasma ghrelin after the meal (ANOVA, p = 0.004). In orexin-deficient narcolepsy, fasting plasma ghrelin is unaltered, and post-prandial suppression is preserved. Fasting plasma obestatin is increased and correlates with autonomic dysfunction. As obestatin affects NREM sleep, we suggest that increased plasma levels contribute to the disrupted sleep-state control in narcolepsy.

  4. Possible mechanism of secondary narcolepsy with a long sleep time following surgery for craniopharyngioma.

    PubMed

    Sakuta, Keisuke; Nakamura, Masaki; Komada, Yoko; Yamada, Shozo; Kawana, Fusae; Kanbayashi, Takashi; Inoue, Yuichi

    2012-01-01

    A 19-year-old woman suffered from severe excessive daytime sleepiness accompanied with long sleep episodes both in the daytime and nighttime and frequent episodes of cataplexy shortly after the removal of craniopharyngioma in the intrasellar space. Multiple sleep latency test showed a typical finding of narcolepsy, and cerebrospinal fluid orexin concentration was below the narcolepsy cut-off value. MRI-tractography showed a clear lack of neuronal fiber connections from the hypothalamus to the frontal lobe. SPECT using (123)I-IMP showed frontal hypoperfusion. These connection damages could have been responsible for the occurrence of narcolepsy-like symptoms and long daytime sleep episodes in this case.

  5. Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010.

    PubMed

    O'Flanagan, D; Barret, A S; Foley, M; Cotter, S; Bonner, C; Crowe, C; Lynch, B; Sweeney, B; Johnson, H; McCoy, B; Purcell, E

    2014-05-01

    In 2011, the Irish Medicines Board received reports of onset of narcolepsy following vaccination against influenza A(H1N1)pdm09 with Pandemrix. A national steering committee was convened to examine the association between narcolepsy and pandemic vaccination. We conducted a retrospective population-based cohort study. Narcolepsy cases with onset from 1 April 2009 to 31 December 2010 were identified through active case finding. Narcolepsy history was gathered from medical records. Pandemic vaccination status was obtained from vaccination databases. Two independent experts classified cases using the Brighton case definition. Date of onset was defined as date of first healthcare contact for narcolepsy symptoms. Incidence of narcolepsy in vaccinated and non-vaccinated individuals was compared. Of 32 narcolepsy cases identified, 28 occurred in children/adolescents and for 24 first healthcare contact was between April 2009 and December 2010. Narcolepsy incidence was 5.7 (95% confidence interval (CI): 3.4–8.9) per 100,000 children/adolescents vaccinated with Pandemrix and 0.4 (95% CI: 0.1–1.0) per 100,000 unvaccinated children/adolescents (relative risk: 13.9; absolute attributable risk: 5.3 cases per 100,000 vaccinated children/adolescents). This study confirms the crude association between Pandemrix vaccination and narcolepsy as observed in Finland and Sweden. The vaccine is no longer in use in Ireland. Further studies are needed to explore the immunogenetic mechanism of narcolepsy.

  6. A survey of steroid-related osteoporosis diagnosis, prevention and treatment practices of pediatric rheumatologists in North America.

    PubMed

    Soybilgic, Arzu; Tesher, Melissa; Wagner-Weiner, Linda; Onel, Karen B

    2014-01-01

    The purpose of our study is to assess practices of North American pediatric rheumatologists regarding monitoring, prevention, and treatment of low bone mineral density (BMD) in children on long-term glucocorticoid treatment. Long-term glucocorticoid therapy is associated with accelerated bone loss. Children with JIA and lupus have low baseline BMD and incident vertebral fractures commonly occur in these groups of patients even after a relatively short period of time being on systemic glucocorticoids. There are no established guidelines for identification, prevention, and treatment of glucocorticoid-induced bone loss in children. A cross-sectional online survey was conducted with 199 physicians who were listed in the ACR database as practicing pediatric rheumatology in North America. 86 physicians (43%) responded; 87% were board-certified in pediatric rheumatology. 95% used dual energy X-ray absorptiometry as their primary modality for assessing BMD. 79% "rarely" or "never" obtained a baseline BMD measurement prior to initiation of glucocorticoid therapy. 42% of respondents followed BMD annually. 93% "frequently" or "always" prescribed calcium for patients on long-term corticosteroid therapy; 81% "frequently" or "always" prescribed vitamin D. In patients diagnosed with osteoporosis, 35%-50 % of the practitioners "sometimes", "frequently" or "always" prescribed bisphosphonates. Bisphosphonates are prescribed at similar rates for male and female patients, and slightly more frequently for pubertal than for pre-pubertal patients. 96% of respondents "rarely" or "never" prescribed calcitonin for patients on long-term glucocorticoid therapy; 92% "rarely" or "never" prescribe this medication for patients with known osteopenia or osteoporosis. Utilization of DXA in children on long-term corticosteroid therapy varies greatly among North American pediatric rheumatologists. Most respondents do not screen for low BMD on a regular basis despite acknowledging the risks of bone

  7. Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system.

    PubMed

    Nishino, Seiji; Kanbayashi, Takashi

    2005-08-01

    Human narcolepsy is a chronic sleep disorder affecting 1:2000 individuals. The disease is characterized by excessive daytime sleepiness, cataplexy and other abnormal manifestations of REM sleep, such as sleep paralysis and hypnagogic hallucinations. Recently, it was discovered that the pathophysiology of (idiopathic) narcolepsy-cataplexy is linked to hypocretin ligand deficiency in the brain and cerebrospinal fluid (CSF), as well as the positivity of the human leukocyte antigen (HLA) DR2/DQ6 (DQB1*0602). The symptoms of narcolepsy can also occur during the course of other neurological conditions (i.e. symptomatic narcolepsy). We define symptomatic narcolepsy as those cases that meet the International Sleep Disorders Narcolepsy Criteria, and which are also associated with a significant underlying neurological disorder that accounts for excessive daytime sleepiness (EDS) and temporal associations. To date, we have counted 116 symptomatic cases of narcolepsy reported in literature. As, several authors previously reported, inherited disorders (n=38), tumors (n=33), and head trauma (n=19) are the three most frequent causes for symptomatic narcolepsy. Of the 116 cases, 10 are associated with multiple sclerosis, one case of acute disseminated encephalomyelitis, and relatively rare cases were reported with vascular disorders (n=6), encephalitis (n=4) and degeneration (n=1), and hererodegenerative disorder (three cases in a family). EDS without cataplexy or any REM sleep abnormalities is also often associated with these neurological conditions, and defined as symptomatic cases of EDS. Although it is difficult to rule out the comorbidity of idiopathic narcolepsy in some cases, review of the literature reveals numerous unquestionable cases of symptomatic narcolepsy. These include cases with HLA negative and/or late onset, and cases in which the occurrences of the narcoleptic symptoms are parallel with the rise and fall of the causative disease. A review of these cases

  8. Narcolepsy and syndromes of primary excessive daytime somnolence.

    PubMed

    Black, Jed E; Brooks, Stephen N; Nishino, Seiji

    2004-09-01

    Excessive daytime sleepiness (EDS) or somnolence is common in our patients and in society in general. The most common cause of EDS is "voluntary" sleep restriction. Other common causes include sleep-fragmenting disorders such as the obstructive sleep apnea syndrome. Somewhat less familiar to the clinician are EDS conditions arising from central nervous system dysfunction. Of these so-called primary disorders of somnolence, narcolepsy is the most well known and extensively studied, yet often misunderstood and misdiagnosed. Idiopathic hypersomnia, the recurrent hypersomnias, and EDS associated with nervous system disorders also must be well-understood to provide appropriate evaluation and management of the patient with EDS. This review summarizes the distinguishing features of these clinical syndromes of primary EDS. A brief overview of the pharmacological management of primary EDS is included. Finally, in view of the tremendous advances that have occurred in the past few years in our understanding of the pathophysiology of canine and human narcolepsy, we also highlight these discoveries.

  9. Redefining the Pediatric Phenotype of X-Linked Monocarboxylate Transporter 8 (MCT8) Deficiency: Implications for Diagnosis and Therapies.

    PubMed

    Matheus, Maria Gisele; Lehman, Rebecca K; Bonilha, Leonardo; Holden, Kenton R

    2015-10-01

    X-linked monocarboxylate transporter 8 (MCT8) deficiency results from a loss-of-function mutation in the monocarboxylate transporter 8 gene, located on chromosome Xq13.2 (Allan-Herndon-Dudley syndrome). Affected boys present early in life with neurodevelopment delays but have pleasant dispositions and commonly have elevated serum triiodothyronine. They also have marked axial hypotonia and quadriparesis but surprisingly little spasticity early in their disease course. They do, however, have subtle involuntary movements, most often dystonia. The combination of hypotonia and dystonia presents a neurorehabili