| 1. |
- Chaplin, John, 1955, et al.
(författare)
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The development of a health-related quality-of-life instrument for young people with narcolepsy: NARQoL-21
- 2017
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Ingår i: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Narcolepsy is a lifelong sleep disorder with a prevalence of between 0.03% and 0.06% and onset at around puberty. It is associated with psychiatric comorbidities and cognitive difficulties. No valid and reliable condition-specific health-related quality-of-life (HrQoL) instrument has been developed for this population. METHODS: A questionnaire based on four mixed-gender age-defined focus group discussions and a patient panel analysis was administered to young people with narcolepsy and a control group. External reliability was measured by a test-retest procedure and internal reliability was measured using Cronbach's alpha. Convergent validity with the KIDSCREEN-10 index was assessed using with intraclass correlation coefficients (ICC) and receiver operating characteristic (ROC) curves. Factor analysis techniques were used to identify suitable items and confirm the factor structure. Baseline values were assessed for convergent validity, ceiling effects, agreement and sensitivity. Comparison with KIDSCREEN-10 was made on the basis of area under the curve (AUC). RESULTS: One hundred young people with narcolepsy and 95 control subjects returned questionnaires. The factor structure revealed two main factors with five domains and 21 questions, which was confirmed with confirmatory factor analysis. The domains of the NARQoL-21 showed good independence while the floor and ceiling effects were acceptable. The external reliability (0.928), convergent validity (rs = 0.769) and internal consistency (Cronbach's alpha = 0.886) were excellent. A Bland-Altman plot revealed some proportional bias. Good discriminant validity was detected for control/patient (Cohen's d = 2.114). ROC analysis showed significantly better AUC for NARQoL-21 (0.939) than KIDSCREEN (0.877). A cut-off score equivalent to KIDSCREEN-10 for suboptimal HrQoL which maximized sensitivity (84%) and specificity (92%) was found at NARQoL-21 score below 42. CONCLUSIONS: Establishing the validity of a disease-specific HrQoL instrument in a population of people with a rare condition poses significant challenges. The mixed-methods approach adopted here has resulted in a questionnaire of 21 items with good discrimination and convergent validity, and excellent internal and external reliability, allowing precise and stable measurements. The cut-off score can be useful to identify patients with very poor HrQoL and thus improve the design of treatment options. Further testing in a longitudinal cohort is recommended in order to establish responsiveness.
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| 2. |
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| 3. |
- Engström, Maria, 1958-, et al.
(författare)
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Functional magnetic resonance imaging in narcolepsy and the Kleine-Levin syndrome
- 2014
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Ingår i: Frontiers in Neurology. - Switzerland : Frontiers Media SA. - 1664-2295. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- This work aims at reviewing the present state of the art when it comes to understanding the pathophysiology of narcolepsy and the Kleine-Levin syndrome (KLS) from a neuroimaging point of view. This work also aims at discussing future perspectives of functional neuroimaging in these sleep disorders. We focus on functional magnetic resonance imaging (fMRI), which is a technique for in vivo measurements of brain activation in neuronal circuitries under healthy and pathological conditions. fMRI has significantly increased the knowledge on the affected neuronal circuitries in narcolepsy and the Kleine-Levin syndrome. It has been shown that narcolepsy is accompanied with disturbances of the emotional and the closely related reward systems. In the Kleine Levin syndrome, fMRI has identified hyperactivation of the thalamus as a potential biomarker that could be used in the diagnostic procedure. The fMRI findings in both narcolepsy and the Kleine-Levin syndrome are in line with previous structural and functional imaging studies. We conclude that fMRI in combination with multi-modal imaging can reveal important details about the pathophysiology in narcolepsy and the Kleine-Levin syndrome. In the future, fMRI possibly gives opportunities for diagnostic support and prediction of treatment response in individual patients.
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| 4. |
- Morales Drissi, Natasha, et al.
(författare)
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Altered Brain Microstate Dynamics in Adolescents with Narcolepsy
- 2016
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- 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 fMRI 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.
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| 5. |
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| 6. |
- Morales Drissi, Natasha, et al.
(författare)
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Structural anomaly in the reticular formation in narcolepsy type 1, suggesting lower levels of neuromelanin
- 2019
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Ingår i: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate structural changes in the brain stem of adolescents with narcolepsy, a disorder characterized by excessive daytime sleepiness, fragmented night-time sleep, and cataplexy. For this purpose, we used quantitative magnetic resonance imaging to obtain R1 and R2 relaxation rates, proton density, and myelin maps in adolescents with narcolepsy (n = 14) and healthy controls (n = 14). We also acquired resting state functional magnetic resonance imaging (fMRI) for brainstem connectivity analysis. We found a significantly lower R2 in the rostral reticular formation near the superior cerebellar peduncle in narcolepsy patients, family wise error corrected p = .010. Narcolepsy patients had a mean R2 value of 1.17 s−1 whereas healthy controls had a mean R2 of 1.31 s−1, which was a large effect size with Cohen d = 4.14. We did not observe any significant differences in R1 relaxation, proton density, or myelin content. The sensitivity of R2 to metal ions in tissue and the transition metal ion chelating property of neuromelanin indicate that the R2 deviant area is one of the neuromelanin containing nuclei of the brain stem. The close proximity and its demonstrated involvement in sleep-maintenance, specifically through orexin projections from the hypothalamus regulating sleep stability, as well as the results from the connectivity analysis, suggest that the observed deviant area could be the locus coeruleus or other neuromelanin containing nuclei in the proximity of the superior cerebellar peduncle. Hypothetically, the R2 differences described in this paper could be due to lower levels of neuromelanin in this area of narcolepsy patients. © 2019 The Authors
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| 7. |
- Szakacs, Attila, et al.
(författare)
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A population-based and case-controlled study of children and adolescents with narcolepsy: Health-related quality of life, adaptive behavior and parental stress
- 2019
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Ingår i: European Journal of Paediatric Neurology. - : Elsevier BV. - 1090-3798. ; 23:2, s. 288-295
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate health-related quality of life (HrQoL) and adaptive behavior in young people with narcolepsy and stress among their parents. Methods: In a cross-sectional exploratory quantitative study design, 37 young people with narcolepsy (8-20 years of age) and their parents were recruited. Thirty-one had post-H1N1 vaccination-related narcolepsy (PHV) and six had narcolepsy not related to PHV (nPHV). In addition, 40 age- and gender-matched controls (aged 5-20 years) were recruited. Results: Thirty-one patients completed the generic HrQoL questionnaire KIDSCREEN and the disease-specific NARQoL-21. HrQoL was found to be significantly diminished in all domains in the PHV group (p = 0.001) and in the School/Concentration domain (p = 0.004) in the nPHV group compared to age- and gender-matched controls. The Adaptive Behavior Assessment System was completed by parents of 32 patients. They rated their children significantly lower in the General adaptive composite (p = 0.026) and the Conceptual (p = 0.050) and Social composite scores (p = 0.001) compared with reference data on healthy Swedish children's and young people's adaptive behavior. Parents of 36 patients filled in the 36-item short form of the Parenting Stress Index questionnaire. They rated significantly higher Total stress, Parent-child dysfunctional interaction, and Difficult child scores compared with parents of controls (p = 0.001, p = 0.005, p < 0.001). Conclusions: Children with narcolepsy have diminished HrQoL compared with controls. Parents of children with narcolepsy experience impaired adaptive behavior in their children and high levels of parenting stress. Identifying the contributory factors is necessary, and early intervention is crucial in order to improve the HrQoL of these children and their families. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
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| 8. |
- Szakacs, Attila, et al.
(författare)
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Endocrine and metabolic aspects of narcolepsy type 1 in children
- 2021
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Ingår i: European Journal of Paediatric Neurology. - : Elsevier BV. - 1090-3798. ; 33, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- Study objectives: To study whether the onset of narcolepsy type 1 (NT1) in children and adolescents affects BMI, specific metabolic risk factors, the onset of puberty, longitudinal growth or other endocrine functions. Methods: A population-based study, comprising 34 patients, was performed with a clinical evaluation, an assessment of puberty and growth, actigraphy and blood samples at fasting, from patients and controls, to evaluate pituitary function, growth factors, thyroid gland, gonads, insulin sensitivity, appetite regulation and blood lipids. Results: In the post-H1N1 vaccination (PHV) narcolepsy group, the median BMI SDS was higher 6-12 months after the onset of narcolepsy (p < 0.01), but it was no different 10 years after the onset of narcolepsy (p = 0.91), compared with 12-24 months before the onset of narcolepsy. There was a correlation between an increase in BMI and a decrease in total energy expenditure (R =-0.74). In the nPHV group, weight and BMI changes were smaller and no significant changes were recorded. Early puberty was more common in patients with puberty onset after narcolepsy onset (n = 16/19) compared with patients with puberty onset before narcolepsy onset (n = 3/11, p = 0.02). There was no significant change in height SDS during the studied period. Although they were within normal ranges, both median HDL and median TSH levels were significantly lower in NT1 patients, compared with controls. Conclusions: We found a high prevalence of large BMI gain in the period immediately after the onset of narcolepsy, which had almost normalized at the long-term follow-up. The onset of narcolepsy led to early puberty in both sexes. Linear growth was not affected. We did not find any strong indicators of metabolic disturbances. (c) 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
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| 9. |
- Szakacs, Attila
(författare)
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Narcolepsy in children: Relationship to the H1N1 influenza vaccination, association with psychiatric and cognitive impairments and consequences in daily life
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background/aims: Narcolepsy is a lifelong sleep disorder with an onset most frequently in the second decade of life. The cardinal symptoms are excessive daytime sleepiness, cataplexy, hypnagogic and hypnopompic hallucinations sleep paralysis and disturbed nighttime sleep. The purpose of this thesis was to study a population-based cohort of children and adolescents with narcolepsy in western Sweden to determine the incidence and relationship with the H1N1 influenza vaccination, psychiatric comorbidity, cognitive profile, health-related quality of life, adaptive behavior and parenting stress. Methods: We aimed to identify all individuals below 18 years of age who developed narcolepsy between January 1, 2000, and December 31, 2010. Post-H1N1 influenza vaccination (PHV) narcolepsy was considered in patients with clinical onset within 10 months of vaccination. Psychiatric comorbidity was investigated using a test battery of semi-structured interviews and screening tools. The cognitive assessments were made by a clinical psychologist using age specific Wechsler Scales. A narcolepsy-specific quality of life questionnaire, the NARQoL was generated based on statements from four focus groups comprising young people with narcolepsy and was used along with the generic KIDSCREEN questionnaire to assess the HrQoL in the study population. The Adaptive Behavior Assessment System was administered to measure adaptive skills in the children and the short form of the Parenting Stress Index questionnaire was used to measure parenting stress in their parents. Results: The incidence of narcolepsy was 25 times higher in the period after the vaccination compared with the period before. The children in the PHV group had a lower age at onset and a more sudden onset than is generally seen. Psychiatric comorbidity was present in 43% of the patients in the PHV group; ADHD in 8/28, major depression in 6/30, general anxiety disorder in 3/30 and oppositional defiant disorder (ODD) in 2/30. In the non-post-H1N1 influenza vaccination (nPHV) narcolepsy group, 1/7 patients had ADHD in combination with ODD. The cognitive assessment showed decreased verbal comprehension and working memory in both patient groups. Parents in the PHV group rated significantly lower scores for adaptive behavior relating to conceptual and social composites. Parents also rated higher in “total stress”, “parent-child dysfunctional interaction” and “difficult child”, significantly so in the PHV group. The pilot NARQoL questionnaire consisted of two patient reported outcome modules: QoL and future perceptions. Test-retest reliability and convergent validity with the KIDSCREEN-10 was good. Children with narcolepsy had significantly diminished scores compared with controls on both the KIDSCREEN and NARQoL; the PHV children in all domains of the NARQoL. Furthermore, patients with psychiatric comorbidity had a significantly lower full-scale IQ, HrQoL and adaptive behavior compared with those without. Conclusions: The H1N1 influenza vaccination with Pandemrix represents a precipitating factor for narcolepsy in children. The identified high prevalence of psychiatric comorbidity and cognitive difficulties highlights the importance of a careful psychiatric and neuropsychological follow-up. The NARQoL revealed a more globally affected QoL than previously reported. Impaired adaptive behavior and high levels of parenting stress indicate considerable impact on daily life.
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| 10. |
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| 11. |
- Witt, Suzanne T., et al.
(författare)
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Evidence for cognitive resource imbalance in adolescents with narcolepsy
- 2018
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Ingår i: Brain Imaging and Behavior. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 12:2, s. 411-424
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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