AIM:The paper aims to show how the biopsychosocial (BPS) model can be applied as a clinical method and guide the assessment and treatment of children and adolescents with somatic symptom disorders (SSD).METHODS:Based on relevant literature and our clinical work with children and adolescents with SSD, we have developed a method to ensure a structured, interdisciplinary examination of biological, psychological and social factors, operationalising the BPS model into a clinical method.RESULTS:The BPS model renders assessment and treatment of complex conditions as a basis for evaluating phenomena not confined by diagnostic tools, but still includes all information from these tools. It requires an interdisciplinary approach, giving individual patient and caregivers a central position. A thorough medical examination is required as a starting point for assessments. Good results rest upon a shared understanding between patient, caregivers and professionals.CONCLUSIONS:'Biopsychosocial' is often claimed as a basis for clinical work with complex cases, medical, functional and psychiatric, but scarcely with a corresponding BPS method or practice. The BPS method should guide further development of holistic, interdisciplinary health care on all levels, to assess and help children and adolescents with SSD.

ObjectivesTo explore factors perceived as positive or negative among young people with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in relation to school and everyday life.DesignA qualitative study with semistructured individual interviews performed at the local hospital or at the informants’ homes between September 2017 and January 2018, with an additional telephone interview to collect data on experiences from the COVID-19 pandemic, conducted in September 2020. Data were analysed using a grounded theory approach.SettingThe informants were recruited from two university hospitals that offer interdisciplinary assessments of young people with CFS/ME from various parts of Norway.ParticipantsFive males and 13 females aged 13–21 years with CFS/ME diagnosed 3–56 months prior to the interviews participated.ResultsThe informants were concerned about a lack of educational adaptations and missed social life at school. Educational and social adaptations could improve schooling and health among young people with CFS/ME. Negative experiences were related to a lack of knowledge about CFS/ME among school personnel and young people’s difficulties to limit activities. Online teaching as experienced during the COVID-19 pandemic was described as positive both for education and social life.ConclusionsYoung people with CFS/ME can benefit from better educational adaptations and increased social interaction with peers. From the participants’ view, factors that limit learning and socialisation include a lack of knowledge about CFS/ME among teachers and school personnel, expectations from teachers of doing more than they could manage at school, feeling alone coping with the disease and not recognising their own limitations regarding what they are able to do. Suggested factors perceived to enhance learning and socialisation were a better understanding of the disease among school personnel and peers, suitable educational adaptations and being able to socialise with peers.

OBJECTIVES:To examine factors that may affect nutritional status in adolescents with esophageal atresia. STUDY DESIGN:Anthropometric measurements, blood samples, pH measuring, mapping of dysphagia with a modified Easting Assessment Test questionnaire, 4-day dietary record, and a semistructured interview about eating habits and nutrition counseling were performed in a cross-sectional cohort of adolescents with esophageal atresia. RESULTS:Out of 102 eligible patients, 68 (67%) participated. The median height-for-age Z score was -0.6 (-4.6 to 1.8). Ten (15%) were classified as stunted (height-for-age Z score <-2). Fourteen (21%) were overweight. More than two-thirds reported symptoms of dysphagia (Easting Assessment Test score ≥3) and avoided specific foods. Forty-eight (71%) completed the 4-day dietary record, which showed daily intake of energy below age-appropriate recommendations. One-third reported an energy intake below their estimated basal metabolic rate. Only 24% had received counselling from a dietitian. CONCLUSIONS:Adolescents with a history of esophageal atresia have growth below reference values and energy intake below recommendations. Energy intake and its relation to stunting needs to be further studied in patients with esophageal atresia.

Abstract Purpose The primary aim was to measure health related quality of life (HRQoL) in a Norwegian cohort of adolescents with Chronic Fatigue Syndrome (CFS/ME). A secondary aim was to identify factors before diagnosis, at time of diagnosis and after diagnosis that were associated with HRQoL. Methods In this cross-sectional population-based study, HRQoL was measured by Pediatric Quality of Life Inventory™ Generic Core scale version 4.0 (PedsQL4.0) in 63 adolescents with CFS/ME. In addition, fatigue was measured by PedsQL Multidimensional Fatigue scale (PedsQL-MFS), depressive symptoms were measured by the Short Mood and Feelings Questionnaire (SMFQ), and disruption in school activities was measured by The De Paul Pediatric Health Questionnaire (DPHQ-N). Data were also collected from medical records and patient interviews. Results Age at diagnosis was 15 (2) years (mean (SD)), and four out of five participants were female. Time from diagnosis to reply was 39 (22) months. Adolescents with CFS/ME reported PedsQL4.0 score 50 (17), and boys reported a better score than girls (64 vs 47, 95% Confidence Interval (CI) for difference (− 27; − 6)). There were positive associations between overall HRQoL and support from a schoolteacher, school attendance or participation in leisure activities. There were negative associations between overall HRQoL and delayed school progression, having been to rehabilitation stay and depressive symptoms. Conclusion HRQoL in adolescents diagnosed with CFS/ME was low. The associations between reported HRQoL, healthcare previously provided, support from a schoolteacher, school attendance and participation in leisure activity may provide information of value when developing refined strategies for healthcare among adolescents with CFS/ME. Possible causal relationships must however be explored in future studies.

Objectives: Lasting, unexplained and high levels of pain may cause anxiety in patients with chronic fatigue syndrome. The objectives of the current study were to test assumptions of the association between pain and anxiety in patients diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and to clarify the role of depression in this relationship. Methods: Data were collected from 664 participants (age 18-65 years) with 133 ME/CFS patients and 201 healthy controls from Norway and 330 CFS patients from Spain. Binary logistic regression model was applied to test relationships between the included variables in the samples. Results: Both pain and depression made significant direct contributions to the level of anxiety. The strongest risk for higher levels of anxiety was the combination of high levels of depression and high levels of pain in the overall sample (OR = 49.70; P < 0.001), not so much in the Spanish cohort (OR = 11.99; P < 0.0001) and most of all in the Norwegian cohort (OR = 88.21; P < 0.001) sample. Conclusions: It was the combination of high pain levels and high levels of depression that to the greatest extent increased the risk of anxiety in patients with CFS/ME. Whatever diagnostic criterion that is applied, anxiety and depression should be mandatory to assess in the clinical assessments performed for diagnosing the ME/CFS. Approaches addressing anxiety-related pain and treatment of depression should be warranted.

Abstract Purpose The primary aim was to measure health related quality of life (HRQoL) in a Norwegian cohort of adolescents with Chronic Fatigue Syndrome (CFS/ME). A secondary aim was to identify factors initial to diagnosis, at time of diagnosis and at follow-up that were associated with HRQoL. Methods In this cross-sectional population-based study, HRQoL was measured by PedsQL Generic Core scale (PedsQL4.0) in 63 adolescents with CFS/ME. In addition, fatigue was measured by PedsQL Multidimentional Fatigue scale (PedsQL-MFS), depressive symptoms were measured by the Short Mood and Feelings Questionnaire (SMFQ), and disruption in school activities was measured by The De Paul Pediatric Health Questionnaire (DPHQ-N). Data were also collected from patient journals and patient interviews.Results Age at diagnosis was 15 (2) years (mean (SD)), and four out of five participants were female. Time from diagnosis to reply was 39 (22) months. Adolescents with CFS/ME reported PedsQL4.0 score 50 (17), and boys reported a better score than girls (64 vs 47, CI (-27;-6)). There were positive associations between overall HRQoL and follow-up by school teacher, school attendance or participation in leisure activities. There were negative associations between overall HRQoL and delayed school progression, having been to rehabilitation stay and depressive symptoms.Conclusion HRQoL in adolescents diagnosed with CFS/ME was low compared to healthy adolescents. The associations between HRQoL, healthcare provided, teacher follow-up, school attendance and participation in leisure activity may provide information of value when developing refined strategies for follow-up of adolescents with CFS/ME. Possible causal relationships must however be explored in future longitudinal studies.

ME/CFS is a chronic, complex, multisystem disease that often limits the health and functioning of the affected patients. Diagnosing patients with ME/CFS is a challenge, and many different case definitions exist and are used in clinical practice and research. Even after diagnosis, medical treatment is very challenging. Symptom relief and coping may affect how patients live with their disease and their quality of life. There is no consensus on which diagnostic criteria should be used and which treatment strategies can be recommended for patients. The purpose of the current project was to map the landscape of the Euromene countries in respect of national guidelines and recommendations for case definition, diagnosis and clinical approaches for ME/CFS patients. A 23 items questionnaire was sent out by email to the members of Euromene. The form contained questions on existing guidelines for case definitions, treatment/management of the disease, tests and questionnaires applied, and the prioritization of information for data sampling in research. We obtained information from 17 countries. Five countries reported having national guidelines for diagnosis, and five countries reported having guidelines for clinical approaches. For diagnostic purposes, the Fukuda criteria were most often recommended, and also the Canadian Consensus criteria, the International Consensus Criteria and the Oxford criteria were used. A mix of diagnostic criteria was applied within those countries having no guidelines. Many different questionnaires and tests were used for symptom registration and diagnostic investigation. For symptom relief, pain and anti-depressive medication were most often recommended. Cognitive Behavioral Therapy and Graded Exercise treatment were often recommended as disease management and rehabilitative/palliative strategies. The lack of consistency in recommendations across European countries urges the development of regulations, guidance and standards. The results of this study will contribute to the harmonization of diagnostic criteria and treatment for ME/CFS in Europe.

Purpose: Juvenile neuronal ceroid lipofuscinosis (CLN3 disease) is the most common neurodegenerative disorder in childhood with survival until young adult age. Visual loss is followed by epilepsy, cognitive, neuropsychiatric, and motor symptoms. We have studied the evolution of electroencephalographic (EEG) and seizure characteristics. Methods: Twenty-four patients were recruited via the Norwegian CLN3 disease parent association. Parents were interviewed. Medical records and EEG reports/recordings were collected. Electroencephalographic elements were classified according to Standardized computer-based organized reporting of EEG (SCORE). The evolution of EEG features along with seizure types was assessed by testing the difference in proportions with standardized normal deviate comparing findings below and above 15 years of age. Results: Mean age at study or death (n = 12) was 21.2 (10-39) years. Twenty-two patients had experienced seizures; the first was usually bilateral tonic-clonic (TC). Later, focal motor seizures frequently occurred, often with increasing multifocal and polymorphic features. Paroxysmal nonepileptic motor and autonomous symptoms were also suspected in several patients. Distinct myoclonic seizures were uncommon. In four patients, we identified episodes of bradycardia/sinus arrest. Electroencephalography showed progressive slowing of the background activity (p = 0.029). Focal epileptiform discharges were rare and mainly seen at age <10. Combined multifocal and bilateral epileptiform discharges increased in adolescence (p = 0.002). Conclusion: Seizure and EEG characteristics change with time in CLN3 disease. Tonic-clonic seizures are common at onset, and multifocal motor seizures increase with age. In contrast, focal epileptiform abnormalities are more common in childhood, compared to later multifocal and bilateral discharges. This seizure disorder belongs to the combined generalized and focal epilepsies. Paucity of myoclonic seizures does not warrant classification as a classic progressive myoclonic epilepsy. When attacks with only behavior arrest occur, cardiac conduction abnormalities should be considered. (C) 2019 Elsevier Inc. All rights reserved.

Background and aims Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is challenging to live with, often accompanied by pervasive fatigue and pain, accompanied by decreased quality of life (QoL) as well as anxiety and/or depression. Associations between higher pain, lower QoL and higher anxiety and depression have been shown in patients with various chronic pain disorders. Few studies have however examined such associations in a sample of patients with ME/CFS. The aims of the current study were to examine the impact of pain levels and compare levels of pain, health related QoL, anxiety and depression between patients with ME/CFS and healthy controls. In addition, the study aimed and to examine these relationships within the patient group only. Methods This is a cross-sectional questionnaire based study comparing 87 well-diagnosed patients with ME/CFS with 94 healthy controls. The De Paul Symptom Questionnaire (DSQ), the Medical Outcomes Study Short-Form Surveys (SF-36) and the Hospital Anxiety and Depression Scale (HADS) were used to examine and compare pain, physical function, QoL, anxiety and depression in patients and healthy controls. Further the pain variables were divided into pain total, pain intensity and a pain frequency score for analyses of the above mentioned variables within the patient group only. Results Significantly higher levels of pain, anxiety and depression, and lower levels of QoL were found in the patient group compared with healthy controls. For the patient group alone, pain was significantly associated with lower QoL in terms of physical functioning, bodily pain, general health functioning, vitality and social functioning capacity. In this patient sample, only frequency of joint pain showed significant difference in psychological variables such as depression and anxiety - depression combined. Conclusions ME/CFS patients differ significantly from healthy controls in pain, health related QoL, anxiety and depression. Pain is significantly associated with reduced QoL and overall a lower level of functioning. The relation between pain and anxiety and depression appears less clear. Implications Pain is for many ME/CFS patients associated with reduced physical functioning and reduced QoL. A thorough pain assessment can therefore be essential for clinicians, and subsequent medical pain treatment combined with good pain coping skills may increase functioning level and QoL for these patients. The link between joint pain and psychological factors should also be focused in clinical practice in terms of mapping and counseling. Pain should be further examined to understand the importance it may have for functioning level as reduced function is a main criteria when diagnosing the patients.

Background: Diagnostic assessment of chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) is largely based on a two part process; screening patients who might meet criteria and following up this assessment with physicians' clinical evaluation of a range of inclusionary symptoms and exclusionary illnesses. Purpose: The aim was to assess how well the DePaul Symptom Questionnaire (DSQ) screened for patients who were ultimately diagnosed by physicians using the Canadian Consensus Criteria (CCC). Methods: Sixty-four patients referred for evaluation of possible CFS or ME were screened initially using the DSQ, and then evaluated and subsequently diagnosed by physicians. To assess the consistency between the self-report DSQ and the physicians' diagnosis, sensitivity and specificity as well as predictive values were calculated. Results: The DSQ identified 60 and the physicians identified 56 as having a CCC diagnosis. The overall agreement between the two ratings on the diagnostic assessment part was moderate (Kappa = 0.45, p<.001). The sensitivity of DSQ was good (98%) while the specificity was 38%. Positive and negative predictive values were 92% and 75%, respectively. Conclusion: DSQ is useful for detecting and screening symptoms consistent with a CCC diagnosis in clinical practice and research. However, it is important for initial screening of self-report symptoms to be followed up by subsequent medical and psychiatric examination in order to identify possible exclusionary medical and psychiatric disorders.

Complex III (cytochrome bc1) is a protein complex of the mitochondrial inner membrane that transfers electrons from ubiquinol to cytochrome c. Its assembly requires the coordinated expression of mitochondrial-encoded cytochrome b and nuclear-encoded subunits and assembly factors. Complex III deficiency is a severe multisystem disorder caused by mutations in subunit genes or assembly factors. Sequence-profile-based orthology predicts C11orf83, hereafter named UQCC3, to be the ortholog of the fungal complex III assembly factor CBP4. We describe a homozygous c.59T>A missense mutation in UQCC3 from a consanguineous patient diagnosed with isolated complex III deficiency, displaying lactic acidosis, hypoglycemia, hypotonia and delayed development without dysmorphic features. Patient fibroblasts have reduced complex III activity and lower levels of the holocomplex and its subunits than controls. They have no detectable UQCC3 protein and have lower levels of cytochrome b protein. Furthermore, in patient cells, cytochrome b is absent from a high-molecular-weight complex III. UQCC3 is reduced in cells depleted for the complex III assembly factors UQCC1 and UQCC2. Conversely, absence of UQCC3 in patient cells does not affect UQCC1 and UQCC2. This suggests that UQCC3 functions in the complex III assembly pathway downstream of UQCC1 and UQCC2 and is consistent with what is known about the function of Cbp4 and of the fungal orthologs of UQCC1 and UQCC2, Cbp3 and Cbp6. We conclude that UQCC3 functions in complex III assembly and that the c.59T>A mutation has a causal role in complex III deficiency.

Chronic Fatigue Syndrome (CFS) is characterized by severe impairment and multiple symptoms. Autonomic dysregulation has been demonstrated in several studies. We aimed at exploring the relationship between indices of autonomic cardiovascular control, the case definition from Centers for Disease Control and Prevention (CDC criteria), important clinical symptoms, and disability in adolescent chronic fatigue syndrome. 38 CFS patients aged 12-18 years were recruited according to a wide case definition (ie. not requiring accompanying symptoms) and subjected to head-up tilt test (HUT) and a questionnaire. The relationships between variables were explored with multiple linear regression analyses. In the final models, disability was positively associated with symptoms of cognitive impairments (p<0.001), hypersensitivity (p<0.001), fatigue (p=0.003) and age (p=0.007). Symptoms of cognitive impairments were associated with age (p=0.002), heart rate (HR) at baseline (p=0.01), and HR response during HUT (p=0.02). Hypersensitivity was associated with HR response during HUT (p=0.001), high-frequency variability of heart rate (HF-RRI) at baseline (p=0.05), and adherence to the CDC criteria (p=0.005). Fatigue was associated with gender (p=0.007) and adherence to the CDC criteria (p=0.04). In conclusion, a) The disability of CFS patients is not only related to fatigue but to other symptoms as well; b) Altered cardiovascular autonomic control is associated with certain symptoms; c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity.

Niemann-Pick disease type C is a rare genetic lysosomal storage disease associated with impaired intracellular lipid trafficking and a range of progressive neurological manifestations. The influence of seizure activity on disease course and response to miglustat therapy is not currently clear.

BACKGROUND:The pathophysiology of chronic fatigue syndrome (CFS) in adolescents is unknown, and the clinical course and prognosis is still questioned. Recent research indicates that abnormalities of autonomic cardiovascular control may play an important role. The aim of this research project was to perform a follow-up study of adolescents with chronic fatigue syndrome, focusing on clinical symptoms and autonomic cardiovascular control.METHODS:47 adolescents (12-18 years old) with CFS were recruited from the outpatient clinic at the Department of Pediatrics, Oslo University Hospital. In a primary visit and a follow-up visit (3-17 months later), we evaluated: a) a wide range of complaints and symptoms and b) cardiovascular variables at baseline and during a 20° head-up tilt-test (HUT).RESULTS:At the second visit, patients reported significant improvement regarding functional impairments, fatigue severity, muscular pain, concentration problems, post-exertional malaise and the problem of non-relieving rest. Also, at the second visit, baseline heart rate (HR), blood pressure, total peripheral resistance index (TPRI) and LF/HF (low-frequency:high-frequency heart rate variability ratio, an index of sinus node sympathovagal balance derived from spectral analyses of heart rate) were significant lower, and the increases in HR, mean blood pressure (MBP), diastolic blood pressure (DBP) and TPRI during tilt were significantly less pronounced as compared to the first visit. There was a significant correlation between changes in autonomic symptom score, fatigue severity score and functional impairment score from the first to the second visit.CONCLUSIONS:The majority of adolescents with CFS experienced an improvement over time in functional impairment, self-reported fatigue and additional symptoms, and a concurrent improvement of autonomic cardiovascular control. A possible connection between clinical symptoms and abnormal autonomic control in CFS might represent a focus for further research.