| 1. |
- Danfors, Torsten, et al.
(författare)
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Tetrahydrobiopterin in the treatment of children with autistic disorder. A double-blind placebo-controlled crossover study
- 2005
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Ingår i: Journal of Clinical Psychopharmacology. - 0271-0749 .- 1533-712X. ; 25:5, s. 485-489
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Tidskriftsartikel (refereegranskat)abstract
- Twelve children, all boys, aged 4 to 7 years, with a diagnosis of autistic disorder and low concentrations of spinal 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (tetrahydrobiopterin) were selected to participate in a double-blind, randomized, placebo-controlled, crossover study. The children received a daily dose of 3 mg tetrahydrobiopterin per kilogram during 6 months alternating with placebo. Treatment-induced effects were assessed with the Childhood Autism Rating Scale every third month. The results showed small nonsignificant changes in the total scores of Childhood Autism Rating Scale after 3- and 6-month treatment. Post hoc analysis looking at the 3 core symptoms of autism, that is, social interaction, communication, and stereotyped behaviors, revealed a significant improvement of the social interaction score after 6 months of active treatment. In addition, a high positive correlation was found between response of the social interaction score and IQ. The results indicate a possible effect of tetrahydrobiopterin treatment.
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| 2. |
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| 3. |
- Ehrstedt, Christoffer, et al.
(författare)
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Cognition, health-related quality of life, and mood in children and young adults diagnosed with a glioneuronal tumor in childhood
- 2018
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Ingår i: Epilepsy & Behavior. - : Elsevier BV. - 1525-5050 .- 1525-5069. ; 83, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to investigate long-term cognitive outcome, health-related quality of life (HRQoL), and psychiatric symptoms in children and young adults diagnosed with a glioneuronal tumor in childhood.Methods: Twenty-eight children and adolescents (0-17.99 years) with a minimum postoperative follow-up time of five years were eligible for the study; four persons declined participation. A cross-sectional long-term follow-up evaluation was performed using the following study measures: Wechsler Intelligence Scale for Children (WISC-IV) or Wechsler Adult Intelligence Scale (WAIS-IV), Reys Complex Figure Test (RCFT), Short Form 36 version 2 (SF-36v2), Short Form 10 (SF-10), Quality of Life in Epilepsy 31 (QOLIE-31), Hospital Anxiety Depression Scale (HADS) or Beck Youth Inventory Scales (BYI), and Rosenberg Self-Esteem Scale. Historical WISC-III and RCFT data were used to compare cognitive longitudinal data.Results: Mean follow-up time after surgery was 12.1 years. Sixty-three percent (15/24) were seizure-free. Despite a successive postoperative gain in cognitive function, a significant reduction relative to norms was seen in the seizure-free group with respect to perceptual reasoning index (PRI), working memory index (WMI), and full-scale intelligence quotient (FSIQ). Seizure freedom resulted in acceptable HRQoL. Thirty-two percent and 16% exceeded the threshold level of possible anxiety and depression, respectively, despite seizure freedom.Conclusion: Although lower than in corresponding reference groups, cognitive outcome and HRQoL are good provided that seizure freedom or at least a low seizure severity can be achieved. There is a risk of elevated levels of psychiatric symptoms. Long-term clinical follow-up is advisable.
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| 4. |
- Ehrstedt, Christoffer, et al.
(författare)
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Glioneuronal tumors in childhood - Before and after surgery. A long-term follow-up study
- 2017
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Ingår i: Epilepsy & Behavior. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1525-5050 .- 1525-5069. ; 72, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To give a detailed description of the long-term outcome of a cohort of children with glioneuronal tumors regarding pre-and postsurgical factors, including "dual" and "double" pathology, seizure freedom, and psychosocial outcome.Methods: During a fifteen-year period (1995-2009), all patients (age 0-17.99 years) with a glioneuronal brain tumor diagnosed and treated at Uppsala University Children's Hospital were identified from the National Brain Tumor Registry and the National Epilepsy Surgery Registry. Hospital medical records were reviewed and neuroradiological and neuropathological findings were re-evaluated. A cross-sectional long-term follow-up prospective evaluation, including an interview, neurologic examination, and electroencephalogram, was accomplished in patients accepting participants in the study.Results: A total of 25 out of 28 (89%) eligible patientswere included. The M: F ratiowas 1.5: 1. Mean follow-up time after surgery was 12.1 years (range 5.0-19.3). Twenty patients were adults (N18 years) at follow-up. Seizure freedomwas achieved in 64%. Gross total resection (GTR) was the only preoperative factor significantly correlating to seizure freedom (p= 0.027). Thirty-eight percent were at some time postoperatively admitted for a psychiatric evaluation. There was a trend towards both higher educational level and employment status in adults who became seizure free.Conclusion: Long-termoutcome is good regarding seizure freedom if GTR can be achieved, but late seizure recurrence can occur. "Dual" and "double" pathology is uncommon and does not influence seizure outcome. Obtaining seizure freedomseems to be important for psychosocial outcome, but there is a risk for psychiatric comorbidities and long-term follow-up by a multi-professional team is advisable.
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| 5. |
- Ehrstedt, Christoffer
(författare)
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Glioneuronal tumours in childhood : Clinical picture, long-term outcome and possible new treatments
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Glioneuronal tumours are a subgroup of low-grade tumours of the central nervous system (CNS), often causing epilepsy. Overall survival is excellent, but data regarding long-term seizure outcome and late effects are scarce.Aims: The overall aim was to gather data about pre- and postsurgical factors of importance and long-term outcomes to improve standards of care. Another aim was to explore the expression of somatostatin receptor (SSTR) subtypes and mTOR pathway markers.Methods: This thesis, based on four population-based studies with both retrospective and cross-sectional parts, was performed through a long-term follow-up of a Swedish cohort of children with glioneuronal tumours in the Uppsala-Örebro health region. Patients were identified from the National Brain Tumour Registry and the National Epilepsy Surgery Registry. Various methods were used: reviews of hospital medical records, patient interviews, health-related quality of life (HRQoL) assessments with generic (Short Form 36version2) and disease specific (Quality of Life in Epilepsy-31) questionnaires, neuropsychological evaluations with Wechsler Intelligence Scale for Children-IV or Wechsler Adult Intelligence Test-IV and Reys Complex Figure Test and evaluation for possible depression with Hospital Anxiety Depression Scale. Immunohistochemical analyses for SSTR subtypes 1, 2a, 3 and 5 and mTOR pathway components ezrin-radixin-moesin and pS6 were performed on tumour specimens.Results: Glioneuronal tumours seem to be more frequent than previously reported, accounting for 13.5% of all childhood CNS tumours. They often cause medically refractory epilepsy resulting in cognitive impairment. Neurosurgery was often delayed; mean time from symptom debut to lesionectomy was 4.6 years. Long-term seizure freedom was achieved in 84% of patients who had a gross total resection (GTR) and is important for long-term cognitive restitution, HRQoL, educational and vocational outcomes. SSTR2a and SSTR3 expression was a frequent finding in glioneuronal tumours. Signs of mTOR pathway activation were abundant in ganglioglioma.Conclusions: A safe GTR should be striven for and considered a first-line treatment. Long-term clinical follow-up should be offered to all patients and for those with an inoperable tumour/tumour remnant causing tumour growth and/or medically refractory epilepsy, somatostatin analogues and/or mTOR inhibitors might represent a therapeutic alternative worth exploring further.
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| 6. |
- Ehrstedt, Christoffer, et al.
(författare)
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Somatostatin receptor expression and mTOR pathway activation in glioneuronal tumours of childhood
- 2020
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Ingår i: Seizure. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 76, s. 123-130
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the expression of somatostatin receptors (SSTRs) and markers of mTOR pathway in paediatric glioneuronal tumours and correlate these findings with tumour type, BRAFV600E mutational status and clinical characteristics such as tumour location, seizure frequency and duration, and age.Method: 37 children and adolescents with a neuropathological diagnosis of glioneuronal tumour were identified over a 22-year period. Immunohistochemical analyses for SSTRs type 1, 2A, 3, 5 and ezrin-radixin-moesin (ERM) and phosphorylated S6 (pS6), which are indicators of mTOR pathway activation, were performed in tumour specimens from 33 patients and evaluated using the immunoreactive score (IRS). The IRS were compared to tumour type, BRAFV600E status and clinical characteristics.Results: Ganglioglioma (GG) was the most frequently encountered subgroup (n = 27), followed by dysembryoplastic neuroepithelial tumour (DNET; n=4). GGs expressed SSTR2A and SSTR3 to a high extent, 56 % and 44 % respectively. Expression of SSTR2A was also found in DNETs. Signs of mTOR pathway activation were abundant in GGs, but only present in one DNET. No correlations with BRAFV600E presence or clinical characteristics were found.Conclusions: Expression of SSTRs and activation of mTOR pathway in paediatric glioneuronal tumour suggest that somatostatin analogues and mTOR inhibitors may have potential therapeutic implications in a subset of inoperable childhood glioneuronal tumours causing medically refractory epilepsy and/or tumour growth. Further clinical studies are warranted to validate these findings.
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| 7. |
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| 8. |
- Hafström, Maria, 1962, et al.
(författare)
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Cerebral Palsy in Extremely Preterm Infants
- 2018
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 141:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: The risk of cerebral palsy (CP) is high in preterm infants and is often accompanied by additional neurodevelopmental comorbidities. The present study describes lifetime prevalence of CP in a population-based prospective cohort of children born extremely preterm, including the type and severity of CP and other comorbidities (ie, developmental delay and/or cognitive impairment, neurobehavioral morbidity, epilepsy, vision and hearing impairments), and overall severity of disability. In this study, we also evaluate whether age at assessment, overall severity of disability, and available sources of information influence outcome results.METHODS: All Swedish children born before 27 weeks' gestation from 2004 to 2007 were included (the Extremely Preterm Infants in Sweden Study). The combination of neonatal information, information from clinical examinations and neuropsychological assessments at 2.5 and 6.5 years of age, original medical chart reviews, and extended chart reviews was used.RESULTS: The outcome was identified in 467 (94.5%) of eligible children alive at 1 year of age. Forty-nine (10.5%) children had a lifetime diagnosis of CP, and 37 (76%) were ambulatory. Fourteen (29%) had CP diagnosed after 2.5 years of age, 37 (76%) had at least 1 additional comorbidity, and 27 (55%) had severe disability. The probability for an incomplete evaluation was higher in children with CP compared with children without CP.CONCLUSIONS: Children born extremely preterm with CP have various comorbidities and often overall severe disability. The importance of long-term follow-up and of obtaining comprehensive outcome information from several sources in children with disabilities is shown.
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| 9. |
- Kristiansen, Ingela, et al.
(författare)
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Clinical characteristics, long-term complications and health related quality of life (HRQoL) in children and young adults treated for low-grade astrocytoma in the posterior fossa in childhood
- 2019
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Ingår i: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 142:1, s. 203-210
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Tidskriftsartikel (refereegranskat)abstract
- Pilocytic astrocytoma is the most common brain tumour in childhood but knowledge concerning its long-term outcome is sparse. The aim of the study was to investigate if children treated for low-grade pilocytic astrocytoma in the posterior fossa had complications affecting physical and psychological health, cognitive functions, learning difficulties and HRQoL.A descriptive single-centre study, where 22 children and young adults out of 27 eligible patients (81%) treated for pilocytic astrocytoma, with a mean follow-up time of 12.4 years (5-19 years) participated (14 adults, two by telephone interviews and eight children). The study included a review of medical records, an interview, neurological investigation, screening tools for psychiatric symptoms (Beck Depression and Anxiety Inventories and Beck Youth Inventory Scales) and HRQoL measures (RAND-36).Motor complications were most common, reported in 12 patients and mainly affecting fine-motor skills. Seven patients reported cognitive difficulties affecting performance in school. Educational support was given in the period immediately after treatment but not after primary school. None had elevated levels of psychiatric symptoms and the level of HRQoL as well as their psychosocial and educational situation was in correspondence with Swedish norms. The HRQoL score for vitality (VT) almost reached statistical significance.The long-term functional outcome for children treated for low-grade astrocytoma is favourable. However, some patients report neurological complications and learning difficulties, which are unmet in school. Therefore, there is a need to identify those who need more thorough medical and cognitive follow-up programmes including interventions in school.
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| 10. |
- Kristiansen, Ingela, et al.
(författare)
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Cognitive, language, and school performance in children and young adults treated for low-grade astrocytoma in the posterior fossa in childhood
- 2022
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Ingår i: Cancer Reports. - : John Wiley & Sons. - 2573-8348. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPilocytic astrocytoma is the most common brain tumour type in childhood located in the posterior fossa, and treated mainly with surgery. These tumours have low mortality, but knowledge concerning its long-term outcome is sparse.AimThe aim of this study was to investigate whether children treated for pilocytic astrocytoma in the posterior fossa had late complications affecting cognition, language and learning.MethodsThis descriptive single-centre study includes eight children and 12 adults treated as children for pilocytic astrocytoma in the posterior fossa, with a mean follow-up time of 12.4 (range 5–19) years. Well-established tests of intelligence, executive, language and academic function were used.ResultsIntelligence tests showed average results compared with norms. Five patients scored <−1 SD (70–84) and 3 low average (85–92) on full scale IQ. The patients scored average on subtests regarding executive function, except for significantly lower results in inhibition/switching (p = .004). In Rey complex figure test half of the patients scored below −1 SD. Language tests were normal except for significantly lower results in naming ability (p = .049) and in inference (p = .046).In academic tests, results were average, except for significantly lower results in reading speed (p = .024). Patients with learning difficulties performed worse in the tests.ConclusionsThe patients' functional outcome was favourable but, a not-negligible part of the patients displayed neurocognitive difficulties as revealed by extensive neuro-cognitive and academic testing. Thus, it is important to identify those in need of more thorough cognitive and pedagogic follow-up programmes, including school interventions.
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| 11. |
- Kristiansen, Ingela, et al.
(författare)
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Motor performance after treatment of pilocytic astrocytoma in the posterior fossa in childhood
- 2022
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Ingår i: Cancer Reports. - : Wiley-Blackwell Publishing Inc.. - 2573-8348. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pilocytic astrocytoma is the most common brain tumour type in childhood located in the posterior fossa, and treated mainly with surgery. These tumours have low mortality, but knowledge concerning its long-term outcome is sparse. Aims: The aim was to investigate if patients treated for pilocytic astrocytoma in the posterior fossa had motor complications, including balance, motor and process skills. Methods and results: This descriptive single-centre study includes eight children and 12 adults, treated for pilocytic astrocytoma as children. Motor performance was investigated with Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, and dynamic balance with the mini-balance evaluation systems test. Physiological cost index, six-minute walk test, hand grip strength and assessment of motor and process skills were also evaluated. Ten patients reported motor difficulties, mainly from the upper limbs. The motor performance test showed results within normal limits except for manual dexterity, which was significantly below mean (p = .008). In the dynamic balance test patients had significantly lower results compared with controls (p = .036). Physiological cost index, six-minute walk tests and hand grip strength showed results within normal limits. In the Assessment of Motor and Process Skills, patients over 16 years had significantly lower results compared with test norms for motor activities of daily living (ADL) and 30% of all patients scored below the cut-off level for difficulties with motor skills. Conclusions: Motor performance for patients treated for pilocytic astrocytoma in the posterior fossa in childhood is satisfactory but some patients display difficulties with balance, manual dexterity and ADL motor skills. Thus, it is important to identify those in need of motor follow-up and training.
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| 12. |
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| 13. |
- Montgomery, Cecilia, et al.
(författare)
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The Structured Observation of Motor Performance in Infants can detect cerebral palsy early in neonatal intensive care recipients
- 2017
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Ingår i: Early Human Development. - : Elsevier BV. - 0378-3782 .- 1872-6232. ; 113, s. 31-39
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe detection of motor problems in infancy requires a detailed assessment method that measures both the infants' level of motor development and movement quality.AimTo evaluate the ability of the Structured Observation of Motor Performance in Infants (SOMP-I) to detect cerebral palsy (CP) in neonatal intensive care recipients.Study designProspective cohort study analyzed retrospectively.Subjects212 (girls: 96) neonatal intensive care recipients (mean gestational age 34 weeks, range: 23–43). Twenty infants were diagnosed with CP.Outcome measuresThe infants were assessed using SOMP-I at 2, 4, 6 and 10 months' corrected age. Accuracy measures were calculated for level of motor development, quality of motor performance and a combination of the two to detect CP at single and repeated assessments.ResultsAt 2 months, 17 of 20 infants with CP were detected, giving a sensitivity of 85% (95% CI 62–97%) and a specificity of 48% (95% CI 40–55%), while the negative likelihood ratio was 0.3 (95% CI 0.1–0.9) and the positive likelihood ratio was 1.6 (95% CI 1.3–2.0). At 6 months all infants with CP were detected using SOMP-I, and all infants had repeatedly been assessed outside the cut-offs. Specificity was generally lower for all assessment ages, however, for repeated assessments sensitivity reached 90% (95% CI 68–99%) and specificity 85% (95% CI 79–90%).ConclusionsSOMP-I is sensitive for detecting CP early, but using the chosen cut-off can lead to false positives for CP. Assessing level and quality in combination and at repeated assessments improved predictive ability.
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| 14. |
- Serenius, Fredrik, 1939-, et al.
(författare)
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Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden.
- 2013
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Ingår i: Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 309:17, s. 1810-20
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Tidskriftsartikel (refereegranskat)abstract
- Importance Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors. Objective To determine neurodevelopmental outcome in extremely preterm children at 2.5 years (corrected age). Design, Setting, and Participants Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007. Of 707 live-born infants, 491 (69%) survived to 2.5 years. Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality. Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences. Main Outcomes and Measures Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), which are standardized to mean (SD) scores of 100 (15). Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments. Assessments were made by week of gestational age. Results At a median age of 30.5 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only). For controls, 701 had information on health status and 366 had Bayley-III assessments. Mean (SD) composite Bayley-III scores (cognition, 94 [12.3]; language, 98 [16.5]; motor, 94 [15.9]) were lower than the corresponding mean scores for controls (cognition, 104 [10.6]; P < .001; adjusted difference in mean scores, 9.2 [99% CI, 6.9-11.5]; language, 109 [12.3]; P < .001; adjusted difference in mean scores, 9.3 [99% Cl, 6.4-12.3]; and motor, 107 [13.7]; P < .001; adjusted difference in mean scores, 12.6 [99% Cl, 9.5-15.6]). Cognitive disability was moderate in 5% of the extremely preterm group vs 0.3% in controls (P < .001) and it was severe in 6.3% of the extremely preterm group vs 0.3% in controls (P < .001). Language disability was moderate in 9.4% of the extremely preterm group vs 2.5% in controls (P < .001) and severe in 6.6% of the extremely preterm group vs 0% in controls (P < .001). Other comparisons between the extremely preterm group vs controls were for cerebral palsy (7.0% vs 0.1%; P < .001), for blindness (0.9% vs 0%; P = .02), and for hearing impairment (moderate and severe, 0.9% vs 0%; P = .02, respectively). Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 7.2%-15%) had severe disability. Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < .001). Conclusions and Relevance Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age. These results are relevant for clinicians counseling families facing extremely preterm birth. JAMA. 2013;309(17):1810-1820
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| 15. |
- Van't Hooft, I, et al.
(författare)
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Multiprofessional follow-up programmes are needed to address psychosocial, neurocognitive and educational issues in children with brain tumours
- 2016
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 105:6, s. 676-683
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to coordinate the structured psychosocial, neurocognitive and educational follow-up of children treated for brain tumours with the medical protocol and apply the model in two Swedish healthcare regions.METHODS: We invited all children living in the two regions, who had been diagnosed with a brain tumour from October 1, 2010, through June 30, 2012, to participate along with their parents. The follow-up programme evaluated the emotional status of the parents and patients and assessed the children's general cognitive level, working memory, speed of performance, executive functions and academic achievement from diagnosis through to adult care.RESULTS: During the study period, 61 children up to the age of 17.1 years were diagnosed with a brain tumour, but 18 of these were excluded for various reasons. The majority of the mothers (70%) displayed significantly poor emotional status, as did 34% of the fathers and 21% of the children. The majority of the children (57%) also showed poor neurocognitive performance and needed special adaptations at school (66%).CONCLUSION: Our findings indicate the need for coordinated, multiprofessional follow-up programmes, well anchored in the healthcare organisation, for children diagnosed with brain tumours.
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