| 1. |
- Darin, Niklas, 1964, et al.
(författare)
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Benign mitochondrial myopathy with exercise intolerance in a large multigeneration family due to a homoplasmic m.3250T>C mutation in MTTL1.
- 2017
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Ingår i: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 24:4, s. 587-593
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Tidskriftsartikel (refereegranskat)abstract
- Most mitochondrial disorders with onset in early childhood are progressive and involve multiple organs. The m.3250T>C mutation in MTTL1 has previously been described in a few individuals with a possibly riboflavin-responsive myopathy and an association with sudden infant death syndrome was suspected. We describe a large family with this mutation and evaluate the effect of riboflavin treatment.Medical data were collected with the help of a standardized data collection form. Sanger sequencing was used to screen for variants in mitochondrial DNA and the proportion of the mutation was analyzed in different tissues. Biochemical and muscle morphological investigations of muscle tissue were performed in two individuals. The effect of riboflavin treatment was evaluated in two individuals.Thirteen family members experienced exercise intolerance with fatigue and weakness. Inheritance was maternal with 100% penetrance. The course was either static or showed improvement over time. There was no evidence of other organ involvement except for a possible mild transient cardiac enlargement in one child. Muscle investigations showed isolated complex I deficiency and mitochondrial proliferation. The level of m.3250T>C was apparently 100%, i.e. homoplasmic, in all examined tissues. Riboflavin treatment showed no effect in any treated family member and there have been no cases of sudden infant death in this family.This study illustrates the importance of considering mitochondrial disorders in the work-up of individuals with exercise intolerance and provides a better understanding of the phenotype associated with the m.3250T>C mutation in MTTL1.
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| 2. |
- Eriksson, Britt-Marie, et al.
(författare)
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Evaluation of hand orthoses in Duchenne muscular dystrophy
- 2018
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Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 40:23, s. 2824-2832
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to evaluate whether treatment of boys with Duchenne muscular dystrophy using hand orthoses could benefit joint mobility, grip strength, or fine motor function. Method: Eight boys with Duchenne muscular dystrophy were provided with individually customised rest orthoses. The results were analysed using single-subject design. The study included a baseline and an intervention phase. A follow-up examination was also performed. Results: Boys with less than 50 degrees passive wrist extension mobility were included. Wrist extension of the dominant hand increased in four and was maintained in four. Wrist extension in the non-dominant hand increased in five, was maintained in two and decreased in one. Thumb abduction in the dominant hand increased in six and two remained stable. In the non-dominant hand five increased and three remained stable. Grip strength and fine motor function showed also positive results. Conclusions: This study indicates that the use of hand orthoses in Duchenne muscular dystrophy can delay development of contractures and improve passive wrist extension and thumb abduction. Hand orthoses can therefore be recommended for boys who start to develop contractures in the long finger flexors. Due to small sample size further studies are needed to confirm this result.
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| 3. |
- Eriksson, M., et al.
(författare)
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Health-related quality of life and orthosis use in a Swedish population with arthrogryposis
- 2018
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Ingår i: Prosthetics and Orthotics International. - : Ovid Technologies (Wolters Kluwer Health). - 0309-3646 .- 1746-1553. ; 42:4, s. 402-409
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Tidskriftsartikel (refereegranskat)abstract
- Background: Joint contractures are the main characteristics for children with arthrogryposis multiplex congenita. Orthoses are often used to enable or facilitate walking. Objectives: To describe health-related quality of life in children with arthrogryposis multiplex congenita and satisfaction with orthoses in those using orthoses. Methods: A total of 33 children with arthrogryposis multiplex congenita participated in the study. Questionnaires were used which measured health-related quality of life (Child Health Questionnaire-Parent Form and EQ-5D youth), mobility and self-care (Paediatric Evaluation of Disability Inventory) and satisfaction with orthoses (Quebec User Evaluation of Satisfaction with Assistive Technology 2.0). Children were divided into groups based on the use of orthoses: Ort-D were dependent on orthoses for walking, Ort-ND used orthoses but were not dependent on them for walking and Non-Ort did not use orthoses. Results: Children with arthrogryposis multiplex congenita had significantly lower Child Health Questionnaire scores in 9 of 12 subscales compared to healthy controls. The children's reported perceived health with EQ-5D youth did not show any difference between children using orthoses or children using only shoes. Paediatric Evaluation of Disability Inventory showed less mobility in Ort-D than in Non-Ort. In total, both orthosis groups were quite satisfied' with their orthoses. Conclusion: Child Health Questionnaire-physical functioning was lowest in children who were dependent on orthoses (Ort-D) for walking. Both Ort-D and Ort-ND were similar satisfied with their orthoses. Clinical relevance This study contributes to knowledge about health-related quality of life in a group of ambulatory children with arthrogryposis multiplex congenita. For children using orthoses, it is relevant to capture their opinion about their orthoses but a questionnaire specifically for children should be developed.
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| 4. |
- Goemans, N. M., et al.
(författare)
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Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Drisapersen induces exon 51 skipping during dystrophin pre-mRNA splicing and allows synthesis of partially functional dystrophin in Duchenne muscular dystrophy (DMD) patients with amenable mutations. This 188-week open-label extension of the dose-escalation study assessed the long-term efficacy, safety, and pharmacokinetics of drisapersen (PRO051/GSK2402968), 6 mg/kg subcutaneously, in 12 DMD subjects. Dosing was once weekly for 72 weeks. All subjects had a planned treatment interruption (weeks 73-80), followed by intermittent dosing (weeks 81-188). Subjects received a median (range) total dose of 5.93 (5.10 to 6.02) mg/kg drisapersen. After 177 weeks (last efficacy assessment), median (mean [SD]) six-minute walk distance (6MWD) improved by 8 (-24.5 [161]) meters for the 10 subjects able to complete the 6MWD at baseline (mean age [SD]: 9.5 [1.9] years). These statistics include 2 subjects unable to complete the test at later visits and who scored "zero". When only the 8 ambulant subjects at week 177 were taken into account, a median (mean [SD]) increase of 64 (33 [121]) meters in 6MWD was observed. Of 7 subjects walking >= 330 m at extension baseline, 5 walked farther at week 177. Of 3 subjects walking <330 m, 2 lost ambulation, while 1 declined overall but walked farther at some visits. Over the 188 weeks, the most common adverse events were injection-site reactions, raised urinary alpha(1)-microglobulin and proteinuria. Dystrophin expression was detected in all muscle biopsies obtained at week 68 or 72. Drisapersen was generally well tolerated over 188 weeks. Possible renal effects, thrombocytopenia and injection-site reactions warrant continued monitoring. Improvements in the 6MWD at 12 weeks were sustained after 3.4 years of dosing for most patients. For a small, uncontrolled study, the outcomes are encouraging, as natural history studies would anticipate a decline of over 100 meters over a 3-year period in a comparable cohort.
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| 5. |
- Kroksmark, Anna-Karin, et al.
(författare)
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Long-term follow-up of motor function and muscle strength in the congenital and childhood forms of myotonic dystrophy type 1
- 2017
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Ingår i: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966. ; 27:9, s. 826-835
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to explore how motor function and muscle strength change over time in the congenital and childhood forms of myotonic dystrophy type 1, further to investigate whether sex, age, disease severity or size of the mutation could explain these changes. Motor function and isometric muscle strength were evaluated at three occasions during 1999-2013 in 57 patients aged 0.7-28.9 years. Median time between first and last assessment was 11.5 years ranging from 9.6 to 13.3 years. The study shows that motor function improves during the first decade, is most pronounced during the first six years, reaches a plateau during adolescence and starts to deteriorate in the beginning of the second decade. The most predictive variables for change are age (p < 0.0001) and number of CTG-repeat expansions (p = 0.0018). Sex or disease severity grade do not predict changes in motor function. Deterioration of muscle strength is most pronounced in ankle dorsiflexors. Knowledge of development and deterioration of motor function is important for clinical decision making and for planning of interventions. This knowledge can also be of interest for patient recruitment in drug trials, since treatment effect might be easier to evaluate in the stable phases of this progressive disorder. (C) 2017 Elsevier B.V. All rights reserved.
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| 6. |
- Lager, C., et al.
(författare)
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Pain in adolescents with spinal muscular atrophy and Duchenne and Becker muscular dystrophy
- 2015
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Ingår i: European journal of paediatric neurology. - : Elsevier BV. - 1090-3798. ; 19:5, s. 537-546
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Tidskriftsartikel (refereegranskat)abstract
- Background/purpose: The purpose of this study was to explore the prevalence, nature and scope of pain in adolescents with spinal muscular atrophy and Duchenne and Becker muscular dystrophy and whether the pain differs between diagnostic groups or between adolescents with different ambulation status. Furthermore to study the consequences of pain and to identify pain-exacerbating and pain-relieving factors. Methods: In a national survey, fifty-five adolescents with spinal muscular atrophy and dystrophinopathy completed a questionnaire assessing pain frequency, duration, location using a body map, intensity and discomfort using visual analogue scales, pain interference using a modified version of Brief Pain Inventory and factors exacerbating and relieving pain. Results: Sixty-nine per cent of the adolescents reported pain during the past three months and 50% reported chronic pain. The pain prevalence did not differ significantly between diagnostic groups or between ambulators and non-ambulators. The average pain intensity was graded as mild and the worst pain as moderate. The pain typically occurred weekly, most frequently in the neck/back or legs. General activity and mood were the areas that were most affected by pain. Common pain-exacerbating factors were sitting, too much movement/activity and being lifted or transferred. Conclusion: Pain is a frequent problem in adolescents with spinal muscular atrophy and dystrophinopathy. The assessments used enable an understanding both of the nature and scope of pain and of the impact of pain in everyday life. The study highlights the importance of assessing pain in a systematic manner and offering an individual approach to interventions designed to reduce pain in this population. (C) 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
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| 7. |
- Lindeblad, G., et al.
(författare)
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Cognitive and adaptive functioning in congenital and childhood forms of myotonic dystrophy type 1: a longitudinal study
- 2019
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Ingår i: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 61:10, s. 1214-1220
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To conduct a longitudinal follow-up of the development of global cognitive abilities and adaptive skills in individuals with congenital and childhood forms of myotonic dystrophy type 1 (DM1). Method: Fifty-one participants (29 males, 22 females, mean age 19y 5mo, SD 4y 11mo, range 10y 10mo–28y 11mo) were divided into severe congenital (n=16), mild congenital (n=17), and childhood DM1 (n=18) subgroups. The average time between the first and second assessments was 7years 8months. Adaptive skills were evaluated using the Vineland Adaptive Behavior Scales and global cognitive functioning using Wechsler scales. Results: There was no statistically significant decline in cognitive abilities and adaptive behaviour. A tendency of decline regarding the level of intellectual disability was found in the congenital DM1 groups but not in the childhood group. In the congenital DM1 groups, the gap in relation to typically developing peers in cognitive and adaptive functioning increased. Predictors of change over time in adaptive skills were age and current level of intellectual disability: individuals with severe intellectual disability and younger individuals deteriorated the most. However, when raw scores were compared, no actual regression in adaptive functioning was found. Interpretation: The participants had not lost any important adaptive skills. Greater cognitive and adaptive development was found in the childhood group than in the congenital groups. What this paper adds: There is no absolute decline in cognitive and adaptive abilities in individuals with congenital and childhood myotonic dystrophy type 1. Pace of development is slow in comparison with normative data. The childhood group tended to show greater cognitive and adaptive development than the congenital groups. © 2019 Mac Keith Press
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| 8. |
- Olsson, Bob, 1969, et al.
(författare)
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NFL is a marker of treatment response in children with SMA treated with nusinersen
- 2019
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:9, s. 2129-2136
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Tidskriftsartikel (refereegranskat)abstract
- Background Recently, the anti-sense oligonucleotide drug nusinersen was approved for spinal muscular atrophy (SMA) and our aim was to find a response marker for this treatment. Methods Twelve children with SMA type 1 and two copies of the SMN2 gene were included in a consecutive single-center study. The children were sampled for CSF at baseline and every time nusinersen was given intrathecally. The neuronal biomarkers NFL and tau and the glial biomarker GFAP were measured. Motor function was assessed using CHOP INTEND. Eleven similarly aged children, who were investigated to rule out neurological or infectious disease, were used as controls. Results Baseline levels of NFL (4598 +/- 981 vs 148 +/- 39, P = 0.001), tau (939 +/- 159 vs 404 +/- 86, P = 0.02), and GFAP (236 +/- 44 vs 108 +/- 26, P = 0.02) were significantly higher in SMA children than controls. Motor function improved by nusinersen treatment in median 13 points corresponding to 5.4 points per month of treatment (P = 0.001). NFL levels typically normalized ( < 380 pg/ml) between the fourth and fifth doses [- 879.5 pg/mL/dose, 95% CI (- 1243.4, - 415.6), P = 0.0001], tau levels decreased [- 112.6 pg/mL/dose, 95% CI (- 206-7, - 18.6), P = 0.01], and minor decreases in GFAP were observed [- 16.9 pg/mL/dose, 95% CI (- 22.8, - 11.2), P = 0.02] by nusinersen treatment. Improvement in motor function correlated with reduced concentrations of NFL (rho = - 0.64, P = 0.03) and tau (rho = - 0.85, P = 0.0008) but not GFAP. Conclusions Nusinersen normalized the axonal damage marker NFL and correlated with motor improvement in children with SMA. NFL may, therefore, be a novel biomarker to monitor treatment response early in the disease course.
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| 9. |
- Stridh, Marie Louise, et al.
(författare)
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Postural control in the congenital and childhood forms of myotonic dystrophy type 1
- 2017
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Ingår i: European Journal of Physiotherapy. - : Informa UK Limited. - 2167-9169 .- 2167-9177. ; 19, s. 24-31
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 Informa UK Limited, trading as Taylor & Francis Group. Aims: To increase knowledge regarding postural control in congenital (CDM1) and childhood (ChDM1) forms of myotonic dystrophy type 1 and to analyze whether variations can be explained by age, joint motion, muscle strength and molecular findings. Methodology: In a cross-sectional study, postural control was measured with the Bruininks-Oseretsky test, sub-test balance, range of motion (ROM) in ankle dorsiflexion and muscle strength in ankle dorsiflexors. Simple linear regression analysis was used to investigate the association between postural control, molecular findings, muscle strength, age and ROM. Major findings: Forty-four individuals participated in the study. All individuals with CDM1 and 80% with ChDM1 had reduced postural control. Simple linear regression analysis shows a negative association between z-BOT2 and CTG repeat expansion (R2=.342, p =.000), a negative association with age (R2=.148, p =.006), a positive association with muscle strength in ankle dorsiflexors (R2=.205, p =.001) and a positive association with ROM in ankle dorsiflexion (R2=.078, p =.037). Principal conclusion: Reduced postural control is common in CDM1 and ChDM1. Size of CTG repeat expansion, muscle strength in ankle dorsiflexors, age and ROM in ankle dorsiflexion all contribute to variations in postural control. These findings provide a better understanding of the disease and contribute to improved health care for the patient group.
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