Objective Neurodevelopmental and cognitive difficulties are known to occur frequently in boys with Duchenne muscular dystrophy but so far none of the published studies have reported both early ...neurodevelopmental assessments and cognitive tests in the same cohort. The aim of the present longitudinal study was to establish the correlation between early neurodevelopmental assessments performed in preschool boys and the cognitive scales performed at school age or later. Methods We performed cognitive tests at school age (mean age 5.7 year plus or minus 1.7 SD) (69 months+19 SD) in a cohort of Duchenne boys, previously assessed using the Griffiths scales before the age of 4 years (mean age when the Griffiths scales were performed 30 months plus or minus 8.9 SD). Results The range of total Developmental quotients on the Griffiths ranged between 56 and 116 (mean 89 plus or minus 15.6 SD). The total Intelligence Quotients on the Wechsler scales ranged between 35 and 119 (mean 87 plus or minus 17.2 SD). There was a significant correlation between the findings on the two scales. P = <0.0001. When we subdivided the cohort according to site of mutations, there was a difference between boys with mutations upstream exon 44 and those with mutations in exon 44-45 affecting Dp140 on both Developmental and Intelligence Quotient (p 0.01 and p 0,003 respectively). Conclusions Our results confirm that Duchenne boys tend to slightly underperform on both neurodevelopmental and cognitive assessments. Early neurodevelopmental findings correlated with the cognitive results obtained at school age with a clear concordance between subscales exploring similar domains on the two scales.
Abstract Background Several studies reported on various aspects of visual function at term age and in the first months after birth but less has been reported in preterm infants before they reach ...termequivalent age. Aims To assess the suitability of a battery of tests of visual function for use in infants born at < 33 weeks gestation (GA) and assessed before 34 weeks post-menstrual age (PMA); to evaluate the distribution of the findings according to GA, and to compare the data with those previously published on preterm infants assessed at 35 weeks PMA. Study design Cross-sectional study. Subjects Sixty-four preterm infants with a GA < 33 weeks were studied. Outcome measures We used a battery of visual function tests previously validated at 35 and 40 weeks PMA in low-risk preterm infants. All the infants in this current study underwent the same assessment before 34 weeks PMA. Results Before 31 weeks PMA most infants could not be reliably assessed because of clinical instability, whilst after 31 weeks PMA most infants could be assessed and they showed progressive maturation in their responses with PMA. Some items (spontaneous ocular motility, horizontal tracking, tracking a coloured stimulus, and ocular fixation) showed similar results at 32–33 weeks PMA to those found in low-risk preterm at 35 weeks PMA. Ocular movements to a target and arc tracking were the items with the most immature responses. Conclusions Our results provide further evidence that a structured assessment of visual function can be used in clinical routine and for research purposes in infants as young as 31 weeks PMA.
To establish the consistency of the previously reported pattern of muscle involvement in a large cohort of patients with molecularly defined ryanodine receptor type 1 (RYR1)-related myopathies, to ...identify possible additional patterns, and to compare magnetic resonance imaging (MRI) findings with clinical and genetic findings.
Blinded analysis of muscle MRI patterns of patients with congenital myopathies with dominant or recessive RYR1 mutations and control patients without RYR1 mutations. We compared MRI findings with the previously reported pattern of muscle involvement.
Data from 3 tertiary referral centers.
Thirty-seven patients with dominant or recessive RYR1 mutations and 23 controls with other myopathies.
Each MRI was classified as typical if it was identical to the reported pattern, consistent if it was similar to the reported one but with some additional features, or different. Images with no or few changes were classified as uninformative.
Twenty-one of 37 patients with RYR1 mutations had a typical pattern; 13 had a consistent pattern. Two patients had uninformative MRIs and only 1 had a different pattern. Compared with patients with dominant mutations, patients with recessive mutations and ophthalmoparesis had a more diffuse pattern, classified as consistent in 6 of 8. In contrast, 10 of 11 with recessive mutations but without ophthalmoparesis had a typical pattern. All MRIs of 23 control patients were classified as different.
Our results suggest that muscle MRI is a powerful predictor of RYR1 involvement in patients with a congenital myopathy, especially if they carry a dominant mutation or recessive mutations without ophthalmoparesis.
Training methodology was established to optimize reliability of outcome measures in the nusinersen clinical trials. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders ...(CHOP INTEND), Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb (RULM) were primary or secondary outcomes.
Video review, quarterly conference calls, and item scoring checks supported evaluator competence. Baseline and screening along with video review established intra and inter-rater reliability.
Inter and intra-rater reliability were both excellent. Intraclass correlation coefficients (ICC) ranged between 0.906-0.994 across initial training meetings and 0.824-0.996 across annual retraining meetings. This was similar for CHOP INTEND (ICC = 0.824-0.951), HFMSE (ICC = 0.981-0.996), and RULM (ICC = 0.966-0.990). Intra-rater reliability for the CHOP INTEND, HFMSE, and RULM were ICC = 0.895 (95% CI: 0.852-0.926; n = 116), ICC = 0.959 (95% CI: 0.942-0.971; n = 125), and ICC = 0.948 (95% CI: 0.927-0.963; n = 126) respectively.
Rigorous evaluator training ensures reliability of assessment of subjects with spinal muscular atrophy (SMA) in multicenter international trials.
Several studies have documented positive effects of beta-adrenergic agonists on human skeletal muscle with regard to muscle mass and strength. The aim of this pilot study was to evaluate the effect ...of the beta2-agonist salbutamol (albuterol) in a group of children with central core disease and multi-minicore disease. Thirteen patients, 8 with central core disease (mean age 17.5 years) and 5 with minicore disease (mean age 13.6 years) received oral salbutamol at a dose of 2 mg four times a day. Measures of efficacy were the change from baseline at 3 and 6 months in muscle strength, assessed by MRC score, myometry, functional measures and forced vital capacity. Statistical analysis was performed using repeated measures ANOVA (significance level < 0.05). Two patients with central core disease stopped the medication after one month because they did not notice any improvement and another one with minicore disease after 4 months because of increased tremors and palpitations. The remaining ten (6 with central core and 4 with minicore disease) completed the course of salbutamol without any significant adverse effects. There were significant increases in myometry, MRC scores and forced vital capacity between baseline and the six-month assessments. For both myometry and MRC the difference was already significant at 3 months and this was associated with a significant increase in functional abilities assessed with a structured functional scale. Our results suggest that salbutamol was overall well tolerated and might be beneficial in both central core and minicore patients. Larger prospective randomised, double-blind, placebo-controlled trials with salbutamol will be needed to confirm these preliminary findings.
To evaluate retrospectively the prevalence of neuromuscular disorders in 83 newborns referred to a tertiary care center because of hypotonia and weakness and/or contractures, with a possible ...diagnosis of neuromuscular disorder. We also aimed to establish whether clinical signs could help to identify infants with neuromuscular disorders.
Sixty-six of the 83 infants who fulfilled the inclusion criteria (79.5%) had an identifiable disorder, which was a neuromuscular disorder in 39 (46.9%).
Absent or extremely reduced antigravity movements were mainly found in infants with neuromuscular disorders (sensitivity and specificity 97.4% and 75%), whereas partial range antigravity movements were more frequent in infants with other diagnosis. Contractures were mainly found in infants with peripheral nerve or muscle involvement but also were relatively frequent in infants with genetic or metabolic syndromes (sensitivity 69.2%, specificity 61.3%). Reduced fetal movements and abnormal liquor were frequent but not present consistently in infants with neuromuscular disorders (sensitivity 46.1% and 38.4%) and were found rarely in infants with other disorders (specificity 88.6% and 75.0%).
Severe muscle weakness and contractures are the most reliable indicators of a neuromuscular disorder and should be carefully assessed in an infant with neonatal hypotonia.
Objective: The Hammersmith Infant Neurological Examination was performed in a cohort of 74 preterm infants whose gestational age ranged between 24 and 30.5 weeks. The infants were examined between 9 ...and 18 months' chronologic age (6-15 months' corrected age) and scored with the optimality score system previously standardized in a cohort of low-risk term infants. The aim of the study was to establish the frequency distribution of the optimality scores in this cohort and to establish whether the scores can predict locomotor function at 2 years of age. Results: The results showed that this standardized neurologic examination can be performed in preterm infants as early as 9 months' chronologic age to predict motor outcome at 2 years old. The scores showed no significant association with the degree of prematurity or the age of assessment. Conclusion: This examination should be particularly useful in very premature infants who are at high risk of severe neurologic and developmental disabilities and for whom the early prediction of motor function can be difficult. (J Pediatr 2002;140:57-60)
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