Orthopaedic management of Hurler’s disease after hematopoietic stem cell transplantation: a systematic review

The introduction of hematopoietic stem cell transplantation (HSCT) has significantly improved the life-span of Hurler patients (mucopolysaccharidosis type I-H, MPS I-H). Yet, the musculoskeletal manifestations seem largely unresponsive to HSCT. In order to facilitate evidence based management, the aim of the current study was to give a systematic overview of the orthopaedic complications and motor functioning of Hurler's patients after HSCT. A systematic review was conducted of the medical literature published from January 1981 to June 2010. Two reviewers independently assessed all eligible citations, as identified from the Pubmed and Embase databases. A pre-developed data extraction form was used to systematically collect information on the prevalence of radiological and clinical signs, and on the orthopaedic treatments and outcomes. A total of 32 studies, including 399 patient reports were identified. The most frequent musculoskeletal abnormalities were odontoid hypoplasia (72%), thoracolumbar kyphosis (81%), genu valgum (70%), hip dysplasia (90%) and carpal tunnel syndrome (63%), which were often treated surgically during the first decade of life. The overall complication rate of surgical interventions was 13.5%. Motor functioning was further hampered due to reduced joint mobility, hand dexterity, motor development and longitudinal growth. Stem cell transplantation does not halt the progression of a large range of disabling musculoskeletal abnormalities in Hurler's disease. Although prospective data on the quantification, progression and treatment of these deformities were very limited, early surgical intervention is often advocated. Prospective data collection will be mandatory to achieve better evidence on the effect of treatment strategies

Development of postural adjustments during reaching in typically developing infants from 4 to 18 months

Knowledge on the development of postural adjustments during infancy, in particular on the development of postural muscle coordination, is limited. This study aimed at the evaluation of the development of postural control during reaching in a supported sitting condition. Eleven typically developing infants participated in the study and were assessed at the ages of 4, 6, 10 and 18 months. We elicited reaching movements by presenting small toys at an arm’s length distance, whilst activity of multiple arm, neck and trunk muscles was recorded using surface EMG. A model-based computer algorithm was used to detect the onset of phasic muscle activity. The results indicated that postural muscle activity during reaching whilst sitting supported is highly variable. Direction-specific postural activity was inconsistently present from early age onwards and increased between 10 and 18 months without reaching a 100 % consistency. The dominant pattern of activation at all ages was the ‘complete pattern’, in which all direction-specific muscles were recruited. At 4 months, a slight preference for top-down recruitment existed, which was gradually replaced by a preference for bottom-up recruitment. We conclude that postural control during the ecological task of reaching during supported sitting between 4 and 18 months of age is primarily characterized by variation. Already from 4 months onwards, infants are—within the variation—sometimes able to select muscle recruitment strategies that are optimal to the task at hand

Early disease progression of Hurler syndrome

BACKGROUND: Newborn screening for mucopolysaccharidosis type I (MPS I) shows promise to improve outcomes by facilitating early diagnosis and treatment. However, diagnostic tests for MPS I are of limited value in predicting whether a child will develop severe central nervous system disease associated with Hurler syndrome, or minimal or no central nervous system involvement associated with the attenuated phenotypes (Hurler–Scheie and Scheie syndromes). Given that the optimal treatment differs between Hurler syndrome and the attenuated MPS I phenotypes, the absence of a reliable prognostic biomarker complicates clinical decision making for infants diagnosed through newborn screening. Information about the natural history of Hurler syndrome may aid in the management of affected infants, contribute to treatment decisions, and facilitate evaluation of treatment effectiveness and prognosis. Thus, the aim of this study was to characterize the progression and timing of symptom onset in infants with Hurler syndrome. RESULTS: Clinical data from 55 patients evaluated at a single center were retrospectively reviewed. Information about each child’s medical history was obtained following a standardized protocol including a thorough parent interview and the review of previous medical records. All patients underwent systematic physical and neurodevelopmental evaluations by a multidisciplinary team. Nearly all patients (98%) showed signs of disease during the first 6 months of life. Common early disease manifestations included failed newborn hearing screen, respiratory symptoms, difficulty latching, and otitis media. Other symptoms such as kyphosis, corneal clouding, cardiac disease, joint restrictions, and enlarged head circumference typically appeared slightly later (median age, 8–10 months). During the first 12 months, gross motor development was the most severely affected area of functioning, and a significant number of patients also experienced language delays. Cognition was typically preserved during this period. CONCLUSIONS: In this large cohort of patients with Hurler syndrome, the vast majority showed signs and symptoms of disease during the first months of life. More research is needed to determine the extent to which early clinical manifestations of MPS I can predict phenotype and treatment outcomes

Long-term neurodevelopmental outcomes of infants born late preterm: a systematic review

Tanya Tripathi,1 Stacey C Dusing2,3 1Rehabilitation and Movement Science Program, Department of Physical Therapy, 2Department of Physical Therapy, 3Department of Pediatrics, Children's Hospital of Richmond, Virginia Commonwealth University, Richmond, VA, USA Purpose: Late preterm (LPT) births constitute a large proportion of the preterm births in the USA. Over the last few decades, there has been an increase in research focusing on the neurodevelopment of infants born LPT. The purpose of this research was to systematically review the long-term neurodevelopmental outcomes in LPT infants. Materials and methods: We identified studies by using PubMed, ERIC, CINAHL, and PsycINFO databases. The references of included papers were reviewed for additional papers that met the inclusion criteria. Included papers compared motor, cognitive, language development, or academic performance outcomes between individuals born LPT and a term control group assessed between 12 months and 18 years of age. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards for systematic reviews were utilized including a two-step, two-investigator review process. Results: Of the 4,720 studies found in the initial search, 20 studies met the inclusion criteria. Approximately 75% of the 16 studies that assessed cognitive outcomes reported cognitive delay in the LPT group when compared to their full-term counterparts. More than 50% of the seven studies that assessed motor outcomes suggested a delay in motor development in the LPT group in comparison to full-term. Fewer papers assessed academic performance and language in children born LPT; however, the majority identified borderline differences when LPT infants were compared to those born full-term. Conclusion: Evidence suggests that infants born LPT are at an increased risk of neurodevelopmental delay between 1 and 18 years of life when compared to those born at term. The delay is most evident in the cognitive domain of neurodevelopment. Children born LPT are also at a risk of delayed language development, motor development, and lower academic performance. The rate of developmental delay is reduced somewhat when controlling for social factors; however, group differences persist. Keywords: late preterm infants, developmental outcomes, motor development, cognitive development, language development and school performanc