Central nervous system stem cell transplantation for children with neuronal ceroid lipofuscinosis.

OBJECT: Infantile and late-infantile neuronal ceroid lipofuscinoses (NCLs) are invariably fatal lysosomal storage diseases associated with defects in lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT-1) or tripeptidyl peptidase 1 (TPP1) activity. Previous preclinical studies have demonstrated that human CNS stem cells (HuCNS-SCs) produce both PPT-1 and TPP1 and result in donor cell engraftment and reduced accumulation of storage material in the brain when tested in an NCL mouse model. METHODS: HuCNS-SC transplantation was tested in an open-label dose-escalation Phase I clinical trial as a potential treatment for infantile and late-infantile NCL. Study design included direct neurosurgical transplantation of allogeneic HuCNS-SCs into the cerebral hemispheres and lateral ventricles accompanied by 12 months of immunosuppression. RESULTS: Six children with either the infantile or late-infantile forms of NCL underwent low- (3 patients) and high- (3 patients) dose transplantation of HuCNS-SCs followed by immunosuppression. The surgery, immunosuppression, and cell transplantation were well tolerated. Adverse events following transplantation were consistent with the underlying disease, and none were directly attributed to the donor cells. Observations regarding efficacy of the intervention were limited by the enrollment criteria requiring that patients be in advanced stages of disease. CONCLUSIONS: This study represents the first-in-human clinical trial involving transplantation of a purified population of human neural stem cells for a neurodegenerative disorder. The feasibility of this approach and absence of transplantation-related serious adverse events support further exploration of HuCNS-SC transplantation as a potential treatment for select subtypes of NCL, and possibly for other neurodegenerative disorders.

Management of symptoms in children with autism spectrum disorders: a comprehensive review of pharmacologic and complementary-alternative medicine treatments.

In the care of children with autism spectrum disorders (ASD), medical treatment is typically considered an adjunct to educational and behavioral interventions. Nonetheless, large proportions of children with ASD are managed medically and receive both pharmacologic and complementary-alternative medicine (CAM) treatments. Although many medical treatments have been studied in children with ASD, studies vary widely in terms of the sample, sample size, research design, purposes of treatment, and measurements of change. Surprisingly, comprehensive reviews of the options for medical management in ASD are lacking, particularly reviews that address both pharmacologic and CAM treatments. Furthermore, reviews to date tend to emphasize general effects of medication; this perspective contradicts medical practice, which targets particular symptoms during treatment selection and monitoring. This review of 115 studies adds to the ASD treatment literature by (1) including studies of individuals 0 to 22 years of age; (2) aggregating studies of pharmacologic treatments and CAM treatments; and importantly, (3) organizing treatment response by ASD symptoms, differentiating core and associated symptoms.

Pediatric constraint-induced movement therapy is associated with increased contralateral cortical activity on functional magnetic resonance imaging.

The mechanism behind constraint-induced movement therapy (constraint therapy) success is unknown. Study objectives were to evaluate cortical change after modified constraint therapy and explore a novel approach to quantify developmental disregard. Five participants underwent modified constraint therapy. Functional magnetic resonance imaging (MRI) and clinical measures were done pretreatment and posttreatment. Developmental disregard indices were calculated. Four participants showed clinical improvement posttreatment. Functional MRI laterality indices were variable pretreatment and exclusively contralateral among participants posttreatment. The disregard index range was -12.9 to 62.6 among participants. Disregard indices were correlated with change scores after treatment on the Pediatric Motor Activity Log amount of use domain (r = .93, P = .02), Assisting Hand Assessment (r = .93, P = .02), and grip strength (r = .92, P = .03). Study results suggest that a shift to or persistence of contralateral cortical activity for affected hand movement is important for constraint therapy mechanism of action; and developmental disregard may be a predictor of positive response to treatment.

School outcomes of late preterm infants: special needs and challenges for infants born at 32 to 36 weeks gestation.

OBJECTIVE: Because limited long-term outcome data exist for infants born at 32 to 36 weeks gestation, we compared school outcomes between 32- to 33-week moderate preterm (MP), 34-36 week late preterm (LP) and full-term (FT) infants. STUDY DESIGN: A total of 970 preterm infants and 13 671 FT control subjects were identified from the Early Childhood Longitudinal Study-Kindergarten Cohort. Test scores, teacher evaluations, and special education enrollment from kindergarten (K) to grade 5 were compared. RESULTS: LP infants had lower reading scores than FT infants in K to first grade (P < .05). Adjusted risk for poor reading and math scores remained elevated in first grade (P < .05). Teacher evaluations of math skills from K to first grade and reading skills from K to fifth grade were worse for LP infants (P < .05). Adjusted odds for below average skills remained higher for math in K and for reading at all grades (P < .05). Special education participation was higher for LP infants at early grades (odds ratio, 1.4-2.1). MP infants had lower test and teacher evaluation scores than FT infants and twice the risk for special education at all grade levels. CONCLUSIONS: Persistent teacher concerns through grade 5 and greater special education needs among MP and LP infants suggest a need to start follow-up, anticipatory guidance, and interventions for infants born at 32 to 36 weeks gestation.

Cortical reorganization after modified constraint-induced movement therapy in pediatric hemiplegic cerebral palsy.

Constraint-induced movement therapy improves motor function in the affected hand of children with hemiplegic cerebral palsy and results in cortical changes in adults with stroke. This study measured clinical improvement and cortical reorganization in a child with hemiplegia who underwent modified constraint-induced movement therapy for 3 weeks. Clinical, functional magnetic resonance imaging and magnetoencephalography measurements were done at baseline, after therapy, and 6 months after therapy. Modified constraint-induced movement therapy resulted in clinical improvement as measured by the Pediatric Motor Activity Log. Functional magnetic resonance imaging showed bilateral sensorimotor activation before and after therapy and a shift in the laterality index from ipsilateral to contralateral hemisphere after therapy. Magnetoencephalography showed increased cortical activation in the ipsilateral motor field and contralateral movement evoked field after therapy. Cortical reorganization was maintained at the 6-month follow-up. This is the first study to demonstrate cortical reorganization after any version of constraint-induced movement therapy in a child with hemiplegia.

Iron depletion is associated with daytime bottle-feeding in the second and third years of life.

OBJECTIVE: To measure the association between daytime bottle-feeding and iron depletion in young children. DESIGN: Cross-sectional design with concurrent measurement of exposure and outcome. The exposure was the current container (bottle or cup) used for daytime milk consumption. Child, maternal, and dietary variables were collected. SETTING: Community-based pediatric practice serving a diverse population in an urban Canadian city. PARTICIPANTS: One hundred fifty healthy children, aged 12 to 38 months, attending a well-child care visit. MAIN OUTCOME MEASURE: Iron depletion (serum ferritin level, <10 microg/L]). RESULTS: Of the 150 children, 82 (55%) were bottle-fed and 68 (45%) were cup fed. Iron depletion occurred in 29 (37%) of 78 bottle-fed and in 12 (18%) of 67 cup-fed children. The crude relative risk for iron depletion was 1.81 (95% confidence interval, 1.09-3.01). In the final logistic regression model, a significant association between bottle use and iron depletion was identified, beginning after the age of 16 months. At 18 months, the relative risk, adjusted for several child, maternal, and dietary variables, for the association between bottle use and iron depletion was 1.31 (95% confidence interval,1.24-1.47); at 24 months, the adjusted relative risk was 2.50 (95% confidence interval, 2.46-2.53). Milk consumption of more than 16 oz/d occurred in 55 (67%) of the 82 bottle-fed and in 22 (32%) of the 68 cup-fed children (P<.001). CONCLUSIONS: In the second and third years of life, there is an almost 2-fold association between iron depletion and daytime bottle-feeding compared with cup feeding. The child's age may be a modifier, and milk volume consumed may be a mediator, of this association. Duration of bottle use is a potentially modifiable practice.