Asymmetry in sleep spindles and motor outcome in infants with unilateral brain injury.

AIM: To determine whether interhemispheric difference in sleep spindles in infants with perinatal unilateral brain injury could link to a pathological network reorganization that underpins the development of unilateral cerebral palsy (CP). METHOD: This was a multicentre retrospective study of 40 infants (19 females, 21 males) with unilateral brain injury. Sleep spindles were detected and quantified with an automated algorithm from electroencephalograph records performed at 2 months to 5 months of age. The clinical outcomes after 18 months were compared to spindle power asymmetry (SPA) between hemispheres in different brain regions. RESULTS: We found a significantly increased SPA in infants who later developed unilateral CP (n=13, with the most robust interhemispheric difference seen in the central spindles. The best individual-level prediction of unilateral CP was seen in the centro-occipital spindles with an overall accuracy of 93%. An empiric cut-off level for SPA at 0.65 gave a positive predictive value of 100% and a negative predictive value of 93% for later development of unilateral CP. INTERPRETATION: Our data suggest that automated analysis of interhemispheric SPA provides a potential biomarker of unilateral CP at a very early age. This holds promise for guiding the early diagnostic process in infants with a perinatally identified brain injury. WHAT THIS PAPER ADDS: Unilateral perinatal brain injury may affect the development of electroencephalogram (EEG) sleep spindles. Interhemispheric asymmetry in sleep spindles can be quantified with automated EEG analysis. Spindle power asymmetry can be a potential biomarker of unilateral cerebral palsy.

Feasibility of Early Intervention Through Home-Based and Parent-Delivered Infant Massage in Infants at High Risk for Cerebral Palsy.

Infant massage (IM) can be considered an early intervention program that leads to the environmental enrichment framework. The effectiveness of IM to promote neurodevelopment in preterm infants has been proved, but studies on infants with early brain damage are still lacking. The main aim of this study was to assess the feasibility, acceptability and usability of IM, carried out by parents at home, on infants at high risk for Cerebral Palsy. An IM daily diary and an ad hoc questionnaire, called Infant Massage Questionnaire Parent-Infant Experiences (IMQPE), were developed. IMQPE consisted of a total of 30 questions, divided into 5 areas. The parents were trained to carry out the IM with a home-based course, conducted by an expert therapist. The intensive IM program was set according to a defined daily length of at least 20 min, with a frequency of at least 5 days per week for a total of 8 weeks. Data collection consisted in the selection of the variables around the characteristics, both of the infants and the mothers, IM dosage and frequency, different body parts of the infants involved and IMQPE scores. Variable selection was carried out by minimizing the Bayesian Information Criteria (BIC) over all possible variable subsets. Nineteen high-risk infants, aged 4.83 ± 1.22 months, received IM at home for 8 weeks. The massage was given by the infants' mothers with a mean daily session dose of 27.79 ± 7.88 min and a total of 21.04 ± 8.49 h. 89.74% and 100% of mothers performed the IM for the minimum daily dosage and the frequency recommended, respectively. All the families filled in the IMQPE, with a Total mean score of 79.59% and of 82.22% in General Information on IM, 76.30% in Infant's intervention-related changes, 76.85% in IM Suitability, 79.07% in Infant's acceptance and 83.52% in Time required for the training. Different best predictors in mothers and in infants have been found. These data provide evidence of the feasibility of performing IM at home on infants at high risk for CP. Study registration: www.clinicaltrial.com (NCT03211533 and NCT03234959).

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.