To our knowledge, we provide first proof of concept that natalizumab diminishes migratory capacity of immune cells. Our prospective study further shows that effects of therapy likely (1) differ for distinct immune cell subsets, (2) are not sustained over current dose interval, (3) have unique profiles in individual patients, and (4) include modulation of activation threshold of immune cells. Monitoring these parameters could be relevant to ongoing safety and efficacy considerations.

Objective To determine the association of antenatal magnesium sulfate with cerebellar hemorrhage in a prospective cohort of premature newborns evaluated by magnetic resonance imaging (MRI). Study design Cross-sectional analysis of baseline characteristics from a prospective cohort of preterm newborns (<33 weeks gestation) evaluated with 3T-magnetic resonance imaging (MRI) shortly after birth. Exclusion criteria were clinical evidence of a congenital syndrome, congenital infection, or clinical status too unstable for transport to MRI. Antenatal magnesium sulfate exposure was abstracted from the medical records and the indication was classified as obstetric or neuroprotection. Two pediatric neuroradiologists, blinded to the clinical history, scored axial T2-weighted and iron-susceptibility MRI sequences for cerebellar hemorrhage. The association of antenatal magnesium sulfate with cerebellar hemorrhage was evaluated using multivariable logistic regression, adjusting for postmenstrual age at MRI and known predictors of cerebellar hemorrhage. Results Cerebellar hemorrhage was present in 27/73 (37%) newborns imaged at a mean postmenstrual age of 32.4 ± 2 weeks. Antenatal magnesium sulfate exposure was associated with a significantly reduced risk of cerebellar hemorrhage. Adjusting for postmenstrual age at MRI, and predictors of cerebellar hemorrhage, antenatal magnesium sulfate was independently associated in our cohort with decreased cerebellar hemorrhage (OR 0.18, 95% CI 0.049–0.65, P=0.009). Conclusion Antenatal magnesium sulfate exposure is independently associated with a decreased risk of MRI-detected cerebellar hemorrhage in premature newborns, which could explain some of the reported neuroprotective effects of magnesium sulfate.

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Objectives To determine the rate of magnetic resonance imaging (MRI) detected non-cystic white matter injury (WMI) in a prospective cohort of premature newborns and to evaluate its associations with changes in clinical predictors of WMI over the study period. Study design Prospective cohort of premature newborns (<33 weeks’ gestation) studied with MRI within 4 weeks of birth and near term-equivalent age. A pediatric neuroradiologist scored the severity of WMI on T1-weighted MRI according to published criteria. WMI was classified as none/mild or moderate/severe. We excluded subjects with severe cystic WMI, periventricular hemorrhagic infarction, or motion artifact on MRI. Changes in clinical characteristics and predictors of WMI over the study period (1998–2011) were evaluated. Predictors of moderate/severe WMI, including birth year, were evaluated using multivariate logistic regression. Results Among 267 newborns, 45 (17%) had moderate/severe WMI. The rate of moderate/severe WMI decreased over the study period (P=0.002, chi-squared test of trends). On multivariate logistic regression, the odds of moderate/severe WMI decreased 11% for each birth year of the cohort (odds ratio 0.89, 95% confidence interval 0.81–0.98, P=0.04). Prolonged exposure to indomethacin was also independently associated with reduced odds of moderate/severe WMI. Conclusions The decreasing burden of MRI-detected moderate/severe non-cystic WMI in our cohort of premature newborns is independent over time of changes in the known clinical predictors of WMI. Prolonged exposure to indomethacin is associated with reduced WMI.