Detecting Asymmetry of Upper Limb Activity with Accelerometry in Infants at Risk for Unilateral Spastic Cerebral Palsy.

AIMS: To examine whether accelerometry can quantitate asymmetry of upper limb activity in infants aged 3-12 months at risk for developing unilateral spastic cerebral palsy (USCP). METHOD: A prospective study was performed in 50 infants with unilateral perinatal brain injury at high risk of developing USCP. Triaxial accelerometers were worn on the ipsilateral and contralesional upper limb during the Hand Assessment for Infants (HAI). Infants were grouped in three age intervals (3-5 months, 5-7.5 months and 7.5 until 12 months). Each age interval group was divided in a group with and without asymmetrical hand function based on HAI cutoff values suggestive of USCP. RESULTS: In a total of 82 assessments, the asymmetry index for mean upper limb activity was higher in infants with asymmetrical hand function compared to infants with symmetrical hand function in all three age groups (ranging from 41 to 51% versus - 2-6%, p < 0.01), while the total activity of both upper limbs did not differ. CONCLUSIONS: Upper limb accelerometry can identify asymmetrical hand function in the upper limbs in infants with unilateral perinatal brain injury from 3 months onwards and is complementary to the Hand Assessment for Infants.

Brain segmentation in patients with perinatal arterial ischemic stroke.

BACKGROUND: Perinatal arterial ischemic stroke (PAIS) is associated with adverse neurological outcomes. Quantification of ischemic lesions and consequent brain development in newborn infants relies on labor-intensive manual assessment of brain tissues and ischemic lesions. Hence, we propose an automatic method utilizing convolutional neural networks (CNNs) to segment brain tissues and ischemic lesions in MRI scans of infants suffering from PAIS. MATERIALS AND METHODS: This single-center retrospective study included 115 patients with PAIS that underwent MRI after the stroke onset (baseline) and after three months (follow-up). Nine baseline and 12 follow-up MRI scans were manually annotated to provide reference segmentations (white matter, gray matter, basal ganglia and thalami, brainstem, ventricles, extra-ventricular cerebrospinal fluid, and cerebellum, and additionally on the baseline scans the ischemic lesions). Two CNNs were trained to perform automatic segmentation on the baseline and follow-up MRIs, respectively. Automatic segmentations were quantitatively evaluated using the Dice coefficient (DC) and the mean surface distance (MSD). Volumetric agreement between segmentations that were manually and automatically obtained was computed. Moreover, the scan quality and automatic segmentations were qualitatively evaluated in a larger set of MRIs without manual annotation by two experts. In addition, the scan quality was qualitatively evaluated in these scans to establish its impact on the automatic segmentation performance. RESULTS: Automatic brain tissue segmentation led to a DC and MSD between 0.78-0.92 and 0.18-1.08 mm for baseline, and between 0.88-0.95 and 0.10-0.58 mm for follow-up scans, respectively. For the ischemic lesions at baseline the DC and MSD were between 0.72-0.86 and 1.23-2.18 mm, respectively. Volumetric measurements indicated limited oversegmentation of the extra-ventricular cerebrospinal fluid in both the follow-up and baseline scans, oversegmentation of the ischemic lesions in the left hemisphere, and undersegmentation of the ischemic lesions in the right hemisphere. In scans without imaging artifacts, brain tissue segmentation was graded as excellent in more than 85% and 91% of cases, respectively for the baseline and follow-up scans. For the ischemic lesions at baseline, this was in 61% of cases. CONCLUSIONS: Automatic segmentation of brain tissue and ischemic lesions in MRI scans of patients with PAIS is feasible. The method may allow evaluation of the brain development and efficacy of treatment in large datasets.

Early predictors of neurodevelopment after perinatal arterial ischemic stroke: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Perinatal arterial ischemic stroke (PAIS) often has lifelong neurodevelopmental consequences. We aimed to review early predictors (<4 months of age) of long-term outcome. METHODS: We carried out a systematic literature search (PubMed and Embase), and included articles describing term-born infants with PAIS that underwent a diagnostic procedure within four months of age, and had any reported outcome parameter ≥12 months of age. Two independent reviewers included studies and performed risk of bias analysis. RESULTS: We included 41 articles reporting on 1395 infants, whereof 1255 (90%) infants underwent follow-up at a median of 4 years. A meta-analysis was performed for the development of cerebral palsy (n = 23 studies); the best predictor was the qualitative or quantitative assessment of the corticospinal tracts on MRI, followed by standardized motor assessments. For long-term cognitive functioning, bedside techniques including (a)EEG and NIRS might be valuable. Injury to the optic radiation on DTI correctly predicted visual field defects. No predictors could be identified for behavior, language, and post-neonatal epilepsy. CONCLUSION: Corticospinal tract assessment on MRI and standardized motor assessments are best to predict cerebral palsy after PAIS. Future research should be focused on improving outcome prediction for non-motor outcomes. IMPACT: We present a systematic review of early predictors for various long-term outcome categories after perinatal arterial ischemic stroke (PAIS), including a meta-analysis for the outcome unilateral spastic cerebral palsy. Corticospinal tract assessment on MRI and standardized motor assessments are best to predict cerebral palsy after PAIS, while bedside techniques such as (a)EEG and NIRS might improve cognitive outcome prediction. Future research should be focused on improving outcome prediction for non-motor outcomes.

Feasibility and safety of intranasally administered mesenchymal stromal cells after perinatal arterial ischaemic stroke in the Netherlands (PASSIoN): a first-in-human, open-label intervention study.

BACKGROUND: Perinatal arterial ischaemic stroke (PAIS) is an important cause of neurodevelopmental disabilities. In this first-in-human study, we aimed to assess the feasibility and safety of intranasally delivered bone marrow-derived allogeneic mesenchymal stromal cells (MSCs) to treat PAIS in neonates. METHODS: In this open-label intervention study in collaboration with all neonatal intensive care units in the Netherlands, we included neonates born at full term (≥36 weeks of gestation) with MRI-confirmed PAIS in the middle cerebral artery region. All eligible patients were transferred to the neonatal intensive care unit of the Wilhelmina Children's Hospital. Neonates received one dose of 45-50 × 106 bone-marrow derived MSCs intranasally within 7 days of presenting signs of PAIS. The primary endpoints were acute and subacute safety outcomes, including vital signs, blood markers, and the occurrence of toxicity, adverse events, and serious adverse events. The occurrence of unexpected cerebral abnormalities by a repeat MRI at 3 months of age was a secondary endpoint. As part of standard clinical follow-up at Wilhelmina Children's Hospital, we assessed corticospinal tract development on MRI and performed motor assessments at 4 months of age. This study is registered with ClinicalTrials.gov, NCT03356821. FINDINGS: Between Feb 11, 2020, and April 29, 2021, ten neonates were enrolled in the study. Intranasal administration of MSCs was well tolerated in all ten neonates. No serious adverse events were observed. One adverse event was seen: a mild transient fever of 38°C without the need for clinical intervention. Blood inflammation markers (C-reactive protein, procalcitonin, and leukocyte count) were not significantly different pre-administration versus post-administration and, although thrombocyte levels increased (p=0·011), all were within the physiological range. Follow-up MRI scans did not show unexpected structural cerebral abnormalities. All ten patients had initial pre-Wallerian changes in the corticospinal tracts, but only four (40%) patients showed asymmetrical corticospinal tracts at follow-up MRI. Abnormal early motor assessment was found in three (30%) infants. INTERPRETATION: This first-in-human study demonstrates that intranasal bone marrow-derived MSC administration in neonates after PAIS is feasible and no serious adverse events were observed in patients followed up until 3 months of age. Future large-scale placebo-controlled studies are needed to determine the therapeutic effect of intranasal MSCs for PAIS. FUNDING: Netherlands Organization for Health Research and Development (ZonMw).

Association of early skin breaks and neonatal thalamic maturation: A modifiable risk?

OBJECTIVE: To test the hypothesis that a strategy of prolonged arterial line (AL) and central venous line (CVL) use is associated with reduced neonatal invasive procedures and improved growth of the thalamus in extremely preterm neonates (<28 weeks' gestation). METHODS: Two international cohorts of very preterm neonates (n = 143) with prolonged (≥14 days) or restricted (<14 days) use of AL/CVL were scanned serially with MRI. General linear models were used to determine the association between skin breaks and thalamic volumes, accounting for clinical confounders and site differences. Children were assessed at preschool age on standardized tests of motor and cognitive function. Outcome scores were assessed in relation to neonatal thalamic growth. RESULTS: Prolonged AL/CVL use in neonates (n = 86) was associated with fewer skin breaks (median 34) during the hospital stay compared to restricted AL/CVL use (n = 57, median 91, 95% confidence interval [CI] 60.35-84.89). Neonates with prolonged AL/CVL use with fewer skin breaks had significantly larger thalamic volumes early in life compared to neonates with restricted line use (B = 121.8, p = 0.001, 95% CI 48.48-195.11). Neonatal thalamic growth predicted preschool-age cognitive (B = 0.001, 95% CI 0.0003-0.001, p = 0.002) and motor scores (B = 0.01, 95% CI 0.001-0.10, p = 0.02). Prolonged AL/CVL use was not associated with greater incidence of sepsis or multiple infections. CONCLUSIONS: Prolonged AL/CVL use in preterm neonates may provide an unprecedented opportunity to reduce invasive procedures in preterm neonates. Pain reduction in very preterm neonates is associated with optimal thalamic growth and neurodevelopment.

Early prediction of unilateral cerebral palsy in infants at risk: MRI versus the hand assessment for infants.

BACKGROUND: Neonates with unilateral perinatal brain injury (UPBI) are at risk for developing unilateral spastic cerebral palsy (USCP). This study compares several predictors for USCP later in life. METHODS: Twenty-one preterm and 24 term born infants with UPBI were included, with an MRI scan including diffusion tensor imaging (DTI) performed at term equivalent age or around 3 months after birth, respectively. T2-weighted images and DTI-based tractography were used to measure the surface area, diameter, and fractional anisotropy (FA) of both corticospinal tracts (CSTs). The hand assessment for infants (HAI) was performed before 5, between 5 and 8 and between 8 and 12 months of (corrected) age. Asymmetry indices were derived from all techniques and related to USCP at ≥2 years of age. RESULTS: MRI measures and HAI scores were significantly lower for the affected compared to the unaffected side. Before 5 months of age, FA asymmetry on DTI yielded the highest area under the curve compared to conventional MRI and HAI. CONCLUSIONS: Prediction of USCP after UPBI is reliable using asymmetry of the CST on MRI, as well as clinical hand assessment. Before 5 months of age, DTI tractography provides strongest predictive information, while HAI specifically aids to prognosis of USCP at later age points.

Brain Activity and Cerebral Oxygenation After Perinatal Arterial Ischemic Stroke Are Associated With Neurodevelopment.

Background and Purpose- In infants with perinatal arterial ischemic stroke (PAIS), early prognosis of neurodevelopmental outcome is important to adequately inform parents and caretakers. Early continuous neuromonitoring after PAIS may improve early prognosis. Our aim was to study early cerebral electrical activity and oxygenation measured by amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in term neonates with PAIS and relate these to the development of cerebral palsy and cognitive deficit. Methods- aEEG patterns and regional cerebral oxygen saturation (rScO2) levels of both hemispheres were studied for 120 hours from the first clinical symptoms of PAIS (ie, seizures) onward. Multivariable analyses were used to investigate the association between aEEG, near-infrared spectroscopy, clinical variables, and neurodevelopmental outcome. Results- In 52 patients with PAIS (gestational age, 40.4±1.4 weeks; birth weight, 3282±479 g), median time to a continuous background pattern was longer in the ipsilesional compared with the contralesional hemisphere (13.5 versus 10.0 hours; P<0.05). rScO2 decreased over time in both hemispheres but less in the ipsilesional one, resulting in a rScO2 asymmetry ratio of 4.5% (interquartile range, -4.3% to 5.9%; P<0.05) between hemispheres from day 3 after symptoms onward. Both time to normal background pattern and asymmetry in rScO2 were negatively affected by gestational age, size of the PAIS, use of antiepileptic drugs, and mechanical ventilation. After correction for size of the PAIS on magnetic resonance imaging, a slower recovery of background pattern on ipsilesional aEEG and increased rScO2 asymmetry between hemispheres was related with an increased risk for cognitive deficit (<-1 SD) at a median of 24.0 (interquartile range, 18.4-24.4) months of age. Conclusions- Recovery of background pattern on aEEG and cerebral oxygenation are both affected by PAIS and related to neurocognitive development. Both measurements may provide valuable early prognostic information. Additionally, monitoring cerebral activity and oxygenation may be useful in identifying infants eligible for early neuroprotective interventions and to detect early effects of these interventions.

Early prediction of unilateral cerebral palsy in infants with asymmetric perinatal brain injury - Model development and internal validation.

BACKGROUND: Early diagnosis of unilateral cerebral palsy is important after asymmetric perinatal brain injury (APBI). Our objective is to estimate the risk of unilateral cerebral palsy (UCP) in infants with APBI during the first months of life using neuroimaging and clinical assessment. PATIENTS AND METHODS: Prognostic multivariable prediction modeling study including 52 infants (27 males), median gestational age 39.3 weeks with APBI from Sweden (n = 33) and the Netherlands (n = 19). INCLUSION CRITERIA: (1) neonatal MRI within one month after term equivalent age (TEA), (2) Hand Assessment for Infants (HAI) between 3.5 and 4.5 months of (corrected) age. UCP was diagnosed ≥24 months of age. Firth regression with cross-validation was used to construct and internally validate the model to estimate the risk for UCP based on the predictors corticospinal tract (CST) and basal ganglia/thalamus (BGT) involvement, contralesional HAI Each hand sum score (EaHS), gestational age and sex. RESULTS: UCP was diagnosed in 18 infants (35%). Infants who developed UCP more often had involvement of the CST and BGT on neonatal MRI and had lower contralesional HAI EaHS compared to those who did not develop UCP. The final model showed excellent accuracy for UCP prediction between 3.5 and 4.5 months (area under the curve, AUC = 0.980; 95% CI 0.95-1.00). CONCLUSIONS: Combining neonatal MRI, the HAI, gestational age and sex accurately identify the prognostic risk of UCP at 3.5-4.5 months in infants with APBI.

Cerebral Blood Flow Measured by Phase-Contrast Magnetic Resonance Angiography in Preterm and Term Neonates.

BACKGROUND: Preterm infants show a decreased tortuosity in all proximal segments of the cerebral vasculature at term-equivalent age (TEA). Recently MRI techniques were developed to measure cerebral blood flow (CBF) based on phase-contrast images. OBJECTIVES: We hypothesized that arterial CBF corrected for brain size differs between full-term and preterm infants at TEA. METHODS: 344 infants without major brain abnormalities had a cranial MRI for clinical reasons including phase-contrast magnetic resonance angiography (PC-MRA) around TEA (mean 41.1 ± SD 1.2 weeks). This cohort consisted of 172 preterm infants (gestational age at birth 24.1-31.9 weeks) and 172 term-born infants (gestational age at birth 37.0-42.6 weeks). The total CBF in milliliters/minute was calculated by adding the blood flow of the carotid and basilar arteries, and compared to age at scan, body weight, and several parameters of estimated brain size. RESULTS: After logarithmic transformation, total CBF was associated with body weight, estimated brain weight, head circumference, and 2D brain surface measurements at TEA. Total CBF was significantly (9-12%) higher in term compared to preterm infants after correction for 2D brain surface measurements, head circumference or postmenstrual age at MRI (p < 0.05). CONCLUSIONS: Total CBF as measured by PC-MRA was associated with body and (estimated) brain weight and 2D brain surface measurements and was higher in term compared to preterm born infants.

Neurodevelopment After Perinatal Arterial Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Perinatal arterial ischemic stroke (PAIS) leads to cerebral palsy in ∼30% of affected children and has other neurologic sequelae. Authors of most outcome studies focus on middle cerebral artery (MCA) stroke without differentiating between site and extent of affected tissue. Our aim with this study was to report outcomes after different PAIS subtypes. METHODS: Between 1990 and 2015, 188 term infants from 2 centers (London [n = 79] and Utrecht [n = 109]) had PAIS on their neonatal MRI. Scans were reevaluated to classify stroke territory and determine specific tissue involvement. At 18 to 93 (median 41.7) months, adverse neurodevelopmental outcomes were recorded as 1 or more of cerebral palsy, cognitive deficit, language delay, epilepsy, behavioral problems, or visual field defect. RESULTS: The MCA territory was most often involved (90%), with posterior or anterior cerebral artery territory strokes occurring in 9% and 1%, respectively. Three infants died, and 24 had scans unavailable for reevaluation or were lost to follow-up. Of 161 infants seen, 54% had an adverse outcome. Outcomes were the same between centers. Main branch MCA stroke resulted in 100% adverse outcome, whereas other stroke subtypes had adverse outcomes in only 29% to 57%. The most important outcome predictors were involvement of the corticospinal tracts and basal ganglia. CONCLUSIONS: Although neurodevelopmental outcome was adverse in at least 1 domain with main branch MCA stroke, in other PAIS subtypes outcome was favorable in 43% to 71% of children. Site and tissue involvement is most important in determining the outcome in PAIS.

MRI Changes in the Thalamus and Basal Ganglia of Full-Term Neonates with Perinatal Asphyxia.

BACKGROUND: Magnetic resonance imaging (MRI) is the standard neuroimaging technique to assess perinatal asphyxia-associated brain injury in full-term infants. Diffusion-weighted imaging (DWI) is most informative when assessed during the first week after the insult. OBJECTIVES: To study the DWI abnormalities of the thalamus and basal ganglia in full-term infants with perinatal asphyxia. METHODS: Fifty-five (near) term infants (normothermia n = 23; hypothermia n = 32) with thalamus and/or basal ganglia injury were included. MRI findings were assessed visually and quantitatively calculating apparent diffusion coefficient (ADC) values. Thalamus/basal ganglia ADC ratios were calculated to analyze the differences between these areas. Infants with an early MRI (days 1-3) or later MRI (days 4-7) were compared. RESULTS: Isolated extensive thalamic injury was seen early, and focal thalamic and basal ganglia injury was seen later. On the early MRI, visual assessment underestimated abnormalities in the basal ganglia (59% abnormal vs. 90% abnormal on quantitative assessment; p = 0.015), suggesting the need for quantitative assessment. In infants treated with hypothermia, the thalamus/basal ganglia ADC ratio was lower. CONCLUSIONS: Both visual analysis and quantitative evaluation of cerebral MRI after perinatal asphyxia are needed, especially during the first few days after birth. Timing of ADC changes is influenced by therapeutic hypothermia.

Association of Histologic Chorioamnionitis With Perinatal Brain Injury and Early Childhood Neurodevelopmental Outcomes Among Preterm Neonates.

Importance: Understanding the role of chorioamnionitis, a major factor leading to preterm birth, in the pathogenesis of neonatal brain injury and adverse neurodevelopmental outcomes may help in identifying potentially modifiable perinatal variables affecting brain health and outcomes among children born preterm. Objective: To evaluate whether histologic chorioamnionitis among neonates born very preterm is associated with intraventricular hemorrhage (IVH) and punctate white matter injury (WMI) or with adverse neurodevelopmental outcomes during early childhood. Design, Setting, and Participants: Prospective cohort study conducted across 3 academic centers (from April 2006 to September 2013 in Canada, from March 2007 to March 2013 in the Netherlands, and from January 2004 to August 2011 in the United States). Children who were born preterm (24-32 weeks' gestation) and who had undergone a placental pathologic evaluation, magnetic resonance imaging as soon as clinically stable, and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessments between 18 and 24 months' corrected age (CA) were included. Magnetic resonance imaging scans were assessed for grade of IVH and volume of punctate WMI. Data analysis occurred between December 2016 and January 2018. Final multivariable analyses examining the association of chorioamnionitis with motor and cognitive outcomes accounted for academic center and perinatal and postnatal factors. Main Outcomes and Measures: Punctate WMI volume and IVH detected on neonatal magnetic resonance imaging scans; motor and cognitive outcomes defined using Bayley-III assessments conducted among these children between 18 and 24 months' CA. Results: Of 350 neonates (182 male) in the final cohort, 145 (41.4%) had histologic chorioamnionitis. Gestational age was significantly lower among those with chorioamnionitis (median, 26.4 weeks; interquartile range [IQR], 25.6-27.7 weeks) than among those without chorioamnionitis (median, 28.0 weeks; IQR, 27.0-29.7 weeks). Chorioamnionitis was not associated with IVH or WMI, nor was it associated with worse motor outcomes in univariable or multivariable analyses (adjusted Bayley-III motor score, -2.2; 95% CI, -5.6 to 1.3). Cognitive scores were marginally yet statistically significantly lower among children with chorioamnionitis (median, 105; IQR, 95-110) than among those without chorioamnionitis (median, 105; IQR, 100-115) in the univariable model. This difference was attenuated in the multivariable model (adjusted Bayley-III cognitive score, -3.0; 95% CI, -6.4 to 0.4). Conclusions and Relevance: Histologic chorioamnionitis was not associated with IVH or WMI near birth or with worse cognitive or motor outcomes from 18 to 24 months' CA after accounting for perinatal factors. Postnatal factors attenuated the association between chorioamnionitis and neurodevelopmental outcomes, highlighting the importance of preventing postnatal illness, such as infection, to promote optimal outcomes among children born preterm.

Promoting neuroregeneration after perinatal arterial ischemic stroke: neurotrophic factors and mesenchymal stem cells.

Newborns suffering from perinatal arterial ischemic stroke (PAIS) are at risk of neurodevelopmental problems. Current treatment options for PAIS are limited and mainly focus on supportive care, as presentation of PAIS is beyond the time window of current treatment strategies. Therefore, recent focus has shifted to interventions that stimulate regeneration of damaged brain tissue. From animal models, it is known that the brain increases its neurogenic capability after ischemic injury, by promoting neural cell proliferation and differentiation. However, neurogenesis is not maintained at the long term, which consequently impedes full repair leading to adverse consequences later in life. Boosting neuroregeneration of the newborn brain using treatment with neurotrophic factors and/or mesenchymal stem cells (MSCs) may be promising novel therapeutic strategies to improve neurological prospects and quality of life of infants with PAIS. This review focuses on effectiveness of neurotrophic growth factors, including erythropoietin, brain-derived neurotrophic factor, vascular endothelial growth factor, glial-derived neurotrophic factor, and MSC therapy, in both experimental neonatal stroke studies and first clinical trials for neonatal ischemic brain injury.

Origin and dynamics of oligodendrocytes in the developing brain: Implications for perinatal white matter injury.

Infants born prematurely are at high risk to develop white matter injury (WMI), due to exposure to hypoxic and/or inflammatory insults. Such perinatal insults negatively impact the maturation of oligodendrocytes (OLs), thereby causing deficits in myelination. To elucidate the precise pathophysiology underlying perinatal WMI, it is essential to fully understand the cellular mechanisms contributing to healthy/normal white matter development. OLs are responsible for myelination of axons. During brain development, OLs are generally derived from neuroepithelial zones, where neural stem cells committed to the OL lineage differentiate into OL precursor cells (OPCs). OPCs, in turn, develop into premyelinating OLs and finally mature into myelinating OLs. Recent studies revealed that OPCs develop in multiple waves and form potentially heterogeneous populations. Furthermore, it has been shown that myelination is a dynamic and plastic process with an excess of OPCs being generated and then abolished if not integrated into neural circuits. Myelination patterns between rodents and humans show high spatial and temporal similarity. Therefore, experimental studies on OL biology may provide novel insights into the pathophysiology of WMI in the preterm infant and offers new perspectives on potential treatments for these patients.

Repair of neonatal brain injury: bringing stem cell-based therapy into clinical practice.

Hypoxic-ischaemic brain injury is one of most important causes of neonatal mortality and long-term neurological morbidity in infants born at term. At present, only hypothermia in infants with perinatal hypoxic-ischaemic encephalopathy has shown benefit as a neuroprotective strategy. Otherwise, current treatment options for neonatal brain injury mainly focus on controlling (associated) symptoms. Regeneration of the injured neonatal brain with stem cell-based therapies is emerging and experimental results are promising. At present, increasing efforts are made to bring stem cell-based therapies to the clinic. Among all progenitor cell types, mesenchymal stromal (stem) cells seem to be most promising for human use given their neuroregenerative properties and favourable safety profile. This review summarizes the actual state, potential hurdles and possibilities of stem cell-based therapy for neonatal brain injury in the clinical setting. An early version of this paper was presented at the Groningen Early Intervention Meeting which was held in April 2016.

MR imaging for accurate prediction of outcome after perinatal arterial ischemic stroke: Sooner not necessarily better.

BACKGROUND: Involvement of the corticospinal tracts after perinatal arterial ischemic stroke (PAIS) is strongly correlated with adverse motor outcome. METHODS: Two full-term infants with PAIS, with two early MRI scans available, are reported. RESULTS: Diffusion weighted imaging (DWI)-MRI, performed within 24 h following onset of seizures and repeated 48 h later, clearly showed restricted diffusion within the middle cerebral artery territory on both MRIs, but clear patterns of signal intensity changes in the descending corticospinal tracts on the second MRI only. CONCLUSION: Since involvement of the corticospinal tracts is essential for prediction of motor outcome, we may need to reconsider optimal timing of MR imaging for prediction of neurodevelopmental outcome after PAIS.

Clinical Risk Factors for Punctate White Matter Lesions on Early Magnetic Resonance Imaging in Preterm Newborns.

OBJECTIVE: To identify clinical risk factors for punctate white matter lesions (PWML) on early magnetic resonance imaging (MRI) in 2 cohorts of newborns born extremely preterm in different neonatal centers. STUDY DESIGN: A total of 250 newborns born preterm at less than 28 weeks of gestation (mean 26.4 ± 1.1 weeks) with an early MRI were identified from 2 neonatal centers, in Vancouver, Canada (cohort A, n = 100) and Utrecht, the Netherlands (cohort B, n = 150). Cohort A was imaged as part of a prospective research study and cohort B was imaged as part of routine clinical care. PWML were defined as cluster type foci of hyperintensity on T1-weighted imaging and were identified at a mean postmenstrual age of 31.1 (±1.9) weeks. Multivariable analysis was used to identify clinical factors predictive of PWML. RESULTS: Cluster type PWML were found in 47 newborns born extremely preterm (18.8%) and were more common in cohort A (32%) than in cohort B (10%). Newborns in cohort A generally were sicker than those in cohort B. Multivariable analyses revealed that greater birth weight (B = 0.002; P < .02), grade II-III intraventricular hemorrhage (B = 0.83; P < .02), and cohort A (B = 1.34; P < .0001) were independent predictors of PWML. CONCLUSION: Several risk factors for PWML on early MRI were identified. The interaction among birth weight, intraventricular hemorrhage, and other aspects of postnatal illness as risk factors for PWML warrants further investigation in newborns born extremely preterm and may help to identify modifiable risk factors for PWML.