Niek E. van der Aa

Does Diffusion Tensor Imaging-Based Tractography at 3 Months of Age Contribute to the Prediction of Motor Outcome After Perinatal Arterial Ischemic Stroke?

Background and Purpose— After perinatal arterial ischemic stroke, diffusion-weighted imaging (DWI) and early evaluation of spontaneous motor behavior can be used to predict the development of unilateral motor deficits. The aim of this study was to investigate whether diffusion tensor imaging-based tractography at 3 months of age contributes to this prediction. Methods— Twenty-two infants with unilateral perinatal arterial ischemic stroke were included and scanned during the neonatal period. DWI was used to assess restricted diffusion in the cerebral peduncle. At the age of 3 months, diffusion tensor imaging-based tractography of the corticospinal tracts was performed along with assessment of the movement repertoire. The role of DWI, diffusion tensor imaging, and motor assessment in predicting unilateral motor deficits were compared by calculating the positive and negative predictive values for each assessment. Results— Eleven infants (50%) showed abnormal motor behavior at 3 months with subsequent development of unilateral motor deficits in 8 as determined at follow-up (9–48 months, positive predictive value 73%). Diffusion tensor imaging-based tractography correctly predicted the development of unilateral motor deficits in all 8 infants (positive predictive value 100%). A diagnostic neonatal DWI was available in 20 of 22 (91%) infants. Seven infants showed an abnormal DWI, resulting in unilateral motor deficits in 6 infants (positive predictive value 86%). All assessments had a negative predictive value of 100%. Conclusions— Diffusion tensor imaging-based tractography at 3 months can be used to predict neurodevelopmental outcome after perinatal arterial ischemic stroke. It has a similar predictive value as DWI in the neonatal period and can especially be of additional value in case of an indecisive neonatal DWI or unexpected abnormal early motor development.

Feasibility and Safety of Erythropoietin for Neuroprotection after Perinatal Arterial Ischemic Stroke

OBJECTIVE To perform a feasibility and safety study with recombinant human erythropoietin (rhEPO) in neonates with perinatal arterial ischemic stroke. STUDY DESIGN Neonates with a magnetic resonance imaging-confirmed perinatal arterial ischemic stroke (n = 21) were treated with 1000 IU/kg rhEPO immediately after diagnosis and at 24 and 48 hours after the first dose. Repeat magnetic resonance imaging was performed when the patients were 3 months of age. Coagulation and hematologic variables (red blood cells, white blood cells, platelet counts) were performed in the first week after initiation of treatment. We also compared 10 patients who were treated with rhEPO with 10 historic infants with perinatal arterial ischemic stroke matched for the involved arterial branch to investigate whether rhEPO reduces the residual size of the infarction and subsequent brain growth between first and second scan. RESULTS Seizures were a first symptom in 20 of 21 neonates. Heart rate, blood pressure, and coagulation function were in the normal range, as were red blood cells, white blood cells, and platelet counts. In a subgroup of 10 rhEPO-treated neonates, no differences were detected in residual infarction volumes or neurodevelopmental outcome compared with their historical nontreated counterparts. CONCLUSIONS rhEPO in neonates with perinatal arterial ischemic stroke had no adverse effects on red blood cells, white blood cells, platelets counts, or coagulation. rhEPO, 3000 IU/kg in total, given during a 3-day period, appears to be a safe therapy. The beneficial effects remains to be demonstrated in a larger, randomized, double-blind, placebo-controlled trial.

Microstructural brain development between 30 and 40 weeks corrected age in a longitudinal cohort of extremely preterm infants

Diffusion tensor imaging (DTI) is frequently used to assess brain development in preterm infants. This study investigates maturational changes in diffusivity measures in 122 regions of the brain between 30 and 40 weeks postmenstrual age (PMA) using the neonatal atlas of Oishi and colleagues (Oishi et al., 2011). Forty infants without cerebral injury and with normal neurodevelopmental outcome were selected from a cohort of preterm infants (gestational age<28 weeks), scanned longitudinally at 30 and 40 weeks PMA. Fractional anisotropy (FA) changed significantly in 84 brain regions, with the largest increase in the central brain regions; by contrast, the cortical brain regions showed a decrease in FA. Mean, radial and axial diffusivity all showed a clear decrease in the majority of brain regions. This study provides longitudinal reference diffusivity values in a cohort of extremely preterm infants, showing a central to peripheral and posterior to anterior directed gradient, in line with our current understanding of brain maturation, and adding to this knowledge. This study further elucidates brain maturation in preterm infants during the last 10 weeks prior to term equivalent age. The presented values can be used as a reference for assessing brain development in other cohorts, when investigating the effects of brain injury in this vulnerable period, and to evaluate the effect of future neuroprotective strategies.

Neonatal posterior cerebral artery stroke: clinical presentation, MRI findings, and outcome

To report the clinical presentation, magnetic resonance imaging (MRI) findings, and follow‐up data of newborn infants with perinatal arterial ischemic stroke in the territory of the posterior cerebral artery (PCA).

Neonatal neuroimaging predicts recruitment of contralesional corticospinal tracts following perinatal brain injury.

Unilateral perinatal brain injury may result in recruitment of ipsilateral projections originating in the unaffected hemisphere and development of unilateral spastic cerebral palsy (USCP). The aim of this study was to assess the predictive value of neonatal neuroimaging following perinatal brain injury for recruitment of ipsilateral corticospinal tracts.

Cognitive outcome in childhood after unilateral perinatal brain injury

The aim of the study was to assess cognitive outcome in children with periventricular haemorrhagic infarction (PVHI) or perinatal arterial ischaemic stroke (PAIS) and relate these findings to early developmental outcome and neonatal magnetic resonance imaging findings.

Neonatal DTI early after birth predicts motor outcome in preterm infants with periventricular hemorrhagic infarction

Background:To determine the association between early neonatal diffusion tensor imaging (DTI) and the development of unilateral spastic cerebral palsy (USCP) in preterm infants with periventricular hemorrhagic infarction (PVHI).Methods:Preterm infants with PVHI were assessed with early (≤4 wk after birth) and term-equivalent age MRI-DTI. Involvement of corticospinal tracts was assessed by visual assessment of the posterior limb of the internal capsule (PLIC) on DTI (classified asymmetrical, equivocal, or symmetrical) and by an atlas-based approach calculating fractional anisotropy asymmetry index in the PLIC. Motor outcome was assessed at ≥15 mo corrected age.Results:Seven out of 23 infants with PVHI developed USCP. Their PLIC was visually scored as asymmetrical in 6 and equivocal in 1 on the early DTI. Thirteen out of 16 infants with a symmetrical motor development had a symmetrical PLIC on early DTI, the remaining 3 were equivocal. All infants with USCP had a fractional anisotropy asymmetry index of >0.05 (optimal cut-off value) on early DTI. In infants with a symmetrical motor development (n = 16), 14 had an asymmetry index ≤0.05 while 2 had an index >0.05.Conclusion:DTI in preterm infants with PVHI within a few weeks after birth is associated with later motor development.

Quantification of white matter injury following neonatal stroke with serial DTI

Background:Diffusion tensor imaging (DTI) can be used to predict outcome following perinatal arterial ischemic stroke (PAIS), although little is known about white matter changes over time.Methods:Infants with PAIS were serially scanned in the neonatal period (n = 15), at 3 mo (n = 16), and at 24 mo (n = 8). Fractional anisotropy (FA) values in five regions of interest (anterior and posterior limb of the internal capsule, corpus callosum, optic radiation, and posterior thalamic radiation) were obtained and compared with FA values of healthy controls and neurodevelopmental outcome.Results:In the neonatal period, no differences in FA values were found. At 3 mo, the six infants who ultimately developed motor deficits showed lower FA values in all affected regions. Four infants developed a visual field defect and showed lower FA values in the affected optic radiation at 3 mo (0.22 vs. 0.29; P = 0.03). Finally, a correlation between FA values of the corpus callosum at 3 mo and the Griffiths developmental quotients was found (r = 0.66; P = 0.03). At 24 mo, a similar pattern was observed.Conclusion:Neonatal FA measurements may underestimate the extent of injury following PAIS. FA measurements at 3 mo could be considered a more reliable predictor of neurodevelopmental outcome and correlate with DTI findings at 24 mo.

The Course of Apparent Diffusion Coefficient Values following Perinatal Arterial Ischemic Stroke

Background Diffusion weighted MR imaging (DWI) plays an important role in the diagnosis of perinatal arterial ischemic stroke (PAIS) during the acute phase. Its derived apparent diffusion coefficient (ADC) can be used to quantify the diffusion restriction. Aim of the current study was to identify the changes in ADC values in the acute phase following PAIS. Methods A cohort of 36 infants with a confirmed PAIS who were examined once during the first ten days of life was studied. ADC values in the core of the ischemic tissue (iADC) were determined and correlated with postnatal age. ADC ratios (rADC) were calculated by dividing the iADC value by the ADC value of the corresponding area in the contralateral ‘healthy’ hemisphere. Results Infants were scanned between days two and ten. A non-linear increase in iADC and rADC values was observed over time and large middle cerebral artery strokes resulted in lower iADC and rADC values. Normalisation of rADC values was observed after day seven. rADC values were lower when compared to previously published rADC values of infants with hypoxic ischemic encephalopathy, suggesting more severe injury. Conclusions Following PAIS, DWI showed decreased ADC values with a non-linear increase during the first week, and pseudonormalization after day 7, which limits the use of DWI to assess PAIS to the first week. Compared to previous studies, ADC values were lower when compared to infants with hypoxic ischemic encephalopathy, most likely due to more severe injury.

Changes in carotid blood flow after unilateral perinatal arterial ischemic stroke

Introduction:Little is known about changes in carotid blood flow after perinatal arterial ischemic stroke (PAIS). The aim of this study was to assess the blood flow in the internal carotid arteries (ICAs) after unilateral PAIS.Methods:The carotid flow (ml/min) was measured noninvasively by means of two-dimensional phase-contrast magnetic resonance angiography (2D PC-MRA) in 25 full-term infants who had unilateral PAIS within 10 d after birth. In 17 infants a second 2D PC-MRA was carried out at the age of 3 mo. Asymmetry of carotid blood flow was calculated at both time points, and the circle of Willis (CoW) was assessed with a three-dimensional (3D) time-of-flight MRA.Results:On the early magnetic resonance imaging (MRI), a significant increase in ipsilateral blood flow was observed (7.7%, 95% confidence interval (CI) 3.0–14.9%), which persisted after correcting for CoW configuration. At 3 mo, this asymmetry was no longer observed. No relationship was found between the asymmetry in blood flow and either stroke size or postnatal age at scan.Discussion:A higher blood flow in the ipsilateral ICA was observed during the acute phase after unilateral PAIS, and this disappeared after 3 mo. Further research into the role of hyperperfusion after PAIS may suggest new approaches to neuroprotection.