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Neurodevelopment After Perinatal Arterial Ischemic Stroke

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Neurodevelopment After Perinatal Arterial Ischemic Stroke Nienke Wagenaar, MD, a Miriam Martinez-Biarge, MD, b Niek E. van der Aa, MD, PhD, a Ingrid C. van Haastert, MA, PhD, a NeurodevelopmentFloris Groenendaal, MD, PhD, a Manon J.N.L. Benders, MD, PhD, After a Frances M. Cowan, Perinatal MD, PhD,b Linda S. de Vries, MD, PhDa Arterial Ischemic Stroke BACKGROUND AND OBJECTIVES: abstract ∼ 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 METHODS: n PAIS subtypes. n Between 1990 and 2015, 188 term infants from 2 centers (London [ = 79] and Utrecht [ = 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, RESULTS: cognitive deficit, language delay, epilepsy, behavioral problems, or visual field defect. 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 CONCLUSIONS: the corticospinal tracts and basal ganglia. 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. WHAT’S KNOWN ON THIS SUBJECT: Perinatal arterial ischemic stroke often leads to adverse aDepartment of Neonatology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; and bDepartment of Paediatrics, Imperial College London, London, United Kingdom neurodevelopmental outcomes. Authors of most outcome studies do not differentiate between site Dr Wagenaar is the main author and drafted the manuscript, contributed to data acquisition and and extent of affected tissue in their association interpretation, and was responsible for communication with all coauthors; Drs Martinez-Biarge with neurodevelopmental outcome. and van Haastert contributed to data acquisition and interpretation and revised the manuscript for intellectual content; Drs van der Aa, Groenendaal, and Benders contributed to the analysis and WHAT THIS STUDY ADDS: With this study, we interpretation of the data and read the manuscript critically for intellectual content; Drs Cowan describe neurodevelopmental outcomes in different and de Vries contributed to the study design, coordination and supervision of data collection and perinatal arterial ischemic stroke subtypes in a analysis, and drafting and critically reviewing the manuscript; and all authors have seen and large and international cohort. Several MRI-based approved the final manuscript as submitted and take full responsibility for the manuscript. risk factors are provided that contribute to the DOI: https:// doi. org/ 10. 1542/ peds. 2017- 4164 prediction of neurodevelopmental outcomes in Accepted for publication May 30, 2018 individual patients with perinatal stroke. Address correspondence to Linda S. de Vries, MD, PhD, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, KE 04.123.1, PO Box 85090, 3508 AB Utrecht, Netherlands. E-mail: l.s.devries@umcutrecht.nl PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2018 by the American Academy of Pediatrics To cite: Wagenaar N, Martinez-Biarge M, van der Aa NE, et al. Neurodevelopment After Perinatal Arterial Ischemic Stroke. Pediatrics. 2018;142(3):e20174164 Downloaded from www.aappublications.org/news by guest on September 30, 2021 PEDIATRICS Volume 142, number 3, September 2018:e20174164 ARTICLE Perinatal arterial ischemic stroke different subtypes of PAIS in term Best, Netherlands, or Picker (PAIS) is an important cause of infants, taking into account its lesion System, Cleveland, OH) by using long-lasting1, 2 neurodevelopmental site and involvement of well-defined a scanning protocol including at problems. With increased use of important brain structures. least T1-weighted, T2-weighted, neuroimaging techniques, especially METHODS and diffusion-weighted imaging MRI, the incidence from hospital- (DWI). In general, infants were ∼ based studies is now considered to sedated to minimize movement be 1 in 2300 to 5000 live-born term3, 4 The neonates in this study comprised artifacts. Because we included infants neonates with a low mortality rate. 2 cohorts of term newborn infants over a long time period, the MRI protocol was not always the same; Adverse consequences of PAIS who were admitted to the NICU or ’ imaging details have been reported include cerebral palsy (CP), usually referred for neurologic assessment to 6,9, 16 Queen Charlotte s or Hammersmith Evaluationpreviously .of MRI Data of a hemiparetic type, cognitive n ’ dysfunction, epilepsy, and language, Hospital in London, United Kingdom visual, and behavioral problems, ( = 79) or the Wilhelmina Children s Hospital of the University Medical which are reported1 to occur in 50% n Neonatologists experienced in to 75% of infants. Several groups Center in Utrecht (UMCU), the neonatal brain MRI (F.C. and L.dV.) have described MRI parameters that Netherlands ( = 117) between reevaluated each (of both centers) October 1990 and January 2015. help in predicting5, 6 adverse outcome MRI scan. The lesions were assessed after PAIS. More specifically, the All infants had acute symptoms in 3 planes, if possible. On the basis development of CP mainly depends in the first week after birth, most of shape, extent, and localization of on involvement of the corticospinal often (hemi) convulsions, but in a the area of signal intensity changes, few infants their symptoms were tracts (CSTs) at the level of the – all infants were classified to 1 of the less neurologically specific. All had posterior limb of the internal 2,capsule 7 11 stroke subtypes shown in Fig 1 on (PLIC) or cerebral peduncles. PAIS confirmed on their neonatal the basis of their most predominant Visual field defects occur most often MRI. Eight infants were excludedn stroke pattern. when PAIS clearly involves the optic because of congenital syndromes 12, 13 Classification was mostly based on radiation. withn known adverse outcome ( = 4) vascular territory of specific named nor other significant brain lesions PAIS most often occurs in the arteries that resulted in characteristic ( = 4), resulting in a ntotal cohort of 15 territory of the middle cerebral = 187 infants. Infants who died in infarctions as described by Govaert. artery (MCA), and most studies on However, we felt that consistency of the neonatal periodn ( = 3), whose outcome are focused on main branch involvement of particular anatomic 1, 14 neonatal MRI nscan could not be MCA stroke. Because occlusion reevaluated ( = 4), or who were lost structures was more important, of the proximal segment (M1) of the to follow-up ( = 20) were excluded and the involvement of specific MCA will lead to infarction of the from further analyses (Supplemental anatomic hallmarks was also used for entire MCA region, including the Table 7). This resulted in a total study classification. A hemispheric lesion in basal ganglia and CST, development cohort of 161 term neonates. the MCA territory located posterior of unilateral CP can be reliably to the central sulcus was attributed predicted. However, often only Informed verbal parental consent to the posterior branch of the MCA, more distal MCA segments or the was obtained to perform an whereas involvement anterior to the anterior cerebral artery (ACA) or MRI for clinical purposes. The central sulcus was attributed to the posterior cerebral artery (PCA) Institutional Review Board of the anterior branch. When the full central are involved resulting in relatively UMCU approved the use of MRI data sulcus was involved, but not regions for anonymous data analysis and characteristic lesion patterns15 that more anterior or posterior, this was can be recognized on MRI. Authors waived the requirement to obtain attributed to the middle branch MCA. of most studies on outcome in PAIS written informed consent. In London, If the anterior or posterior areas and do not differentiate between these neonatal MRI scans were performed middle branch MCA were involved, lesion patterns involving various after obtaining written informed the most predominant branch sites and extent of affected tissue. consent and permission to use these was chosen, and central sulcus We hypothesized that outcome scansMRI and clinical data for research. involvement was noted separately. of PAIS primarily depends on Involvement of the central sulcus the brain area that is affected by region was best assessed in the the stroke. Therefore, our aim In both centers, MRI was performed parasagittal plane. Where >1 MCA with this study was to report on on a 1.0, 1.5, or 3T whole-body branch artery was involved this was neurodevelopmental outcomes of system (Philips Medical Systems, also noted separately as multiple Downloaded from www.aappublications.org/news
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