Jonathan Murnick

Third Trimester Brain Growth in Preterm Infants Compared With In Utero Healthy Fetuses

BACKGROUND AND OBJECTIVES: Compared with term infants, preterm infants have impaired brain development at term-equivalent age, even in the absence of structural brain injury. However, details regarding the onset and progression of impaired preterm brain development over the third trimester are unknown. Our primary objective was to compare third-trimester brain volumes and brain growth trajectories in ex utero preterm infants without structural brain injury and in healthy in utero fetuses. As a secondary objective, we examined risk factors associated with brain volumes in preterm infants over the third-trimester postconception. METHODS: Preterm infants born before 32 weeks of gestational age (GA) and weighing <1500 g with no evidence of structural brain injury on conventional MRI and healthy pregnant women were prospectively recruited. Anatomic T2-weighted brain images of preterm infants and healthy fetuses were parcellated into the following regions: cerebrum, cerebellum, brainstem, and intracranial cavity. RESULTS: We studied 205 participants (75 preterm infants and 130 healthy control fetuses) between 27 and 39 weeks’ GA. Third-trimester brain volumes were reduced and brain growth trajectories were slower in the ex utero preterm group compared with the in utero healthy fetuses in the cerebrum, cerebellum, brainstem, and intracranial cavity. Clinical risk factors associated with reduced brain volumes included dexamethasone treatment, the presence of extra-axial blood on brain MRI, confirmed sepsis, and duration of oxygen support. CONCLUSIONS: These preterm infants exhibited impaired third-trimester global and regional brain growth in the absence of cerebral/cerebellar parenchymal injury detected by using conventional MRI.

Cerebellar Microstructural Organization is Altered by Complications of Premature Birth: A Case-Control Study

Objectives To compare regional cerebellar microstructure, as measured by diffusion tensor imaging (DTI), between preterm infants at term‐equivalent age and healthy term‐born control neonates, and to explore associations between DTI findings and clinical risk factors. Study design In this case‐control study, DTI studies were performed in 73 premature infants born ≤32 weeks and ≤1500 g birth weight and 73 full‐term‐born controls from healthy pregnancies. Using a region of interest approach, fractional anisotropy (FA) and mean diffusivity (MD) were extracted in 7 cerebellar regions including the anterior vermis, the right/left superior cerebellar peduncles, the middle cerebellar peduncle, and the dentate nuclei. To validate further our DTI measurements, we measured FA and MD in the genu of the corpus callosum and splenium. FA and MD were compared between groups using analyses of multiple linear regression models. Results Preterm infants at term‐equivalent age presented with higher FA in the dentate nuclei (<.001) and middle cerebellar peduncle (.028), and lower MD in the vermis (.023) compared with controls. Conversely, preterm infants showed reduced FA and increased MD in both the genu of the corpus callosum and splenium (P < .001). Independent risk factors associated with altered FA and MD in the cerebellum included low Apgar score, supratentorial injury, compromised cardiorespiratory function, and surgery for necrotizing enterocolitis and patent ductus arteriosus. Conclusions This DTI study provides evidence that complications of premature birth are associated with altered cerebellar microstructural organization when compared with term‐born control infants.

Intraoperative MRI–guided resection of focal cortical dysplasia in pediatric patients: technique and outcomes

OBJECTIVE Previous meta-analysis has demonstrated that the most important factor in seizure freedom following surgery for focal cortical dysplasia (FCD) is completeness of resection. However, intraoperative detection of epileptogenic dysplastic cortical tissue remains a challenge, potentially leading to a partial resection and the need for reoperation. The objective of this study was to determine the role of intraoperative MRI (iMRI) in the intraoperative detection and localization of FCD as well as its impact on surgical decision making, completeness of resection, and seizure control outcomes. METHODS The authors retrospectively reviewed the medical records of pediatric patients who underwent iMRI-assisted resection of FCD at the Childrens National Health System between January 2014 and April 2015. Data reviewed included demographics, length of surgery, details of iMRI acquisition, postoperative seizure freedom, and complications. Postsurgical seizure outcome was assessed utilizing the Engel Epilepsy Surgery Outcome Scale. RESULTS Twelve consecutive pediatric patients (8 females and 4 males) underwent iMRI-guided resection of FCD lesions. The mean age at the time of surgery was 8.8 years ± 1.6 years (range 0.7 to 18.8 years), and the mean duration of follow up was 3.5 months ± 1.0 month. The mean age at seizure onset was 2.8 years ± 1.0 year (range birth to 9.0 years). Two patients had Type 1 FCD, 5 patients had Type 2A FCD, 2 patients had Type 2B FCD, and 3 patients had FCD of undetermined classification. iMRI findings impacted intraoperative surgical decision making in 5 (42%) of the 12 patients, who then underwent further exploration of the resection cavity. At the time of the last postoperative follow-up, 11 (92%) of the 12 patients were seizure free (Engel Class I). No patients underwent reoperation following iMRI-guided surgery. CONCLUSIONS iMRI-guided resection of FCD in pediatric patients precluded the need for repeat surgery. Furthermore, it resulted in the achievement of complete resection in all the patients, leading to a high rate of postoperative seizure freedom.

The role of intraoperative MRI in resective epilepsy surgery for peri-eloquent cortex cortical dysplasias and heterotopias in pediatric patients.

OBJECTIVE Previous studies have demonstrated that an important factor in seizure freedom following surgery for lesional epilepsy in the peri-eloquent cortex is completeness of resection. However, aggressive resection of epileptic tissue localized to this region must be balanced with the competing objective of retaining postoperative neurological functioning. The objective of this study was to investigate the role of intraoperative MRI (iMRI) as a complement to existing epilepsy protocol techniques and to compare rates of seizure freedom and neurological deficit in pediatric patients undergoing resection of perieloquent lesions. METHODS The authors retrospectively reviewed the medical records of pediatric patients who underwent resection of focal cortical dysplasia (FCD) or heterotopia localized to eloquent cortex regions at the Childrens National Health System between March 2005 and August 2015. Patients were grouped into two categories depending on whether they underwent conventional resection (n = 18) or iMRI-assisted resection (n = 11). Patient records were reviewed for factors including demographics, length of hospitalization, postoperative seizure freedom, postoperative neurological deficit, and need for reoperation. Postsurgical seizure outcome was assessed at the last postoperative follow-up evaluation using the Engel Epilepsy Surgery Outcome Scale. RESULTS At the time of the last postoperative follow-up examination, 9 (82%) of the 11 patients in the iMRI resection group were seizure free (Engel Class I), compared with 7 (39%) of the 18 patients in the control resection group (p = 0.05). Ten (91%) of the 11 patients in the iMRI cohort achieved gross-total resection (GTR), compared with 8 (44%) of 18 patients in the conventional resection cohort (p = 0.02). One patient in the iMRI-assisted resection group underwent successful reoperation at a later date for residual dysplasia, compared with 7 patients in the conventional resection cohort (with 2/7 achieving complete resection). Four (36%) of the patients in the iMRI cohort developed postoperative neurological deficits, compared with 15 patients (83%) in the conventional resection cohort (p = 0.02). CONCLUSIONS These results suggest that in comparison with a conventional surgical protocol and technique for resection of epileptic lesions in peri-eloquent cortex, the incorporation of iMRI led to elevated rates of GTR and postoperative seizure freedom. Furthermore, this study suggests that iMRI-assisted surgeries are associated with a reduction in neurological deficits due to intraoperative damage of eloquent cortex.

Altered Cerebral Perfusion in Infants Born Preterm Compared with Infants Born Full Term.

Objectives To compare regional cerebral cortical blood flow (CBF) in infants born very preterm at term‐equivalent age (TEA) and healthy newborns born full term and to examine the impact of clinical risk factors on CBF in the cohort born preterm. Study design This prospective, cross‐sectional study included infants born very preterm (gestational age at birth <32 weeks; birth weight <1500 g) and healthy infants born full term. Using noninvasive 3T arterial spin labeling magnetic resonance imaging, we quantified regional CBF in the cerebral cortex: sensorimotor/auditory/visual cortex, superior medial/dorsolateral prefrontal cortex, anterior cingulate cortex (ACC)/posterior cingulate cortex, insula, and lateral posterior parietal cortex, as well as in the brainstem, and deep gray matter. Analyses were performed controlling for sex, gestational age, and age at magnetic resonance imaging. Results We studied 202 infants: 98 born preterm and 104 born full term at TEA. Infants born preterm demonstrated greater global CBF (&bgr; = 9.03; P < .0001) and greater absolute regional CBF in all brain regions except the insula. Relative CBF in the insula, ACC and auditory cortex were decreased significantly in infants born preterm compared with their peers born at full term (P < .0001; P = .026; P = .036, respectively). In addition, the presence of parenchymal brain injury correlated with lower global and regional CBF (insula, ACC, sensorimotor, auditory, and visual cortices) whereas the need for cardiac vasopressor support correlated with lower regional CBF in the insula and visual cortex. Conclusions Altered regional cortical CBF in infants born very preterm at TEA may reflect early brain dysmaturation despite the absence of cerebral cortical injury. Furthermore, specific cerebral cortical areas may be vulnerable to early hemodynamic instability and parenchymal brain injury.

Clinical impact of term-equivalent magnetic resonance imaging in extremely low-birth-weight infants at a regional NICU

Objective:To evaluate the clinical impact of routine term-equivalent magnetic resonance imaging (TE-MRI) for extremely low-birth-weight infants at a regional neonatal intensive care unit.Study Design:This is a single-center retrospective study evaluating preterm survivors who underwent TE-MRI. MRI abnormalities were compared between infants with and without cranial ultrasonography (CUS) abnormalities. Cost analysis comparing imaging modalities was also performed.Results:TE-MRI use increased from 17% in 2006 to 76% in 2010. MRI detected new findings in nearly half of infants, whether or not they had known ultrasound abnormalities. MRI detected more cerebellar (18% vs 6%, P=0.04) and moderate white matter injury (12% vs 7%, P<0.001), and altered simulated neurological prognosis across developmental domains. The cost of TE-MRI was

Regional Brain Biometrics at Term-Equivalent Age and Developmental Outcome in Extremely Low-Birth-Weight Infants

1600, which was comparable to serial CUSs.Conclusion:TE-MRI detects new abnormalities and impacts developmental prognosis in the extremely low birth weight, which supports its use despite the added financial cost.

Altered Cerebellar Biochemical Profiles in Infants Born Prematurely

OBJECTIVE This study aims to evaluate individual regional brain biometrics and their association with developmental outcome in extremely low-birth-weight (ELBW) infants. STUDY DESIGN This is a retrospective study evaluating term-equivalent magnetic resonance imaging (TE-MRI) from 27 ELBW infants with known developmental outcomes beyond 12 months corrected age. Regional biometric measurements were performed by a pediatric neuroradiologist blinded to outcome data. Measures included biparietal width, transcerebellar diameter (TCD), deep gray matter area (DGMA), ventricular dilatation, corpus callosum, and interhemispheric distance. The relationship between regional biometrics and Bayley-II developmental scores were evaluated with linear regression models. RESULTS The study cohort had an average±standard deviation birth weight of 684±150 g, gestational age of 24.6±2 weeks and 48% males. DGMA was significantly associated with both cognitive and motor outcomes. Significant associations were also observed between TCD and corpus callosum splenium with cognitive and motor outcomes, respectively. Other biometric measures were not associated with outcome (p>0.05). DGMA<10.26 cm2 was highly specific for poor motor and cognitive outcome. CONCLUSION TE-MRI biometrics reflecting impaired deep gray matter, callosal, and cerebellar size is associated with worse early childhood cognitive and motor outcomes. DGMA may be the most robust single biometric measure to predict adverse developmental outcome in preterm survivors.

Author Correction: Altered Cerebellar Biochemical Profiles in Infants Born Prematurely

This study aims to compare the cerebellar biochemical profiles in preterm (PT) infants evaluated at term equivalent age (TEA) and healthy full-term newborns using proton magnetic resonance spectroscopy (1H-MRS). We explore the associations between altered cerebellar metabolite profiles and brain injury topography, severity of injury, and prematurity-related clinical complications. We prospectively collected high quality 1H-MRS in 59 premature infants born ≤32 weeks and 61 healthy full term controls. 1H-MRS data were processed using LCModel software to calculate absolute metabolite concentration for N-acetyl-aspartate (NAA), choline (Cho) and creatine (Cr). PT infants had significantly lower cerebellar NAA (p < 0.025) and higher Cho (p < 0.001) at TEA when compared to healthy controls. Creatine was not different between the two groups. The presence of cerebellar injury was consistently associated with reduced concentrations for NAA, Cho, and Cr. Postnatal infection was negatively associated with NAA and Cr (p < 005), while cerebral cortical brain injury severity was inversely associated with both Cho and Cr (p < 0.01). We report for the first time that premature birth is associated with altered cerebellar metabolite profiles when compared to term born controls. Infection, cerebellar injury and supratentorial injury are important risk factors for impaired preterm cerebellar biochemistry.

Regional microstructural organization of the cerebral cortex is affected by preterm birth

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