OBJECTIVE: The prognosis of adrenoleukodystrophy (ALD)with neurological involvement is generally dismal; however, allogeneic stem cell transplantation (SCT) is recognized as effective to stabilize or improve the clinical symptoms of ALD. Herein, we report the clinical outcomes of patients with ALD who consecutively underwent allogeneic stem cell transplantation with reduced intensity conditioning at our institution.
METHODS: Sixteen patients with ALD, who were symptomatic (n = 14) or presymptomatic (n = 2), received SCT from 2010 to 2016. The stem cell source was cord blood (n = 14), or bone marrow from a human leukocyte antigen identical sibling (n = 2). The conditioning regimen prior to transplantation was reduced intensity and consisted of fludarabine (125 mg/m2), melphalan (140 mg/m2) and low dose total body irradiation (TBI) of 4Gy (n = 15) or 3Gy (n = 1).
RESULTS: Primary engraftment was obtained in 11 patients, and 4 of the 5 patients who lost the primary graft received a second cord blood transplantation and were engrafted. Five years overall and event-free survival were 90.9% and 61.1% respectively, with a median of 45 months (range 16-91). Loes score stabilized or improved by 18 months after transplantation except for patients with internal capsule involvement.
CONCLUSIONS: Allogeneic SCT with reduced intensity conditioning for patients with ALD was safely performed without major transplant-related complications even in symptomatic patients and neurological symptoms were stabilized after SCT in patients without internal capsule involvement.

UNASSIGNED: Repetitive subconcussive head impacts (RSHI) may lead to structural, functional, and metabolic alterations of the brain. While differences between males and females have already been suggested following a concussion, whether there are sex differences following exposure to RSHI remains unknown. The aim of this study was to identify and to characterize sex differences following exposure to RSHI.
UNASSIGNED: Twenty-five collegiate ice hockey players (14 males and 11 females, 20.6 ± 2.0 years), all part of the Hockey Concussion Education Project (HCEP), underwent diffusion-weighted magnetic resonance imaging (dMRI) before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011-2012 and did not experience a concussion during the season. Whole-brain tract-based spatial statistics (TBSS) were used to compare pre- and postseason imaging in both sexes for fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Pre- and postseason neurocognitive performance were assessed by the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT).
UNASSIGNED: Significant differences between the sexes were primarily located within the superior longitudinal fasciculus (SLF), the internal capsule (IC), and the corona radiata (CR) of the right hemisphere (RH). In significant voxel clusters (p < 0.05), decreases in FA (absolute difference pre- vs. postseason: 0.0268) and increases in MD (0.0002), AD (0.00008), and RD (0.00005) were observed in females whereas males showed no significant changes. There was no significant correlation between the change in diffusion scalar measures over the course of the season and neurocognitive performance as evidenced from postseason ImPACT scores.
UNASSIGNED: The results of this study suggest sex differences in structural alterations following exposure to RSHI. Future studies need to investigate further the underlying mechanisms and association with exposure and clinical outcomes.

OBJECTIVE: The nature of cerebral edema in acute-on-chronic liver failure (ACLF) is not well studied. We aimed to characterize cerebral edema in ACLF using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI).
METHODS: Forty-six patients with cirrhosis and acute decompensation were included. Patients were divided into groups A (no cerebral failure, n = 39) and B (cerebral failure, n = 7). Group A was subdivided into no-ACLF (n = 11), grade 1 (n = 10), grade 2 (n = 9) and grade 3 (n = 9) ACLF as per CANONIC study. MRI brain and plasma TNF-alpha, IL-1beta and IL-6 were measured at baseline and 7-10 days after admission. Ten age- and sex-matched healthy controls were also included.
RESULTS: Mean diffusivity (MD) values, an MRI marker of water content, progressively increased from controls to no-ACLF to ACLF grade 1, 2 and 3 in group A in frontal white matter (FWM) and basal ganglia (P < 0.0001). MD values improved only in survivors on follow-up. MD values correlated with IL-6 levels at baseline. On multivariate analysis MELD score ≥28 and MD values (>8 × 10-9 M2/s) in FWM were independent predictors of 90-day mortality. There was no significant difference in clinical and MRI parameters between group A and B.
CONCLUSIONS: Cerebral edema increases with severity of ACLF. Correlation between MD values and IL-6 levels suggests pathogenic role of inflammation in cerebral edema. Patients with grade 3 ACLF have cerebral edema irrespective of presence of clinically evident cerebral failure. MELD score and cerebral edema have prognostic significance in ACLF.

Multi-modal magnetic resonance imaging (MRI) that included high resolution structural imaging, diffusion tensor imaging (DTI), magnetization transfer ratio (MTR) imaging, and magnetic resonance spectroscopic imaging (MRSI) were performed in mild traumatic brain injury (mTBI) patients with negative computed tomographic scans and in an orthopedic-injured (OI) group without concomitant injury to the brain. The OI group served as a comparison group for mTBI. MRI scans were performed both in the acute phase of injury (~24 h) and at follow-up (~90 days). DTI data was analyzed using tract based spatial statistics (TBSS). Global and regional atrophies were calculated using tensor-based morphometry (TBM). MTR values were calculated using the standard method. MRSI was analyzed using LC Model. At the initial scan, the mean diffusivity (MD) was significantly higher in the mTBI cohort relative to the comparison group in several white matter (WM) regions that included internal capsule, external capsule, superior corona radiata, anterior corona radiata, posterior corona radiata, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major and forceps minor of the corpus callosum, superior longitudinal fasciculus, and corticospinal tract in the right hemisphere. TBSS analysis failed to detect significant differences in any DTI measures between the initial and follow-up scans either in the mTBI or OI group. No significant differences were found in MRSI, MTR or morphometry between the mTBI and OI cohorts either at the initial or follow-up scans with or without family wise error (FWE) correction. Our study suggests that a number of WM tracts are affected in mTBI in the acute phase of injury and that these changes disappear by 90 days. This study also suggests that none of the MRI-modalities used in this study, with the exception of DTI, is sensitive in detecting changes in the acute phase of mTBI.

Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 weeks), who were admitted to the Lucile Packard Children\'s Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p= .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p= .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = -.322, p = .009; r= -.381, p= .002), lower mean albumin (r = -.276, p= .029; r= -.385, p= .002), and lower mean bilirubin (r = -.293, p= .020; r= -.337 p= .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.