Background: Pandemics may promote hospital avoidance among patients with emergencies, and added precautions may exacerbate treatment delays. Methods: We used linked administrative data and data from the Quality Improvement and Clinical Research Alberta Stroke Program – a registry capturing stroke-related data on the entire Albertan population(4.3 million) – to identify all patients hospitalized with stroke in the pre-pandemic(01/01/2016-27/02/2020) and COVID-19 pandemic(28/02/2020-30/08/2020) periods. We examined changes in stroke presentation rates and use of thrombolysis and endovascular therapy(EVT), adjusted for age, sex, comorbidities, and pre-admission care needs; and in workflow, stroke severity(National Institutes of Health Stroke Scale/NIHSS), and in-hospital outcomes. Results: We analyzed 19,531 patients with ischemic stroke pre-pandemic versus 2,255 during the pandemic. Hospitalizations/presentations dropped(weekly adjusted-incidence-rate-ratio[aIRR]:0.48,95%CI:0.46-0.50), as did population-level incidence of thrombolysis(aIRR:0.49,0.44-0.56) or EVT(aIRR:0.59,0.49-0.69). However, proportions of presenting patients receiving thrombolysis/EVT did not decline (thrombolysis:11.7% pre-pandemic vs 13.1% during-pandemic, aOR:1.02,0.75-1.38). For out-of-hospital strokes, onset-to-door times were prolonged(adjusted-coefficient:37.0-minutes, 95%CI:16.5-57.5), and EVT recipients experienced greater door-to-reperfusion delays(adjusted-coefficient:18.7-minutes,1.45-36.0). NIHSS scores and in-hospital mortality did not differ. Conclusions: The first COVID-19 wave was associated with a halving of presentations and acute therapy utilization for ischemic stroke at a population level, and greater pre-/in-hospital treatment delays. Our data can inform public health messaging and stroke care in future pandemic waves.

Background: Amyotrophic lateral sclerosis (ALS) is highly heterogeneous with survival rate ranging from months to decades. Approximately 10-20% of patients develop a rapidly progressive disease and may die within the first year. Therefore, there is an increasing need for an early detection of unique molecular signatures associated with more aggressive forms of disease as it may help identify therapeutic targets. Methods: To identify a unique molecular signature in fast progressing patients, we recruited 45 sporadic ALS (sALS) patients and 35 age-matched healthy controls and measured 62 immune markers in plasma using cytokines array. Results: We found that leptin was significantly downregulated in plasma of sALS patients and more importantly in fast progressing disease. Immune markers CCL16 and sTNF-RII were significantly increased in rapidly progressing disease. We also found that leptin was significantly downregulated in plasma of SOD1G93A mice across disease stage. This was caused by an increased in levels of phospho-AMPK in mice adipocytes and in adipocytes exposed to fast sALS patients’ plasma. Conclusions: We propose that the combination of decreased plasma leptin levels and up-regulation in CCL16/sTNF-RII may be used as a prognostic biomarker to identify fast progressing ALS patients. This unique immune/metabolic profile may cause dysfunction in metabolic homeostasis.

Background: The mechanism of aneurysmal healing after flow-diversion treatment of cerebral aneurysms remains unknown. The purpose of this research to is to utilize a novel technology called endovascular optical coherence tomography (OCT) to characterise and improve our understanding of aneurysmal healing after flow-diversion using a rabbit aneurysm model. Methods: Saccular aneurysms were created in 10 New Zealand white rabbits. The aneurysms were treated with a flow-diverting stent 28 days after creation. OCT and histopathologic examinations included: luminal thrombosis, endothelial loss, inflammation, fibrin, smooth muscle cell loss, disruption of the internal and external elastic lamina, and tunica adventitia changes Results: OCT revealed endothelialization across the stent, appearing to originate from the parent vessel, along with small amounts of thrombus on the stent-struts. Minimal thrombus was visualized within the aneurysm sac. Histologic examination revealed that OCT can accurately define endothelialization across the sent, and define patent segments across the neck. Conclusions: Aneurysmal healing appears to originate at the parent vessel/stent interface, and use the stent as a scaffold to grow across the neck of the aneurysm. Minimal thrombus was visualized within the aneurysm sac, with ongoing flow observed in the setting of incomplete neck endothelialization. This technology has great potential for assessing aneurysmal healing in real-time.

Background: Quantitative susceptibility mapping (QSM) is an MR sequence that has potential as a biomarker in concussion. We compared QSM in pediatric concussion patients versus a comparison group of children with orthopedic injuries (OI) and assessed QSM’s performance relative to the current clinical benchmark (5P risk score) for predicting persistent postconcussion symptoms (PPCS). Methods: Children (N=967) aged 8-16.99 years with either concussion or OI were prospectively recruited from 5 Canadian centers. Participants completed QSM at a post-acute assessment 2-33 days post-injury. QSM z-score metrics for 9 regions of interest (ROI) were derived from 371 children (concussion=255, OI=116). PPCS at 1-month post-injury was defined using reliable change methods. Results: The concussion and OI groups did not differ significantly in QSM across ROI. Increased frontal white matter (WM) susceptibility predicted reliable increases in parent-rated cognitive symptoms (p=0.001). Together, frontal WM susceptibility and the 5P risk score were better at predicting persistent cognitive symptoms than the 5P risk score alone (p=0.0021). AUC were 0.71(95%CI: 0.62-0.80) for frontal WM susceptibility, 0.67(95%CI: 0.56-0.78) for the 5P risk score, and 0.73(95%CI: 0.64-0.82) for both. Conclusions: This is the first study to demonstrate a potential imaging biomarker that predicts persistent symptoms in children with concussion compared to the current clinical benchmark.

Background: Sample entropy (SampEn) can quantify the unpredictability of a physiological signal. We sought to assess if SampEn on EEG could reflect recent seizure activity. Methods: Charts of all patients undergoing an outpatient EEG between January and March 2018 were reviewed to assess seizure occurrences in the follow-up period between the two clinical visits surrounding the EEG. 9s-EEG segments were extracted at pre-specified time points. SampEn was calculated for all segments and values aggregated at the 25thpercentile. We performed a multivariate zero-inflated analysis to test the association between SampEn and seizure rate around the EEG, after controlling for age, presence of IED, presence of abnormal slowing, and presence of a focal brain lesion. Results: 269 EEGs were screened and 133 met inclusion criteria (112 patients). 80 EEGs (60%) were from patients with epilepsy, of which 47 had at least one seizure within the year preceding the EEG. Remaining EEGs were from patients who were deemed not to have epilepsy at last follow-up. Each 1SD decrease in SampEn was associated with a 3.93-fold increase in the rate of daily seizures (95% CI: 1.19–12.99, p = 0.02). Conclusions: Sample entropy of EEG is a potential objective method to assess contemporary seizure occurrence.

Background: Infantile spasms (IS) is a devastating pediatric seizure disorder for which EEG referrals are prioritized at the Hospital for Sick Children, representing a resource challenge. The goal of this study was to improve the triaging system for these referrals. Methods: Part 1: descriptive analysis was performed retrospectively on EEG referrals. Part 2: prospective questionnaires were used to determine relative risk of various predictive factors. Part 3: electronic referral form was amended to include 5 positive predictive factors. A triage point system was tested by assigning EEGs as high risk (3 days), standard risk (1 week), or low risk (2 weeks). A machine learning model was developed. Results: Most EEG referrals were from community pediatricians with a low yield of IS diagnoses. Using the 5 predictive factors, the proposed triage system accurately diagnosed all IS within 3 days. No abnormal EEGs were missed in the low-risk category. The machine learning model had over 90% predictive accuracy and will be prospectively tested. Conclusions: Improving EEG triaging for IS may be possible to prioritize higher risk patients. Machine Learning techniques can potentially be applied to help with predictions. We hope that our findings will ultimately improve resource utilization and patient care.

Background: Treatment decisions for patients with autoimmune encephalitis (AE) frequently need to be made before results from autoantibody testing are available, as early treatment is associated with better outcomes. Cerebrospinal fluids (CSF) white blood cell (WBC) count and protein concentration measured early on in the disease process is often used, in combination with other clinical factors, to evaluate the likelihood that a patient has AE. Methods: CSF characteristics (WBC count, protein concentration, and oligoclonal banding) measured in a first AE presentation, prior to results of autoantibodies being available, were retrospectively analyzed at two tertiary care centers. Results: Ninety-five patients were included in the study. CSF WBC counts and protein levels were within normal limits for 27% (CI95%: 19–37) of patients with AE. When results of oligoclonal banding were added, 14% (CI95%: 6–16) of patients had “normal” CSF. The median CSF white blood cell count was 8 cells/mm3 (range: 0–544) and the median CSF protein concentration was 0.42 g/L (range: 0.15–3.92). Conclusions: A substantial proportion of patients with early active AE had a CSF WBC count or protein concentration within the normal. Inclusion of CSF oligoclonal banding may help identify a higher proportion of patients with an inflammatory CSF profile early in the disease process.

Background: Novel magnetic resonance (MR) imaging techniques prompted the emergence of T1-w/T2-w images or “myelin-sensitive maps (MMs)” to measure myelin in vivo. However, acquisition-related variations in MR intensities prevent meaningful quantitative comparisons between MMs. We propose an improved pipeline to standardize MMs that is applied to patients with classic trigeminal neuralgia (CTN) and trigeminal neuralgia secondary to multiple sclerosis (MSTN). Methods: 3T scanner was used to obtain T1-w and T2-w images for 17 CTN and 17 MSTN patients. Template images were obtained from ICBM152 database. MS plaques and normal-appearing white matter (NAWM) were labelled. A Gaussian curve-fit was applied to the histogram of the intensity distribution of each patient image, and transformed to match the Gaussian curve-fit of the template image. Results: MM intensities were decreased within MS plaques, compared to NAWM in MSTN patients (p<0.001) and its corresponding regions in CTN patients (p<0.001). Qualitatively, the standardized patient image and its histogram better resembled the ICBM152 template. Conclusions: MM analysis revealed reduced myelin content in MS plaques compared to corresponding regions in CTN patients and surrounding NAWM in MSTN patients. The standardized MM serves as a non-invasive, clinical tool for quantitative analyses of myelin content between different brain regions and different patients in vivo.

Background: Limbic encephalitis (LE) classically causes medial temporal lobe T2-hyperintensity on magnetic resonance imaging (MRI), but this can also occur with seizure activity. Identifying neuroimaging patterns that can distinguish between LE and seizure activity may help avoid diagnostic confusion in such challenging cases. Methods: Through retrospective review of Mayo Clinic patients who had medial temporal lobe T2-hyperintensity on MRI, we identified non-LE patients with seizure-related medial temporal lobe T2-hyperintensity. Their diffusion-weighted imaging (DWI) was reviewed to look for diffusion restriction patterns potentially unique to seizure activity. Next, a control cohort of LE patients with medial temporal lobe T2-hyperintensity was identified, and their DWI was reviewed to see if these diffusion restriction patterns could help distinguish seizure activity from LE. Results: We identified 10 non-LE patients who had medial temporal lobe T2-hyperintensity due to seizure activity; 9/10 had one of two medial temporal lobe diffusion restriction patterns we uncovered as being potentially unique to seizure activity. In contrast, only 5/57 LE patients had one of these diffusion restriction patterns identified, all of whom had seizures reported. Conclusions: We report two diffusion restriction patterns that may help distinguish seizure activity from LE. Recognition of these diffusion restriction patterns should prompt evaluation for possible seizure activity.

Background: Mutations in the slow skeletal muscle troponin T (TNNT1) gene cause a congenital nemaline myopathy resulting in death from respiratory insufficiency in early infancy. We report on four French Canadians with a novel congenital TNNT1 myopathy. Methods: Patients underwent lower extremity and paraspinal MRI, quadriceps biopsy and genetic testing. TNNT1 expression in muscle was assessed by quantitative PCR and immunoblotting. Wild type or mutated TNNT1 mRNAs were co-injected with morpholinos in a zebrafish knockdown model to assess for rescue of the morphant phenotype. Results: Four patients shared a novel missense homozygous mutation in TNNT1. They developed from childhood slowly progressive limb-girdle weakness with spinal rigidity and contractures. They suffered from restrictive lung disease and recurrent episodes of rhabdomyolysis. Older patients remained ambulatory into their sixties. Lower extremity MRI showed symmetrical myopathic changes. Paraspinal MRI showed diffuse fibro-fatty involution. Biopsies showed multi-minicores. Nemaline rods were seen in half the patients. TNNT1 mRNA expression was similar in controls and patients, while levels of TNNT1 protein were reduced in patients. Wild type TNNT1 mRNA rescued the zebrafish morphants but mutant transcripts failed to do so. Conclusions: This study expands the spectrum of TNNT1-related myopathy to include a milder clinical phenotype caused by a functionally-confirmed novel mutation.

Background: Erenumab is an antibody anti-calcitonin gene related peptide (CGRP) receptor approved for the treatment of episodic (EM) and chronic migraine (CM). In this study, we aimed to identify the predictors of response to the treatment. Methods: This is an ongoing retrospective cohort study of 120 patients (49 with cervicalgia) with EM or CM treated with Erenumab. The first endpoint was to identify the success rate of this treatment (at least 50% reduction in monthly migraine days during the third month of the treatment). The second endpoint was to identify the predictors of response to Erenumab treatment. Results: Seventy one percent of patients achieved a favorable response (P-value<0.001) to Erenumab. Patients with cervicalgia showed a lower treatment success rate (21.1% with vs 40.8% without cervicalgia) while patients without cervicalgia showed a higher treatment success rate (78. 9% without vs 59.2% with cervicalgia) with a P-value of 0.025 and an odd ratio of 0.388 (95% CI 0.174-0.869, P-value=0.021). A similar trend was observed in patients with occipital neuralgia and obesity (P-value<0.08). Conclusions: The preliminary analysis of this study demonstrates that cervicalgia (and to a lesser extend occipital neuralgia and obesity) is a negative predictor of response to Erenumab in patients with migraine.

Background: For patients with generalized epilepsy who do not respond to anti-seizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox Gastaut Syndrome(LGS) and genetic generalized epilepsy(GGE). Methods: We identified patients with a diagnosis of Lennox-Gastaut Syndrome or Genetic Generalized Epilepsy, who underwent VNS implantation, between1997 and July 2018. Results: A total of 46 patients were included in this study with a history of therapy resistant generalized epilepsy. The mean age at implantation was 24 years(IQR= 17.8-31 years) and 50%(n=23) were female. The most common etiologies were GGE in 37%(n=17) and LGS in 63%(n=29). Median follow-up since VNS implantation was 63 months(IQR:31-112.8months). 41.7%(n=12) of the LGS group became responders, and 64.7%(n=11) in the GGE group. The best response in seizure reduction was seen in generalized tonic-clonic seizures. There was a reduction of seizure-related hospital admissions from 89.7%(N=26) pre-implantation, to 41.4%(N=12) post-implantation (p<0.0001). The frequency of side effects due to the stimulation was similar in both groups(62.1% in LGS and 61.1% in GGE). Conclusions: VNS is an effective treatment in patients with therapy resistant generalized epilepsy, especially GGE.

Background: PET imaging of [11C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [11C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Methods: [11C]ABP688-PET was obtained from 31 unilateral MTLE patients and 30 controls. Hippocampal subfields were automatically segmented into 1) CA1-3, 2) CA4/dentate gyrus (DG), and 3) Subiculum and manually corrected. Partial volume corrected [11C]ABP688 non-displaceable binding potential (BPND) was calculated in the subfields and compared between seizure-free and non-seizure-free patients. Results: [11C]ABP688 BPND was significantly reduced in ipsilateral CA1-3 & CA4/DG (p<0.001) compared to controls. No difference was seen in Subiculum. Ipsilateral CA1-3 [11C]ABP688 BPND was lower in seizure-free (p=0.012; Engel Ia, n=13) vs non-seizure-free (Engel Ic-III, n=10) patients, and this effect was independent of subfield volume. In a subset of patients with [18F]FDG-PET, CA1-3 [11C]ABP688 BPND was significantly lower in seizure-free patients (p=0.03), while no difference was found for [18F]FDG uptake. Conclusions: Reduced CA1-3 mGluR5 availability was associated with post-surgical seizure-freedom independent of atrophy and hypometabolism. Thus, [11C]ABP688-PET may offer a potential biomarker for surgical outcomes and may be particularly relevant for pre-surgical workup in MRI- and [18F]FDG-negative MTLE patients.

Background: Transition from pediatric to adult care can be a difficult time for adolescents with epilepsy. This period is often a period of extreme vulnerability and stress. As a result, research has recommended transition clinics to help these adolescents develop needed transition skills. However, the skills that need to be focused on remain unclear. Methods: Baseline transition skills in 113 adolescents with epilepsy, aged 14 to 18 (M= 16.46, male= 56) were analyzed. Results: Analyses showed that older adolescents showed significantly more transition skills than younger adolescents (F(4,108)=5.522, p=000). Although positive, older adolescents only scored, on average, 16.3/28 on the transition questionnaire; suggesting that many skills are still lacking, even at the time of transition. Specifically, although the majority of these older adolescents demonstrated being able to manage their condition independently (e.g., summarizing medical history, taking/knowing medications), these adolescents were less likely to demonstrate skills needed to be advocates for themselves and their health (e.g., asking questions, discussing concerns, speaking to the doctor instead of letting their parents). Conclusions: Results suggest it may be beneficial to restructure adolescent clinic visits; encouraging these patients to attend the initial portion of visits independently to help them feel more comfortable and confident championing for themselves.

Background: Studies evaluating long-term neurologic outcomes following NAIS are scanty. We aimed to study the emergence pattern of neurologic deficits following NAIS. Methods: Neonates diagnosed with AIS were prospectively enrolled and outcomes were evaluated using the validated Pediatric Stroke Outcome Measure-Severity Classification Scheme. Neurologic outcomes were classified as normal/mild, moderate or severe. Trend analysis was conducted using Cochran-Armitage test. Results: A total of 126 neonates (59% males) were followed for a median of 5.2 years (IQR:3.4-6.4 years). The proportion of children classified as normal/mild declined from 94% to 76% >5 years post-stroke (p<0.01). Moderate and severe outcomes increased from 5% to 15% and 1% to 8% (p=0.01), respectively. Sensorimotor, language and cognitive deficits emerged in 16%, 14%, and 17% of enrolled neonates, respectively. Of those who had normal/mild outcomes at baseline, 83 remained stable throughout the study. Improvement in neurologic outcomes was seen in 8 children. Thirty-five neonates had emerging deficits at one point during follow-up. Congenital heart disease predicted the emergence of deficits (odds ratio=3.3, 95% confidence interval:1.01-10.5). Conclusions: Emerging deficits following NAIS are not uncommon and can equally manifest in sensorimotor, language or cognitive domains. Thus, long-term follow-up and close monitoring of outcomes following NAIS is crucial.

Background: Perinatal stroke encompasses six cerebrovascular syndromes which occur between the 20th week of gestation and the 28th post-natal day. Subtypes are neonatal arterial ischemic stroke (NAIS), neonatal cerebral sinovenous thrombosis (CSVT), neonatal hemorrhagic stroke (NHS), arterial presumed perinatal ischemic stroke (APPIS), periventricular venous infarction (PVI), and presumed perinatal hemorrhagic stroke (PPHS). Inconsistent terminology and lack of population-based case series has limited accurate measurement of disease-specific perinatal stroke incidence. Our objective was to define the incidence of the subtypes of perinatal stroke using a population-based cohort. Methods: The Alberta Perinatal Stroke Project is a research cohort established in 2008 in Southern Alberta. Case acquisition included retrospective hospital and ICD code searches (1990-2008) and prospective enrollment from all NICU and neurology/stroke clinics (2008-2017). Results: The overall incidence of perinatal stroke in Southern Alberta was 9.0 cases per 10,000 births, or 1:1200 births. Per 10,000 births, the incidence of each subtype was: NAIS = 3.2 (~1:3000), APPIS =1.2 (~1:8500), PVI = 1.5 (~1:6500), CSVT = 1.0 (~1:9900), NHS = 1.4 (~1/7300), PPHS = 0.1 (1/82,000). Conclusions: The overall incidence of perinatal stroke in Southern Alberta is 1:1200 live births. Population-based sampling of disease-specific states may explain why this rate is much higher than previous estimates

Background: Headache is a prevalent and disabling condition in children. It is a frequent cause of medication and health resource use in children. We examined the incidence and nature of health service use of the pediatric patient population in Alberta using provincial linked administrative databases. Methods: We used linked administrative data to identify patients under the age of 18 years from 2010-2017 and ICD-10 headache type at diagnosis and health service utilization including cost, medication use, outpatient/ED visits and hospitalizations. Patient geographic location was mapped. We explored health system use in the 3 years before and after diagnosis by identifying visits to community physicians, outpatient clinics emergency departments an inpatient admissions. Results: Over the 7 year study period 45,454 patients were identified under 18 years, 60% of patients first diagnosed with migraine, 11.7% (5308) with tension headache and 28.2 (12,833) with unspecified headache. Higher health system utilization seen immediately before and after headache diagnosis, returning to pre-diagnosis values within the 3 years following. Conclusions: This is the first population based reporting of pediatric headache prevalence and health resource utilization in Alberta. This contemporary prevalence and health resource data use should help inform future policy and headache care in the province of Alberta.

Background: Predictors of hospitalization and reasons for admissions can inform healthcare planning and prevention. We sought to characterize the hospitalization pattern and risk factors for admission of children with cerebral palsy (CP). Methods: Data from the Registre de paralysie cérébrale du Québec and provincial administrative databases were linked. The CP cohort contained children born between 1999 and 2002. Data related to admissions were captured in 2012. Relative risks (RR) were calculated to identify factors increasing hospitalization risk. Peers without CP were matched from administrative databases in a 20:1 ratio. Chi-square tests and Student’s T-tests were used to compare cohorts. Results: 301 children with CP and 6040 peer controls were selected. Hospitalizations were increased in children with CP (raw mean difference (RMD) 5.0 95% CI 4.7 to 5.2), with significantly longer lengths of stay (RMD 2.8 95% CI 1.8 to 3.8) and number of diagnoses per hospitalization (RMD 1.6 95% CI 1.4 to 1.8). Increased risk of any hospitalization was observed in children with a more complex profile. Conclusions: Children with a more severe profile of CP and greater health care complexity face more frequent and longer hospital stays. Coordinated interdisciplinary care is needed in school-aged children with CP and medical complexity.

Background: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is a pediatric epilepsy syndrome with sleep induced epileptic discharges and acquired impairment in cognition, language and/or behavior. Despite the widespread use of high dose diazepam, there is limited research on its efficacy. Methods: Single-center, retrospective case-series of children presenting with cognitive/ language regression and ESES from 2014-2019. All children underwent baseline overnight EEG followed by diazepam (1mg/kg) administered per rectum, and continuation of 0.5 mg/kg of oral diazepam for 3 months. Follow up EEGs were performed following the first dose and after 6-9 weeks of treatment. Results: 23 children were included [male 14 (60%); mean age 7 years (4 -12)]. 10 children (45%) had symptomatic epilepsy (defined by abnormal MRI and/or genetic evaluation). Decrease in more than 25% of the spike activity was seen in 18 (78%). This effect was sustained in 11 children (47%) after 6 weeks. Only 6 (60%) children from the symptomatic group had EEG response, while 11 (91%) responded from the idiopathic group. 5 children (21%) had clinically significant cognitive/ language improvement. Conclusions: Treatment with diazepam reduces epileptiform activity in ESES in majority of children. Despite this reduction only minority of patients experience clinically significant cognitive improvement.

Background: Nutrition in early life plays a critical role in the growth and neurodevelopment of preterm neonates. However, whether early nutrition modified the association of white matter injury (WMI) with brain maturation and neurodevelopmental outcomes remains unclear. Methods: In this prospective cohort study, very preterm neonates were recruited from the NICU at BC Women’s Hospital. MRI and measures of NAA/choline were obtained. Energy intake was recorded over the first two weeks of life and the cohort was dichotomized. Neurodevelopmental outcomes were assessed at 4.5 years of age using WPPSI-III. Results: Neonates in the high lipid group had higher levels of NAA/choline in the basal ganglia. When accounting for confounders, this relationship was only significant in neonates without WMI (p=0.04).

Overall, neonates with larger WMI volumes had lower IQ scores at 4.5 years (p<0.001). However, this relationship was attenuated in the high lipid group (p=0.002) relative to the lower lipid intake group. Conclusions: In this cohort, higher energy intake is associated with increased brain maturation. Similarly, neonates with large WMI had higher full-scale IQ if they received greater lipid intake in the neonatal period, suggesting that greater early lipid intake may contribute to blunting the deleterious effects of WMI on neurodevelopmental outcomes.