Posthemorrhagic Hydrocephalus Research Articles

Radiologic and clinical outcome of isolated fourth ventricle following post-hemorrhagic hydrocephalus in children.

Few studies report radiologic and clinical outcome of post-hemorrhagic isolated fourth ventricle (IFV) with focus on surgical versus conservative management in neonates and children. Our aim is to investigate differences in radiological and clinical findings of IFV between patients who had surgical intervention versus patients who were treated conservatively. A retrospective analysis of patients diagnosed with IFV was performed. Data included demographics, clinical exam findings, surgical history, and imaging findings (dilated FV extent, supratentorial ventricle dilation, brainstem and cerebellar deformity, tectal plate elevation, basal cistern and cerebellar hemisphere effacement, posterior fossa upward/downward herniation). Sixty-four (30 females) patients were included. Prematurity was 94% with 90% being < 28weeks of gestation. Mean age at first ventricular shunt was 3.6 (range 1-19); at diagnosis of IFV, post-lateral ventricular shunting was 26.2 (1-173) months. Conservatively treated patients were 87.5% versus 12.5% treated with FV shunt/endoscopic fenestration. Severe FV dilation (41%), severe deformity of brainstem (39%) and cerebellum (47%) were noted at initial diagnosis and stable findings (34%, 47%, and 52%, respectively) were seen at last follow-up imaging. FV dilation (p = 0.0001) and upward herniation (p = 0.01) showed significant differences between surgery versus conservative management. No other radiologic or clinical outcome parameters were different between two groups. Only radiologic outcome results showed stable or normal FV dilation and stable or decreased upward herniation in the surgically treated group.

Pathogenesis of posthemorrhagic hydrocephalus of prematurity: New horizons

Posthemorrhagic hydrocephalus of prematurity (PHHP) remains a vexing problem for patients, their families, and the healthcare system. The complexity of the pathogenesis of PHHP also presents a unique challenge within the fields of neonatology, neurology and neurosurgery. Here we focus on pathogenesis of PHHP and its impact on the development of CSF dynamics including choroid plexus, ependymal motile cilia and glymphatic system. PHHP is contrasted with infantile hydrocephalus from other etiologies, and with other types of posthemorrhagic hydrocephalus that occur later in life. The important concept that distinguishing ventricular volume from brain health and function is highlighted. The influence of the pathogenesis of PHHP on current interventions is reviewed, with particular emphasis on how the unique pathogenesis of PHHP contributes to the high rate of failure of current existing interventions. Finally, we discuss emerging interventions. A thorough understanding of the pathogenesis of PHHP is essential to developing effective non-surgical therapeutics to prevent the transformation from severe IVH to PHHP

New insights into the management of post-hemorrhagic hydrocephalus

During the last decade, an increasing number of studies have been conducted to improve the outcome of post-hemorrhagic hydrocephalus (PHH), a complication of severe intraventricular hemorrhage (IVH) in preterm infants. Two randomized controlled trials have shown that treatment should be initiated prior to the onset of clinical symptoms. Ventricular access devices and subgaleal shunts are used as temporary neurosurgical interventions whereas ventriculoperitoneal shunts are performed for infants with progressive hydrocephalus. Recently, techniques such as neuro-endoscopic lavage have also been introduced to eliminate toxic blood products and debris from the cerebral ventricles and have shown promise in early clinical studies. The objective of this review is to provide an update on management of PHVD and PHH in the preterm infant.

Neurodevelopmental outcomes of premature infants with intraventricular hemorrhage across a lifespan

Neurodevelopmental impairment rates remain high among extremely preterm and very low birth weight infants. This review describes the rates of brain injury and neuro-developmental impairment at 2,3 years, early school age, adolescence, and young adulthood for survivors with intraventricular hemorrhage (IVH). Former preterm infants with a history of high-grade IVH are at the greatest risk of adverse neurodevelopmental outcomes. There is variability, however, in definitions of brain injury, methods for assessing brain injury, and definitions of adverse outcomes among multicenter networks. Despite differences in methods described in publications, perinatal grade III-IV intraventricular hemorrhage, post-hemorrhagic hydrocephalus, and white matter injury are consistently associated with increased rates of adverse motor and cognitive outcomes in the first 2,3 years of life, at early school age, in adolescence and early adulthood. Effects of socioeconomic status on outcomes, however, increase with the increasing age of the child. In summary, although preterm survivors of IVH are at an increased risk of adverse outcomes across a lifetime, there is evidence that social and environmental factors contribute to recovery over time.

Emerging therapies for brain recovery after IVH in neonates: Cord blood derived Mesenchymal Stem Cells (MSC) and Unrestricted Somatic Stem Cells (USSC)

In this report, we summarize evidence on mechanisms of injury after intraventricular hemorrhage resulting in post-hemorrhagic white matter injury and hydrocephalus and correlate that with the possibility of cellular therapy. We describe how two stem cell lines (MSC & USSC) acting in a paracrine fashion offer promise for attenuating the magnitude of injury in animal models and for improved functional recovery by: lowering the magnitude of apoptosis and neuronal cell death, reducing inflammation, and thus, mitigating white matter injury that culminates in improved motor and neurocognitive outcomes. Animal models of IVH are analyzed for their similarity to the human condition and we discuss merits of each approach. Studies on stem cell therapy for IVH in human neonates is described. Lastly, we offer suggestions on what future studies are needed to better understand mechanisms of injury and recovery and argue that human trials need to be expanded in parallel to animal research.

A Role of Complement in the Pathogenic Sequelae of Mouse Neonatal Germinal Matrix Hemorrhage.

Germinal matrix hemorrhage (GMH) is a devastating disease of infancy that results in intraventricular hemorrhage, post-hemorrhagic hydrocephalus (PHH), periventricular leukomalacia, and neurocognitive deficits. There are no curative treatments and limited surgical options. We developed and characterized a mouse model of GMH based on the injection of collagenase into the subventricular zone of post-natal pups and utilized the model to investigate the role of complement in PHH development. The site-targeted complement inhibitor CR2Crry, which binds deposited C3 complement activation products, localized specifically in the brain following its systemic administration after GMH. Compared to vehicle, CR2Crry treatment reduced PHH and lesion size, which was accompanied by decreased perilesional complement deposition, decreased astrocytosis and microgliosis, and the preservation of dendritic and neuronal density. Complement inhibition also improved survival and weight gain, and it improved motor performance and cognitive outcomes measured in adolescence. The progression to PHH, neuronal loss, and associated behavioral deficits was linked to the microglial phagocytosis of complement opsonized neurons, which was reversed with CR2Crry treatment. Thus, complement plays an important role in the pathological sequelae of GMH, and complement inhibition represents a novel therapeutic approach to reduce the disease progression of a condition for which there is currently no treatment outside of surgical intervention.

Development of Machine Learning–Based Predictor Algorithm for Conversion of an Ommaya Reservoir to a Permanent Cerebrospinal Fluid Shunt in Preterm Posthemorrhagic Hydrocephalus

An Ommaya reservoir can be used to treat posthemorrhagic hydrocephalus secondary to intraventricular hemorrhage of prematurity until an acceptable weight can be obtained to place a permanent shunt. Identifying newborns at higher risk of developing shunt conversion may improve the management of these patients. This study aimed to develop a predictive algorithm for conversion of an Ommaya reservoir to a permanent shunt using artificial intelligence techniques and classical statistics. A database of 43 preterm patients weighing ≤1500 g with posthemorrhagic hydrocephalus (Papile grades III and IV with Levene ventricular index >4 mm above the 97th percentile) managed with an Ommaya reservoir at our institution between 2002 and 2017 was used to train a k-nearest neighbor algorithm. Validation of results was done with cross-validation technique. Three scenarios were calculated: 1) considering all features regardless whether or not they are correlated with the output variable; 2) considering the features as predictors if they have a correlation >30% with the output variable; 3) considering the output of the previous analysis. When considering the outputs of a previous multivariate analysis, the algorithm reached 86% of cross-validation accuracy. The use of machine learning-based algorithms can help in early identification of patients with permanent need of a shunt. We present a predictive algorithm for a permanent shunt with an accuracy of 86%; accuracy of the algorithm can be improved with larger volume of data and previous analysis.

130 Development of an Integrated Risk Scale for Prediction of Shunt Placement After Neonatal Intraventricular Hemorrhage

INTRODUCTION: Neonatal intraventricular hemorrhage (IVH) is a major source of mortality and morbidity in infants, particularly following premature birth. Even after the acute phase, post-hemorrhagic hydrocephalus is a long-term complication, frequently requiring permanent ventriculoperitoneal shunt placement (VPS). Currently, there are no risk classification methods integrating the constellation of clinical data to predict short- and long-term prognosis in neonatal IVH. METHODS: Neonates with IVH were identified from the Optum Clinformatics DataMart administrative claims database using ICD-9/10 codes. Matched maternal-childbirth characteristics were obtained. Primary endpoints were short-term (30-day) mortality and long-term VPS placement. Classification of short-term mortality risk was evaluated using five different machine learning approaches and the best-performing method was validated using a withheld validation subset. Prediction of long-term shunt risk was performed using a multivariable Cox regression model with stepwise variable selection, which was subsequently converted to an easily applied integer risk scale. RESULTS: A total of 5,926 neonate-maternal pairs were included. Empiric 30-day neonatal mortality risk was 10.9% across all IVH grades and highest among grade IV IVH (34.3%). Among those surviving beyond 30 days, actuarial 12-month risk of shunt placement was 5.4% across all IVH grades and 31.3% for grade IV IVH. The optimal short-term risk classifier was a random forest model achieving an AUROC of 0.882 with important predictors ranging from gestational age to diverse comorbid medical conditions. The final multivariable Cox regression model for long-term shunt risk stratification following stepwise feature selection included IVH grade, respiratory distress syndrome, disseminated intravascular coagulation, and maternal preeclampsia/eclampsia. An integer risk scale termed the Shunt Prediction After IVH in Neonates (SPAIN) scale was developed from these four features which, evaluated on withheld validation cases, demonstrated improved risk stratification compared to IVH grade alone (Harrell’s concordance index 0.869 vs 0.852). CONCLUSION: We developed an integrated risk classification approach to anticipate short-term mortality and long-term shunt risk. Application of such approaches may improve outcome prognostication and identification of higher risk individuals warranting careful surveillance and early intervention.

A robotic magnetic resonance-guided high-intensity focused ultrasound platform for neonatal neurosurgery: Assessment of targeting accuracy and precision in a brain phantom.

Intraventricular hemorrhage (IVH) is one of the most serious neurovascular complications resulting from premature birth. It can result in clotting of blood within the ventricles, which causes a buildup of cerebrospinal fluid that can lead to posthemorrhagic ventricular dilation and posthemorrhagic hydrocephalus. Currently, there are no direct treatments for these blood clots as the standard of care is invasive surgery to insert a shunt. Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) has been investigated as a noninvasive treatment to lyse blood clots. However, current MRgHIFU systems are not suitable in the context of treating IVH in neonates. We have developed a robotic MRgHIFU neurosurgical platform designed to treat the neonatal brain. This platform facilitates ergonomic patient positioning and directs treatment through their open anterior fontanelle while providing a larger treatment volume. The platform is based on an MR-compatible robot developed by our group. Further development of the platform has warranted investigation of its targeting ability to assess its feasibility in the neonatal brain. This study aimed to quantify the platform's targeting accuracy, precision, and repeatability using a brain phantom and clinical MRI system. A thermosensitive brain-mimicking phantom was developed to test the platform's targeting accuracy. Rectangular grid patterns were created with HIFU thermal energy "lesions" in the phantoms by targeting specific coordinate points. The intended target locations were demarcated by inserting carbon fiber rods through a targeting assessment template. Coordinates for the intended and actual targets were derived from T2-weighted MRI scans, and the centroid distance between them was measured. Subsequently, the platform's targeting accuracy was quantified according to equations derived from ISO Standard 9283:1998. HIFU ablation resulted in distinct thermal lesions within the thermosensitive phantoms, which appeared as discrete hypointense regions in T2-weighted MR scans. A total of 127 target points were included in the data analysis, which yielded a targeting accuracy of 0.6mm and targeting precision of 1.2mm. The robotic MRgHIFU platform was shown to have a high degree of accuracy, precision, and repeatability. The results demonstrate the platform's functionality when targeting through simulated brain matter. These results serve as an initial verification of the platform targeting ability and showed promise toward the final application in a neonatal brain.

Pathophysiology and Clinical Management of Intraventricular Hemorrhage and Post-Hemorrhagic Hydrocephalus

Intraventricular hemorrhage(IVH)in patients with intracerebral hemorrhage is an independent risk factor. IVH can cause acute hydrocephalus by impairing cerebrospinal fluid dynamics. However, the pathological mechanism remains clear. In addition to the conventional concept of ventricular system obstruction by hematoma clots, secondary effects of heme and iron originating from hemoglobin might contribute to ventricular enlargement. The toxicity of accumulated hematoma in the ventricles might also influence the hydrocephalus and cause poor outcomes. An external ventricular drainage should be inserted promptly to control the intracranial pressure. Moreover, the hematoma should be removed as soon as possible to minimize the toxicity of the hematoma. The use of thrombolytic agents significantly reduces both the duration of ventricular drainage and mortality compared to external ventricular drainage alone. However, the functional outcome is not improved in patients with IVH. As another surgical option, endoscopy may be useful to evacuate the hematoma immediately. Finally, more evidence is essential for establishing the effectiveness of endoscopic techniques.

197 Gold Nanoparticle Enhanced X-ray Nanotomography Reveals Region-Specific CSF Pathways Through the Brain and Spinal Cord that are Altered in Post-hemorrhagic Hydrocephalus

INTRODUCTION: Cerebrospinal fluid (CSF) is essential for the healthy development and function of the brain, but understanding the mechanisms of its distribution in and around the central nervous system (CNS) remains a major challenge. To address this need, we developed a new technique, gold nanoparticle-enhanced x-ray nanotomography (AuNp-XRM), to achieve micrometer-scale resolution visualization of CSF pathways across the entire brain and spinal cord of rodents with further applications to a model of interventricular hemorrhage/post-hemorrhagic hydrocephalus (IVH/PHH). METHODS: P4 rodents were injected with aCSF or hemoglobin to create the control and IVH conditions. 72 hours later, animals underwent MRIs to determine onset of PHH. Animals were then injected with 1.9 nm and 15 nm gold nanoparticles and imaged using XRM. Following XRM, the brains, spines and meninges were harvested for histology. RESULTS: Using AuNp-XRM, we demonstrate visualization of previously characterized glymphatic, cranial nerve, and choroid plexus-mediated CSF circulation patterns, and present evidence to further identify CSF interactions with the leptomeninges, choroid plexus, and parenchyma of the brain and spinal cord. We also identified an intraparenchymal CSF circulation that targets stem-cell rich and cholinergic neuronal populations. CSF distribution to these areas was mediated by flow of CSF through the paravascular spaces of perforators originating from the large blood vessels of the basal cisterns and was significantly decreased in an animal model of PHH. CONCLUSION: Our findings using AuNp-XRM show that cholinergic cell populations in the brain and spinal cord differentially handle CSF, and that PHH alters CSF distribution to these areas of the brain. These region-specific patterns of CSF distribution may have critical relevance to normal brain development, brain development following PHH, and other neuropathological conditions.

Lumboperitoneal shunting in pediatric patients and the role of imaging in its evaluation

Lumboperitoneal shunting makes it possible to regulate the flow of cerebrospinal fluid by establishing a connection between the thecal sac and the peritoneal cavity. The main indication for lumboperitoneal shunting in children is idiopathic intracranial hypertension, but the technique is also useful in the treatment of postinfectious, posthemorrhagic, and normotensive hydrocephalus, as well as in the treatment of postsurgical pseudomeningocele or leakage of cerebrospinal fluid.This article reviews nine cases treated at our centre to show the normal imaging findings for lumboperitoneal shunts in children and to provide a succinct review of the possible neurological and abdominal complications associated with this treatment.

La derivación lumbo-peritoneal en la edad pediátrica y el papel de la imagen en su valoración

Lumboperitoneal shunting makes it possible to regulate the flow of cerebrospinal fluid by establishing a connection between the thecal sac and the peritoneal cavity. The main indication for lumboperitoneal shunting in children is idiopathic intracranial hypertension, but the technique is also useful in the treatment of postinfectious, posthemorrhagic, and normotensive hydrocephalus, as well as in the treatment of postsurgical pseudomeningocele or leakage of cerebrospinal fluid.This article reviews nine cases treated at our center to show the normal imaging findings for lumboperitoneal shunts in children and to provide a succinct review of the possible neurological and abdominal complications associated with this treatment.

Risk Factor of Posthemorrhagic Hydrocephalus: Cerebrospinal Fluid Total Protein.

ObjectiveCerebrospinal fluid total protein (CSF-TP) levels in adults with posthemorrhagic hydrocephalus (PHH) are poorly studied. The objective of this study was to explore the characteristics of CSF-TP levels in patients with PHH.MethodsThe clinical data of 156 patients with hemorrhagic brain disease were retrospectively studied and divided into PHH and NPHH groups. Single-factor and multi-factor analyses were performed, and the key role of CSF-TP was evaluated using linear analysis.ResultsAmong the 156 patients, 85 (54.5%) had PHH and 34 (21.8%) underwent surgeries. Hypertension (p = 0.017), days [total fever time when body temperature ≥ 38.5°C (p = 0.04)], Glasgow Coma Scale (GCS) score (p < 0.001), and time (from the onset of the disease to the obtainment of CSF-TP after lumbar puncture (p < 0.001) were important factors for PHH. Logistic regression analysis revealed that GCS score < 8 [odds ratio (OR) = 2.943 (1.421–6.097), p = 0.004] and CSF-TP × time ≥ 9,600 [OR = 2.317 (1.108–4.849), p = 0.026] were independent risk factors for PHH. All CSF-TP values were averaged every 2 days. CSF-TP was negatively correlated with time. Linear analysis showed that CSF-TP in the PHH group was higher than that in the NPHH group at the same onset time, and that the duration of detectionin the CSF was longer.ConclusionCerebrospinal fluid total protein (CSF-TP) × time ≥ 9,600 and GCS score <8 were independent risk factors for PHH. CSF-TP was higher in the PHH group than in the NPHH group.

Elevation of brain gamma‐aminobutyric acid levels is associated with vigabatrin‐associated brain abnormalities on magnetic resonance imaging

ObjectiveVigabatrin (VGB) is an effective antiseizure medication for West syndrome. It works by irreversibly inhibiting gamma-aminobutyric acid (GABA) transaminase and increasing central GABA levels. Vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM) are an adverse effect of VGB that has only been reported in children, but the pathophysiology of this effect is unknown. In this study, we evaluated the relationship of VGB and brain GABA levels as well as the association between VABAM and GABA. MethodsFor the 15 consecutive pediatric patients treated with VGB, free GABA, glutamine, and glutamate in cerebrospinal fluid (CSF) and plasma, GABA to creatine and phosphocreatine (Cr) peak ratio (GABA/Cr), glutamine (Gln)/Cr, and glutamate (Glu)/Cr as quantified by proton MR spectroscopy (1H-MRS) were retrospectively examined. GABA/Cr was compared with in-house normal pediatric controls. Differences in the levels of each metabolite in VABAM and non-VABAM cases were also examined. ResultsThirteen of the included subjects underwent magnetic resonance imaging (MRI) and 1H-MRS, and two of them presented VABAM; both cases were very-low-birth-weight preterm infants with post-hemorrhagic hydrocephalus. CSF levels of free GABA were significantly higher in VABAM (5.26 ± 1.95 μmol/L) than in non-VABAM (0.59 ± 0.63 μmol/L) cases (P = 0.03). The GABA/Cr was significantly higher in patients with VGB (0.34 ± 0.16) than in pediatric controls (0.20 ± 0.05) (P = 0.02). The GABA/Cr tended to be higher in VABAM (0.48 ± 0.10) than in non-VABAM cases (0.31 ± 0.15) (P = 0.31). SignificanceElevated brain GABA levels were observed in VABAM patients, suggesting its involvement in the pathogenesis of this condition. In particular, a marked increase in CSF-free GABA was characteristic. Although the elevation of the GABA/Cr is mild, it may be useful for early identification of patients with risk of VABAM.

Spotlight on the January 25 Issue

#### Notable in Neurology This Week This issue features an article that investigates the roles of cerebrovascular collaterals in children with stroke; another explores how physical activity affects the association of air pollution with brain volume. A featured Special Article examines ethical considerations for the use of aducanumab to treat Alzheimer disease. ### Microstructural Periventricular White Matter Injury in Post-hemorrhagic Ventricular Dilation ![Graphic][1]</img> In a cohort of very preterm infants, diffusion basis spectrum imaging (DBSI) showed that infants with post-hemorrhagic hydrocephalus (PHH) had more severe white matter … [1]: /embed/inline-graphic-1.gif

Automatic brain segmentation in preterm infants with post-hemorrhagic hydrocephalus using 3D Bayesian U-Net.

Post‐hemorrhagic hydrocephalus (PHH) is a severe complication of intraventricular hemorrhage (IVH) in very preterm infants. PHH monitoring and treatment decisions rely heavily on manual and subjective two‐dimensional measurements of the ventricles. Automatic and reliable three‐dimensional (3D) measurements of the ventricles may provide a more accurate assessment of PHH, and lead to improved monitoring and treatment decisions. To accurately and efficiently obtain these 3D measurements, automatic segmentation of the ventricles can be explored. However, this segmentation is challenging due to the large ventricular anatomical shape variability in preterm infants diagnosed with PHH. This study aims to (a) propose a Bayesian U‐Net method using 3D spatial concrete dropout for automatic brain segmentation (with uncertainty assessment) of preterm infants with PHH; and (b) compare the Bayesian method to three reference methods: DenseNet, U‐Net, and ensemble learning using DenseNets and U‐Nets. A total of 41 T2‐weighted MRIs from 27 preterm infants were manually segmented into lateral ventricles, external CSF, white and cortical gray matter, brainstem, and cerebellum. These segmentations were used as ground truth for model evaluation. All methods were trained and evaluated using 4‐fold cross‐validation and segmentation endpoints, with additional uncertainty endpoints for the Bayesian method. In the lateral ventricles, segmentation endpoint values for the DenseNet, U‐Net, ensemble learning, and Bayesian U‐Net methods were mean Dice score = 0.814 ± 0.213, 0.944 ± 0.041, 0.942 ± 0.042, and 0.948 ± 0.034 respectively. Uncertainty endpoint values for the Bayesian U‐Net were mean recall = 0.953 ± 0.037, mean negative predictive value = 0.998 ± 0.005, mean accuracy = 0.906 ± 0.032, and mean AUC = 0.949 ± 0.031. To conclude, the Bayesian U‐Net showed the best segmentation results across all methods and provided accurate uncertainty maps. This method may be used in clinical practice for automatic brain segmentation of preterm infants with PHH, and lead to better PHH monitoring and more informed treatment decisions.

Pathophysiologic mechanisms and strategies for the treatment of post-hemorrhagic hydrocephalus of prematurity.

Post-hemorrhagic hydrocephalus (PHH) of prematurity is a devastating pathology. Neurodevelopmental disabilities, including cognitive and motor deficits are very commonly seen among this population. Thus, there is interest to delineate the pathophysiology of PHH to uncover potential therapeutic targets. We performed a systematic review of the current literature on pathophysiological mechanisms and progressive strategies in the management of post-hemorrhagic hydrocephalus of prematurity. Our literature search identified a total of 58 articles pertaining to the pathophysiology, risk factors and management of post-hemorrhagic hydrocephalus. Presence of high-grade germinal matrix hemorrhage does not always predict PHH and neither does obstruction of pathways seen on ultrasound or MRI scan. We also describe the management options for posthemorrhagic hydrocephalus, including surgical and non-surgical. We conclude that pathogenesis of post-hemorrhagic hydrocephalus of prematurity is clearly multifactorial and definitive prediction of who will eventually develop PHH continues to be elusive.

Does ventricle size contribute to cognitive outcomes in posthemorrhagic hydrocephalus? Role of early definitive intervention.

Posthemorrhagic hydrocephalus (PHH) is associated with significant morbidity, smaller hippocampal volumes, and impaired neurodevelopment in preterm infants. The timing of temporary CSF (tCSF) diversion has been studied; however, the optimal time for permanent CSF (pCSF) diversion is unknown. The objective of this study was to determine whether cumulative ventricle size or timing of pCSF diversion is associated with neurodevelopmental outcome and hippocampal size in preterm infants with PHH. Twenty-five very preterm neonates (born at ≤ 32 weeks' gestational age) with high-grade intraventricular hemorrhage (IVH), subsequent PHH, and pCSF diversion with a ventriculoperitoneal shunt (n = 20) or endoscopic third ventriculostomy (n = 5) were followed until 2 years of age. Infants underwent serial cranial ultrasounds from birth until 1 year after pCSF diversion, brain MRI at term-equivalent age, and assessment based on the Bayley Scales of Infant and Toddler Development, Third Edition, at 2 years of age. Frontooccipital horn ratio (FOHR) measurements were derived from cranial ultrasounds and term-equivalent brain MRI. Hippocampal volumes were segmented and calculated from term-equivalent brain MRI. Cumulative ventricle size until the time of pCSF diversion was estimated using FOHR measurements from each cranial ultrasound performed prior to permanent intervention. The average gestational ages at tCSF and pCSF diversion were 28.9 and 39.0 weeks, respectively. An earlier chronological age at the time of pCSF diversion was associated with larger right hippocampal volumes on term-equivalent MRI (Pearson's r = -0.403, p = 0.046) and improved cognitive (r = -0.554, p = 0.047), motor (r = -0.487, p = 0.048), and language (r = -0.414, p = 0.021) outcomes at 2 years of age. Additionally, a smaller cumulative ventricle size from birth to pCSF diversion was associated with larger right hippocampal volumes (r = -0.483, p = 0.014) and improved cognitive (r = -0.711, p = 0.001), motor (r = -0.675, p = 0.003), and language (r = -0.618, p = 0.011) outcomes. There was no relationship between time to tCSF diversion or cumulative ventricle size prior to tCSF diversion and neurodevelopmental outcome or hippocampal size. Finally, a smaller cumulative ventricular size prior to either tCSF diversion or pCSF diversion was associated with a smaller ventricular size 1 year after pCSF diversion (r = 0.422, p = 0.040, R2 = 0.178 and r = 0.519, p = 0.009, R2 = 0.269, respectively). In infants with PHH, a smaller cumulative ventricular size and shorter time to pCSF diversion were associated with larger right hippocampal volumes, improved neurocognitive outcomes, and reduced long-term ventriculomegaly. Future prospective randomized studies are needed to confirm these findings.

Neonatal motor functional connectivity and motor outcomes at age two years in very preterm children with and without high-grade brain injury

Preterm-born children have high rates of motor impairments, but mechanisms for early identification remain limited. We hypothesized that neonatal motor system functional connectivity (FC) would relate to motor outcomes at age two years; currently, this relationship is not yet well-described in very preterm (VPT; born <32 weeks’ gestation) infants with and without brain injury.We recruited 107 VPT infants – including 55 with brain injury (grade III–IV intraventricular hemorrhage, cystic periventricular leukomalacia, post-hemorrhagic hydrocephalus) – and collected FC data at/near term-equivalent age (35–45 weeks postmenstrual age). Correlation coefficients were used to calculate the FC between bilateral motor and visual cortices and thalami. At two years corrected-age, motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development, 3rd edition. Multiple imputation was used to estimate missing data, and regression models related FC measures to motor outcomes.Within the brain-injured group only, interhemispheric motor cortex FC was positively related to gross motor outcomes. Thalamocortical and visual FC were not related to motor scores. This suggests neonatal alterations in motor system FC may provide prognostic information about impairments in children with brain injury.