Influence of interaction of cerebral fluids on ventricular deformation: A mathematical approach.

This paper describes the effects of the interaction of cerebral fluids (arterial, capillary and venous blood, cerebrospinal fluid) on ventricular wall displacement and periventricular pressure using a mathematical multiphase poroelasticity model for the cerebral parenchyma. The interaction of cerebral fluids is given by a set of four numerical coefficients. A multiple linear regression with interaction is constructed that allows us to quantify the effect of these coefficients on the average ventricular wall displacement. The prevailing influence of an arterial-liquor component was observed. The sets of coefficients associated with such pathological conditions were found: normal pressure hydrocephalus, intracranial hypertension, and replacement ventriculomegaly under a prolonged hypoperfusion.

A neonatal neuroNICU collaborative approach to neuromonitoring of posthemorrhagic ventricular dilation in preterm infants.

Morbidity and mortality in prematurely born infants have significantly improved due to advancement in perinatal care, development of NeuroNICU collaborative multidisciplinary approaches, and evidence-based management protocols that have resulted from a better understanding of perinatal risk factors and neuroprotective treatments. In premature infants with intraventricular hemorrhage (IVH), the detrimental secondary effect of posthemorrhagic ventricular dilation (PHVD) on the neurodevelopmental outcome can be mitigated by surgical intervention, though management varies considerably across institutions. Any benefit derived from the use of neuromonitoring to optimize surgical timing and technique stands to improve neurodevelopmental outcome. In this review, we summarize (1) the approaches to surgical management of PHVD in preterm infants and outcome data; (2) neuromonitoring modalities and the effect of neurosurgical intervention on this data; (3) our resultant protocol for the monitoring and management of PHVD. In particular, our protocol incorporates cerebral near-infrared spectroscopy (NIRS) and transcranial doppler ultrasound (TCD) to better understand cerebral physiology and to enable the hypothesis-driven study of the management of PHVD. IMPACT: Review of the published literature concerning the use of near-infrared spectroscopy (NIRS) and a cerebral Doppler ultrasound to study the effect of cerebrospinal fluid drainage on infants with posthemorrhagic ventricular dilation. Presentation of our institution's evidence-based protocol for the use of NIRS and cerebral Doppler ultrasound to study the optimal neurosurgical treatment of posthemorrhagic ventricular dilation, an as yet inadequately studied area.

Higher Concentration of Taenia Antigens in the CSF is Related to Slight Ventricle Enlargement and Periventricular Neuronal Decrease in Young Rats

Purpose Experimental models might help understand the pathophysiology of neurocysticercosis-associated hydrocephalus. The present study aimed to compare the extent of hydrocephalus and tissue damage in rats with subarachnoid inoculation of different concentrations of Taenia crassiceps cyst proteins. Methods Sixty young rats were divided into two groups: low- and high-concentration groups. The animals in the low concentration group received 0.02ml of 2.4mg/ml T. crassiceps cyst proteins while those in the high concentration group received 0.02 ml of 11.6mg/ml T. crassiceps cyst proteins. The animals underwent magnetic resonance imaging at 1, 3, and 6 months postinoculation to assess the ventricle volume. Morphological assessment was performed at the end of the observation period. Results Repeated measures of ventricle volumes at 1, 3, and 6 months showed progressive enlargement of the ventricles. At 1 and 3 months, we observed no differences in ventricle volumes between the 2 groups. However, at 6 months, the ventricles were larger in the high concentration group (median » 3.86mm3, range: 2.37­12.68) compared with the low concentration group (median » 2.00mm3, range: 0.37­11.57), p » 0.003. The morphological assessment revealed a few inflammatory features in both groups. However, the density of oligodendrocytes and neurons within the periventricular region was lower in the high concentration group (5.18 versus 9.72 for oligodendrocytes and 15.69 versus 21.00 for neurons; p < 0.001 for both). Conclusion Our results suggest that, in rats, a higher concentration of T. crassiceps cyst proteins in the subarachnoid space could induce ventricle enlargement and reduce the number of neurons within the periventricular area.

Brain Magnetic Resonance Imaging Volumetric Measures of Functional Outcome after Severe Traumatic Brain Injury in Adolescents.

Adolescent traumatic brain injury (TBI) is a major public health concern, resulting in >35,000 hospitalizations in the United States each year. Although neuroimaging is a primary diagnostic tool in the clinical assessment of TBI, our understanding of how specific neuroimaging findings relate to outcome remains limited. Our study aims to identify imaging biomarkers of long-term neurocognitive outcome after severe adolescent TBI. Twenty-four adolescents with severe TBI (Glasgow Coma Scale ≤8) enrolled in the ADAPT (Approaches and Decisions after Pediatric TBI) study were recruited for magnetic resonance imaging (MRI) scanning 1-2 years post-injury at 13 participating sites. Subjects underwent outcome assessments ∼1-year post-injury, including the Wechsler Abbreviated Scale of Intelligence (IQ) and the Pediatric Glasgow Outcome Scale-Extended (GOSE-Peds). A typically developing control cohort of 38 age-matched adolescents also underwent scanning and neurocognitive assessment. Brain-image segmentation was performed on T1-weighted images using Freesurfer. Brain and ventricular cerebrospinal fluid volumes were used to compute a ventricle-to-brain ratio (VBR) for each subject, and the corpus callosum cross-sectional area was determined in the midline for each subject. The TBI group demonstrated higher VBR and lower corpus callosum area compared to the control cohort. After adjusting for age and sex, VBR was significantly related with GOSE-Peds score in the TBI group (n = 24, p = 0.01, cumulative odds ratio = 2.18). After adjusting for age, sex, intracranial volume, and brain volume, corpus callosum cross-sectional area correlated significantly with IQ score in the TBI group (partial cor = 0.68, n = 18, p = 0.007) and with PSI (partial cor = 0.33, p = 0.02). No association was found between VBR and IQ or between corpus callosum and GOSE-Peds. After severe adolescent TBI, quantitative MRI measures of VBR and corpus callosum cross-sectional area are associated with global functional outcome and neurocognitive outcomes, respectively.

Potential biomarkers of childhood brain tumor identified by proteomics of cerebrospinal fluid from extraventricular drainage (EVD).

Brain tumors are the most common solid tumors in childhood. There is the need for biomarkers of residual disease, therapy response and recurrence. Cerebrospinal fluid (CSF) is a source of brain tumor biomarkers. We analyzed the proteome of waste CSF from extraventricular drainage (EVD) from 29 children bearing different brain tumors and 17 controls needing EVD insertion for unrelated causes. 1598 and 1526 proteins were identified by liquid chromatography-coupled tandem mass spectrometry proteomics in CSF control and brain tumor patients, respectively, 263 and 191 proteins being exclusive of either condition. Bioinformatic analysis revealed promising protein biomarkers for the discrimination between control and tumor (TATA-binding protein-associated factor 15 and S100 protein B). Moreover, Thymosin beta-4 (TMSB4X) and CD109, and 14.3.3 and HSP90 alpha could discriminate among other brain tumors and low-grade gliomas plus glyoneuronal tumors/pilocytic astrocytoma, or embryonal tumors/medulloblastoma. Biomarkers were validated by ELISA assay. Our method was able to distinguish among brain tumor vs non-tumor/hemorrhagic conditions (controls) and to differentiate two large classes of brain tumors. Further prospective studies may assess whether the biomarkers proposed by our discovery approach can be identified in other bodily fluids, therefore less invasively, and are useful to guide therapy and predict recurrences.

Dynamic disequilibrium of macromolecular transport as possible mechanism for hydrocephalus associated with long-term spaceflight.

Hydrocephalus associated with long term spaceflight (HALS) for missions lasting over five months is well described but poorly understood. While structural changes of the brain due to microgravitational forces affecting the circulation of cerebrospinal fluid (CSF) have been described as one potential cause, we propose an alternative hypothesis based on dynamic disequilibrium of macromolecular transport across the blood brain barrier. We propose that factors altering physiology under conditions of spaceflight such as microgravity, hypercapnia, venous hypertension, medications, and dietary substances contribute to increased protein load in the ventricles and/or contribute to impairment of transport out of the ventricles that results in HALS. Individual variation in the genetic expression of efflux transporters (p-glycoprotein) has been shown to correlate with the presence and degree of hydrocephalus in animal studies. We describe the evidence behind this concept and propose how these factors can be studied in order to determine the underlying pathogenesis which is imperative in order to cure or prevent HALS.

Craniopharyngioma treatment: an updated summary of important clinicopathological concepts.

INTRODUCTION: Craniopharyngiomas (CPs) are benign histological tumors that may develop at different positions along the hypothalamic-pituitary axis. Their close, heterogenous relationship to the hypothalamus makes surgical removal challenging even though this remains the primary treatment strategy. AREAS COVERED: This article presents a critical overview of the pathological and clinical concepts regarding CPs that should be considered when planning treatment. Thus, we have performed a comprehensive review of detailed CP reports published between 1839 and 2020. EXPERT OPINION: CP surgery should pursue maximal tumor resection while minimizing the risk of injuring the hypothalamus. Therefore, surgical strategies should be individualized for each patient. Accurate assessment of presenting symptoms and preoperative MRI has proven useful to predict the type of CP-hypothalamus relationship that will be found during surgery. CPs with dense and extensive adhesions to the hypothalamus should be highly suspected when MRI shows the hypothalamus positioned around the mid-third of the tumor and an amputated upper portion of the pituitary stalk. Symptoms related to functional impairment of the infundibulo-tuberal area of the third ventricle floor, such as obesity/hyperphagia, Fröhlich's syndrome, diabetes insipidus, and/or somnolence, also indicate risky CP-hypothalamic adhesions. In these cases, limited tumor removal is strongly advocated followed by radiation therapy.

Intracranial Pressure during External Ventricular Drainage Weaning Is an Outcome Predictor of Traumatic Brain Injury.

External ventricular drainage (EVD) is widely used in patients with a traumatic brain injury (TBI). However, the EVD weaning trial protocol varies and insufficient studies focus on the intracranial pressure (ICP) during the weaning trial. We aimed to establish the relationship between ICP during an EVD weaning trial and the outcomes of TBI. We enrolled 37 patients with a TBI with an EVD from July 2018 to September 2019. Among them, 26 were allocated to the favorable outcome group and 11 to the unfavorable outcome group (death, post-traumatic hydrocephalus, persistent vegetative state, and severe disability). Groups were well matched for sex, pupil reactivity, admission Glasgow Coma Scale score, Marshall computed tomography score, modified Fisher score, intraventricular hemorrhage, EVD days, cerebrospinal fluid output before the weaning trial, and the complications. Before and during the weaning trial, we recorded the ICP at 1-hour intervals to calculate the mean ICP, delta ICP, and ICP burden, which was defined as the area under the ICP curve. There were significant between-group differences in the age, surgery types, and intensive care unit days (p = 0.045, p = 0.028, and p = 0.004, respectively). During the weaning trial, 28 (75.7%) patients had an increased ICP. Although there was no significant difference in the mean ICP before and during the weaning trial, the delta ICP was higher in the unfavorable outcome group (p = 0.001). Moreover, patients who experienced death and hydrocephalus had a higher ICP burden, which was above 20 mmHg (p = 0.016). Receiver operating characteristic analyses demonstrated the predictive ability of these variables (area under the curve [AUC] = 0.818 [p = 0.002] for delta ICP and AUC = 0.758 [p = 0.038] for ICP burden > 20 mmHg). ICP elevation is common during EVD weaning trials in patients with TBI. ICP-related parameters, including delta ICP and ICP burden, are significant outcome predictors. There is a need for larger prospective studies to further explore the relationship between ICP during EVD weaning trials and TBI outcomes.

Transcallosal approach for intraventricular gliomas: neuropsychological outcome and functionality of the corpus callosum.

The transcallosal approach is commonly used for surgery of lateral and third ventricle lesions. Cognitive deficits due to the transcallosal approach still remain controversial. Even if enormous efforts have been made in order to understand specific functions of the corpus callosum, still little is known. The present study was aimed to evaluate the neuropsychological results and the functionality of the corpus callosum in transferring visual, auditory and tactile information between the two hemispheres in a group of patients who were treated using the transcallosal approach. The study evaluated the neuropsychological status of five selected patients presenting low-grade lesions of lateral ventricles that had not previously undergone surgical treatments and that did not receive radiotherapy and chemotherapy. All patients were administered an extensive neuropsychological testing postoperatively and the interhemispheric transfer of visual, auditory and tactile information was also evaluated. Two patients were tested preoperatively. Incisions of 2.4 cm maximum of the corpus callosum length were operated. The postoperative cognitive profile was normal. In some patients, a postoperative subnormal performance in memory functions was found but it cannot be attributable to the surgical approach given that it was altered even pre-surgically. Small incisions of the corpus callosum preserved the integrity of this anatomical structure in transferring lateralized information between the two hemispheres. The transcallosal approach is a safe surgical route to lateral ventricles lesions and the neuropsychological evaluation of these cases could give new insights in the comprehension of corpus callosum functions.

Intraventricular Medium B Treatment Benefits an Ischemic Stroke Rodent Model via Enhancement of Neurogenesis and Anti-apoptosis.

Enhancement of endogenous neurogenesis after ischemic stroke may improve functional recovery. We previously demonstrated that medium B, which is a combination with epidermal growth factor (EGF) and fibronectin, can promote neural stem/progenitor cell (NSPC) proliferation and migration. Here, we showed that medium B promoted proliferation and migration of cultured NSPCs onto various 3-dimentional structures. When rat cortical neurons with oxygen glucose deprivation (OGD) were co-cultured with NSPCs, medium B treatment increased neuronal viability and reduced cell apoptosis. In a rat model with transient middle cerebral artery occlusion (MCAO), post-insult intraventricular medium B treatment enhanced proliferation, migration, and neuronal differentiation of NSPCs and diminished cell apoptosis in the infarct brain. In cultured post-OGD neuronal cells and the infarct brain from MCAO rats, medium B treatment increased protein levels of Bcl-xL, Bcl-2, phospho-Akt, phospho-GSK-3ß, and ß-catenin and decreased the cleaved caspase-3 level, which may be associated with the effects of anti-apoptosis. Notably, intraventricular medium B treatment increased neuronal density, improved motor function and reduced infarct size in MCAO rats. In summary, medium B treatment results in less neuronal death and better functional outcome in both cellular and rodent models of ischemic stroke, probably via promotion of neurogenesis and reduction of apoptosis.

A design of brain port with a built-in bi-directional check valve improves the ventriculostomy.

The increase of intracranial pressure is a life-threatening condition which requires urgent treatment to prevent the further neurologic problem. A design of the brain port is proposed, in which a bi-directional check valve controls the flow of the cerebrospinal fluid depending on the intracranial pressure in accordance with the other devices. Drug administration and cerebrospinal fluid drainage could be performed easily without any additional surgery other than the transplant of a brain port. The intracranial pressure value at which the cerebrospinal fluid should be drained is adjustable by altering the pressure of the drainage bag. The results of the experiment with the simulated brain system are supporting and verifying the substance of this article.

Default Mode Network structural alterations in Kocher-Monro trajectory white matter transection: A 3 and 7 tesla simulation modeling approach.

The Kocher-Monro trajectory to the cerebral ventricular system represents one of the most common surgical procedures in the field of neurosurgery. Several studies have analyzed the specific white matter disruption produced during this intervention, which has no reported adverse neurological outcomes. In this study, a graph-theoretical approach was applied to quantify the structural alterations in whole-brain level connectivity. To this end, 132 subjects were randomly selected from the Human Connectome Project dataset and used to create 3 independent 44 subjects groups. Two of the groups underwent a simulated left/right Kocher-Monro trajectory and the third was kept as a control group. For the right Kocher-Monro approach, the nodal analysis revealed decreased strength in the anterior cingulate gyrus of the transected hemisphere. The network-based statistic analysis revealed a set of right lateralized subnetworks with decreased connectivity strength that is consistent with a subset of the Default Mode Network, Salience Network, and Cingulo-Opercular Network. These findings could allow for a better understanding of structural alterations caused by Kocher-Monro approaches that could reveal previously undetected clinical alterations and inform the process of designing safer and less invasive cerebral ventricular approaches.

Longitudinal morphological changes during recovery from brain deformation due to idiopathic normal pressure hydrocephalus after ventriculoperitoneal shunt surgery.

The present study aimed to examine time-dependent change in cerebrospinal fluid distribution and various radiological indices for evaluating shunt effectiveness in patients with idiopathic normal pressure hydrocephalus (iNPH). This study included 54 patients with iNPH who underwent MRI before and after ventriculoperitoneal shunt surgery. The volume of the total ventricles and subarachnoid spaces decreased within 1 month after shunting. However, more than 1 year after shunting, the volume of the total ventricles decreased, whereas that of the total subarachnoid spaces increased. Although cerebrospinal fluid distribution changed considerably throughout the follow-up period, the brain parenchyma expanded only 2% from the baseline brain volume within 1 month after shunting and remained unchanged thereafter. The volume of the convexity subarachnoid space markedly increased. The changing rate of convexity subarachnoid space per ventricle ratio (CVR) was greater than that of any two-dimensional index. The brain per ventricle ratio (BVR), callosal angle and z-Evans index continued gradually changing, whereas Evans index did not change throughout the follow-up period. Both decreased ventricular volume and increased convexity subarachnoid space volume were important for evaluating shunt effectiveness. Therefore, we recommend CVR and BVR as useful indices for the diagnosis and evaluation of treatment response in patients with iNPH.

Intraoperative measurement of intraventricular pressure in dogs with communicating internal hydrocephalus.

Collapse of the lateral cerebral ventricles after ventriculo-peritoneal drainage is a fatal complication in dogs with internal hydrocephalus. It occurs due to excessive outflow of cerebrospinal fluid into the peritoneal cavity (overshunting). In most shunt systems, one-way valves with different pressure settings regulate flow into the distal catheter to avoid overshunting. The rationale for the choice of an appropriate opening pressure is a setting at the upper limit of normal intracranial pressure in dogs. However, physiological intraventricular pressure in normal dogs vary between 5 and 12 mm Hg. Furthermore, we hypothesise that intraventricular pressure in hydrocephalic dogs might differ from pressure in normal dogs and we also consider that normotensive hydrocephalus exists in dogs, as in humans. In order to evaluate intraventricular pressure in hydrocephalic dogs, twenty-three client owned dogs with newly diagnosed communicating internal hydrocephalus were examined before implantation of a ventriculo-peritoneal shunt using a single use piezo-resistive strain-gauge sensor (MicroSensor ICP probe). Ventricular volume and brain volume were measured before surgery, based on magnetic resonance images. Total ventricular volume was calculated and expressed in relation to the total volume of the brain, including the cerebrum, cerebellum, and brainstem (ventricle-brain index). Multiple logistic regression analysis was performed to assess the influence of the covariates "age", "gender", "duration of clinical signs", "body weight", and "ventricle-brain index" on intraventricular pressure. The mean cerebrospinal fluid pressure in the hydrocephalic dogs was 8.8 mm Hg (standard deviation 4.22), ranging from 3-18 mm Hg. The covariates "age", (P = 0.782), "gender" (P = 0.162), "body weight", (P = 0.065), or ventricle-brain index (P = 0.27)" were not correlated with intraventricular pressure. The duration of clinical signs before surgery, however, was correlated with intraventricular pressure (P< 0.0001). Dogs with internal hydrocephalus do not necessarily have increased intraventricular pressure. Normotensive communicating hydrocephalus exists in dogs.

Kaolin-induced hydrocephalus causes acetylcholinesterase activity dysfunction following hypothalamic damage in infant rats.

In hydrocephalus, the progressive accumulation of cerebrospinal fluid (CSF) causes dilatation of the lateral ventricles affecting the third ventricle and diencephalic structures such as the hypothalamus. These structures play a key role in the regulation of several neurovegetative functions by the production of the hormones. Since endocrine disturbances are commonly observed in hydrocephalic children, we investigated the impact of progressive ventricular dilation on the hypothalamus of infant rats submitted to kaolin-induced hydrocephalus. Seven-day-old infant rats were submitted to hydrocephalus induction by kaolin 20% injection method. After 14 days, the animals were decapitated and brain was collected to analyze mitochondrial function, neuronal activity by acetylcholinesterase (AChE) enzyme, oxidative damage, glial activation, and, neurotransmission-related proteins and anti-apoptotic processes in the hypothalamus. The hydrocephalic animals showed reduction in respiratory rates in the States of phosphorylation (P < 0.01) and non-phosphorylation (P < 0.05); increase in AChE activity in both the cytosol (P < 0.05) and the membrane (P < 0.01); decrease in synaptophysin (P < 0.05) and Bcl-2 (P < 0.05) contents and; increase in protein carbonyl (P < 0.01), GFAP (P < 0.01) and Iba-1 (P < 0.05) levels. The results demonstrate that ventricular dilation causes hypothalamic damage characterized by cholinergic dysfunction and suggests further investigation of the synthesis and secretion of hormones to generate new approaches and to assist in the treatment of hydrocephalic patients with hormonal alterations.

Intracerebroventricular endothelin receptor-A blockade in rats decreases phase-II ventricular tachyarrhythmias during acute myocardial infarction.

Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis are unknown. We examined ventricular tachyarrhythmias after endothelin receptor-A blockade in the brain of Wistar rats with acute myocardial infarction. For this aim, BQ-123 (n=6) or phosphate-buffered saline (n=6) were injected intracerebroventricularly. After 10 min, the left coronary artery was ligated, followed by implantation of telemetry transmitters. Electrocardiography and voluntary activity (as a surrogate of acute left ventricular failure) were continuously monitored for 24 h. Infarct-size was similar in the two groups. There were fewer episodes of ventricular tachyarrhythmias of shorter average duration in treated rats, leading to markedly shorter total duration (12.3+/-8.9 s), when compared to controls (546.2+/-130.3 s). Voluntary activity increased in treated rats during the last hours of recording, but bradyarrhythmic episodes were comparable between the two groups. Endothelin receptor-A blockade in the brain of rats decreases the incidence of ventricular tachyarrhythmias post-ligation, without affecting bradyarrhythmic episodes. These findings call for further research on the pathophysiologic role of endothelin during acute myocardial infarction.

Clinical Significance of the CSF Pulsation Flow Sign in the Foramen of Monro on FLAIR in Patients with Aneurysmal SAH -Preliminary Report.

It is known that the cerebrospinal fluid (CSF) pulsation flow sign in the lateral ventricles directly above the foramen of Monro (CPF-M) on axial fluid attenuated inversion recovery (FLAIR) is a normal physiological finding as an artifact of FLAIR. In this study, whether CPF-M can be used as a neuroradiological finding related to pathological conditions in patients with acute aneurysmal subarachnoid hemorrhage (aSAH) was investigated. CPF-M-related clinical features were retrospectively evaluated in 147 aSAH patients who underwent adequate serial MRI examinations without massive intraventricular hemorrhage (IVH) of the lateral ventricle within 48 h of ictus. The frequency of the CPF-M in the control group was 32% (57/178), 33% (40/123), and 38% (45/117) for the normal control, chronic cerebral infarction, and deep white matter lesion (WML) groups, respectively. In aSAH patients, the overall prevalence of the CPF-M was 57% (84/147), significantly higher than in the three control groups. Multivariate analysis showed that age <70 years, lower IVH Hijdra score of the fourth ventricle, absence of T1-FLAIR mismatch, deep WMLs, old infarction, diffuse brain swelling, symptomatic delayed cerebral ischemia (DCI), shunt-dependent chronic hydrocephalus (SDCH), and favorable outcome were significantly associated with the CPF-M. Although limited to SAH patients without massive IVH of the lateral ventricles, one can conclude that, in acute aSAH, the presence of CPF-M on admission MRI suggests that the circulatory dynamics of the CSF from the basal cistern to the ventricles are approximately normal. Thus, this finding may appear to offer an indicator of a good outcome without DCI and SDCH.

Changing the Currently Held Concept of Cerebrospinal Fluid Dynamics Based on Shared Findings of Cerebrospinal Fluid Motion in the Cranial Cavity Using Various Types of Magnetic Resonance Imaging Techniques.

The "cerebrospinal fluid (CSF) circulation theory" of CSF flowing unidirectionally and circulating through the ventricles and subarachnoid space in a downward or upward fashion has been widely recognized. In this review, observations of CSF motion using different magnetic resonance imaging (MRI) techniques are described, findings that are shared among these techniques are extracted, and CSF motion, as we currently understand it based on the results from the quantitative analysis of CSF motion, is discussed, along with a discussion of slower water molecule motion in the perivascular, paravascular, and brain parenchyma. Today, a shared consensus regarding CSF motion is being formed, as follows: CSF motion is not a circulatory flow, but a combination of various directions of flow in the ventricles and subarachnoid space, and the acceleration of CSF motion differs depending on the CSF space. It is now necessary to revise the currently held concept that CSF flows unidirectionally. Currently, water molecule motion in the order of centimeters per second can be detected with various MRI techniques. Thus, we need new MRI techniques with high-velocity sensitivity, such as in the order of 10 µm/s, to determine water molecule movement in the vessel wall, paravascular space, and brain parenchyma. In this paper, the authors review the previous and current concepts of CSF motion in the central nervous system using various MRI techniques.

Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled ELVIS Trial.

OBJECTIVE: To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI. STUDY DESIGN: In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index >p97 and anterior horn width >6 mm) or high-threshold (ventricular index >p97 + 4 mm and anterior horn width >10 mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured. Automatic segmentation was used for volumetric analysis. RESULTS: The total Kidokoro score of the infants in the low-threshold group (n = 44) was lower than in the high-threshold group (n = 44; median, 8 [IQR, 5-12] vs median 12 [IQR, 9-17], respectively; P < .001). More infants in the low-threshold group had a normal or mildly increased score vs more infants in the high-threshold group with a moderately or severely increased score (46% vs 11% and 89% vs 54%, respectively; P = .002). The frontal and occipital horn ratio was lower in the low-threshold group (median, 0.42 [IQR, 0.34-0.63]) than the high-threshold group (median 0.48 [IQR, 0.37-0.68], respectively; P = .001). Ventricular cerebrospinal fluid volumes could be calculated in 47 infants and were smaller in the low-threshold group (P = .03). CONCLUSIONS: More brain injury and larger ventricular volumes were demonstrated in the high vs the low-threshold group. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation. TRIAL REGISTRATION: ISRCTN43171322.

Ten-year follow-up of a randomised trial of drainage, irrigation and fibrinolytic therapy (DRIFT) in infants with post-haemorrhagic ventricular dilatation.

BACKGROUND: The drainage, irrigation and fibrinolytic therapy (DRIFT) trial, conducted in 2003-6, showed a reduced rate of death or severe disability at 2 years in the DRIFT compared with the standard treatment group, among preterm infants with intraventricular haemorrhage (IVH) and post-haemorrhagic ventricular dilatation. OBJECTIVES: To compare cognitive function, visual and sensorimotor ability, emotional well-being, use of specialist health/rehabilitative and educational services, neuroimaging, and economic costs and benefits at school age. DESIGN: Ten-year follow-up of a randomised controlled trial. SETTING: Neonatal intensive care units (Bristol, Katowice, Glasgow and Bergen). PARTICIPANTS: Fifty-two of the original 77 infants randomised. INTERVENTIONS: DRIFT or standard therapy (cerebrospinal fluid tapping). MAIN OUTCOME MEASURES: Primary - cognitive disability. Secondary - vision; sensorimotor disability; emotional/behavioural function; education; neurosurgical sequelae on magnetic resonance imaging; preference-based measures of health-related quality of life; costs of neonatal treatment and of subsequent health care in childhood; health and social care costs and impact on family at age 10 years; and a decision analysis model to estimate the cost-effectiveness of DRIFT compared with standard treatment up to the age of 18 years. RESULTS: By 10 years of age, 12 children had died and 13 were either lost to follow-up or had declined to participate. A total of 52 children were assessed at 10 years of age (DRIFT, n = 28; standard treatment, n = 24). Imbalances in gender and birthweight favoured the standard treatment group. The unadjusted mean cognitive quotient (CQ) score was 69.3 points [standard deviation (SD) 30.1 points] in the DRIFT group compared with 53.7 points (SD 35.7 points) in the standard treatment group, a difference of 15.7 points, 95% confidence interval (CI) -2.9 to 34.2 points; p = 0.096. After adjusting for the prespecified covariates (gender, birthweight and grade of IVH), this evidence strengthened: children who received DRIFT had a CQ advantage of 23.5 points (p = 0.009). The binary outcome, alive without severe cognitive disability, gave strong evidence that DRIFT improved cognition [unadjusted odds ratio (OR) 3.6 (95% CI 1.2 to 11.0; p = 0.026) and adjusted OR 10.0 (95% CI 2.1 to 46.7; p = 0.004)]; the number needed to treat was three. No significant differences were found in any secondary outcomes. There was weak evidence that DRIFT reduced special school attendance (adjusted OR 0.27, 95% CI 0.07 to 1.05; p = 0.059). The neonatal stay (unadjusted mean difference £6556, 95% CI -£11,161 to £24,273) and subsequent hospital care (£3413, 95% CI -£12,408 to £19,234) costs were higher in the DRIFT arm, but the wide CIs included zero. The decision analysis model indicated that DRIFT has the potential to be cost-effective at 18 years of age. The incremental cost-effectiveness ratio (£15,621 per quality-adjusted life-year) was below the National Institute for Health and Care Excellence threshold. The cost-effectiveness results were sensitive to adjustment for birthweight and gender. LIMITATIONS: The main limitations are the sample size of the trial and that important characteristics were unbalanced at baseline and at the 10-year follow-up. Although the analyses conducted here were prespecified in the analysis plan, they had not been prespecified in the original trial registration. CONCLUSIONS: DRIFT improves cognitive function when taking into account birthweight, grade of IVH and gender. DRIFT is probably effective and, given the reduction in the need for special education, has the potential to be cost-effective as well. A future UK multicentre trial is required to assess efficacy and safety of DRIFT when delivered across multiple sites. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80286058. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 4. See the NIHR Journals Library website for further project information. The DRIFT trial and 2-year follow-up was funded by Cerebra and the James and Grace Anderson Trust.