Ventricular Cerebrospinal Fluid Volumes Research Articles

Abstract 16099: Life’s Essential 8 and Genetic Predisposition Predict Brain Volume Change, Mild Cognitive Impairment and Dementia Risk

Introduction: Life’s Essential 8 (LE8) are the key measures for improving and maintaining cardiovascular health, as defined by the American Heart Association in 2022. The associations of LE8 with future brain volume change, mild cognitive decline (MCI), and dementia have been unclear. Hypothesis: We hypothesized that LE8 status might be related to future brain volume change, and predict risk of MCI and all-cause dementia. Apolipoprotein E (APOE) gene and polygenic risk score (PRS) may modify the association between them. Methods: We used cohort data from UK Biobank. LE8 was categorized into low (<50 score), moderate (50-79 score), and high (≥80 score) levels. Genetic predisposition was measured by APOE e4 carrier status and a polygenic risk score (PRS) calculated based on 39 non-APOE genetic variants. Linear regression models were used to analyze LE8 every 10-score increase and change of brain volume (total and hippocampus etc.). Cox regression models were used to estimate the hazard ratio (HR) and 95%CI on the association between LE8 and MCI and dementia. Results: We included 126,785 participants with a mean (SD) age of 56.0 (8.0) years and 53.5% were female. After a median of 13.0 years follow-up, we recorded 1797 (1.4%) people with MCI, and 1055 (0.8%) with dementia. Every 10-score increase of LE8 was related to 2826.11mm 3 increase in total brain volume, 8.41 and 12.04 mm 3 increase in left and right hippocampus volume respectively, while 393.41mm 3 decrease in ventricular cerebrospinal fluid volume (p values all <0.001). Compared to people with a low LE8, those with a high LE8 were associated with decreased risk of MCI (HR 0.54, 95% CI 0.44-0.68) and dementia (0.63, 0.47-0.85). Compared to people with high LE8 and no APOE e4 allele, those with low LE8 and one or two APOE e4 alleles were associated with increased risk of MCI (2.36, 1.69-3.29) and dementia (4.37, 2.86-6.68). The joint effects of LE8 and PRS showed that people with high LE8 and low PRS had lower risk of dementia. Conclusions: High LE8 was associated with increased total brain volume, hippocampus volume and decreased ventricular cerebrospinal fluid volume. Higher LE8 was also linked to reduced risk of MCI and dementia. There were joint effects between LE8 and APOE, PRS on MCI and dementia risk.

Evaluation of transorbital sonography measures of optic nerve diameter in the context of global and regional brain volume in multiple sclerosis

Transorbital sonography (TOS) could be a swift and convenient method to detect the atrophy of the optic nerve, possibly providing a marker that might reflect other quantitative structural markers of multiple sclerosis (MS). Here we evaluate the utility of TOS as a complementary tool for assessing optic nerve atrophy, and investigate how TOS-derived measures correspond to volumetric brain markers in MS. We recruited 25 healthy controls (HC) and 45 patients with relapsing–remitting MS and performed B-mode ultrasonographic examination of the optic nerve. Patients additionally underwent MRI scans to obtain T1-weighted, FLAIR and STIR images. Optic nerve diameters (OND) were compared between HC, MS patients with and without history of optic neuritis (non-ON) using a mixed-effects ANOVA model. The relationship between within-subject-average OND and global and regional brain volumetric measures was investigated using FSL SIENAX, voxel-based morphometry and FSL FIRST. OND was significantly different between HC-MS (HC = 3.2 ± 0.4 mm, MS = 3 ± 0.4 mm; p < 0.019) and we found significant correlation between average OND and normalised whole brain (β = 0.42, p < 0.005), grey matter (β = 0.33, p < 0.035), white matter (β = 0.38, p < 0.012) and ventricular cerebrospinal fluid volume (β = − 0.36, p < 0.021) in the MS group. History of ON had no impact on the association between OND and volumetric data. In conclusion, OND is a promising surrogate marker in MS, that can be simply and reliably measured using TOS, and its derived measures correspond to brain volumetric measures. It should be further explored in larger and longitudinal studies.

Automated analysis of low-field brain MRI in cerebral malaria.

A central challenge of medical imaging studies is to extract biomarkers that characterize disease pathology or outcomes. Modern automated approaches have found tremendous success in high-resolution, high-quality magnetic resonance images. These methods, however, may not translate to low-resolution images acquired on magnetic resonance imaging (MRI) scanners with lower magnetic field strength. In low-resource settings where low-field scanners are more common and there is a shortage of radiologists to manually interpret MRI scans, it is critical to develop automated methods that can augment or replace manual interpretation, while accommodating reduced image quality. We present a fully automated framework for translating radiological diagnostic criteria into image-based biomarkers, inspired by a project in which children with cerebral malaria (CM) were imaged using low-field 0.35 Tesla MRI. We integrate multiatlas label fusion, which leverages high-resolution images from another sample as prior spatial information, with parametric Gaussian hidden Markov models based on image intensities, to create a robust method for determining ventricular cerebrospinal fluid volume. We also propose normalized image intensity and texture measurements to determine the loss of gray-to-white matter tissue differentiation and sulcal effacement. These integrated biomarkers have excellent classification performance for determining severe brain swelling due toCM.

The role of head circumference and cerebral volumes to phenotype male adults with autism spectrum disorder.

BackgroundAutism spectrum disorder (ASD) has been repeatedly associated with enlargements of head circumference in children with ASD. However, it is unclear if these enlargements persist into adulthood. This is the first study to investigate head circumference in a large sample of adults with ASD.MethodsWe apply a fully automated magnetic resonance imaging (MRI) based measurement approach to compute head circumference by combining 3D and 2D image processing. Head circumference was compared between male adults with ASD (n = 120) and healthy male controls (n = 136), from the Autism Brain Imaging Data Exchange (ABIDE) database. To explain which brain alterations drive our results, secondary analyses were performed for 10 additional morphological brain metrics.ResultsASD subjects showed an increase in head circumference (p = .0018). In addition, ASD patients had increased ventricular surface area (SA) (p = .0013). Intracranial volume, subarachnoidal cerebrospinal fluid (CSF) volume, and gray matter volume explained 50% of head circumference variance. Using a linear support vector machine, we gained an ASD classification accuracy of 73% (sensitivity 92%, specificity 68%) using head circumference and brain‐morphological metrics as input features. Head circumference, ventricular SA, ventricular CSF volume, and ventricular asymmetry index contributed to 85% of feature weighting relevant for classification.ConclusionOur results suggest that head circumference increases in males with ASD persist into adulthood. Results may be driven by morphological alterations of ventricular CSF. The presented approach for an automated head circumference measurement allows for the retrospective investigation of large MRI datasets in neuropsychiatric disorders.

Associations Between Brain Volumes and Cognitive Tests with Hypertensive Burden in UK Biobank.

Background:Mid-life hypertension is an established risk factor for cognitive impairment and dementia and related to greater brain atrophy and poorer cognitive performance. Previous studies often have small sample sizes from older populations that lack utilizing multiple measures to define hypertension such as blood pressure, self-report information, and medication use; furthermore, the impact of the duration of hypertension is less extensively studied.Objective:To investigate the relationship between hypertension defined using multiple measures and length of hypertension with brain measure and cognition.Methods:Using participants from the UK Biobank MRI visit with blood pressure measurements (n = 31,513), we examined the cross-sectional relationships between hypertension and duration of hypertension with brain volumes and cognitive tests using generalized linear models adjusted for confounding.Results:Compared with normotensives, hypertensive participants had smaller brain volumes, larger white matter hyperintensities (WMH), and poorer performance on cognitive tests. For total brain, total grey, and hippocampal volumes, those with greatest duration of hypertension had the smallest brain volumes and the largest WMH, ventricular cerebrospinal fluid volumes. For other subcortical and white matter microstructural regions, there was no clear relationship. There were no significant associations between duration of hypertension and cognitive tests.Conclusion:Our results show hypertension is associated with poorer brain and cognitive health however, the impact of duration since diagnosis warrants further investigation. This work adds further insights by using multiple measures defining hypertension and analysis on duration of hypertension which is a substantial advance on prior analyses—particularly those in UK Biobank which present otherwise similar analyses on smaller subsets.

D* from diffusion MRI reveals a correspondence between ventricular cerebrospinal fluid volume and flow in the ischemic rodent model

Quantitative measurement of cerebrospinal fluid (CSF) flow and volume and longitudinal monitoring of CSF dynamics provide insights into the compensatory characteristics of post-stroke CSF. In this study, we compared the MRI pseudo-diffusion index (D*) of live and sacrificed rat brains to confirm the effect of ventricular CSF flow on diffusion signals. We observed the relationship between the CSF peak velocities and D* through Monte Carlo (MC) simulations to further understand the source of D* contrast. We also determined the dominant CSF flow using D* in three directions. Finally, we investigated the dynamic evolutions of ventricular CSF flow and volume in a stroke rat model (n = 8) from preoperative to up to 45 days after surgery and determined the correlation between ventricular CSF volume and flow. MC simulations showed a strong positive correlation between the CSF peak velocity and D* (r = 0.99). The dominant CSF flow variations in the 3D ventricle could be measured using the maximum D* map. A longitudinal positive correlation between ventricular CSF volume and D* was observed in the lateral (r = 0.74) and ventral-third (r = 0.81) ventricles, respectively. The directional D* measurements provide quantitative CSF volume and flow information, which would provide useful insights into ischemic stroke with diffusion MRI.

Monro-Kellie Hypothesis: Increase of Ventricular CSF Volume after Surgical Closure of a Spinal Dural Leak in Patients with Spontaneous Intracranial Hypotension.

CSF loss in spontaneous intracranial hypotension disrupts a well-regulated equilibrium. We aimed to evaluate the volume shift between intracranial compartments in patients with spontaneous intracranial hypotension before and after surgical closure of the underlying spinal dural breach. In total, 19 patients with spontaneous intracranial hypotension with a proved spinal CSF leak investigated at our institution between July 2014 and March 2017 (mean age, 41.8 years; 13 women) were included. Brain MR imaging-based volumetry at baseline and after surgery was performed with FreeSurfer. In addition, the spontaneous intracranial hypotension score, ranging from 0 to 9, with 0 indicating very low and 9 very high probability of spinal CSF loss, was calculated. Total mean ventricular CSF volume significantly increased from baseline (15.3 mL) to posttreatment MR imaging (18.0 mL), resulting in a mean absolute and relative difference, +2.7 mL and +18.8% (95% CI, +1.2 to +3.9 mL; P < .001). The change was apparent in the early follow-up (mean, 4 days). No significant change in mean total brain volume was observed (1136.9 versus 1133.1 mL, P = .58). The mean spontaneous intracranial hypotension score decreased from 6.9 ± 1.5 at baseline to 2.9 ± 1.5 postoperatively. Our study demonstrated a substantial increase in ventricular CSF volume in the early follow-up after surgical closure of the underlying spinal dural breach and may provide a causal link between spinal CSF loss and spontaneous intracranial hypotension. The concomitant decrease in the spontaneous intracranial hypotension score postoperatively implies the restoration of an equilibrium within the CSF compartment.

Brain volume changes in spontaneous intracranial hypotension: Revisiting the Monro-Kellie doctrine.

In the application of the Monro-Kellie doctrine in spontaneous intracranial hypotension, the brain tissue volume is generally considered as a fixed constant. Traditionally, cerebral venous dilation is thought to compensate for decreased cerebrospinal fluid. However, whether brain tissue volume is invariable has not yet been explored. The objective of this study is to evaluate whether brain tissue volume is fixed or variable in spontaneous intracranial hypotension patients using automatic quantitative methods. This retrospective and longitudinal study analyzed spontaneous intracranial hypotension patients between 1 January 2007 and 31 July 2015. Voxel-based morphometry was used to examine brain volume changes during and after the resolution of spontaneous intracranial hypotension. Brain structure volume was analyzed using Statistical Parametric Mapping version 12 and FMRIB Software Library v6.0. Post-treatment neuroimages were used as surrogate baseline measures. Forty-four patients with spontaneous intracranial hypotension were analyzed (mean [standard deviation] age, 37.8 [8.5] years; 32 female and 12 male). The whole brain tissue volume was decreased during spontaneous intracranial hypotension compared to follow-up (1180.3 [103.5] mL vs. 1190.4 [93.1] mL, difference: -10.1 mL [95% confidence interval: -18.4 to -1.8 mL], p = 0.019). In addition, ventricular cerebrospinal fluid volume was decreased during spontaneous intracranial hypotension compared to follow-up (15.8 [6.1] mL vs. 18.9 [6.9] mL, difference: -3.2 mL [95% confidence interval: -4.5 to -1.8 mL], p < 0.001). Longer anterior epidural cerebrospinal fluid collections, as measured by number of vertebral segments, were associated with greater reduction of ventricular cerebrospinal fluid volume (Pearson's r = -0.32, p = 0.036). The current study found the brain tissue volume and ventricular cerebrospinal fluid are decreased in spontaneous intracranial hypotension patients. The change in ventricular cerebrospinal fluid volume, but not brain tissue volume change, was associated with the severity of spinal cerebrospinal fluid leakage. These results challenge the assumption that brain tissue volume is a fixed constant.

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

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. In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index>p97 and anterior horn width >6mm) or high-threshold (ventricular index>p97+4mm and anterior horn width >10mm) 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. 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). More brain injury and larger ventricular volumes were demonstrated in the high vs the low-thresholdgroup. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation. ISRCTN43171322.

Diffusion Tensor Imaging of the Superior Thalamic Radiation and Cerebrospinal Fluid Distribution in Idiopathic Normal Pressure Hydrocephalus.

Ventricular enlargement in elderly raises a challenging differential diagnosis to physicians. While Alzheimer's disease is the most common form of dementia, idiopathic normal pressure hydrocephalus (iNPH) constitutes a potentially reversible syndrome. iNPH has a unique pathophysiology pertaining to cerebrospinal fluid (CSF) dynamics and periventricular white matter. We aimed to determine the effects of iNPH on periventricular white matter bundles and to further characterize its ventricular and sulcal CSF distribution by using diffusion tensor tractography (DTT) and CSF volumetrics on high resolution T1-weighted magnetic resonance imaging data. Deterministic DTT and validated volumetric parcellation were performed on 20 healthy elderly, 13 Alzheimer's disease (AD), and 9 iNPH patients. The superior thalamic radiation, corticospinal tract, and dentatorubrothalamic tract were traced and quantified using DTI studio software. Cloud-based volumetric parcellation was also performed on 138 healthy subjects across the lifespan, 13 AD, and 9 iNPH-patients. Ventricular and sulcal CSF volumes in the three groups were compared. Combining increased mean diffusivity of the superior thalamic radiation with ventricular volume resulted in clear separation of iNPH from the AD and age-matched healthy subject groups. Additionally, ventricular to sulcal CSF ratio, utilizing fully automated methods, was significantly greater in the iNPH patients compared to AD and healthy age-matched controls. Combined microstructural (DTT) and macrostructural (ventricular volume) changes is a promising radiological approach in studying ventriculomegaly. Automated estimation of the disproportionate ventricular and sulcal CSF ratio in patients presenting with ventriculomegaly may be important as radiologic markers in differentiating iNPH from other causes of ventriculomegaly.

Quantitative Diffusion Tensor Tractography of the Superior Thalamic Radiation and the Corticospinal tract in relation to Ventricular and Sulcal CSF Volumes in Patients with Ventriculomegaly Diagnosed with Normal Pressure Hydrocephalus (P4.192)

Quantitative Diffusion Tensor Tractography of the Superior Thalamic Radiation and the Corticospinal tract in relation to Ventricular and Sulcal CSF Volumes in Patients with Ventriculomegaly Diagnosed with Normal Pressure Hydrocephalus (P4.192)

Four-way multimodal fusion of 7T imaging data using an mCCA+jICA model in first-episode schizophrenia.

Acquisition of multimodal brain imaging data for the same subject has become more common leading to a growing interest in determining the intermodal relationships between imaging modalities to further elucidate the pathophysiology of schizophrenia. Multimodal data have previously been individually analyzed and subsequently integrated; however, these analysis techniques lack the ability to examine true modality inter-relationships. The utilization of a multiset canonical correlation and joint independent component analysis (mCCA + jICA) model for data fusion allows shared or distinct abnormalities between modalities to be examined. In this study, first-episode schizophrenia patients (nSZ =19) and matched controls (nHC =21) completed a resting-state functional magnetic resonance imaging (fMRI) scan at 7 T. Grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), and amplitude of low frequency fluctuation (ALFF) maps were used as features in a mCCA + jICA model. Results of the mCCA + jICA model indicated three joint group-discriminating components (GM-CSF, WM-ALFF, GM-ALFF) and two modality-unique group-discriminating components (GM, WM). The joint component findings are highlighted by GM basal ganglia, somatosensory, parietal lobe, and thalamus abnormalities associated with ventricular CSF volume; WM occipital and frontal lobe abnormalities associated with temporal lobe function; and GM frontal, temporal, parietal, and occipital lobe abnormalities associated with caudate function. These results support and extend major findings throughout the literature using independent single modality analyses. The multimodal fusion of 7T data in this study provides a more comprehensive illustration of the relationships between underlying neuronal abnormalities associated with schizophrenia than examination of imaging data independently.

Spaceflight-Induced Visual Impairment and Globe Deformations in Astronauts Are Linked to Orbital Cerebrospinal Fluid Volume Increase.

Most of the astronauts onboard the International Space Station (ISS) develop visual impairment and ocular structural changes that are not fully reversible upon return to earth. Current understanding assumes that the so-called visual impairments/intracranial pressure (VIIP) syndrome is caused by cephalad vascular fluid shift. This study assesses the roles of cerebrospinal fluid (CSF) and intracranial pressure (ICP) in VIIP. Seventeen astronauts, 9 who flew a short-duration mission on the space shuttle (14.1 days [SD 1.6]) and 7 who flew a long-duration mission on the ISS (188 days [SD 22]) underwent MRI of the brain and orbits to assess the pre-to-post spaceflight changes in four categories: VIIP severity measures: globe flattening and nerve protrusion; orbital and ventricular CSF volumes; cortical gray and white matter volumes; and MR-derived ICP (MRICP). Significant pre-to-post-flight increase in globe flattening and optic nerve protrusion occurred only in the long-duration cohort (0.031 [SD 0.019] vs -0.001 [SD 0.006], and 0.025 [SD 0.013] vs 0.001 [SD 0.006]; p < 0.00002 respectively). The increased globe deformations were associated with significant increases in orbital and ventricular CSF volumes, but not with increased tissue vascular fluid content. Additionally, a moderate increase in MRICP of 6 mmHg was observed in only two ISS astronauts with large ocular structure changes. These findings are evidence for the primary role of CSF and a lesser role for intracranial cephalad fluid-shift in the formation of VIIP. VIIP is caused by a prolonged increase in orbital CSF spaces that compress the globes' posterior pole, even without a large increase in ICP.

Spaceflight-induced changes in white matter hyperintensity burden in astronauts.

To assess the effect of weightlessness and the respective roles of CSF and vascular fluid on changes in white matter hyperintensity (WMH) burden in astronauts. We analyzed prespaceflight and postspaceflight brain MRI scans from 17 astronauts, 10 who flew a long-duration mission on the International Space Station (ISS) and 7 who flew a short-duration mission on the Space Shuttle. Automated analysis methods were used to determine preflight to postflight changes in periventricular and deep WMH, CSF, and brain tissue volumes in fluid-attenuated inversion recovery and high-resolution 3-dimensional T1-weighted imaging. Differences between cohorts and associations between individual measures were assessed. The short-term reversibility of the identified preflight to postflight changes was tested in a subcohort of 5 long-duration astronauts who had a second postflight MRI scan 1 month after the first postflight scan. Significant preflight to postflight changes were measured only in the long-duration cohort and included only the periventricular WMH and ventricular CSF volumes. Changes in deep WMH and brain tissue volumes were not significant in either cohort. The increase in periventricular WMH volume was significantly associated with an increase in ventricular CSF volume (ρ = 0.63, p = 0.008). A partial reversal of these increases was observed in the long-duration subcohort with a 1-month follow-up scan. Long-duration exposure to microgravity is associated with an increase in periventricular WMH in astronauts. This increase was linked to an increase in ventricular CSF volume documented in ISS astronauts. There was no associated change in or abnormal levels of WMH volumes in deep white matter as reported in U-2 high-altitude pilots.

Correlation of CSF flow using phase-contrast MRI with ventriculomegaly and CSF opening pressure in mucopolysaccharidoses

BackgroundVery little is known about the incidence and prevalence of hydrocephalus in patients with mucopolysaccharidoses (MPS). The biggest challenge is to distinguish communicating hydrocephalus from ventricular dilatation secondary to brain atrophy, because both conditions share common clinical and neuroradiological features. The main purpose of this study is to assess the relationship between ventriculomegaly, brain and cerebrospinal fluid (CSF) volumes, aqueductal and cervical CSF flows, and CSF opening pressure in MPS patients, and to provide potential biomarkers for abnormal CSF circulation.MethodsForty-three MPS patients (12 MPS I, 15 MPS II, 5 MPS III, 9 MPS IV A and 2 MPS VI) performed clinical and developmental tests, and T1, T2, FLAIR and phase-contrast magnetic resonance imaging (MRI) followed by a lumbar puncture with the CSF opening pressure assessment. For the analysis of MRI variables, we measured the brain and CSF volumes, white matter (WM) lesion load, Evans’ index, third ventricle width, callosal angle, dilated perivascular spaces (PVS), craniocervical junction stenosis, aqueductal and cervical CSF stroke volumes, and CSF glycosaminoglycans concentration.ResultsAll the scores used to assess the supratentorial ventricles enlargement and the ventricular CSF volume presented a moderate correlation with the aqueductal CSF stroke volume (ACSV). The CSF opening pressure did not correlate either with the three measures of ventriculomegaly, or the ventricular CSF volume, or with the ACSV. Dilated PVS showed a significant association with the ventriculomegaly, ventricular CSF volume and elevated ACSV.ConclusionsIn MPS patients ventriculomegaly is associated with a severe phenotype, increased cognitive decline, WM lesion severity and enlarged PVS. The authors have shown that there are associations between CSF flow measurements and measurements related to CSF volumetrics. There was also an association of volumetric measurements with the degree of dilated PVS.

DISPROPORTIONATE INCREASE IN VENTRICULAR RELATIVE TO SULCAL CEREBROSPINAL FLUID VOLUME AND COGNITIVE FUNCTIONING: THE SMART-MR STUDY

Global cerebral volume loss is associated with neurodegenerative diseases but also with normal aging. To understand their etiology studies aim to pinpoint specific brain tissue regions that are affected early in the disease process or investigate disproportionate volume loss of specific brain tissue regions. Here, we take a different perspective by examining the disproportionate increase in ventricular relative to sulcal cerebrospinal fluid (CSF) and the association with age and cognitive functioning. Within the SMART-MR study a 1.5T MRI was performed in 1232 patients with vascular disease (mean age 58±10 years, 80% male). Automated brain segmentation was used to quantify brain tissue volumes, CSF and lesions. The ventricular-sulcal CSF (VS) ratio was calculated by dividing ventricular volume by sulcal CSF volume. Z-scores for the domains memory and executive functioning were calculated. Multiple linear regression analysis was used to estimate the associations of VS ratio with age and with memory performance and executive functioning. The mean ventricular and sulcal CSF volumes were 31±15ml and 276±43ml, respectively. The VS ratio was 0.11±0.05. Pearson correlation coefficients between the natural log-transformed VS ratio and total brain volume, intracranial volume, brain parenchymal fraction, log-deep WMH, log-periventricular WMH, and age were 0.02 (p=0.52), 0.18, -0.40, 0.21, 0.33, and 0.35, respectively (p-values <0.0001). The VS ratio increased with older age (p<0.0001) independent of sex, total WMH, and ICV. It was also significantly associated with poorer memory performance (b of Z-score=-1.29; 95% CI -2.41 to -0.17) and poorer executive functioning (b of Z-score=-1.72; 95% CI -2.78 to -0.67), adjusted for age, sex, log-WMH, and ICV. In this population, a disproportionate increase in ventricular volume relative to sulcal CSF is associated with older age and with poorer memory and executive functioning. Future studies should investigate to what extent this is a biomarker of accelerated cognitive aging.

Association between total-Tau and brain atrophy one year after first-ever stroke

BackgroundAlthough the most serious consequence of neuronal ischemia is acute neuronal death, mounting evidence suggests similarities between stroke and neurodegenerative disease. Brain atrophy visualized on structural MRI and pathological cerebrospinal fluid (CSF) concentrations of microtubule-associated protein tau (T-tau) and phosphorylated microtubule-associated protein tau indicate neurofibrillary degeneration. We aimed to explore the association between CSF T-tau and brain atrophy 1 year post-stroke.MethodsWe included 210 patients with first-ever ischemic stroke or transitory ischemic attack without pre-existing cognitive impairment. After 12 months, subjects underwent MRI, and CSF biomarkers were assessed. Using SIENAX (part of FSL), ventricular CSF volume and total brain volume were estimated and normalized for subject head size. The association between T-tau as explanatory variable and ventricular and total brain volume as outcome variables were studied using linear regression.ResultsOne hundred eighty-two patients completed the follow-up. Forty-four had a lumbar puncture. Of these, 31 had their MRI with identical scan parameters. Mean age was 70.2 years (SD 11.7). Ventricular volume on MRI was significantly associated with age, but not with gender. In the multiple regression model, there was a significant association between T-tau and both ventricular (beta 0.44, 95% CI 376.3, 394.9, p = 0.021) and global brain volume (beta −0.50, 95% CI −565.9, −78.3, p = 0.011). There was no significant association between CSF T-tau 1 year post-stroke and baseline volumes.ConclusionT-tau measured 1 year post-stroke is associated with measures of brain atrophy. The findings indicate that acute stroke may enhance or trigger tau-linked neurodegeneration with loss of neurons.Trial registrationClinicaltrials.gov NCT00506818, July 23, 2007.Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.

Alzheimer's Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not Correlate with CSF Volumes or CSF Production Rate.

Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively. To examine the outstanding question if CSF concentrations of AD associated biomarkers are influenced by variations in CSF volumes, CSF production rate, and intracranial pressure in healthy individuals. CSF concentrations of Aβ42, P-tau, and T-tau, as well as a number of other AD-related CSF biomarkers were analyzed together with intracranial subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic resonance imaging volumetric measurements, and CSF production rate in 19 cognitively normal healthy subjects (mean age 70.6, SD 3.6 years). Negative correlations were seen between the concentrations of three CSF biomarkers (albumin ratio, Aβ38, and Aβ40), and ventricular CSF volume, but apart from this finding, no significant correlations were observed. These results speak against inter-individual variations in CSF volume and production rate as important confounds in the AD biomarker research field.

Comparative observational study on the clinical presentation, intracranial volume measurements, and intracranial pressure scores in patients with either Chiari malformation Type I or idiopathic intracranial hypertension.

OBJECTIVE Several lines of evidence suggest common pathophysiological mechanisms in Chiari malformation Type I (CMI) and idiopathic intracranial hypertension (IIH). It has been hypothesized that tonsillar ectopy, a typical finding in CMI, is the result of elevated intracranial pressure (ICP) combined with a developmentally small posterior cranial fossa (PCF). To explore this hypothesis, the authors specifically investigated whether ICP is comparable in CMI and IIH and whether intracranial volumes (ICVs) are different in patients with CMI and IIH, which could explain the tonsillar ectopy in CMI. The authors also examined whether the symptom profile is comparable in these 2 patient groups. METHODS The authors identified all CMI and IIH patients who had undergone overnight diagnostic ICP monitoring during the period from 2002 to 2014 and reviewed their clinical records and radiological examinations. Ventricular CSF volume (VV), PCF volume (PCFV), and total ICV were calculated from initial MRI studies by using volumetric software. The static and pulsatile ICP scores during overnight monitoring were analyzed. Furthermore, the authors included a reference (REF) group consisting of patients who had undergone ICP monitoring due to suspected idiopathic normal-pressure hydrocephalus or chronic daily headache and showed normal pressure values. RESULTS Sixty-six patients with CMI and 41 with IIH were identified, with comparable demographics noted in both groups. The occurrence of some symptoms (headache, nausea, and/or vomiting) was comparable between the cohorts. Dizziness and gait ataxia were significantly more common in patients with CMI, whereas visual symptoms, diplopia, and tinnitus were significantly more frequent in patients with IIH. The cranial volume measurements (VV, PCFV, and ICV) of the CMI and IIH patients were similar. Notably, 7.3% of the IIH patients had tonsillar descent qualifying for diagnosis of CMI (that is, > 5 mm). The extent of tonsillar ectopy was significantly different between the CMI and IIH cohorts (p < 0.001) but also between these 2 cohorts and the REF group. Pulsatile ICP was elevated in both cohorts without any significant between-group differences; however, static ICP was significantly higher (p < 0.001) in the IIH group. CONCLUSIONS This study showed comparable and elevated pulsatile ICP, indicative of impaired intracranial compliance, in both CMI and IIH cohorts, while static ICP was higher in the IIH cohort. The data did not support the hypothesis that reduced PCFV combined with increased ICP causes tonsillar ectopy in CMI. Even though impaired intracranial compliance seems to be a common pathophysiological mechanism behind both conditions, the mechanisms explaining the different clinical and radiological presentations of CMI and IIH remain undefined.

Comparison of pulsatile and static pressures within the intracranial and lumbar compartments in patients with Chiari malformation type 1: a prospective observational study.

In Chiari malformation type 1 (CMI), the obstruction of cerebrospinal fluid (CSF) flow through the foramen magnum is believed to cause alterations of intracranial pressure (ICP) pulsations. Foramen magnum decompression (FMD) is therefore considered a treatment of choice. However, the pathophysiology of CMI is poorly understood and it remains unknown how ICP alterations relate to symptoms and radiological findings. This study was undertaken to measure pulsatile pressure and its gradient between intracranial and lumbar compartments, and to determine its relationship to clinical and radiological findings. In patients with symptomatic CMI, we simultaneously measured ICP and lumbar CSF pressure, with particular focus on analysis of pulsatile pressure. Ventricular CSF volume (VV), intracranial volume (ICV) and posterior cranial fossa volume (PCFV) were calculated using volumetry software. In 26 patients (median 35 years), we found clearly abnormal or borderline values of pulsatile ICP in 18/26 patients (69 %; median 4.5 mmHg) and abnormal pulsatile pressure gradient in 17/24 patients (71 %; median 2.6 mmHg). The correlation between pulsatile ICP and the pulsatile pressure gradient was significantly positive (p < 0.001). We found no significant correlation between pulsatile or static pressure and extent of tonsillar ectopy, VV, ICV or PCFV. The pulsatile pressure gradient was significantly higher in patients with syringomyelia (p = 0.02). In this cohort, the pulsatile ICP was elevated in 69 %. The intracranial-lumbar pulsatile pressure gradient was abnormal in 71 % and significantly higher in patients with syringomyelia. The elevated pulsatile ICP significantly correlated with pulsatile pressure gradient; no similar correlation was found for static ICP. We interpret the results as providing evidence of impaired intracranial compliance as an important pathophysiological mechanism in CMI.