Microstructural White Matter Abnormalities and Cognitive Impairment After Aneurysmal Subarachnoid Hemorrhage.

Background and Purpose- Aneurysmal subarachnoid hemorrhage (aSAH) may have detrimental effects on white matter microstructure, which may in turn explain the cognitive impairments that occur often after aSAH. We investigated (1) whether the white matter microstructure is altered in patients with aSAH compared with patients with an unruptured intracranial aneurysm and (2) whether these abnormalities are associated with cognitive impairment 3 months after ictus. Methods- Forty-nine patients with aSAH and 22 patients with an unruptured intracranial aneurysm underwent 3T brain magnetic resonance imaging, including a high-resolution diffusion tensor imaging sequence. Patients with aSAH were scanned 2 weeks and 6 months after ictus. Microstructural white matter alterations were quantified by the fractional anisotropy and mean diffusivity (MD). Cognition was evaluated 3 months after ictus. Results- Patients with aSAH had higher white matter MD 2 weeks after ictus than patients with an unruptured intracranial aneurysm (mean difference±SEM, 0.3±0.01×10-3 mm2/s; P≤0.01), reflecting an abnormal microstructure. After 6 months, the MD had returned to the level of the unruptured intracranial aneurysm group. No between-group differences in fractional anisotropy were found (-0.01±0.01; P=0.16). Higher MD at 2 weeks was associated with cognitive impairment after 3 months (odds ratio per SD increase in MD, 2.6; 95% CI, 1.1-6.7). The association between MD and cognitive impairment was independent of conventional imaging markers of aSAH-related brain injury (ie, cerebral infarction, hydrocephalus, total amount of subarachnoid blood, total brain volume, or white matter hyperintensity severity). Conclusions- Patients with aSAH have temporary white matter abnormalities in the subacute phase that are associated with cognitive impairment at 3 months after ictus.

Arterial CO2 pressure changes during hypercapnia are associated with changes in brain parenchymal volume.

The Monro-Kellie hypothesis (MKH) states that volume changes in any intracranial component (blood, brain tissue, cerebrospinal fluid) should be counterbalanced by a co-occurring opposite change to maintain intracranial pressure within the fixed volume of the cranium. In this feasibility study, we investigate the MKH application to structural magnetic resonance imaging (MRI) in observing compensating intracranial volume changes during hypercapnia, which causes an increase in cerebral blood volume. Seven healthy subjects aged from 24 to 64 years (median 32), 4 males and 3 females, underwent a 3-T three-dimensional T1-weighted MRI under normocapnia and under hypercapnia. Intracranial tissue volumes were computed. According to the MKH, the significant increase in measured brain parenchymal volume (median 6.0 mL; interquartile range 4.5, 8.5; p = 0.016) during hypercapnia co-occurred with a decrease in intracranial cerebrospinal fluid (median -10.0 mL; interquartile range -13.5, -6.5; p = 0.034). These results convey several implications: (i) blood volume changes either caused by disorders, anaesthesia, or medication can affect outcome of brain volumetric studies; (ii) besides probing tissue displacement, this approach may assess the brain cerebrovascular reactivity. Future studies should explore the use of alternative sequences, such as three-dimensional T2-weighted imaging, for improved quantification of hypercapnia-induced volume changes.

Subarachnoid Hemorrhage and Cerebral Perfusion Are Associated with Brain Volume Decrease in a Cohort of Predominantly Mild Traumatic Brain Injury Patients.

Biomarkers are needed to identify traumatic brain injury (TBI) patients at risk for accelerated brain volume loss and its associated functional impairment. Subarachnoid hemorrhage (SAH) has been shown to affect cerebral volume and perfusion, possibly by induction of inflammation and vasospasm. The purpose of this study was to assess the impact of SAH due to trauma on cerebral perfusion and brain volume. For this, magnetic resonance imaging (MRI) was performed <48 h and at 90 days after TBI. The <48-h scan was used to assess SAH presence and perfusion. Brain volume changes were assessed quantitatively over time. Differences in brain volume change and perfusion were compared between SAH and non-SAH patients. A linear regression analysis with clinical and imaging variables was used to identify predictors of brain volume change. All patients had a relatively good status on admission, and 83% presented with the maximum Glasgow Coma Scale (GCS) score. Brain volume decrease was greater in the 11 SAH patients (-3.2%, interquartile range [IQR] -4.8 to -1.3%) compared with the 46 non-SAH patients (-0.4%, IQR -1.8 to 0.9%; p < 0.001). Brain perfusion was not affected by SAH, but it was correlated with brain volume change (ρ = 0.39; p < 0.01). Forty-three percent of brain volume change was explained by SAH (ß -0.40, p = 0.001), loss of consciousness (ß -0.24, p = 0.035), and peak perfusion curve signal intensity height (0.27, p = 0.012). SAH and lower perfusion in the acute phase may identity TBI patients at increased risk for accelerated brain volume loss, in addition to loss of consciousness occurrence. Future studies should determine whether the findings apply to TBI patients with worse clinical status on admission. SAH predicts brain volume decrease independent of brain perfusion. This indicates the adverse effects of SAH extend beyond vasoconstriction, and that hypoperfusion also occurs separately from SAH.

Magnetic resonance imaging and brain injury in the chronic phase after aneurysmal subarachnoid hemorrhage: A systematic review.

Background Case-fatality rates after aneurysmal subarachnoid hemorrhage have decreased over the past decades. However, many patients who survive an aneurysmal subarachnoid hemorrhage have long-term functional and cognitive impairments. Aims We sought to review all data on conventional brain MRI obtained in the chronic phase after aneurysmal subarachnoid hemorrhage to (1) analyze the proportion of patients with cerebral infarction or brain volume changes; (2) investigate baseline determinants predictive of MRI-detected damage; and (3) assess if brain damage is predictive of patient outcome. Summary of review All original data published between 1 January 2000 and 4 October 2017 was searched using the PUBMED, EMBASE, and Web of Science databases. Based on preset inclusion criteria, 15 from 5200 articles were included with a total of 996 aneurysmal subarachnoid hemorrhage patients. Quality assessment, risk of bias assessment, and level of evidence assessment were performed. The results according to aim, with levels of evidence, were: (1) 25 to 81% of aneurysmal subarachnoid hemorrhage patients show infarcts (strong); there is a higher ratio of cerebrospinal fluid-to-intracranial volume in patients compared to controls (strong); (2) there is a negative relation between age (moderate), DCI (low) and brain volume measurement outcomes; (3) lower brain parenchymal volume (strong) and the presence of infarcts or infarct volumes (moderate) are associated with a worse outcome. Conclusion Patients after aneurysmal subarachnoid hemorrhage may demonstrate brain infarcts and decreased brain parenchyma, which is related to worse outcome. Thereby, both brain infarcts and brain volume measurements could be used as outcome markers in pharmaceutical trials. Systematic Review Registration PROSPERO CRD42016040095.

The effect of physical exercise on cerebral blood flow in Alzheimer's disease.

In recent years there has been an increasing focus on the relation between cerebrovascular health, physical exercise and Alzheimer's disease. The aim of the current study was to determine the effect of moderate-to-high-intensity aerobic exercise on cerebral blood flow in patients with mild to moderate Alzheimer's disease. Fifty-one patients were randomized to either usual care or moderate-to-high intensity aerobic exercise for 16 weeks. Exercise had no consistent effect on whole brain or regional cerebral blood flow. Sixteen weeks of exercise are, therefore, not sufficient to produce a consistent increase in cerebral blood flow in a relatively small sample of Alzheimer's patients.

Fast CSF MRI for brain segmentation; Cross-validation by comparison with 3D T1-based brain segmentation methods.

OBJECTIVE: In previous work we have developed a fast sequence that focusses on cerebrospinal fluid (CSF) based on the long T2 of CSF. By processing the data obtained with this CSF MRI sequence, brain parenchymal volume (BPV) and intracranial volume (ICV) can be automatically obtained. The aim of this study was to assess the precision of the BPV and ICV measurements of the CSF MRI sequence and to validate the CSF MRI sequence by comparison with 3D T1-based brain segmentation methods. MATERIALS AND METHODS: Ten healthy volunteers (2 females; median age 28 years) were scanned (3T MRI) twice with repositioning in between. The scan protocol consisted of a low resolution (LR) CSF sequence (0:57min), a high resolution (HR) CSF sequence (3:21min) and a 3D T1-weighted sequence (6:47min). Data of the HR 3D-T1-weighted images were downsampled to obtain LR T1-weighted images (reconstructed imaging time: 1:59 min). Data of the CSF MRI sequences was automatically segmented using in-house software. The 3D T1-weighted images were segmented using FSL (5.0), SPM12 and FreeSurfer (5.3.0). RESULTS: The mean absolute differences for BPV and ICV between the first and second scan for CSF LR (BPV/ICV: 12±9/7±4cc) and CSF HR (5±5/4±2cc) were comparable to FSL HR (9±11/19±23cc), FSL LR (7±4, 6±5cc), FreeSurfer HR (5±3/14±8cc), FreeSurfer LR (9±8, 12±10cc), and SPM HR (5±3/4±7cc), and SPM LR (5±4, 5±3cc). The correlation between the measured volumes of the CSF sequences and that measured by FSL, FreeSurfer and SPM HR and LR was very good (all Pearson's correlation coefficients >0.83, R2 .67-.97). The results from the downsampled data and the high-resolution data were similar. CONCLUSION: Both CSF MRI sequences have a precision comparable to, and a very good correlation with established 3D T1-based automated segmentations methods for the segmentation of BPV and ICV. However, the short imaging time of the fast CSF MRI sequence is superior to the 3D T1 sequence on which segmentation with established methods is performed.

Regionality of disease progression predicts prognosis in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurological syndrome in which motor neurons degenerate relentlessly. Although the site of onset and the rate of spread have been studied extensively, little is known about whether focal as opposed to diffuse disease affects prognosis. We therefore tested the hypothesis that regionality of disease burden is a prognostic factor in ALS. We analysed clinical data from two large multicentre, longitudinal trials. Regionality was defined as the difference in progression rates in three domains as measured by the revised ALS Functional Rating Scale, omitting the respiratory domain from analysis. We used death by trial end as the outcome variable and tested this by logistic regression against predictor variables including regionality and overall rate of disease progression. There were 561 patients. Regionality of disease was independently associated with significantly higher chance of death by study end (odds ratio most diffuse against most focal category 0.354 (0.191, 0.657), p = 0.001), with a direct relationship between degree of regionality and odds of death. We have shown using clinical trial data that focal disease is associated with a worse prognosis in ALS. Measures of regionality warrant further independent consideration in the development of future prognostic models.