Brain arterial dilatation modifies the association between extracranial pulsatile hemodynamics and brain perivascular spaces: the Northern Manhattan Study.

Pulsatile hemodynamics are associated with brain small perivascular spaces (SPVS). It is unknown whether the stiffness of intermediary arteries connecting the aorta and brain modifies this association. Participants from the Northern Manhattan Study were assessed for SPVS (defined as ≤3 mm T1 voids) and white matter hyperintensity volume (WMH) using MRI. Middle (MCA) and anterior cerebral arterial (ACA) diameters (measured on time-of-flight MRA) and CCA strain (assessed by ultrasound) were used as surrogates of stiffness. Brachial and aortic pulse pressure (PP) and aortic augmentation index (Aix, assessed by applanation tonometry) were used as markers of pulsatility. We tested whether stiffness in intermediary arteries modifies the association between extracranial pulsatility with SPVS and WMH. We found that among 941 participants (mean age 71 ± 9 years, 60% women, 66% Hispanic), the right MCA/ACA diameter was associated with right anterior SPVS (B = 0.177, P = 0.002). Brachial PP was associated with right anterior SPVS (B = 0.003, P = 0.02), and the effect size was bigger with right MCA/ACA diameter in the upper tertile (P = 0.001 for the interaction). The association between right CCA strain and ipsilateral SPVS was modified by MCA/ACA diameter, with the largest effect size in those with ipsilateral MCA/ACA diameter in the upper tertile (P = 0.001 for the interaction). Similar dose-effects and statistical interactions were replicated using aortic AIx or aortic PP. We found no evidence of effect modification between pulsatile measures and WMH by stiffness measures. In summary, pulsatile hemodynamics relate to brain SPVS, and the association is the strongest among individuals with dilated brain arteries.

Regional Subclinical Cerebrovascular Disease Is Associated with Balance in an Elderly Multi-Ethnic Population.

INTRODUCTION: White matter hyperintensity volume (WMHV) and subclinical brain infarcts (SBI) are associated with impaired mobility, but less is known about the association of WMHV in specific brain regions. We hypothesized that anterior WMHV would be associated with lower scores on the Short Physical Performance Battery (SPPB), a well-validated mobility scale. METHODS: The SPPB was measured a median of 5 years after enrollment into the Northern Manhattan MRI sub study. Volumetric distributions for WMHV in 14 brain regions as a proportion of total cranial volume were determined. Multi-variable linear regression was performed to examine the association of SBI and regional log-WMHV with the SPPB score. RESULTS: Among 668 participants with SPPB measurements (mean 74 ± 9 years, 37% male and 70% Hispanic), the mean SPPB score was 8.2 ± 2.9. Total (beta = -0.3 per SD, p = 0.001), anterior periventricular (beta = -0.4 per SD, p = 0.001), parietal (beta = -0.2 per SD, p = 0.02) and frontal (beta = -0.3 per SD, p = 0.002) WMHVs were associated with SPPB; other WMHV and SBI were not associated with the SPPB. CONCLUSIONS: WMHV, especially in the anterior -cerebral regions, is associated with a lower SPPB. Prevention of subclinical cerebrovascular disease is a potential target to prevent physical decline in the elderly.

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

OBJECTIVE: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Periventricular White Matter Hyperintensities and Functional Decline.

BACKGROUND/OBJECTIVES: We previously showed that global brain white matter hyperintensity volume (WMHV) was associated with accelerated long-term functional decline. The objective of the current study was to determine whether WMHV in particular brain regions is more predictive of functional decline. DESIGN: Prospective population-based study. SETTING: Northern Manhattan magnetic resonance imaging (MRI) study. PARTICIPANTS: Individuals free of stroke at baseline (N = 1,195; mean age 71 ± 9; n = 460 (39%) male). MEASUREMENTS: Participants had brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences. Volumetric WMHV distribution across 14 brain regions (brainstem; cerebellum; bilateral frontal, occipital, temporal, and parietal lobes; and bilateral anterior and posterior periventricular white matter (PVWM)) was determined using a combination of bimodal image intensity distribution and atlas-based methods. Participants had annual functional assessments using the Barthel Index (BI) (range 0-100) over a mean of 7.3 years and were followed for stroke, myocardial infarction (MI), and mortality. Because there were multiple collinear variables, least absolute shrinkage and selection operator (LASSO) regression-selected regional WMHV variables most associated with outcomes and adjusted generalized estimating equations models were used to estimate associations with baseline BI and change over time. RESULTS: Using LASSO regularization, only right anterior PVWM was found to meet criteria for selection, and each standard deviation greater WMHV was associated with accelerated functional decline of 0.95 additional BI points per year (95% confidence interval (CI) = -1.20 to -0.70) in an unadjusted model, -0.92 points per year (95% CI = -1.18 to -0.67) with baseline covariate adjustment, and -0.87 points per year (95% CI = -1.12 to -0.62) after adjusting for incident stroke and MI. CONCLUSION: In this large population-based study with long-term repeated measures of function, periventricular WMHV was particularly associated with accelerated functional decline.

Differential Effect of Left vs. Right White Matter Hyperintensity Burden on Functional Decline: The Northern Manhattan Study.

Asymmetry of brain dysfunction may disrupt brain network efficiency. We hypothesized that greater left-right white matter hyperintensity volume (WMHV) asymmetry was associated with functional trajectories. Methods: In the Northern Manhattan Study, participants underwent brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences, with baseline interview and examination. Volumetric WMHV distribution across 14 brain regions was determined separately by combining bimodal image intensity distribution and atlas based methods. Participants had annual functional assessments with the Barthel index (BI, range 0-100) over a mean of 7.3 years. Generalized estimating equations (GEE) models estimated associations of regional WMHV and regional left-right asymmetry with baseline BI and change over time, adjusted for baseline medical risk factors, sociodemographics, and cognition, and stroke and myocardial infarction during follow-up. Results: Among 1,195 participants, greater WMHV asymmetry in the parietal lobes (-8.46 BI points per unit greater WMHV on the right compared to left, 95% CI -3.07, -13.86) and temporal lobes (-2.48 BI points, 95% CI -1.04, -3.93) was associated with lower overall function. Greater WMHV asymmetry in the parietal lobes (-1.09 additional BI points per year per unit greater WMHV on the left compared to right, 95% CI -1.89, -0.28) was independently associated with accelerated functional decline. Conclusions: In this large population-based study with long-term repeated measures of function, greater regional WMHV asymmetry was associated with lower function and functional decline. In addition to global WMHV, WHMV asymmetry may be an important predictor of long-term functional status.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Systemic Atherosclerosis Relate to Brain Arterial Diameters: The Northern Manhattan Study.

BACKGROUND: Phenotypic expressions of arterial disease vary throughout the body and it is not clear to what extent systemic atherosclerosis influences brain arterial remodeling. We aim to test the hypothesis that systemic atherosclerosis is associated with brain arterial diameters. METHODS: Stroke-free participants in the Northern Manhattan Study MRI subcohort in whom carotid ultrasound, transthoracic echocardiogram, and brain MRA (n = 482) were performed were included in this analysis. Brain arterial diameters were measured with semi-automated software as continuous and categorical variables. Ultrasound and echocardiography provided the sum of maximum carotid plaque thickness (sMCPT) and aortic plaque thickness. Associations between brain arterial diameters and aortic and carotid plaque thickness were assessed with semi-parametric generalized additive models. RESULTS: Aortic plaque thickness was inversely and linearly associated with brain arterial diameters (B per mm = -0.073 ± 0.034, p = 0.03), while sMCPT was associated nonlinearly in a u-shaped curve with anterior brain arterial diameters (spline regression χ2 = 9.19, p = 0.02). Coexisting carotid and aortic atherosclerosis were more prevalent in participants with small luminal diameters (40%) compared with participants with average (30%) or with large (13%) luminal diameters, while carotid atherosclerosis without aortic atherosclerosis was more prevalent among participants with large luminal diameters (31%) compared with those with average (12%) or small luminal diameters (2%, p < 0.001 for both trends). CONCLUSIONS: We confirmed the hypothesis that systemic arterial disease is associated with brain arterial diameters. Gaining knowledge about the origin of these phenotypic expressions of atherosclerosis in the human body may lead to a better understanding of the cerebrovascular consequences of the systemic arterial disease.

Magnetic resonance imaging-based measures predictive of short-term surgical outcome in patients with Chiari malformation Type I: a pilot study.

OBJECTIVE This study identifies quantitative imaging-based measures in patients with Chiari malformation Type I (CM-I) that are associated with positive outcomes after suboccipital decompression with duraplasty. METHODS Fifteen patients in whom CM-I was newly diagnosed underwent MRI preoperatively and 3 months postoperatively. More than 20 previously described morphological and physiological parameters were derived to assess quantitatively the impact of surgery. Postsurgical clinical outcomes were assessed in 2 ways, based on resolution of the patient's chief complaint and using a modified Chicago Chiari Outcome Scale (CCOS). Statistical analyses were performed to identify measures that were different between the unfavorable- and favorable-outcome cohorts. Multivariate analysis was used to identify the strongest predictors of outcome. RESULTS The strongest physiological parameter predictive of outcome was the preoperative maximal cord displacement in the upper cervical region during the cardiac cycle, which was significantly larger in the favorable-outcome subcohorts for both outcome types (p < 0.05). Several hydrodynamic measures revealed significantly larger preoperative-to-postoperative changes in the favorable-outcome subcohort. Predictor sets for the chief-complaint classification included the cord displacement, percent venous drainage through the jugular veins, and normalized cerebral blood flow with 93.3% accuracy. Maximal cord displacement combined with intracranial volume change predicted outcome based on the modified CCOS classification with similar accuracy. CONCLUSIONS Tested physiological measures were stronger predictors of outcome than the morphological measures in patients with CM-I. Maximal cord displacement and intracranial volume change during the cardiac cycle together with a measure that reflects the cerebral venous drainage pathway emerged as likely predictors of decompression outcome in patients with CM-I.

Brain Arterial Diameters as a Risk Factor for Vascular Events.

BACKGROUND: Arterial luminal diameters are routinely used to assess for vascular disease. Although small diameters are typically considered pathological, arterial dilatation has also been associated with disease. We hypothesize that extreme arterial diameters are biomarkers of the risk of vascular events. METHODS AND RESULTS: Participants in the Northern Manhattan Study who had a time-of-flight magnetic resonance angiography were included in this analysis (N=1034). A global arterial Z-score, called the brain arterial remodeling (BAR) score, was obtained by averaging the measured diameters within each individual. Individuals with a BAR score <-2 SDs were considered to have the smallest diameters, individuals with a BAR score >-2 and <2 SDs had average diameters, and individuals with a BAR score >2 SDs had the largest diameters. All vascular events were recorded prospectively after the brain magnetic resonance imaging. Spline curves and incidence rates were used to test our hypothesis. The association of the BAR score with death (P=0.001), vascular death (P=0.02), any vascular event (P=0.05), and myocardial infarction (P=0.10) was U-shaped except for ischemic stroke (P=0.74). Consequently, incidence rates for death, vascular death, myocardial infarction, and any vascular event were higher in individuals with the largest diameters, whereas individuals with the smallest diameters had a higher incidence of death, vascular death, any vascular event, and ischemic stroke compared with individuals with average diameters. CONCLUSIONS: The risk of death, vascular death, and any vascular event increased at both extremes of brain arterial diameters. The pathophysiology linking brain arterial remodeling to systemic vascular events needs further research.

Imaging-Based Features of Headaches in Chiari Malformation Type I.

BACKGROUND: Suboccipital cough-induced headaches are considered a hallmark symptom of Chiari malformation type I (CMI). However, non--Valsalva-related suboccipital headaches and headaches in other locations are also common in CMI. The diagnostic significance and the underlying factors associated with these different headaches types are not well understood. OBJECTIVE: To compare cranial morphology and hydrodynamics in 3 types of headaches in CMI to better understand the pathophysiological basis for the different headache characteristics. METHODS: Twenty-two cranial physiological and morphological measures were obtained with specialized magnetic resonance imaging scans from 63 symptomatic pretreated CMI patients, 40 with suboccipital headaches induced by Valsalva maneuvers (34 women; age, 36 ± 10 years), 15 with non--Valsalva-related suboccipital headaches (10 women; age, 33 ± 9 years), 8 with nonsuboccipital non--Valsalva-induced headaches (8 women; age, 39 ± 13 years), and 37 control subjects (24 women; age, 36 ± 12 years). Group differences were identified with the use of the 2-tailed Student t test. RESULTS: Posterior cranial fossa markers of CMI were similar among the 3 headache subtypes. However, the Valsalva-related suboccipital headaches cohort demonstrated a significantly lower intracranial compliance index than the non--Valsalva-related suboccipital headaches cohort (7.5 ± 3.4 vs 10.9 ± 4.9), lower intracranial volume change during the cardiac cycle (0.48 ± 0.19 vs 0.61 ± 0.16 mL), and higher magnetic resonance imaging--derived intracranial pressure (11.1 ± 4.3 vs 7.7 ± 2.8 mm Hg; P = .02). The Valsalva-related suboccipital headaches cohort had smaller intracranial and lateral ventricular volumes compared with the healthy cohort. The non--Valsalva-related suboccipital headaches cohort had reduced venous drainage through the jugular veins. CONCLUSION: Valsalva-induced worsening of occipital headaches appears to be related to a small intracranial volume rather than the smaller posterior cranial fossa. This explains the reduced intracranial compliance and corresponding higher pressure measured in CMI patients with headaches affected by Valsalva maneuvers.

Relationship Between Optic Nerve Protrusion Measured by OCT and MRI and Papilledema Severity.

PURPOSE: To develop measures of optic nerve protrusion length (NPL) from optical coherence tomography (OCT) and magnetic resonance imagining (MRI) and compare these measures with papilledema severity in idiopathic intracranial hypertension (IIH). METHODS: Optical coherence tomography and MRI scans were obtained from 11 newly diagnosed untreated IIH patients (30 ± 10 years; body mass index [BMI] 36 ± 4 kg/m2). Optic nerve protrusion length was measured for each eye using OCT and MRI independently. The relationship between the NPL measures and their association with the Frisen scale for papilledema severity were assessed. Two different OCT-based measures of NPL were derived to assess the influence of the retinal thickness on the association with papilledema severity. Additional OCT scans from 11 healthy subjects (38 ± 7 years) were analyzed to establish reliability of the NPL measurement. RESULTS: Optical coherence tomography and MRI measurements of NPL were significantly linearly correlated (R = 0.79, P < 0.0001). Measurements of NPL from OCT and MRI were significantly associated with Frisen papilledema grade (P < 0.0001). Mean OCT measurement of NPL in the papilledema cohort was significantly larger than in the healthy cohort (0.62 ± 0.24 vs. 0.09 ± 0.03 mm, P < 0.0001). CONCLUSIONS: Significant linear correlation between OCT and MRI measurements of NPL supports the reliability of the OCT-based measurements of NPL in papilledema. Significant association between the papilledema grade and OCT- and MRI-based measurements of NPL highlights the potential of NPL as an objective and more sensitive marker of papilledema severity than the Frisen scale.

Compensatory intracranial arterial dilatation in extracranial carotid atherosclerosis: the Northern Manhattan study.

BACKGROUND: There is a scarcity of data supporting the association between atherosclerosis and dolichoectasia in unbiased samples. AIMS: To test the hypothesis that the association between dolichoectasia and extracranial carotid atherosclerosis depends on the degree of collateral circulation. METHODS: The Northern Manhattan Study magnetic resonance imaging substudy consists of 1290 participants who remained stroke-free at the time of magnetic resonance imaging. Arterial diameters were collected in all participants with available magnetic resonance angiography. Dolichoectasia was defined as a head-size adjusted diameter >2 standard deviation for each artery. Carotid Doppler was used to evaluate for carotid atherosclerosis (carotid plaque, maximum plaque thickness and carotid intima media thickness). RESULTS: We included 994 participants with available Doppler and magnetic resonance angiography data (mean age 63 years, 60% female). Any dolichoectasia was reported in 16% of participants, 54% had at least one carotid plaque and the mean carotid intima media thickness was 0·92 ± 0·09 mm. After adjusting for demographic and clinical characteristics, there was no association between markers of carotid atherosclerosis and dolichoectasia. However, stratifying by collaterals, it was observed that dolichoectasia was more likely in the anterior and posterior circulations when collaterals were available among participants with carotid atherosclerosis. These associations were confirmed by noting an increment in arterial diameters in the corresponding arteries ipsilateral and contralateral to each carotid as well as in the posterior circulation. CONCLUSIONS: We did not find an association of extracranial carotid atherosclerosis with dolichoectasia. However, we found that dolichoectasia is more frequent when intracranial collaterals are available suggesting a compensatory process that needs further investigation.

MRI measurements of intracranial pressure in the upright posture: The effect of the hydrostatic pressure gradient.

PURPOSE: To add the hydrostatic component of the cerebrospinal fluid (CSF) pressure to magnetic resonance imaging (MRI)-derived intracranial pressure (ICP) measurements in the upright posture for derivation of pressure value in a central cranial location often used in invasive ICP measurements. MATERIALS AND METHODS: Additional analyses were performed using data previously collected from 10 healthy subjects scanned in supine and sitting positions with a 0.5T vertical gap MRI scanner (GE Medical). Pulsatile blood and CSF flows to and from the brain were quantified using cine phase-contrast. Intracranial compliance and pressure were calculated using a previously described method. The vertical distance between the location of the CSF flow measurement and a central cranial location was measured manually in the mid-sagittal T1 -weighted image obtained in the upright posture. The hydrostatic pressure gradient of a CSF column with similar height was then added to the MR-ICP value. RESULTS: After adjustment for the hydrostatic component, the mean ICP value was reduced by 7.6 mmHg. Mean ICP referenced to the central cranial level was -3.4 ± 1.7 mmHg compared to the unadjusted value of +4.3 ± 1.8 mmHg. CONCLUSION: In the upright posture, the hydrostatic pressure component needs to be added to the MRI-derived ICP values for compatibility with invasive ICP at a central cranial location.

Magnetic resonance imaging measures of posterior cranial fossa morphology and cerebrospinal fluid physiology in Chiari malformation type I.

BACKGROUND: It has been well documented that, along with tonsillar herniation, Chiari Malformation Type I (CMI) is associated with smaller posterior cranial fossa (PCF) and altered cerebrospinal fluid (CSF) flow and tissue motion in the craniocervical junction. OBJECTIVE: This study assesses the relationship between PCF volumetry and CSF and tissue dynamics toward a combined imaging-based morphological-physiological characterization of CMI. Multivariate analysis is used to identify the subset of parameters that best discriminates CMI from a healthy cohort. METHODS: Eleven length and volumetric measures of PCF, including crowdedness and 4th ventricle volume, 4 measures of CSF and cord motion in the craniocervical junction, and 5 global intracranial measures, including intracranial compliance and pressure, were measured by magnetic resonance imaging (MRI) in 36 symptomatic CMI subjects (28 female, 37 ± 11 years) and 37 control subjects (24 female, 36 ± 12 years). The CMI group was further divided based on symptomatology into "typical" and "atypical" subgroups. RESULTS: Ten of the 20 morphologic and physiologic measures were significantly different between the CMI and the control cohorts. These parameters also had less variability and stronger significance in the typical CMI compared with the atypical. The measures with the most significance were clival and supraocciput lengths, PCF crowdedness, normalized PCF volume, 4th ventricle volume, maximal cord displacement (P < .001), and MR measure of intracranial pressure (P = .007). Multivariate testing identified cord displacement, PCF crowdedness, and normalized PCF as the strongest discriminator subset between CMI and controls. MR measure of intracranial pressure was higher in the typical CMI cohort compared with the atypical. CONCLUSION: The identified 10 complementing morphological and physiological measures provide a more complete and symptomatology-relevant characterization of CMI than tonsillar herniation alone.

Normobaric hypoxia and symptoms of acute mountain sickness: Elevated brain volume and intracranial hypertension.

OBJECTIVE: The study was undertaken to determine whether normobaric hypoxia causes elevated brain volume and intracranial pressure in individuals with symptoms consistent with acute mountain sickness (AMS). METHODS: Thirteen males age = (26 (sd 6)) years were exposed to normobaric hypoxia (12% O2 ) and normoxia (21% O2 ). After 2 and 10 hours, AMS symptoms were assessed alongside ventricular and venous vessel volumes, cerebral blood flow, regional brain volumes, and intracranial pressure, using high-resolution magnetic resonance imaging. RESULTS: In normoxia, neither lateral ventricular volume (R(2) = 0.07, p = 0.40) nor predominance of unilateral transverse venous sinus drainage (R(2) = 0.07, p = 0.45) was related to AMS symptoms. Furthermore, despite an increase in cerebral blood flow after 2 hours of hypoxia (hypoxia vs normoxia: Δ148ml/min(-1) , 95% confidence interval [CI] = 58 to 238), by 10 hours, when AMS symptoms had developed, cerebral blood flow was normal (Δ-51ml/min(-1) , 95% CI = -141 to 39). Conversely, at 10 hours brain volume was increased (Δ59ml, 95% CI = 8 to 110), predominantly due to an increase in gray matter volume (Δ73ml, 95% CI = 25 to 120). Therefore, cerebral spinal fluid volume was decreased (Δ-40ml, 95% CI = -67 to -14). The intracranial pressure response to hypoxia varied between individuals, and as hypothesized, the most AMS-symptomatic participants had the largest increases in intracranial pressure (AMS present, Δ7mmHg, 95% CI = -2.5 to 17.3; AMS not present, Δ-1mmHg, 95% CI = -3.3 to 0.5). Consequently, there was a significant relationship between the change in intracranial pressure and AMS symptom severity (R(2) = 0.71, p = 0.002). INTERPRETATION: The data provide the strongest evidence to date to support the hypothesis that the "random" nature of AMS symptomology is explained by a variable intracranial pressure response to hypoxia.

Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH.

OBJECTIVE: To assess the effects of low-dose acetazolamide treatment on volumetric MRI markers and clinical outcome in idiopathic normal-pressure hydrocephalus (iNPH). METHODS: We analyzed MRI and gait measures from 8 patients with iNPH with serial MRIs from an institutional review board-approved imaging protocol who had been treated off-label with low-dose acetazolamide (125-375 mg/day). MRI studies included fluid-attenuated inversion recovery and 3D T1-weighted high-resolution imaging. Automated analyses were employed to quantify each patient's ventricular, global white matter hyperintensities (WMH), and periventricular WMH (PVH) volumes prior to and throughout treatment. Clinical outcome was based on gait changes assessed quantitatively using the Boon scale. RESULTS: Five of 8 patients responded positively to treatment, with median gait improvement of 4 points on the Boon scale. A significant decrease in PVH volume (-6.1 ± 1.9 mL, p = 0.002) was seen in these patients following treatment. One patient's gait was unchanged and 2 patients demonstrated worsened gait and were referred for shunt surgery. No reduction in PVH volume was detected in the latter 2 patients. Nonperiventricular WMH and lateral ventricle volumes remained largely unchanged in all patients. CONCLUSIONS: These preliminary findings provide new evidence that low-dose acetazolamide can reduce PVH and may improve gait in iNPH. PVH volume, reflecting transependymal CSF, is shown to be a potential MRI indicator of pharmacologic intervention effectiveness. Further studies of pharmacologic treatment of iNPH are needed and may be enhanced by incorporating quantitative MRI outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that low-dose acetazolamide reverses PVH volume and, in some cases, improves gait in iNPH.

Dolichoectasia diagnostic methods in a multi-ethnic, stroke-free cohort: results from the northern Manhattan study.

BACKGROUND AND PURPOSE: Dolichoectasia (DE) is a vasculopathy that consists of abnormal elongation and dilatation of arteries. The objective of this study is to evaluate the frequency of DE in an unselected population and assess different diagnostic methods. METHODS: The Northern Manhattan Study is a multiethnic population based cohort of stroke-free participants. The definition proposed for DE was total cranial volume (TCV)-adjusted arterial diameter ≥2 SD. Other methods studied included visual assessment, unadjusted arterial diameters cutoff, Smoker's criteria and basilar artery (BA) volume. RESULTS: A total of 718 subjects were included in the analysis (mean age 71.6 ± 8.0 years, 40% men, 61% Hispanic). Using the TCV-adjusted DE definition, 19% of the sample had at least one dolichoectatic artery. In 7% of the subjects, two or more arteries were affected. The BA was the most common dolichoectatic artery. Reproducibility for arterial diameter measurements was good to excellent (.70-.95), while for visual assessment ranged from fair to good (.49-.79). CONCLUSIONS: A TCV-adjusted intracranial arterial diameter ≥2 SD is proposed as a useful DE definition. The variability in the prevalence of DE depending on the methods used underscores the need to agree on a reliable, universal definition of DE.

Circle of Willis configuration as a determinant of intracranial dolichoectasia.

BACKGROUND: Circle of Willis (COW) variants might influence arterial caliber in the brain. We hypothesized that these variants would be associated with the prevalence of intracranial dolichoectasia (DE). METHODS: We examined COW variants and DE in a sample of stroke-free participants (n = 436) undergoing magnetic resonance angiography (MRA) as part of a population-based study. Large intracranial arterial diameters were obtained when available; if not, the artery was defined as hypoplastic or absent according to its visibility on MRA. Subscores for the anterior and the posterior circulations were created. DE was defined as arterial diameters ≥2 SD above the population mean for that artery, adjusting for intracranial volume. Generalized linear models with a Poisson distribution were used to evaluate predictors of both absent and hypoplastic vessels, and logistic regression was used to assess the odds ratio (OR) and 95% confidence interval (95% CI) of DE depending on COW variants. RESULTS: Only 44% of the sample had all 14 arteries present, 32% lacked 1 artery, 18% lacked 2 and 6% lacked 3 or more. DE of at least 1 artery was not associated with the total number of hypoplastic or absent arteries, but DE in a posterior circulation artery was weakly associated with the number of absent arteries in the posterior circulation (ß coefficient = 0.36, p = 0.06). DE of at least 1 artery was more frequent in those with 1 or more absent arteries (OR 1.27, 95% CI 1.03-1.57). Posterior circulation DE was more frequent in participants with at least 1 or more absent arteries at any location (OR 1.35, 95% CI 1.02-1.78). Participants with an incomplete posterior COW were more likely to have DE in the anterior circulation (OR 1.52, 95% CI 1.01-2.33). Having an absent left anterior cerebral artery (ACA) A1 segment was associated with right ACA DE (OR 34.1, 95% CI 3.16-368.2); an absent right ACA was associated with left ACA DE (OR 14.1, 95% CI 1.69-118.28). Absence of 1 (OR 1.9, 95% CI 1.1-3.4) or 2 (OR 3.0, 95% CI 1.4-6.6) of the 2 arteries connecting the anterior to the posterior circulation was associated with basilar artery DE. CONCLUSION: The COW is a pleomorphic structure that allows collateral flow to compensate for an insufficient or absent arterial component at the base of the skull. By presumed flow diversion, arteries might undergo outward remodeling. Whether this compensatory arterial dilatation is beneficial or not remains unknown.

Determination of cranio-spinal canal compliance distribution by MRI: Methodology and early application in idiopathic intracranial hypertension.

PURPOSE: To develop a method for derivation of the cranial-spinal compliance distribution, assess its reliability, and apply to obese female patients with a diagnosis of idiopathic intracranial hypertension (IIH). MATERIALS AND METHODS: Phase contrast-based measurements of blood and cerebrospinal fluid (CSF) flows to, from, and between the cranial and spinal canal compartments were used with lumped-parameter modeling to estimate systolic volume and pressure changes from which cranial and spinal compliance indices are obtained. The proposed MRI indices are analogous to pressure volume indices (PVI) currently being measured invasively with infusion-based techniques. The consistency of the proposed method was assessed using MRI data from seven aged healthy subjects. Measurement reproducibility was assessed using five repeated MR scans from one subject. The method was then applied to compare spinal canal compliance contribution in seven IIH patients and six matched healthy controls. RESULTS: In the healthy subjects, as expected, spinal canal contribution was consistently larger than the cranial contribution (average value of 69%). Measurement variability was 8%. In IIH, the spinal canal contribution is significantly smaller than normal controls (60 versus 78%, P < 0.03). CONCLUSION: An MRI-based method for derivation of compliance indices analogous to PVI has been implemented and applied to healthy subjects. The application of the method to obese IIH patients suggests a spinal canal involvement in the pathophysiology of IIH.