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Glostrup, Denmark

Asghar M.S.,Copenhagen University | Hansen A.E.,Functional Imaging Unit | Kapijimpanga T.,Copenhagen University | Van Der Geest R.J.,Leiden University | And 4 more authors.
Neurology | Year: 2010

Background: Calcitonin gene-related peptide (CGRP) plays a fundamental role in the pathophysiology of neurovascular headaches. CGRP infusion causes headache and dilation of cranial vessels. However, it is unknown to what extent CGRP-induced vasodilation contributes to immediate head pain and whether the migraine-specific abortive drug sumatriptan, a 5-hydroxytryptamine 1B/1D agonist, inhibits CGRP-induced immediate vasodilation and headache. Methods: We performed a double-blind, randomized, placebo-controlled, crossover study in 18 healthy volunteers. We recorded circumference changes of the middle meningeal artery (MMA) and middle cerebral artery (MCA) using magnetic resonance angiography before and after infusion (20 minutes) of 1.5 μg/min human αCGRP or placebo (isotonic saline) as well as after a 6-mg sumatriptan subcutaneous injection. Results: Compared with placebo, CGRP caused significant dilation of MMA (p = 0.006) and no dilation of MCA (p = 0.69). Sumatriptan caused a marked contraction of MMA (15%-25.2%) and marginal contraction of MCA (3.9% to 5.3%). Explorative analysis revealed that sumatriptan had a more selective action on MMA compared with MCA on the CGRP day (p < 0.0001) and on the placebo day (p = 0.007). Conclusion: These data suggest that exogenous CGRP dilates extracranial vessels and not intracranial, and that sumatriptan exerts part of its antinociceptive action by constricting MMA and not MCA. Classification of Evidence: This study provides Class I evidence that IV GCRP causes dilation of the MMA but not the MCA in healthy volunteers, and that sumatriptan reverses the dilation of the MMA caused by CGRP. Copyright © 2010 by AAN Enterprises, Inc.

Mikati A.G.,University of Chicago | Tan H.,University of Chicago | Shenkar R.,University of Chicago | Li L.,University of Chicago | And 14 more authors.
Stroke | Year: 2014

Background and Purpose - Hyperpermeability and iron deposition are 2 central pathophysiological phenomena in human cerebral cavernous malformation (CCM) disease. Here, we used 2 novel MRI techniques to establish a relationship between these phenomena. Methods - Subjects with CCM disease (4 sporadic and 17 familial) underwent MRI imaging using the dynamic contrastenhanced quantitative perfusion and quantitative susceptibility mapping techniques that measure hemodynamic factors of vessel leak and iron deposition, respectively, previously demonstrated in CCM disease. Regions of interest encompassing the CCM lesions were analyzed using these techniques. Results - Susceptibility measured by quantitative susceptibility mapping was positively correlated with permeability of lesions measured using dynamic contrast-enhanced quantitative perfusion (r=0.49; P≤0.0001). The correlation was not affected by factors, including lesion volume, contrast agent, and the use of statin medication. Susceptibility was correlated with lesional blood volume (r=0.4; P=0.0001) but not with lesional blood flow. Conclusions - The correlation between quantitative susceptibility mapping and dynamic contrast-enhanced quantitative perfusion suggests that the phenomena of permeability and iron deposition are related in CCM; hence, more leaky lesions also manifest a more cumulative iron burden. These techniques might be used as biomarkers to monitor the course of this disease and the effect of therapy. © 2013 American Heart Association, Inc.

Arngrim N.,Copenhagen University | Schytz H.W.,Copenhagen University | Asghar M.S.,Copenhagen University | Amin F.M.,Copenhagen University | And 6 more authors.
Pain | Year: 2014

The carbonic anhydrase inhibitor acetazolamide causes extracellular acidosis and dilatation of cerebral arterioles. In this study, we tested the hypothesis that acetazolamide also may induce headache and dilatation of cranial arteries. In a randomized double-blind crossover study design, 12 young healthy women were allocated to injection of 1 g acetazolamide or placebo on 2 separate days. We recorded headache on a verbal rating scale from 0 to 10 during an immediate phase (0-90 minutes) and a delayed phase (2-12 hours). The circumference of cranial arteries was measured using 3T high-resolution magnetic resonance angiography 30 and 60 minutes after injection. Acetazolamide provoked immediate headache in 9 participants compared to 3 participants after placebo (P =.031). Eleven participants reported headache in the delayed phase after acetazolamide, compared with 4 after placebo (P =.016). The area under the curve for headache was increased after acetazolamide compared to placebo in the delayed phase (2-12 h) (P =.005). Compared to placebo, arterial circumference increased after acetazolamide in the basilar artery (P =.002) as well as the cerebral (P =.003), cavernous (P =.002), and cervical (P =.005) parts of the internal carotid artery, but no other extracranial arteries changed after acetazolamide. In conclusion, acetazolamide caused immediate and delayed headache as well as dilatation of intracranial arteries in healthy volunteers. It is possible that extracellular acidosis induced by acetazolamide causes sensitization of cephalic perivascular nociceptors, which, in combination with vasodilatation, leads to delayed headache. © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Hansen N.L.,Functional Imaging Unit | Hansen N.L.,Copenhagen University | Lauritzen M.,Copenhagen University | Mortensen E.L.,Copenhagen University | And 7 more authors.
Human Brain Mapping | Year: 2014

Cognitive abilities decline with age, but with considerable individual variation. The neurobiological correlate of this variation is not well described. Functional brain imaging studies have demonstrated reduced task-induced deactivation (TID) of the brain's default mode network (DMN) in a wide range of neurodegenerative diseases involving cognitive symptoms, in conditions with increased risk of Alzheimer's disease, and even in advanced but healthy aging. Here, we investigated brain activation and deactivation during a visual-motor task in 185 clinically healthy males from a Danish birth cohort, whose cognitive function was assessed in youth and midlife. Using each individual as his own control, we defined a group with a large degree of cognitive decline, and a control group. When correcting for effects of total cerebral blood flow and hemoglobin level, we found reduced TID in the posterior region of the DMN in the cognitive decline group compared to the control group. Furthermore, increased visual activation response was found in the cognitive decline group, indicating that the TID reduction was not exclusively due to overall impaired vascular reactivity. These results suggest a neurobiological basis for subclinical cognitive decline in late midlife, which includes TID alterations similar to the pattern seen in patients with AD and mild cognitive impairment. Hence, TID reduction might be suggested as an early marker for subtle cognitive decline in aging. © 2014 Wiley Periodicals, Inc.

Vitanis V.,ETH Zurich | Manka R.,ETH Zurich | Manka R.,University of Zurich | Giese D.,ETH Zurich | And 7 more authors.
Magnetic Resonance in Medicine | Year: 2011

Three-dimensional myocardial perfusion imaging requires significant acceleration of data acquisition to achieve whole-heart coverage with adequate spatial and temporal resolution. The present article introduces a compartment-based k-t principal component analysis reconstruction approach, which permits three-dimensional perfusion imaging at 10-fold nominal acceleration. Using numerical simulations, it is shown that the compartment-based method results in accurate representations of dynamic signal intensity changes with significant improvements of temporal fidelity in comparison to conventional k-t principal component analysis reconstructions. Comparison of the two methods based on rest and stress three-dimensional perfusion data acquired with 2.3 × 2.3 × 10 mm3 during a 225 msec acquisition window in patients confirms the findings and demonstrates the potential of compartment-based k-t principal component analysis for highly accelerated three-dimensional perfusion imaging. © 2010 Wiley-Liss, Inc.

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