Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura

TY - JOUR

T1 - Increased brainstem perfusion, but no blood-brain barrier disruption, during attacks of migraine with aura

AU - Hougaard, Anders

AU - Amin, Faisal M

AU - Christensen, Casper E

AU - Younis, Samaira

AU - Wolfram, Frauke

AU - Cramer, Stig P

AU - Larsson, Henrik B W

AU - Ashina, Messoud

N1 - © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected].

PY - 2017/6

Y1 - 2017/6

N2 - The migraine aura is characterized by transient focal cortical disturbances causing dramatic neurological symptoms that are usually followed by migraine headache. It is currently not understood how the aura symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering of migraine headache. We used the sensitive and validated technique of dynamic contrast-enhanced high-field magnetic resonance imaging to simultaneously investigate blood-brain barrier permeability and tissue perfusion in the brainstem (at the level of the lower pons), visual cortex, and brain areas of the anterior, middle and posterior circulation during spontaneous attacks of migraine with aura. Patients reported to our institution to undergo magnetic resonance imaging during the headache phase after presenting with typical visual aura. Nineteen patients were scanned during attacks and on an attack-free day. The mean time from attack onset to scanning was 7.6 h. We found increased brainstem perfusion bilaterally during migraine with aura attacks. Perfusion also increased in the visual cortex and posterior white matter following migraine aura. We found no increase in blood-brain barrier permeability in any of the investigated regions. There was no correlation between blood-brain barrier permeability, brain perfusion, and time from symptom onset to examination or pain intensity. Our findings demonstrate hyperperfusion in brainstem during the headache phase of migraine with aura, while the blood-brain barrier remains intact during attacks of migraine with aura. These data thus contradict the preclinical hypothesis of cortical spreading depression-induced blood-brain barrier disruption as a possible mechanism linking aura and headache.

AB - The migraine aura is characterized by transient focal cortical disturbances causing dramatic neurological symptoms that are usually followed by migraine headache. It is currently not understood how the aura symptoms are related to the headache phase of migraine. Animal studies suggest that cortical spreading depression, the likely mechanism of migraine aura, causes disruption of the blood-brain barrier and noxious stimulation of trigeminal afferents leading to activation of brainstem nuclei and triggering of migraine headache. We used the sensitive and validated technique of dynamic contrast-enhanced high-field magnetic resonance imaging to simultaneously investigate blood-brain barrier permeability and tissue perfusion in the brainstem (at the level of the lower pons), visual cortex, and brain areas of the anterior, middle and posterior circulation during spontaneous attacks of migraine with aura. Patients reported to our institution to undergo magnetic resonance imaging during the headache phase after presenting with typical visual aura. Nineteen patients were scanned during attacks and on an attack-free day. The mean time from attack onset to scanning was 7.6 h. We found increased brainstem perfusion bilaterally during migraine with aura attacks. Perfusion also increased in the visual cortex and posterior white matter following migraine aura. We found no increase in blood-brain barrier permeability in any of the investigated regions. There was no correlation between blood-brain barrier permeability, brain perfusion, and time from symptom onset to examination or pain intensity. Our findings demonstrate hyperperfusion in brainstem during the headache phase of migraine with aura, while the blood-brain barrier remains intact during attacks of migraine with aura. These data thus contradict the preclinical hypothesis of cortical spreading depression-induced blood-brain barrier disruption as a possible mechanism linking aura and headache.

KW - Adult

KW - Blood-Brain Barrier

KW - Brain Stem

KW - Female

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Migraine with Aura

KW - Visual Cortex

KW - White Matter

KW - Young Adult

KW - Journal Article

U2 - 10.1093/brain/awx089

DO - 10.1093/brain/awx089

M3 - Journal article

C2 - 28430860

SN - 0006-8950

VL - 140

SP - 1633

EP - 1642

JO - Brain

JF - Brain

IS - 6

ER -