Table 1.

MRI contrast agent studies in migraine patients with (MA) and without aura (MO) to detect an inflammatory phenotype

MO/MA studies which reported on dural enhancement
Reference	Population (MA/MO)	Modality and contrast agent	Assumptions of technique	Delay after migraine onset	Comparisons	Results	Comments
Khan et al. [9] 2019 Cephalalgia	MO w/ unilateral headache (cilostazol induced) N = 28	MRI w/ USPIO (ferumoxytol) Injected neat	USPIO binds to macrophages reflecting increased cell number and activation.	>24 h after headache onset	Ictal and post-ictal MO:	• No asymmetric uptake within brain parenchyma or ICA or MCA walls • No visual enhancement in MO or controls in brain parenchyma, vessels walls and dura • Uptake unaffected by ongoing headache • Uptake reduced by sumatriptan in ACA territory on pain-side (post-hoc analysis)	• USPIO tracer and sample size did not allow detection of minor changes in BBB permeability changes • Acute treatment of migraine attacks with sumatriptan may have abrogated inflammation • Scan conducted 27 h after contrast infusion
					Pain-side vs. non pain-side
					Sumatriptantreated vs. w/o treatment
Merli et al. [15] 2022 Headache	Mx N = 7 (5 MA, 2 MO) Episodic CH N = 8	Vessel-wall MRI w/ Gadolinium (unspecified)	Gadolinium passes a disrupted BBB	<24 h	Mx (ictal) vs. Mx (interictal)	• Focal linear enhancement in vertebral artery in one patient, present during and outside attack (attributable to an atheromatous plaque) • No vessels wall enhancement in intradural intracranial vessels during or outside attacks for remaining patients with migraine or cluster headache	• Case series • Acute treatment of migraine attacks (NSAID and triptans) may have abrogated inflammation • Diffuse vasoconstriction in two sumatriptan treated patients (one with migraine, one with cluster headache)
MO/MA studies which did not report on dural enhancement
Reference	Population (MA/MO)	Modality and contrast agent	Assumptions of technique	Delay after migraine onset	Comparisons	Results	Comments
Kim et al. [16] 2019 Neuroradiology	Mx N = 35 (14 MO, 21 MA) HC N = 21	DCE MRI w/ Gadolinium (Gadobutrol)	Gadolinium passes a disrupted BBB	NA (interictal)	Mx (interictally) vs. HC	• Vascular permeability parameters similar for migraine patients and HCs	• MO and MA were not analyzed separately • Major variability in transfer constant for gadolinium compared to previous studies • Lower age of migraine patients as compared to control group (contrary to age related increases in BBB permeability) • Gadobutrol may be unable to extravasate during minor increases in BBB permeability
Amin et al. [11] 2017 European Journal of Neurology	MO (spontaneous) N = 19	DCE MRI w/ Gadolinium	Gadolinium passes a disrupted BBB	6.5 h (range 4.0-15.5 h)	MO (headache phase) vs MO (interictal) MO (pain-side vs. non-pain side)	• No increased permeability of gadolinium during attacks • No correlation between permeability and clinical features • No difference between early scan (less than 6.5h after attack onset) and late scan (more than 6.5h)	• Gadobutrol may be unable to extravasate during minor increases in BBB permeability • Permeability changes smaller than 35% could not be excluded • Mean of 28 days (range 12-87 days) between scans • No HC group
Hougaard et al. [10] 2017 Brain	MA with visual aura (spontaneous) N = 19	DCE MRI: Gadolinium (Gadobutrol)	Gadolinium passes a disrupted BBB	7.6 ± 5.8 h (time from aura onset)	MA (post-aura) vs. MA (interictal)	• BBB permeability was not different between post-aura and interictal scans, lateralized to one side, or different between patients experiencing scotomas with or without sharp edges • Increase in CBF for brainstem (bilateral), visual cortex (bilateral), and posterior cerebral hemisphere (symptomatic hemisphere)	• Gadobutrol may not be sensitive for minor increases in BBB permeability • Timing of scan may be unable to detect transient changes • Permeability differences smaller than 11% could not be excluded (post hoc analysis) • No HC group
Rotstein et al. [17] 2012 Cephalalgia	MA (spontaneous) N = 1	MRI w/ Gadolinium (Gd-DTPA)	Gadolinium passes a disrupted BBB	3 h after aura onset	MA (left hemisphere) vs. MA (right hemisphere)	• Unilateral (left sided) holohemispheric increase in BBB permeability during aura phase • Decreased CBF (hypoperfusion) in left hemisphere	• Case report • Left-sided headache with aphasia. • Prolonged aura (8 h)
Smith et al. [18] 2002 Neurology	MA (spontaneous) N = 1	MRI w/ Gadolinium (un-specified)	Gadolinium passes a disrupted BBB	48 h	MA (aura + headache phase) vs. MA (interictal) MA (symptomatic hemisphere) vs. MA (asymptomatic hemisphere)	• Vascular permeability increased in anterior temporal lobe of symptomatic hemisphere • MTT reduced in symptomatic hemisphere • Increased CBF (hyperperfusion) in symptomatic hemisphere	• Case report • Prolonged aura with hemiplegia in a patient with urinary tract infection, recent withdrawal of migraine preventive treatment (verapamil) and with an unremarkable lumbar puncture
Lanfranconi et al. [19] 2009 Journal of the Neurological Sciences	MA (spontaneous) N = 1	MRI w/ Gadolinium (un-specified)	Gadolinium passes a disrupted BBB	3h after relapse of aura	MA (aura and headache phase) vs. MA (interictal)	• Extravasation to CSF in left hemisphere	• Case report • 67-year old woman with debut of prolonged aura accompanied by aphasia, apraxia, and right-sided hemianopsia (right-handed patient)
Arnold et al. 1998 [20] Cephalalgia	MA/SHM (spontaneous sensorimotor aura) N = 1	MRI w/ Gadolinium (Gd-DTPA)	Gadolinium passes a disrupted BBB	One day after third attack	MA (interictal one day after attack) MA (interictal seven months later)	• Hyperintensity in left parieto-occipital white-matter on T2 and enhancement on T1 gadolinium	• Case report Lumbar puncture with slight lymphocytic pleocytosis (10 cells/mm3). No fever, elevated blood leukocytes, or elevated CRP • Only three episodes within an interval of 14 days
Gómez-Choco et al. 2008 [21] Neurology	MA (spontaneous sensorimotor aura) N = 1	MRI FLAIR w/ Gadolinium	Gadolinium passes a disrupted BBB	>10 h	MA (symptomatic hemisphere) vs. MA (asymptomatic hemisphere) MA (post-aura phase) vs. MA (interictal)	• Sulcal hyperintensity surrounding the left temporal lobe all the way up to the convexity during the post-aura phase on FLAIR 10 h after gadolinium infusion	• Case report • Sensory aura

¹¹C-DHE 11-carbon dihydroergotamine, BBB blood-brain barrier, CH cluster headache, CT computed tomography, DCE-MRI dynamic-contrast enhanced magnetic resonance imaging, Gd-DTPA gadopentetic acid, MA migraine with aura, MO migraine without aura, MTT mean transit time, Mx migraine with or without aura unspecified, PET positron emission tomography, SPECT single-photon emission computed tomography, USPIO ultrasmall superparamagnetic iron oxides, VAS visual analogue scale (for pain)