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 |