Right-to-left shunts and hormonal therapy influence cerebral vasomotor reactivity in patients with migraine with aura

Abstract

Patent Foramen Ovale and impaired cerebral hemodynamics were proposed among the pathophysiological mechanisms explaining the increased risk for stroke in patients with Migraine with Aura (MA). Our study aimed at comparing the vasomotor reactivity (VMR) of the anterior and the posterior cerebral circulation in patients with Migraine with Aura, in patients with acute vascular ischemic accidents, and in controls. We hypothesized that VMR in MA patients is preserved in the anterior circulation and reduced in the posterior circulation. We prospectively assessed with Transcranial Doppler the vasomotor reactivity to breath holding of the Middle and Posterior Cerebral Arteries (MCA, PCA) in MA patients, in acute vascular patients and healthy controls. We also evaluated the possible effect of clinical characteristics of MA (attack frequency, aura length or type, disease history), vascular factors and the presence of right-to-left shunt on VMR. Diverging from our hypothesis, MA patients displayed a higher breath-holding index (BHI) than controls in the MCA (1.84±0.47%/s vs 1.53±0.47%/s, p = .001) as well as in the PCA (1.87±0.65%/s vs 1.47±0.44%/s, p < .001). In MA patients, MCA BHI was higher in those with large right-to-left shunts (2.09±0.42 vs 1.79±0.47, p = .046) and lower in those taking estrogens (1.30±0.30%/s vs 1.9±0.45%/s, p = .009). We did not observe an effect of MA characteristics on BHI. The increased BHI in MA patients with large right-to-left shunts could be explained by the vasoactive effect in the cerebral circulation of substances bypassing the deactivating pulmonary filters or by a constitutional trait of the vascular system associating persistent right-to-left shunts and hyper-reactive hemodynamics. Our results discourage the hypothesis that altered hemodynamics contribute to increasing the stroke risk in all MA patients. However, estrogens can lower VMR, curtailing the hemodynamic resources of MA patients.

Enhanced Hemodynamic and Clinical Response to αCGRP in Migraine Patients—A TCD Study

“…However, previous studies demonstrated that patients with migraine with aura might have excessive response to several stimuli ( 20 , 21 ). Further studies are needed to investigate the CGRP induced differences between migraine with aura and migraine without aura ( 21 , 22 ).…”

Erenumab does not alter cerebral hemodynamics and endothelial function in migraine without aura

“…Peculiar cerebral and peripheral hemodynamics profiles (23,26) and increased stroke risk (38) differentiate these patients from those without aura. Specifically, migraineurs with aura seem to present a more reactive cerebral and peripheral vascular tree (12,23,26). At the moment, it cannot be ruled out that this hyperactive vascular system may be more prone to the inhibition of the CGRP pathway.…”

“…The breath-holding index (BHI) was calculated by dividing the percent increase in mean flow velocity (MFV) occurring during breath holding by the time (30 sec) the subjects held their breath after a normal inspiration ([MFV at the end of breath-holding−rest MFV/rest MFV] × 100/sec of breath holding). The mean BHI observed in other cohorts of healthy subjects is around 1.5%/sec (23); wheareas a cutoff value of less than 0.69%/sec has clearly been demonstrated to have a high predictive value for cerebrovascular disease (24).…”

“…All subjects were screened by continuous-wave Doppler and colour flow B-mode Doppler ultrasound (Philips iU22, Bothell, WA, USA) to exclude carotid, vertebral and intracranial steno-occlusive diseases. Cerebral VMR to hypercapnia of the right posterior cerebral artery (PCA) and left middle cerebral artery (MCA) were measured using the breath-holding test (Multidop-X DWL; Elektronische Systeme GmbH, Germany) (23). With the subject lying supine, two transducers placed on the temporal bone window, held on a headband, and with a stable angle of insonation, were used to obtain a bilateral continuous measurement of the flow velocity of middle and posterior cerebral arteries.…”

Commentary: Enhanced Hemodynamic and Clinical Response to αCGRP in Migraine Patients—A TCD Study

“…Nitric oxide super-sensitivity of the cerebral circulation has been consistently demonstrated in migraineurs (endothelial and parasympathetic control) ( 8 ). Similarly, migraine patients, in particular those with migraine with aura (MA), can display a higher response to hypercapnia (i.e., vasomotor reactivity, metabolic control) ( 9 , 10 ). Finally, the vascular tree of MA patients is also more reactive to sensory inputs such as visual stimulation (i.e., neurovascular coupling) ( 11 ).…”