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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.

SUBMITTER: Altamura C

PROVIDER: S-EPMC6675040 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Altamura Claudia C Paolucci Matteo M Brunelli Nicoletta N Cascio Rizzo Angelo A Cecchi Gianluca G Assenza Federica F Silvestrini Mauro M Vernieri Fabrizio F

PloS one 20190801 8

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 r ...[more]

PMID: 31369637

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Project description:IntroductionIt is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.AimUsing a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO.MethodsGene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.ResultsWe found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.ConclusionsOur results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.

Project description:The purpose of this study was to test the hypothesis that changes in cerebral vasomotor reactivity (CVMR) after 1-yr aerobic exercise training (AET) are associated with cognitive performances in individuals with amnestic mild cognitive impairment (MCI). Seventy sedentary patients with amnestic MCI were randomized to 1-yr moderate-to-vigorous intensity AET or stretching and toning (SAT) interventions. Cerebral blood flow velocity (CBFV) with transcranial Doppler, mean arterial pressure (MAP) with finapres plethysmograph, and EtCO2 with capnography were measured during hyperventilation (hypocapnia) and a modified rebreathing protocol (hypercapnia) to assess CVMR. Cerebrovascular conductance index (CVCi) was calculated by CBFV/MAP, and CVMR by ΔCBFV/ΔEtCO2 and ΔCVCi/ΔEtCO2. Episodic memory and executive function were assessed using standard neuropsychological tests (CVLT-II and D-KEFS). Cardiorespiratory fitness was assessed by peak oxygen uptake (V̇o2peak). A total of 37 patients (19 in SAT and 18 in AET) completed 1-yr interventions and CVMR assessments. AET improved V̇o2peak, increased hypocapnic CVMR, but decreased hypercapnic CVMR. The effects of AET on cognitive performance were minimal when compared with SAT. Across both groups, there was a negative correlation between changes in hypocapnic and hypercapnic CVMRs in CBFV% and CVCi% (r = -0.741, r = -0.725, P < 0.001). Attenuated hypercapnic CVMR, but not increased hypocapnic CVMR, was associated with improved cognitive test scores in the AET group. In conclusion, 1-yr AET increased hypocapnic CVMR and attenuated hypercapnic CVMR which is associated cognitive performance in patients with amnestic MCI.NEW & NOTEWORTHY One-year moderate-to-vigorous intensity aerobic exercise training (AET) improved cardiorespiratory fitness (V̇o2peak), increased hypocapnic cerebral vasomotor reactivity (CVMR), whereas it decreased hypercapnic CVMR when compared with stretching and toning in patients with amnestic mild cognitive impairment (MCI). Furthermore, changes in hypercapnic CVMR with AET were correlated with improved memory and executive function. These findings indicate that AET has an impact on cerebrovascular function which may benefit cognitive performance in older adults who have high risk of Alzheimer's disease.

Dataset Information

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

Publications

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

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