Evaluating the influence of altered cerebral hemodynamics on cognitive performance in asymptomatic carotid artery stenosis: A systematic review.

OBJECTIVE: Substantial controversy exists regarding asymptomatic carotid stenosis (ACS) and its potential role in the pathophysiology of cognitive impairment. If proven, this hypothesis may suggest an additional definition for symptomatic carotid disease that would alter current management. This study aimed to synthesize the literature evaluating the relationship between impaired cerebral hemodynamics and cognition in patients with ACS. METHODS: A literature search was performed using MEDLINE, Embase, and EBM Reviews through May 2022. We included prospective case-control studies that used validated, objective measure(s) of either global cognition or one or more domains of cognitive function and assessed cerebrovascular reserve (CVR). RESULTS: Five studies were included, comprising a total of 782 patients with moderate (50%-69%) to severe (70%-99%) ACS. Patients with ACS and impaired ipsilateral CVR demonstrated significant cognitive impairment compared with controls. Patients with unilateral or bilateral ACS and normal CVR had cognitive scores similar to controls. Those with bilateral CVR impairment demonstrated the lowest cognitive scores. CONCLUSIONS: This review lends support to the claim that cognitive impairment, likely the result of impaired cerebral hemodynamics, is an under-recognized morbidity in patients with ACS. CVR may serve as an additional tool to determine whether patients are in fact symptomatic from their carotid stenosis and warrant consideration for intervention.

Effect of surgical mask and N95 respirator mask use on cerebrovascular reactivity.

Background and purpose:

Face masks are crucial parts of personal protective equipment (PPE) to reduce the risk of respiratory infections. The COVID-19 outbreak has increased healthcare workers’ use of face masks. This study aimed to evaluate changes in cerebrovascular response among healthcare workers using surgical and N95 respirator masks. 

90 healthcare workers: 30 wearing surgical masks, 30 wearing N95 respirators, and 30 without masks were included. After two-hour of face mask use, the baseline mean flow velocity (MFV) and the mean breath-holding index (BHI) of the bilateral middle cerebral arteries (MCAs) were evaluated with transcranial Doppler ultrasound. The presence of de-novo headache was recorded. BHI values ​​below 0.69 were evaluated as a sign of impaired cerebrovascular reactivity (CVR). 

The rate of de-novo headache was significantly higher in the N95 respirator mask group (p = 0.004). Compared to the control and surgical mask groups, the N95 respirator mask group had significantly lower values of the baseline MFV of the right MCA (p = 0.003 and p = 0.021, respectively) and mean BHI (p = 0.003 and p = 0.012, respectively). Still, only one N95 respirator mask user had a mean BHI value below 0.69.

Surgical masks did not signi­fi­cantly affect cerebral hemodynamics. Although N95 respirator mask use significantly decreased BHI values, the CVR is still within normal limits, and the development of de-novo headache is not directly associated with low CVR. 

Cerebrovascular Phenotype in Fabry Disease Patients Assessed by Ultrasound.

OBJECTIVES: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with variable phenotypes, including neurological symptoms. These can be influenced by vascular impairment. Extracranial and transcranial vascular sonography is an effective and noninvasive method for measuring arterial structures and blood flow. The study aims to investigate cerebrovascular phenotype characteristics in FD patients compared to controls using neurosonology. METHODS: This is a single-center, cross-sectional study of 130 subjects-65 patients (38 females), with genetically confirmed FD, and 65 sex- and age-matched controls. Using ultrasonography, we measured structural and hemodynamic parameters, including distal common carotid artery intima-media thickness, inner vertebral artery diameter, resting blood flow velocity, pulsatility index, and cerebral vasoreactivity (CVR) in the middle cerebral artery. To assess differences between FD and controls and to identify factors influencing investigated outcomes, unadjusted and adjusted regression analyses were performed. RESULTS: In comparison to sex- and age-matched controls, FD patients displayed significantly increased carotid artery intima-media thickness (observed FD 0.69 ± 0.13 mm versus controls 0.63 ± 0.12 mm; Padj = .0014), vertebral artery diameter (observed FD 3.59 ± 0.35 mm versus controls 3.38 ± 0.33 mm; Padj = .0002), middle cerebral artery pulsatility index (observed FD 0.98 ± 0.19 versus controls 0.87 ± 0.11; Padj < .0001), and significantly decreased CVR (observed FD 1.21 ± 0.49 versus controls 1.35 ± 0.38; Padj = .0409), when adjusted by age, BMI, and sex. Additionally, FD patients had significantly more variable CVR (0.48 ± 0.25 versus 0.21 ± 0.14; Padj < .0001). CONCLUSIONS: Our results suggest the presence of multiple vascular abnormalities and changes in hemodynamic parameters of cerebral arteries in patients with FD.

Evaluation of Cerebral Vasomotor Reactivity by Transcranial Doppler Ultrasound in Patients with Diabetic Retinopathy.

The aim of this study was to assess the correlation between cerebral vasomotor reactivity (CVR) and the grade of diabetic retinopathy. A total of 43 diabetic patients with matched severity of diabetic retinopathy between their right and left eyes were included in this study. Diabetic retinopathy was graded in three groups. Right and left middle cerebral artery CVR was assessed by the breath-holding index (BHI) using transcranial Doppler ultrasound (TCD). The mean age of the patients was 56.51 ± 9.34 years with a mean duration of having diabetes mellitus of 14.49 ± 8.06 years. Diabetic retinopathy was graded as mild, moderately severe, and severe in 27.9%, 34.9%, and 37.2% of the patients, respectively. The grade of diabetic retinopathy was associated with the HbA1c level (p < .049), microalbuminuria (p < .024), and BHI (p = .001). In patients with severe diabetic retinopathy, the right-sided BHI was significantly lower as compared to those with mild or moderately severe retinopathy (p = .001 and p = .008, respectively). The left-sided BHI value in patients with severe diabetic retinopathy was significantly lower as compared to those with mild or moderately severe retinopathy (p = .001 and p = .012, respectively). In subjects with moderately severe diabetic retinopathy, both-sided BHI was significantly reduced compared to those with mild retinopathy (p = .001). Our results indicate that the grade of diabetic retinopathy was associated with impaired CVR.

Cerebrovacular Reserve Predicts the Cerebral Hyperperfusion Syndrome After Carotid Endarterectomy.

BACKGROUND: Cerebral hyperperfusion syndrome is a rare but potentially severe complication of carotid artery revascularisation that develops under conditions of resistant postoperative hypertension and impaired cerebrovascular autoregulation. OBJECTIVE: Was to determine which preoperative and operative factors affect the development of cerebral hyperperfusion syndrome after carotid endarterectomy. METHODS: This prospective observational study enrolled 93 asymptomatic patients who underwent carotid endarterectomy. Cerebral hyperperfusion was registered in patients who had 100% postoperative increase in mean flow in middle cerebral artery registered by Transcranial Doppler ultrasound. Cerebral hyperperfusion syndrome was diagnosed in patients with cerebral hyperperfusion who postoperatively developed at least one of the symptoms. Pre-operative and operative risk factors for cerebral hyperperfusion syndrome were analysed by multivariate binary logistic regression. RESULTS: Out of 93 operated patients, cerebral hyperperfusion was registered in 23 and cerebral hyperperfusion syndrome in 18 patients. Risk factors for cerebral hyperperfusion syndrome were included in the binary logistic regression model. Incomplete Circle of Willis morphology on 3D TOF magnetic resonance image (p = 0.002), Breath holding index below the 0.69 cut-off (p = 0.006), positive criteria for insufficient collateral flow through circle of Willis registered by TCD (p = 0.03), and poorly controlled hypertension (p = 0.023) showed statistically significant independent predictive value for cerebral hyperperfusion syndrome. The model was statistically significant (p = 0.012) and correctly classified 90.3 % of patients. CONCLUSIONS: Incomplete circle of Willis and insufficient collateral flow, low cerebrovascular reserve, and poorly regulated hypertension are significant predictors of post- carotid endarterectomy hyperperfusion development.

Impaired endothelial function may predict treatment response in restless legs syndrome.

While dopaminergic dysfunction is believed to be a crucial role in restless legs syndrome (RLS), changes in peripheral microvasculature system such as peripheral hypoxia and altered skin temperature, have been found. This study aimed to investigate whether patients with RLS would have a cerebral and peripheral endothelial dysfunction, and this may have association with treatment responsiveness. We evaluated cerebral endothelial function using breath-holding index (BHI) on transcranial Doppler in bilateral middle cerebral artery (MCA), posterior cerebral artery (PCA) and basilar artery (BA) and peripheral endothelial function using brachial flow-mediated dilation (FMD) in 34 patients with RLS compared with age and sex-matched controls. The values of BHI in both MCA and BA were significantly lower in RLS group than control group. The values of FMD also were significantly lower in RLS patients. There was a weak correlation between BHI and FMD (p = 0.038 in Rt MCA, p = 0.032 in Lt MCA, p = 0.362 in BA) in RLS, but not in controls. BHI differed according to treatment responsiveness. (p < 0.005). Our study suggests that RLS patients have poorer cerebral and peripheral endothelial function than controls, showing an underlying mechanism of RLS and further evidence of a possible association between RLS and cardiovascular disease.

Cerebral Vasoreactivity in Children with Sickle Cell Disease: A Transcranial Doppler Study.

BACKGROUND: Impairment of vasodilatory capacity reflecting reduced cerebrovascular reserve was previously shown in adults with sickle cell disease (SCD) and might play a role in the pathophysiology of stroke in such patients. We examined the hypothesis that children with SCD would also have a higher frequency of impaired cerebral vasoreactivity when compared with healthy age- and gender-matched controls. METHODS: Patients were recruited from our hematology outpatient clinic. All SCD patients aged 10-18 years without a history of symptomatic stroke as well as age- and gender-matched healthy children were evaluated with transcranial Doppler (TCD) ultrasonography, with breath-holding maneuver. Breath-holding index (BHI) was calculated by dividing the percentage increase in mean flow velocity occurring during breath holding by the length of time subjects hold their breath after a normal inspiration. BHI was considered abnormal if less than .69. RESULTS: TCD was performed in 42 patients (mean age 12.7 ± 2.2 years) and 20 controls (mean age 13.90 ± 3.04 years). Blood flow velocities were higher in patients with SCD than in controls in all arteries evaluated (P < .001). BHI values in patients with SCD were significantly lower than in control subjects (1.27 ± .65 versus 1.74 ± .15, P = .013 on the left and 1.16 ± .45 versus 1.61 ± .11, P = .002 on the right). BHI was abnormal in 19% of the patients and in none of the controls, P = .036. CONCLUSIONS: Children with SCD may have impaired cerebral vasoreactivity, with low BHI values suggesting a reduced autoregulation capacity.

Cerebral endothelial dysfunction in reversible cerebral vasoconstriction syndrome: a case-control study.

BACKGROUND: The aim of this study is to investigate cerebral endothelial dysfunction in patients with reversible cerebral vasoconstriction syndrome (RCVS). METHODS: We prospectively recruited patients with RCVS, age-matched controls with episodic migraine, and age-matched healthy controls at Samsung Medical Center from Apr 2015 to Jul 2016. All participants underwent transcranial Doppler evaluation, with a breath-holding maneuver, for the evaluation of bilateral middle cerebral arteries (MCAs), posterior cerebral arteries (PCAs), and the basilar artery (BA). The breath-holding index (BHI) was used to measure cerebral endothelium-dependent vasodilation. Follow-up BHIs were recorded in selected patients with RCVS after 3 months. RESULTS: A total of 84 subjects were recruited for this study (n = 28 in each group of RCVS, episodic migraine, and healthy control; mean age, 49.8 years). The RCVS group showed lower BHIs in all basal arteries, in comparison to healthy controls (p < 0.001, 0.009 for bilateral MCAs, p < 0.001 and 0.028 for bilateral PCAs, and p = 0.060 for the BA). Compared to migraineurs, RCVS patients had lower BHIs only in the anterior circulation (p = 0.002 and 0.038 for bilateral MCAs; p = 0.069 and 0.247 for bilateral PCAs; p = 0.120 for the BA). Of the 10 patients who had follow-up BHIs at 3 months, 7 showed complete normalization, while three did not. CONCLUSIONS: Cerebral endothelial function is impaired in a widespread distribution in RCVS. Its role in the pathogenesis and clinical outcome of RCVS should be determined in further studies.

Young smoker "ABCD" vascular assessment: a four-step ultrasound examination for detecting peripheral, extra and intra-cranial early arterial damage.

BACKGROUND: Cigarette smoking is known as a major risk factor in the pathogenic mechanisms of stroke, coronary and peripheral artery disease (CAD and PAD), even in young subjects. The aim of this study is the creation of a four-step ultrasound examination to evaluate and monitor the peripheral, the extra and the intra-cranial assessment of the arterial early damage in smokers. The evaluations of A, the Ankle-brachial index, ABI, B, the Breath holding index, BHI, C, the Carotid intima media thickness, CIMT, and D, the Diameter of the abdominal aorta represent the "ABCD" assessment. METHODS: Thirty-eight healthy smokers and 43 controls underwent A, calculated for each leg. B was calculated after determination of subjects' flow velocity of middle cerebral artery (MCA) by trans-cranial colour Doppler (TCCD) before and after 30 s of apnoea at baseline and just after smoking a cigarette, to simulate the chronic and acute effects of smoking. Finally, C and D evaluation were assessed using a high-resolution B-mode ultrasound. RESULTS: Smokers presented higher values of CIMT (mean and maximal), and lower BHI both at baseline and just after smoking (p < 0.01), though in the normal range. No significant differences were found for A and D between smokers and non- smokers. CONCLUSIONS: Our results underline the importance of the assessment of B and C, that, though in the normal range, present significant differences between smokers and non-smokers. These data could drive the screening between smokers in age-related manner. Moreover, the "ABCD" examination could represent a valid method to detect and then monitor smokers' vascular damage. Although it is far to be considered a screening and routine tool, it should be contemplated in a wider context of possible not-invasive practical screening and follow-up modalities. This would be designed to implement preventive strategies and tools aimed at discouraging tobacco addiction and monitoring cardiovascular risk patients.

Correction for blood pressure improves correlation between cerebrovascular reactivity assessed by breath holding and 6% CO(2) breathing.

BACKGROUND: Changes in cerebral blood flow velocity to hypercapnia are associated with changes in systemic blood pressure (BP). These confounding BP-dependent changes in cerebral blood flow velocity cause misinterpretation of cerebrovascular reactivity (CVR) results. The objective of the study was to determine the relationship between CVR assessed by breath holding and 6% CO2 breathing after correcting for BP-dependent changes in cerebral blood flow velocity. METHODS: In 33 patients of uncomplicated type 2 diabetes mellitus, CVR was assessed as percentage changes in cerebral blood flow velocity and cerebrovascular conductance index. RESULTS: Percentage change in cerebral blood flow velocity during breath holding was positively correlated with that of during 6% CO2 breathing (r = .35; P = .0448). CVR during breath holding and 6% CO2 breathing were better correlated when expressed as percentage changes in cerebrovascular conductance index (r = .49; P = .0040). Similarly, breath-holding test results expressed as percentage changes in cerebral blood flow velocity correctly identified only 37.5% of the poor reactors to 6% CO2 breathing. However, when the breath-holding test results were expressed as percentage changes in cerebrovascular conductance index, 62.5% of the poor reactors to 6% CO2 breathing were correctly identified indicating a better agreement between the test results obtained by the 2 methods. CONCLUSION: Cerebrovascular response to breath holding is better correlated with that of 6% CO2 breathing when changes in cerebral blood flow velocity were corrected for associated changes in BP.

A randomised crossover trial of the acute effects of a deep-fried Mars bar or porridge on the cerebral vasculature.

INTRODUCTION: The deep-fried Mars bar has been cited as 'all that is wrong with the high-fat, high-sugar Scottish diet'. We investigated the effect of ingestion of a deep-fried Mars bar or porridge on cerebrovascular reactivity. We hypothesised that deep-fried Mars bar ingestion would impair cerebrovascular reactivity, which is associated with increased risk of ischaemic stroke. METHODS: Twenty-four fasted volunteers were randomised to receive a deep-fried Mars bar and then porridge (control), or vice-versa. We used transcranial Doppler ultrasound to calculate Breath Holding Index as a surrogate measure of cerebrovascular reactivity. Change in Breath Holding Index post-ingestion was the primary outcome measure. RESULTS: Twenty-four healthy adults (mean (SD) age 21.5 (1.7) years, 14 males) completed the protocol. Deep-fried Mars bar ingestion caused a non-significant reduction in cerebrovascular reactivity relative to control (mean difference in absolute Breath Holding Index after deep-fried Mars bar versus porridge -0.11, p = 0.40). Comparison of the difference between the absolute change in Breath Holding Index between genders demonstrated a significant impairment of cerebrovascular reactivity in males (mean difference women minus men of 0.65, 95% CI 0.30 to 1.00, p = 0.0003). CONCLUSION: Ingestion of a bolus of sugar and fat caused no overall difference in cerebrovascular reactivity, but there was a modest decrease in males. Impaired cerebrovascular reactivity is associated with increased stroke risk, and therefore deep-fried Mars bar ingestion may acutely contribute to cerebral hypoperfusion in men.

Statin treatment intensity and cerebral vasomotor reactivity response in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Cerebral vasomotor reactivity (VMR) is vital for regulating brain blood flow and maintaining neurological function. Impaired cerebral VMR is linked to a higher risk of stroke and poor post-stroke outcomes. This study explores the relationship between statin treatment intensity and VMR in patients with ischemic stroke. METHODS: Seventy-four consecutive patients (mean age 69.3 years, 59.4% male) with recent ischemic stroke were included. VMR levels were assessed 4 weeks after the index stroke using transcranial Doppler, measuring the breath-holding index (BHI) as an indicator of the percentage increase in middle cerebral artery blood flow (higher BHI signifies higher VMR). Multistep multivariable regression models, adjusted for demographic and cerebrovascular risk factors, were employed to examine the association between statin intensity treatment and BHI levels. RESULTS: Forty-one patients (55%) received high-intensity statins. Patients receiving high-intensity statins exhibited a mean BHI of 0.85, whereas those on low-intensity statins had a mean BHI of 0.67 (mean difference 0.18, 95% confidence interval: 0.13-0.22, p-value<.001). This significant difference persisted in the fully adjusted model (adjusted mean values: 0.84 vs. 0.68, p-value: .008). No significant differences were observed in BHI values within patient groups on high-intensity or low-intensity statin therapy (all p-values>.05). Furthermore, no significant association was found between baseline low-density lipoprotein (LDL) levels and BHI. CONCLUSIONS: High-intensity statin treatment post-ischemic stroke is linked to elevated VMR independent of demographic and clinical characteristics, including baseline LDL level. Further research is needed to explore statin therapy's impact on preserving brain vascular function beyond lipid-lowering effects.

Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients.

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = -0.27 and -0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.

Correlation between Morphological and Hemodynamic Parameters of Carotid Arteries and Cerebral Vasomotor Reactivity.

The function of cerebral small vessels can be assessed using cerebral vasomotor reactivity (VMR). Our aim in this retrospective cross-sectional study was to investigate a correlation between carotid artery stenosis measured through ultrasonographic morphological and hemodynamic parameters and cerebral VMR. A total of 285 patients (125 males; mean age 54) were included. The breath-holding index (BHI) was used to evaluate cerebral VMR. Ultrasonographic carotid artery parameters were collected: the presence and characteristics of carotid plaques, the degree of carotid diameter stenosis, intima-media thickness (IMT), peak systolic velocity (PSV), and end diastolic velocity (EDV). Additionally, hemodynamic parameters of the middle cerebral artery (MCA) were evaluated, including the mean flow velocity (MFV) and pulsatility index (PI). The following was collected from patients' medical histories: age, gender, and vascular risk factors. A negative correlation between the BHI and age (r = -0.242, p < 0.01), BHI and the presence of carotid plaques, BHI and IMT (r = -0.203, p < 0.01), and BHI and the PI of MCA on both sides (r = -0.268, p < 0.01) was found. We found a positive correlation between the BHI in the left MCA and EDV in the left internal carotid artery (r = 0.121, p < 0.05). This study shows the correlation between cerebral VMR and carotid stenosis but indicates a higher influence of morphological parameters on VMR values.

Cerebral Vasoreactivity in a Fabry Disease Patient.

BACKGROUND: Fabry disease (FD) is a rare X-linked multisystem lysosomal storage disease caused by partial or total deficiency of a-galactosidase A (GLA). A progressive involvement of the kidneys, heart, and brain arteries has been reported. Using the transcranial color-coded duplex Doppler (TCCD), we report the case of a Fabry disease (FD) patient with a reduction in the cerebrovascular reactivity of the basilar artery (BA). METHODS: A 46-year-old male asymptomatic FD patient underwent ultrasound intracranial investigation. CASE PRESENTATION: We report the case of a 46-year-old man affected by asymptomatic FD, who presented to our observation for episodes of vertigo. Cerebral MRI and AngioMRI were found to be normal. There was no postural hypotension observed. Otolaryngology and cardiac examinations revealed no pathological condition. A TCCD showed normal cerebral vascular reactivity (CVR) in the bilateral middle cerebral arteries (MCA), breath-holding index (BHI) was 1.3 in the right MCA (RMCA) and 1.4 in left MCA (LMCA), and BHI in the basilar artery (BA) was reduced (BHI: 0,56). CONCLUSION: This case suggests an earlier alteration of CVR in the posterior cerebral circulation than in the anterior cerebral circulation in an asymptomatic FD patient. This alteration of CVR may be an earlier marker of FD diagnosis.

Ubiquinol Supplementation Improves Gender-Dependent Cerebral Vasoreactivity and Ameliorates Chronic Inflammation and Endothelial Dysfunction in Patients with Mild Cognitive Impairment.

Ubiquinol can protect endothelial cells from multiple mechanisms that cause endothelial damage and vascular dysfunction, thus contributing to dementia. A total of 69 participants diagnosed with mild cognitive impairment (MCI) received either 200 mg/day ubiquinol (Ub) or placebo for 1 year. Cognitive assessment of patients was performed at baseline and after 1 year of follow-up. Patients' cerebral vasoreactivity was examined using transcranial Doppler sonography, and levels of Ub and lipopolysaccharide (LPS) in plasma samples were quantified. Cell viability and necrotic cell death were determined using the microvascular endothelial cell line bEnd3. Coenzyme Q10 (CoQ) levels increased in patients supplemented for 1 year with ubiquinol versus baseline and the placebo group, although higher levels were observed in male patients. The higher cCoQ concentration in male patients improved cerebral vasoreactivity CRV and reduced inflammation, although the effect of Ub supplementation on neurological improvement was negligible in this study. Furthermore, plasma from Ub-supplemented patients improved the viability of endothelial cells, although only in T2DM and hypertensive patients. This suggests that ubiquinol supplementation could be recommended to reach a concentration of 5 µg/mL in plasma in MCI patients as a complement to conventional treatment.

A Breath-Holding Index Applied to the Internal Carotid Artery Siphon in Transcranial Doppler Studies.

BACKGROUND AND PURPOSE: The breath-holding index (BHI) is a useful method to assess cerebrovascular reactivity. It is calculated based on the mean flow velocities of the middle cerebral artery (MCA) using transcranial Doppler (BHIMCA ). Therefore, it is not feasible in patients with poor temporal windows. This study tested the feasibility of a BHI using the internal carotid artery (ICA) siphon flow velocity (BHIICA ). METHODS: Twenty-four patients (aged 38-79 years) with unilateral or bilateral stenosis of the cervical ICAs were prospectively recruited. The 48 examined bilateral ICAs were divided into three groups according to the stenosis degree: <50%, 50-99%, and occlusion. We investigated the reproducibility of both BHI methods (BHIMCA and BHIICA ), the correlation between the two BHI methods, and the tendency for the BHIs to decrease with increasing degree of cervical ICA stenosis. RESULTS: For the BHIMCA , we found a good reproducibility (intraclass correlation coefficient, rI  > .9) and a significantly decreased BHI with increasing stenosis of the ICA (P = .001). For the BHIICA , good reproducibility was demonstrated (rI  > or ≒ .9), but there was no significant decrease in the BHI related to the increasing degree of ICA stenosis (P = .952). Furthermore, the correlation between the two BHI methods was not robust (kappa coefficient, right .259; left .619). CONCLUSIONS: Our study suggests that the BHIICA is not a feasible alternative method to the BHIMCA.

Objective Diagnosis of Migraine without Aura with Migraine Vascular Index: A Novel Formula to Assess Vasomotor Reactivity.

This pilot study was aimed at developing an objective method to diagnose migraine by measuring the difference in vasomotor reactivity between migraineurs and non-migraineurs. Thirty patients diagnosed with migraine without aura and 30 healthy patients were recruited. Vasomotor reactivity of all patients was then assessed by measuring the breath holding index (BHI), hyperventilation index and a novel formula, the migraine vascular index (MVI), of the middle cerebral artery using transcranial Doppler ultrasonography. Migraineurs were found to have significantly lower BHI and MVI values (p < 0.001). Logistic regression analysis revealed that MVI was a significant independent predictor of migraine (p = 0.007). The sensitivity and specificity of MVI in diagnosing migraine with a cutoff value of 1.035 were 86.7% and 86.7%, respectively. In conclusion, MVI measurement is a reliable method for objectively diagnosing migraine. Further research is needed to validate the usage of MVI for migraine diagnosis.

Impaired cerebrovascular reactivity in chronic obstructive pulmonary disease.

Impaired cerebrovascular reactivity (CVR) is associated with stroke. Cerebrovascular diseases are common comorbidity in chronic obstructive pulmonary disease (COPD) patients. The aim of our study was to quantify CVR in the anterior and posterior cerebral circulation during voluntary breath-holding in COPD patients according to airflow limitation severity. In this cross-sectional study, we compared 90 COPD patients without previous cerebrovascular disease and 30 age- and sex-matched healthy volunteers (mean age 67 ± 7.9, 87 males). Using transcranial Doppler ultrasound and breath-holding index (BHI), we analysed baseline mean flow velocities (MFV) and CVR of middle cerebral artery (MCA) and basilar artery (BA). Our results demonstrated that COPD patients had lower baseline MFV of both MCA and BA than controls. COPD patients had significantly lower BHImMCA and BHImBA than controls (0.8 and 0.7 versus 1.24 and 1.07, respectively; p < 0.001). With the severity of airflow obstruction, there were significant declines of BHImMCA and BHImBA in mild (0.94 and 0.83), moderate (0.8 and 0.7) and severe to very severe COPD (0.7 and 0.6), respectively (p < 0.001). For all participants, we found a significant and positive correlation between forced expiratory volume in one second (FEV1) and BHImMCA (Rho = 0.761, p < 0.001) and between FEV1 and BHImBA (Rho = 0.409, p < 0.001). COPD patients have impaired CVR in anterior and posterior cerebral circulation. Impairment of CVR increase with the airflow limitation severity. CVR is an appropriate marker to identify vulnerable COPD subjects at high risk to develop cerebrovascular disease. Prospective studies are needed for further evaluation.