Mauro Silvestrini

Outcome of Carotid Artery Occlusion Is Predicted by Cerebrovascular Reactivity

BACKGROUND AND PURPOSE The purpose of this study was to investigate the possibility of obtaining prognostic indications in patients with internal carotid occlusion on the basis of intracranial hemodynamic status, presence of previous symptoms of cerebrovascular failure, and baseline characteristics. METHODS Cerebral hemodynamics were studied with transcranial Doppler ultrasonography. Cerebrovascular reactivity to apnea was calculated by means of the breath-holding index (BHI) in the middle cerebral arteries. Sixty-five patients with internal carotid artery occlusion were followed-up prospectively (median, 24 months), 23 patients were asymptomatic and 42 symptomatic (20 with transient ischemic attack and 22 with stroke). RESULTS During the follow-up period, 11 symptomatic patients and 1 asymptomatic patient had another ischemic event ipsilateral to carotid occlusion. Among factors considered, only lower BHI values in the middle cerebral arteries ipsilateral to carotid occlusion and older age were significantly associated with the risk of developing symptoms (P=0.002 and P=0.003, respectively; Cox regression multivariate analysis). Based on our data, a cut point of the BHI value for distinguishing between pathological and normal cerebrovascular reactivity was determined to be 0.69. All patients except one, who developed TIA or stroke during the follow-up period, had BHI values ipsilateral to carotid occlusion of <0.69. CONCLUSIONS These data suggest that impaired cerebrovascular reactivity is predictive for cerebral ischemic events in patients with carotid occlusion.

Carotid Artery Wall Thickness in Patients With Obstructive Sleep Apnea Syndrome

Background and Purpose— Epidemiological studies have suggested a pathophysiological link between sleep apnea syndrome and cerebrovascular diseases. The mechanism by which sleep disturbance can affect the predisposition to developing stroke is not clear. The aim of this study was to investigate whether patients with obstructive sleep apnea syndrome have an increase in atherosclerosis indicators at the carotid artery level. Methods— We included 23 male patients with severe obstructive sleep apnea syndrome (respiratory disturbance index >30). Intima-media thickness and the presence of steno-occlusive lesions in the common carotid arteries were investigated with B-mode high-resolution ultrasonography. Results of the ultrasonographic examination were compared with those of a group of 23 subjects without obstructive sleep apnea syndrome who were matched for age and comorbid factors. Results— The intima-media thickness of the common carotid arteries of patients with obstructive sleep apnea syndrome was significantly higher (P <0.0001) than that of control subjects (1.429±0.34 versus 0.976±0.17 mm). Conclusions— Results of the present study show that carotid wall thickness is increased in patients with severe sleep apnea syndrome. There is strong evidence that an increase in the thickness of the carotid artery wall is a valid marker of the risk of stroke. For this reason, our finding seems to further strengthen the hypothesis that patients with obstructive sleep apnea syndrome are at risk of developing cerebrovascular diseases regardless of the association with other vascular risk factors.

Sex-Hormone-Related Events in Migrainous Females. A Clinical Comparative Study between Migraine with Aura and Migraine without Aura

In this study, the relationship between hormonal-related events and migraine with aura (MA) and without aura (MO) was investigated. Subjects included 268 women suffering from MA (88) and MO (180). Data were collected on the relationship between sex-hormone-related events and migraine. Migraine during menses was observed in a significantly higher percentage of MO than MA patients (p < 0.03). Menstrual migraine was significantly more common in MO than in MA patients (p < 0.01). Migraine began during pregnancy in a significantly higher percentage of MA than of MO patients (p < 0.01). No significant difference was observed between the two groups of patients regarding the onset of migraine at menarche, after menopause, in the postpartum period or during the early cycles of oral contraceptives. Also, both groups of patients showed a similar migraine course during pregnancy, oral contraceptive use and menopause. Eight patients with coexisting migraine with aura and migraine without aura attacks reported the appearance of the aura symptom for the first time in the early cycles of oral contraceptive intake. These findings suggest that gonadal hormone fluctuation may influence both types of migraine.

Age and Sex Differences in Cerebral Hemodynamics: A Transcranial Doppler Study

BACKGROUND AND PURPOSE Hemodynamic factors seem to play an important role in the pathogenesis of cerebral ischemic events. The aim of this study was to evaluate whether changes in cerebrovascular reactivity occur in women after menopause. METHODS Using transcranial Doppler ultrasonography, we studied the changes of flow velocity after hypercapnia in the middle cerebral arteries of 45 healthy premenopausal women (mean age, 32.3 years; range, 20 to 47 years) and 40 postmenopausal women (mean age, 54.4 years; range, 48 to 64 years). The same measurements were recorded in two groups of healthy male subjects age matched with premenopausal (45 subjects) and postmenopausal women (40 subjects). Moreover, a subgroup of postmenopausal women aged 48 to 53 years (15 subjects) were compared with a group of 15 premenopausal women of the same age. We obtained hypercapnia with breath holding and evaluated cerebrovascular reactivity with the breath-holding index (BHI). RESULTS BHI was significantly lower in postmenopausal women (0.89+/-0.3) than in premenopausal women (1.59+/-0.3; P<0.0001) and in young (1.34+/-0.5; P<0.001) and old men (1.20+/-0.4; P<0.04). In the latter group, BHI was significantly lower than in premenopausal women (P<.0001). BHI values were also significantly lower in postmenopausal than in premenopausal women of the same age (0.81+/-0.1 versus 1.34+/-0.1; P<0.0001). CONCLUSIONS These findings suggest that the large reduction of cerebrovascular reactivity in postmenopausal women cannot be considered a simple factor related to aging but is probably influenced by hormonal changes. The alteration in cerebrovascular regulation could be involved in the increase of cerebrovascular disease in postmenopausal women.

Transcranial Doppler Assessment of Cerebrovascular Reactivity in Symptomatic and Asymptomatic Severe Carotid Stenosis

BACKGROUND AND PURPOSE Some studies have suggested a link between impaired cerebral hemodynamics and stroke in patients with carotid stenosis. The aim of this study was to assess the effects of severe carotid stenosis on cerebrovascular reactivity and the possible changes after endarterectomy. METHODS Using bilateral transcranial Doppler ultrasound, we studied the changes of flow velocity after hypercapnia in the middle cerebral arteries of 10 control subjects and 24 patients (13 symptomatic and 11 asymptomatic) with unilateral severe carotid stenosis before and after endarterectomy. Cerebrovascular reactivity was evaluated with the breath-holding index (BHI). RESULTS Before endarterectomy, BHI (mean value +/- SD) was significantly lower (P < .001) in the stenotic side of symptomatic patients (0.40 +/- 0.2) than in control subjects (1.12 +/- 0.3), the stenotic side of asymptomatic patients (0.80 +/- 0.4), and the normal side of both symptomatic (0.93 +/- 0.3) and asymptomatic ultrasonics (1.03 +/- 0.2) patients. On the other hand, no significant difference in BHI was detected in control subjects, on the normal side of symptomatic and asymptomatic patients, and the stenotic side of asymptomatic patients. After endarterectomy, BHI significantly increased (P < .0001) on the stenotic side of symptomatic patients (1.06 +/- 0.2) while remaining substantially stable on the normal side of both symptomatic and asymptomatic patients and on the stenotic side of asymptomatic patients. CONCLUSIONS These findings suggest that the study of cerebrovascular reactivity to hypercapnia may be relevant in evaluating the functional effects of carotid stenosis. Further investigations are needed to confirm the reliability of the breath-holding method in the selection of patients who might benefit most from carotid endarterectomy.

Impairment of daytime cerebrovascular reactivity in patients with obstructive sleep apnoea syndrome

Several studies have demonstrated a clear association between snoring, sleep apnoea and increased risk of stroke. However, the possible role of sleep apnoea in the pathophysiogenetic mechanisms of cerebrovascular disease is still unknown. Our aim in this study was to investigate cerebral haemodynamic changes during the waking state in eight patients with sleep apnoea syndrome (OSAS) by means of transcranial Doppler (TCD). In particular, we studied cerebral vascular reactivity (CVR) to hypercapnia calculated by means of the breath holding index (BHI). The investigation was performed in the early morning, soon after awakening, and in the late afternoon. Data were compared with those of eight healthy subjects matched for age and vascular risk factors. OSAS patients showed significantly lower BHI values with respect to controls both in the morning (0.56 vs. 1.36; P< 0.0001) and in the afternoon (1.12 vs. 1.53; P< 0.0001). In patients, BHI values in the afternoon were significantly higher than in the morning (P< 0.0001). These data demonstrate a diminished vasodilator reserve in OSAS patients, particularly evident in the morning. This reduction of the possibility of cerebral vessels to adapt functionally in response to stimulation could be linked to hyposensitivity of cerebrovascular chemoreceptors after the continuous stress caused by nocturnal hypercapnia.

Cytotoxin-Associated Gene-A–Positive Helicobacter pylori Strains Are Associated With Atherosclerotic Stroke

Background—It is uncertain whether Helicobacter pylori is associated with ischemic syndromes and whether this association is mediated by the induction of atherosclerosis. In this study, we tested the hypothesis that atherosclerotic stroke shows a selective association with virulent H pylori strains. Methods and Results—The seroprevalence of infection by H pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, was assessed by ELISA in 138 patients with large-vessel stroke (group A), in 61 patients with cardioembolic stroke (group B), and in 151 healthy control subjects. The 3 groups had a similar socioeconomic status. Serum levels of C-reactive protein were also measured by ELISA. The prevalence of infection was 71% in group A, 63.9% in group B, and 70.2% in the control group (P =NS), whereas the prevalence of CagA-positive strains was higher in group A than in group B (42.8% versus 19.7%, respectively; odds ratio 3.04, 95% CI 1.43 to 6.49;P <0.001) and higher in group A than in the control group (42.8% versus 17.9%, respectively; odds ratio 4.3, 95% CI 2.12 to 8.64;P <0.001), after adjusting for main cardiovascular risk factors and social class. A trend toward a difference in C-reactive protein was observed between CagA-positive (2.00±3.43 [mean±SD] mg/dL) and CagA-negative (1.31±1.72 [mean±SD] mg/dL) patients (P =0.072, Mann-Whitney U test). Conclusions—The association between H pylori and acute cerebrovascular disease seems to be due to a higher prevalence of more virulent H pylori strains in patients with atherosclerotic stroke.

Effect of Smoking on Cerebrovascular Reactivity

Current smoking is a risk factor for stroke. The aim of this study was to evaluate the effect of smoking one cigarette on cerebral hemodynamics. Using transcranial Doppler ultrasound, we studied the changes of flow velocity after hypercapnia in the middle cerebral arteries (MCAs) of 24 healthy young smokers and 24 healthy controls matched for age and sex. We obtained hypercapnia with breath-holding and evaluated cerebrovascular reactivity with the breath-holding index. In smokers, the evaluation was performed during basal condition, immediately after smoking one cigarette, and at 10-, 20-, and 30-min intervals thereafter. In controls, the evaluation was performed at corresponding time intervals. Breath-holding index (BHI) values at rest were similar for both controls and smokers. In the former, breath-holding index values remained constant for each of the different evaluations. On the contrary, in smokers, breath-holding index values were significantly lower immediately (p < 0.0001), at 10 min (p < 0.001), and at 20 min (p < 0.0001) after smoking with respect to baseline values. Smoking also caused more short-lasting changes, in this case increases in mean flow velocity (MFV), heart rate (HR), and mean blood pressure (MBP). These results suggest that a failure of cerebrovascular regulation occurs after smoking. This phenomenon might contribute to the increased risk of cerebrovascular disease in current smokers.

Transcranial Doppler and Near-Infrared Spectroscopy Can Evaluate the Hemodynamic Effect of Carotid Artery Occlusion

Background and Purpose— Cerebral hemodynamic and metabolic changes can compensate for the decrease in cerebral blood flow occurring in patients with carotid occlusive disease. At present, a complete assessment of the cerebral adaptive status is only possible with positron-emission tomography. Near-infrared spectroscopy (NIRS) is a noninvasive technique that, providing a real time assessment of fluctuations in cerebral hemoglobin, has been used to estimate the cerebral blood volume and to measure cerebral vasomotor reactivity (VMR). Moreover, NIRS technology, by allowing the absolute measurement of absorption and scattering coefficients of brain, can determine the oxyhemoglobin and deoxyhemoglobin concentrations in situ in the blood stream. Methods— In order to evaluate different aspects of the cerebral hemodynamic status, 27 subjects with symptomatic and asymptomatic carotid artery occlusion and 30 healthy subjects underwent a simultaneous examination by means of transcranial Doppler (TCD), able to reliably detect collateral circulation and VMR, and NIRS at rest condition and during CO2 reactivity test. Results— The main finding of this study was the demonstration of a difference between asymptomatic and symptomatic patients in terms of mean flow velocity increase (52.4% versus 21.0%; P <0.001) estimated by TCD and of hemoglobin saturation increase measured by NIRS (6.8% versus 3.8%; P =0.015). Conclusions— The opportunity to perform NIRS and TCD simultaneously provides useful information about both hemodynamic and metabolic cerebral adaptive status in patients with occlusive disease in a simple, noninvasive, and reliable way.

Bilateral Simultaneous Assessment of Cerebral Flow Velocity during Mental Activity

The purpose of this study was to assess the potential of transcranial Doppler (TCD) ultrasonography for detecting selective changes in cerebral blood flow velocity during mental activity. Mean flow velocity was continuously and simultaneously measured in the right and left middle cerebral arteries in 26 healthy right-handed young subjects at rest and during performance of verbal and visual-imaging mental tasks. These two mental tasks produced significantly different effects on the right and left sides: the verbal task produced a higher increase of flow velocity (mean absolute difference above baseline ± SD) with respect to the basal values in the left than in the right middle cerebral artery (5.56 ±3.8 cm/s vs 1.25 ± 3.1 cm/s); the visual-imaging task was accompanied by a higher increase in the right than in the left middle cerebral artery (3.92 ± 3.3 cm/s vs 1.52 ± 3.1 cm/s)—analysis of variance (ANOVA) three-fold interaction side of recording × task × condition, F = 25.67, p < .0001). Heart rate, blood pressure, and skin conductance showed comparable increases during performance of both mental tasks. Respiratory activity showed no modification during the mental activity with respect to the rest phase. These results demonstrate the possibility of delivering specific functional information via bilateral TCD and suggest wider utilization of this noninvasive technique in neuropsychological studies.