Giosué Gulli

Vertebrobasilar Stenosis Predicts High Early Recurrent Stroke Risk in Posterior Circulation Stroke and TIA

Background and Purpose— 20% of ischemic stroke is in the posterior circulation, but there is little prospective data on early recurrent stroke risk and whether vertebrobasilar stenosis predicts a high recurrence risk. This natural history data are important as it is technically possible to stent such lesions. Contrast enhanced MRA (CE-MRA) and CT angiography (CTA) now allow noninvasive identification of vertebrobasilar stenosis. Methods— 216 consecutive patients presenting with posterior circulation TIA or stroke were recruited and prospectively followed for 90 days. 8 patients with vertebral dissection were excluded. CE-MRA or CTA at presentation and 90-day follow-up was available in 182. Any posterior circulation TIA/stroke in the month before the presenting episode was recorded. Results— Taking the first event (including TIA/stroke in the previous month) as the index case recurrent stroke risk in patients with stenosis was 30.5% versus 8.9% in those without; RR 3.4 (95% CI 1.7 to 7.0), P<0.001). Taking the presenting episode as the index case the risk was 13.8% versus 4.1%; RR 3.4 (95% CI 1.1 to 10.5) P=0.0274. The probability of recurrence was highest soon after the initial event. Conclusions— The presence of vertebro-basilar stenosis identifies a group of patients with posterior circulation stroke who have a high early recurrent stroke risk. Early intervention might reduce recurrent stroke risk. Vertebral stenosis can now be treated by stenting, but determining whether this reduces the early stoke risk requires randomized controlled trials.

Stroke Risk After Posterior Circulation Stroke/Transient Ischemic Attack and Its Relationship to Site of Vertebrobasilar Stenosis Pooled Data Analysis From Prospective Studies

Background and Purpose— Recent prospective studies have shown vertebrobasilar (VB) stenosis predicts stroke risk in posterior circulation stroke and transient ischemic attack. It is unclear whether this association is independent of other risk factors, and whether intracranial or extracranial stenosis confers different risks. Methods— A pooled individual patient analysis of data from 2 prospective studies was performed in 359 patients presenting with VB transient ischemic attack or stroke. Contrast-enhanced magnetic resonance angiography, or computed tomography angiogram, and clinical follow-up were available in 323 patients. Risk of stroke was calculated from any VB transient ischemic attack/stroke in the month before the presenting episode (first event) and from the presenting event. A systematic review of similar prospective studies was performed. Results— Ninety-day risk of stroke from the first event was 24.6% in patients with VB stenosis versus 7.2% in those without (odds ratio, 4.2; 95% confidence interval, 2.1–8.6; P<0.0001). Risk was higher (33%) with intracranial (odds ratio, 6.5; 2.8–15.0; P<0.0001) than extracranial stenosis (16.2%; odds ratio, 2.5; 0.9–6.8; P=0.06). Risk from the presenting event was 9.6% in patients with stenosis versus 2.8% in those without (odds ratio, 3.7; 1.2–11.0; P=0.012), and again the risk was higher with intracranial stenosis. Cox regression showed the risk associated with VB stenosis was independent of other cardiovascular risk factors. The systematic review identified only 1 other report, which included only 6 patients. Conclusions— Symptomatic VB stenosis, particularly intracranial stenosis, is a strong independent predictor of stroke recurrence. The high early risk of stroke provides a strong rationale for randomized trials to determine whether stenting can reduce risk.

Cross-spectral analysis of cardiovascular parameters whilst supine may identify subjects with poor orthostatic tolerance.

An easy and low-cost method for identification of subjects prone to orthostatic vasovagal syncope would be of clinical benefit. An orthostatic test with 60 degrees head-up tilt and progressive lower-body negative pressure was performed on 79 patients with histories of unexplained syncope and 26 control subjects. The test was stopped at the onset of presyncope and time to presyncope was taken as a measure of orthostatic tolerance. Spectral and cross-spectral analysis was performed on the supine time series of the R-R interval (ECG) and systolic pressure (Finapres) recorded before the beginning of the test. According to reference values, 38 patients and 11 controls were classified as having poor orthostatic tolerance (PPT and CPT respectively), whereas 41 patients and 15 controls displayed normal orthostatic tolerance (PNT and CNT respectively). The central frequency of the low-frequency (LF approximately equal to 0.1 Hz.) oscillations in PNT and CNT was significantly higher than that in PPT and CPT. In addition, it was significantly linearly correlated with the time of presyncope. Using our test of orthostatic tolerance as a comparison, the LF central frequency allows the classification of subjects with poor or normal tolerance with 80% sensitivity and 82% specificity. These results suggest that the LF central frequency in the supine position may provide a useful index in the diagnosis of orthostatic intolerance.

Cerebral Vasodilatation to Exogenous NO Is a Measure of Fitness for Life at Altitude

Background and Purpose— Andean highlanders, unlike Ethiopians, develop chronic mountain sickness (CMS), a maladaptation to their native land. Ambient hypoxia induces NO-mediated vasodilatation. Fitness for life at altitude might be revealed by cerebrovascular responses to NO. Methods— Nine altitude-native men were examined at 3622 and 794 m in Ethiopia and compared with 9 altitude-native Andean men tested at 4338 and 150 m in Peru. We assessed CMS scores, hematocrits, end-tidal pressure of carbon dioxide (PETco2), oxygen saturations, and cerebral blood flow velocity (CBV). We evaluated fitness for life at altitude from the cerebrovascular response to an exogenous NO donor. Results— At high altitude, CMS scores and hematocrits were higher in Andeans, and they had lower oxygen saturations. Ethiopians had higher PETco2 at all study sites. At low altitude, saturations were similar in both groups. Responsiveness of the cerebral circulation to NO was minimal in Ethiopians at low altitude, whereas Andeans had a large response. In contrast, at high altitude, Ethiopians showed large responses, and Peruvians had minimal responses. Conclusions— By our measure, high altitude–native Peruvians were well-adapted lowlanders, whereas Ethiopian highlanders were well adapted to altitude life. Environmental pressures were sufficient for human adaptation to chronic hypoxia in Africa but not South America. The mechanisms underlying these differences are unknown, although studies of neurovascular diseases suggest that this may be related to a NO receptor polymorphism.

R–R interval–blood pressure interaction in subjects with different tolerances to orthostatic stress

In addition to the gain, the time delay in the input–output response in a feedback system is crucial for the maintenance of its stability. Patients with posturally related (vasovagal) syncope have inadequate control of blood pressure and one possible explanation for this could be prolonged latency of the baroreflex. We studied 14 patients with histories of syncope and poor orthostatic tolerance (assessed by a progressive orthostatic stress test) and 16 healthy controls. We performed spontaneous sequence analysis of the fluctuations of R–R period (ECG) and systolic arterial pressure (SAP, Finapres) recorded during a 20 min supine period and during 20 min 60 deg head‐up tilt (HUT). The baroreflex latency was determined by identifying the lag between the changes in SAP and in R–R interval from which the highest correlation coefficient was obtained. During the supine period, 74% of sequences in control subjects and 54% in patients occurred with zero beats of delay (i.e. R–R interval changed within the same R–R interval). The remaining sequences occurred with delays of up to four beats. HUT shifted the baroreflex delay to be approximately one heartbeat slower and again patients showed more sequences with prolonged response. The delay in heartbeats was transformed into delay in time. In control subjects, 75% of baroreflex responses occurred within 1 s. In patients, 75% of baroreflex responses took more than 2 s to occur. The results showed that syncopal patients with poor orthostatic tolerance have increased baroreflex latency. This may lead to instability and inadequate blood pressure control and may predispose to vasovagal syncope.

Prolonged latency in the baroreflex mediated vascular resistance response in subjects with postural related syncope

In addition to the gain, the delay of the baroreflex response plays an important role in the maintenance of cardiovascular system stability. Additionally when postural changes induce sudden drops in blood pressure, a delayed response may fail to maintain sufficient cerebral perfusion pressure. We tested the hypothesis that the delay of the carotid baroreceptor reflex is impaired in subjects with poor orthostatic tolerance. An orthostatic test with 60° head-up tilt, and progressive lower-body negative pressure was performed on 27 patients with histories of unexplained syncope and 13 control subjects. The test was stopped at the onset of presyncope and time to presyncope was taken as a measure of orthostatic tolerance. Twelve patients had normal tolerance and thirteen patients had low tolerance. We measured beat-to-beat blood pressure (Finapres) and brachial artery blood flow velocity (Doppler ultrasonography). Before the test, we determined the response of forearm vascular resistance (mean arterial pressure/mean brachial artery velocity) to loading/unloading of carotid baroreceptors by the application of neck suction/pressure (–/+30 mmHg) to a chamber fitted overlying the carotid sinus. We measured the gain in the response (maximum percentage change from baseline value in vascular resistance divided by the neck collar pressure) and the latency in the response (delay of the maximum change in vascular resistance after neck-collar stimulation). Results are reported as means ± SEM. In the three groups, there were no differences in the sensitivity of the vascular resistance response after baroreceptor loading/unloading. Following baroreceptor unloading, the latency of the response was 14.0±1.3 seconds in early fainters, 9.3±0.7 seconds in normal patients and 10.1±1.2 seconds in controls. The latency in blood pressure rise was 11.1±1.3 seconds in early fainters, 7.9±0.9 seconds in normal patients and 7.2±1.0 seconds in controls. The results following baroreceptor loading were more scattered. The early fainters still had a tendency to show prolonged latency. These results suggest that the delay in the baroreflex response plays an important role in postural related syncope.

The use of FAST and ABCD2 scores in posterior circulation, compared with anterior circulation, stroke and transient ischemic attack.

The effectiveness of early interventions to prevent stroke after transient ischemic attack (TIA) has led to the need for simple screening methods to identify patients with acute stroke and TIA for intervention.1 The Face Arm Speech Test (FAST) score has been developed to assess whether a patient is likely to have an acute stroke and in particular to identify patients as potential candidates for thrombolysis.2 The ABCD2 score has been developed as a screening tool to identify patients with TIA and minor stroke who are at particularly high risk of recurrent stroke and therefore need urgent investigation and treatment.3 Both have been primarily evaluated in groups of unselected stroke and TIA patients, the majority of whom have anterior circulation stroke. Symptoms and signs associated with posterior circulation stroke differ significantly from those associated with anterior circulation stroke. We tested whether FAST and ABCD2 are less sensitive in patients with posterior, compared with anterior, cerebrovascular events. Two hundred and sixteen consecutive patients with posterior circulation ischaemic stroke or TIA presenting as emergencies to our stroke service were recruited as previously described.4 Clinical details including history, examination and results of investigations were collected prospectively within 12 h from hospital admission, on a standard stroke register proforma. As a control group, data …

Cerebrovascular Responses to Hypoxia and Hypocapnia in Ethiopian High Altitude Dwellers

Background and Purpose— Cerebrovascular responses to hypoxia and hypocapnia in Peruvian altitude dwellers are impaired. This could contribute to the high incidence of altitude-related illness in Andeans. Ethiopian high altitude dwellers may show a different pattern of adaptation to high altitude. We aimed to examine cerebral reactivity to hypoxia and hypocapnia in healthy Ethiopian high altitude dwellers. Responses were compared with our previous data from Peruvians. Methods— We studied 9 Ethiopian men at their permanent residence of 3622 m, and one day after descent to 794 m. We continuously recorded cerebral blood flow velocity (CBFV; transcranial Doppler). End-tidal oxygen (PETo2) was decreased from 100 mm Hg to 50 mm Hg with end-tidal carbon dioxide (PETco2) clamped at the subject’s resting level. PETco2 was then manipulated by voluntary hyper- and hypoventilation, with PETo2 clamped at 100 mm Hg (normoxia) and 50 mm Hg (hypoxia). Results— During spontaneous breathing, PETco2 increased after descent, from 38.2±1.0 mm Hg to 49.8±0.6 mm Hg (P<0.001). There was no significant response of CBFV to hypoxia at either high (−0.19±3.1%) or low (1.1±2.9%) altitudes. Cerebrovascular reactivity to normoxic hypocapnia at high and low altitudes was 3.92±0.5%.mm Hg−1 and 3.09±0.4%.mm Hg−1; reactivity to hypoxic hypocapnia was 4.83±0.7%.mm Hg−1 and 2.82±0.5%.mm Hg−1. Responses to hypoxic hypocapnia were significantly smaller at low altitude. Conclusions— The cerebral circulation of Ethiopian high altitude dwellers is insensitive to hypoxia, unlike Peruvian high altitude dwellers. Cerebrovascular responses to PETco2 were greater in Ethiopians than Peruvians, particularly at high altitude. This, coupled with their high PETco2 levels, would lead to high cerebral blood flows, and may be advantageous for altitude living.

Cross-spectral analysis of cardiovascular variables in supine diabetic patients.

Cardiovascular autonomic neuropathy in diabetes is associated with a high risk of mortality, which makes its early identification clinically important. An easy method for identification of subjects with autonomic dysfunction would be of clinical benefit.We evaluated the autonomic function in 28 diabetic patients and 21 control subjects recording 12 min time series of heart period (RR) and systolic arterial pressure (SAP, Finapres) during supine rest and 60° head-up tilt. The power of the high (respiratory) and low (LF ~ 0.1 Hz) frequency oscillations was quantified by spectral analysis. The central frequency of the LF oscillations (LF_freq), phase shift, and the transfer function gain between RR interval and SAP fluctuations were provided by cross-spectral analysis, and measured at the point of maximal coherence.In the supine position 15 patients (LF–) displayed atypical LF variability with the LF_freq being shifted towards lower frequencies (about 0.06 Hz). They also showed larger phase angle, lower values or even absence of coherence and smaller transfer function gain between RR and SAP fluctuations. 13 patients (LF+) and the controls showed the LF_freq around 0.1 Hz, higher coherence and transfer function gain values. The orthostatic maneuver induced the expected changes in the spectral parameters (increase in the LF components of both RR and SAP and decrease in the HF variability of RR) into the LF+ patients and all the control subjects and abnormal response in the other 15 LF-patients.These findings indicate that diabetic subjects with uncharacteristic response to the orthostatic test present abnormal LF variability already in the supine position. Crossspectral parameters while supine may be used for the identification of these subjects.