Dynamic but not static cerebral autoregulation is impaired in acute ischaemic stroke

It remains unclear as to whether dynamic and static cerebral autoregulation (CA) are impaired in acute ischaemic stroke, and whether these changes are related to stroke subtype. This could have important implications with regard to post-stroke prognosis and the management of blood pressure (BP) in the acute post-ictal period. Using transcranial Doppler ultrasonography and non-invasive manipulation of BP, we compared both mechanisms in 61 patients with ischaemic stroke within 96 h of ictus, and 54 age- and sex-matched controls. There was no difference in static and dynamic CA indices between the various stroke subtypes. Combining all stroke subtypes dynamic autoregulation, as measured using thigh cuff release, was significantly impaired in both the affected and non-affected stroke hemispheres compared to controls (mean autoregulation index 4.1 +/- 3.3, 4.8 +/- 3.1 and 6.2 +/- 2.3, respectively, p < 0.05). By comparison static autoregulation, assessed using isometric hand grip and thigh cuff inflation, was not significantly different. In conclusion, dynamic but not static CA appears to be globally impaired in acute ischaemic stroke. This deserves further study and may identify possibilities for therapeutic intervention.     

Dynamic cerebral autoregulation and beat to beat blood pressure control are impaired in acute ischaemic stroke

OBJECTIVES: Hypertension and chronic cerebrovascular disease are known to alter static cerebral autoregulation (CA) but the effects of acute stroke on dynamic CA (dCA) have not been studied in detail. Those studies to date measuring dCA have used sympathetically induced blood pressure (BP) changes, which may themselves directly affect dCA. This study assessed whether dCA is compromised after acute stroke using spontaneous blood pressure (BP) changes as the stimulus for the dCA response. METHODS: 56 patients with ischaemic stroke (aged 70 (SD 9) years), studied within 72 hours of ictus were compared with 56 age, sex, and BP matched normal controls. Cerebral blood flow velocity was measured using transcranial Doppler ultrasound (TCD) with non-invasive beat to beat arterial BP levels, surface ECG, and transcutaneous CO(2) levels and a dynamic autoregulatory index (dARI) calculated. RESULTS: Beat to beat BP, but not pulse interval variability was significantly increased and cardiac baroreceptor sensitivity (BRS) decreased in the patients with stroke. Dynamic CA was significantly reduced in patients with stroke compared with controls (strokes: ARI 3.8 (SD 2.2) and 3.2 (SD 2.0) for pressor and depressor stimuli respectively v controls: ARI 4.7 (SD 2.2) and 4.5 (SD 2.0) respectively (p<0.05 in all cases)). There was no difference between stroke and non-stroke hemispheres in ARI, which was also independent of severity of stroke, BP, BP variability, BRS, sex, and age. CONCLUSION: Dynamic cerebral autoregulation, as assessed using spontaneous transient pressor and depressor BP stimuli, is globally impaired after acute ischaemic stroke and may prove to be an important factor in predicting outcome.     

Bendrofluazide fails to reduce elevated blood pressure levels in the immediate post-stroke period

INTRODUCTION: Blood pressure (BP) levels, beat-to-beat blood pressure variability, dynamic cerebral autoregulation and cardiac baroreceptor sensitivity are frequently abnormal following acute stroke and are associated with an adverse short- and long-term prognosis. Thiazide diuretics are effective antihypertensive agents in preventing primary and secondary stroke, but their hypotensive and cerebral autoregulatory effects in the immediate post-stroke period have not been studied. METHODS: Thirty-seven hypertensive neuroradiologically proven ischaemic stroke patients were randomized in a double-blind, placebo controlled, parallel group study to bendrofluazide 2.5 mg daily or matching placebo, within 96 h of stroke onset, for a 7-day period. Casual and non-invasive beat-to-beat arterial BP levels, cerebral blood flow velocity, ECG and transcutaneous carbon dioxide levels were measured within 70 +/- 20 h of cerebral infarction and again 7 days later. Dynamic cerebral autoregulatory indices, pulse interval, BP variability and cardiac baroreceptor sensitivity were also calculated. RESULTS: Small, non-significant falls were seen in casual and beat-to-beat BP levels over the 7-day period in both active and placebo-treated patients with no differences between treatments. No significant changes were seen in dynamic cerebral autoregulation or in cardiac baroreceptor sensitivity during the follow-up in either group. CONCLUSION: Following acute ischaemic stroke, the standard dose of bendrofluazide at 2.5 mg daily in this study sample did not lower systemic BP levels over the subsequent 7-day period. There was no evidence that bendrofluazide significantly altered cerebral autoregulation or improved cardiac baroreceptor sensitivity post-ictus. Bendrofluazide appears to be an ineffective hypotensive agent at the standard dosage in the initial post-stroke period.     

Impaired dynamic cerebral autoregulation in middle cerebral artery stenosis

BACKGROUND AND PURPOSE: Analysis of dynamic cerebral autoregulation during transient falls in blood pressure is considered a sensitive and convenient method for evaluating patients with carotid artery stenosis. To this point, there have been few reports on the efficacy of using the thigh cuffs technique to analyse middle cerebral artery (MCA) stenosis. If it could be determined whether cerebral blood flow can be maintained (autoregulated) during sudden falls in arterial blood pressure (ABP), then it might be possible to identify patients with MCA stenosis who are at risk of stroke. METHODS: We used the thigh cuff technique to estimate dynamic cerebral autoregulation in 57 patients with MCA stenosis and 72 normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of the rise of MCA blood velocity and compared it with the rate of the rise of arterial blood pressure. In this manner, the dynamic cerebral autoregulation of 11 patients undergoing MCA M1 stent angioplasty was estimated both pre- and post-operation. RESULTS: The autoregulatory index (ARI) was significantly reduced in patients with stenosed/occluded MCA (3.24 +/- 1.52), as compared with normal controls (5.25 +/- 1.39; p<0.001) (results reported as mean +/- SD). Poor ARI values are usually observed in patients with a higher degree of stenosis and particularly in patients with insufficient collateral compensation. ARI was significantly reduced in severe stroke patients (modified ranking scale>or=1), as compared with asymptomatic or TIA patients (p<0.05). After MCA stent angioplasty was performed, there was a significant improvement in ARI in 11 subjects, which caused a mean increase in ARI from 2.08 +/- 1.10 to 3.80 +/- 1.36 (p=0.008). CONCLUSIONS: Dynamic cerebral autoregulation is impaired in patients with middle cerebral artery stenosis. Assessing dynamic cerebral autoregulation may allow a subgroup of patients with MCA stenosis who are at risk of hemodynamic stroke to be identified. Dynamic cerebral disautoregulation in patients with severe MCA stenosis is mostly remedied by stent angioplasty.     

CXCL1 (GRO-alpha) chemokine in acute ischaemic stroke patients

The inflammation accompanies and exacerbates cerebral ischaemia. The infiltrated leucocytes are thought to contribute to tissue injury in stroke patients. GRO-alpha (CXCL1) is a potent neutrophil chemoattractant which may play an important role in pathophysiology of stroke. 23 ischaemic stroke patients and 15 controls have been studied. CSF and blood sampling together with cranial CT were performed within first 24 hours of stroke. CXCL1 levels were determined by ELISA, and volume of stroke-related brain CT hypodense areas was calculated. Stroke patients displayed significantly higher CSF CXCL1 level than controls (65.6+/-22.3 vs 43.8+/-2.3 pg/ml; p<0.01). Serum CXCL1 levels in stroke patients did not differ from controls. CSF CXCL1 level correlated positively with volume of brain CT hypodense areas (p<0.001). The results suggest that CXCL1 may be involved in inflammatory reaction during an early phase of ischaemic stroke.     

The Effect of Valsartan versus Non-RAAS Treatment on Autoregulation of Cerebral Blood Flow

Background: Cerebral autoregulation (CA) is a protective mechanism which maintains the steadiness of the cerebral blood flow (CBF) through a broad range of systemic blood pressure (BP). Acute hypertension has been shown to reduce the cerebrovascular adaptation to BP variations. However, it is still unknown whether CA is impaired in chronic hypertension. This study evaluated whether a strict control of BP affects the CA in patients with chronic hypertension, and compared a valsartan-based regimen to a regimen not inhibiting the renin-angiotensin-aldosterone system (non-RAAS). Methods: Eighty untreated patients with isolated systolic hypertension were randomized to valsartan 320 mg or to a non-RAAS regimen during 6 months. The medication was upgraded to obtain BP <140/90 mm Hg. Continuous recordings of arterial BP and CBF velocity (transcranial Doppler) were performed during periods of 5 minutes, at rest, and at different levels of alveolar CO(2) pressure provided by respiratory maneuvers. The dominant frequency of CBF oscillations was determined for each patient. Dynamic CA was measured as the mean phase shift between BP and CBF by cross-spectral analysis in the medium frequency and in the dominant CBF frequency. Results: Mean ambulatory 24-hour BP fell from 144/87 to 127/79 mm Hg in the valsartan group and from 144/87 to 134/81 mm Hg in the non-RAAS group (p = 0.13). Both groups had a similar reduction in the central BP and in the carotido-femoral pulse wave velocity. The average phase shift between BP fluctuations and CBF response at rest was normal at randomization (1.82 ± 0.08 s), which is considered a preserved autoregulation and increased to 1.91 ± 0.12 s at the end of study (p = 0.45). The comparison of both treatments showed no significant difference (-0.01 ± 0.17 s vs. 0.16 ± 0.16 s, p = 0.45) for valsartan versus non-RAAS groups. The plasmatic level of glycosylated hemoglobin decreased in the valsartan arm compared to the non-RAAS arm (-0.23 ± 0.06 vs. -0.08 ± 0.07%, p = 0.07). Conclusions: In elderly hypertensive men with isolated chronic systolic hypertension, CA seems efficient at baseline and is not significantly affected by 6 months of BP-lowering treatment. This suggests that the preventive effects of BP medication against stroke are not mediated through a restoration of the CA.     

Is cerebral autoregulation impaired in Parkinson's disease? A transcranial Doppler study

Orthostatic hypotension (OH) is one of the many autonomic disturbances observed in Parkinson's disease (PD). It has been debated whether an additional impairment of cerebral autoregulation (CA) in PD patients may exacerbate the consequences of OH upon brain perfusion. We assessed CA in PD patients and the potential influence of dopaminergic agents. CA was determined by means of transcranial Doppler (TCD) monitoring of the middle cerebral artery (MCA) at rest and during a thigh cuff release test inducing a systemic blood pressure (BP) drop. Fourteen patients were investigated when taking their usual dopaminergic medication and after drug discontinuation for 12 h. A control group was composed of 11 age-matched subjects (CS). In comparison with PD patients, CS presented a significantly higher increase of the mean cerebral blood flow velocities in the MCA after the BP drop. Mean velocities were increased above the initial values in all CS, whereas a flattened curve was observed in PD patients. No significant differences could be further observed between the PD patients regarding the BP, the cerebrovascular resistance, the heart rate and the pulsatility index. These results provide evidence of an impaired cerebral autoregulation in PD patients which appears independent of dopaminergic treatment.     

Assessment of the thigh cuff technique for measurement of dynamic cerebral autoregulation

BACKGROUND AND PURPOSE: Dynamic methods of measuring cerebral autoregulation have become an accepted alternative to static evaluation. This article aims to describe a set of data collected from healthy volunteers by a dynamic method, the purpose being to qualify and quantify expected results for those who may be designing a study using this technique. METHODS: Cerebral blood flow velocity (CBFV) (measured by transcranial Doppler) and arterial blood pressure (Finapres) were recorded in 16 normal subjects before, during, and after the induction of a blood pressure drop (release of bilateral thigh cuffs). This procedure was repeated 6 times for each subject. A mathematical model was applied to the data to generate an autoregulatory index (ARI) with values between 0 and 9. RESULTS:The ARI values for this sample population follow a normal distribution, with a mean+/-SD of 4.98+/-1.06 (n=15). Analysis of the cumulative mean ARI values of all subjects showed an exponential-type convergence of ARI toward the sample mean as the number of test iterations increased. The population average blood pressure drop on thigh cuff release was 26.4+/-7.1 mm Hg (n=16), occurring in 4.6+/-1. 7 seconds. The corresponding population average drop for CBFV was 15. 6+/-5.8 cm/s, taking 2.5+/-1.0 seconds. No significant trend was noted in the measurements as the number of test iterations increased. The correlation between the predicted and actual CBFV, having a mean value of 0.76+/-0.19, showed evidence of a nonlinear relationship to ARI values. Significant correlation was also found between ARI and (1) arterial blood pressure before cuff release and (2) the magnitude of the drop in CBFV on cuff release. CONCLUSIONS: The distribution of ARI values is not significantly different from normal. At least 3 iterations of the test procedure should be performed and averaged to obtain the mean ARI for each subject. There is no significant evidence of physiological accommodation as the number of test iterations increases. The effects of mean blood pressure and the magnitude of the change in CBFV should be considered as possible covariates when ARI data are analyzed.     

Relationship between the concentration of antibodies to myosin heavy chains in serum and symptomatic carotid atherosclerosis

It is believed that atherosclerosis could result from inflammatory-fibroproliferative response to various forms of injury of endothelium and smooth muscle cells of arterial wall. The aim of this study was to examine whether immunological reaction against myosin filaments of carotid artery (CA) wall smooth muscle cells is involved in atherogenesis. 43 patients (22 females) with first-ever ischaemic stroke proven by CT were investigated. The results were compared with those obtained in 40 (21 females) healthy sex- and age-matched subjects. Anti-myosin antibodies (AMA) were evaluated by solid phase radioimmunoassay using rabbit myosin heavy chains as an antigen. The intima-media thickness (IMT) of common and CA--a measure for atherosclerosis--was estimated with the use of high-resolution ultrasonography. The AMA serum concentration in stroke patients was significantly greater than in control subjects (p < 0.001). Mean IMT for CA in stroke patients was significantly increased compared with the controls (0.98 +/- 0.17 mm vs. 0.68 +/- 0.13 mm; p < 0.0001). There was a significant correlation between AMA serum antibodies concentration and IMT (r = 0.51; p < 0.001). CONCLUSION: The significant correlation between AMA concentration and IMT of CA is the basis of the hypothesis that immunological reaction against myosin heavy chains of smooth muscle cells in CA is involved in atherogenesis.     

Impaired dynamic cerebral autoregulation in middle cerebral artery stenosis

Abstract

Background and purpose: Analysis of dynamic cerebral autoregulation during transient falls in blood pressure is considered a sensitive and convenient method for evaluating patients with carotid artery stenosis. To this point, there have been few reports on the efficacy of using the thigh cuffs technique to analyse middle cerebral artery (MCA) stenosis. If it could be determined whether cerebral blood flow can be maintained (autoregulated) during sudden falls in arterial blood pressure (ABP), then it might be possible to identify patients with MCA stenosis who are at risk of stroke.

Methods: We used the thigh cuff technique to estimate dynamic cerebral autoregulation in 57 patients with MCA stenosis and 72 normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of the rise of MCA blood velocity and compared it with the rate of the rise of arterial blood pressure. In this manner, the dynamic cerbral autoregulation of 11 patients undergoing MCA M1 stent angioplasty was estimated both pre- and post-operation.

Results: The autoregulatory index (ARI) was significantly reduced in patients with stenosed/occluded MCA (3.24 ± 1.52), as compared with normal controls (5.25 ± 1.39; p<0.001) (results reported as mean ± SD). Poor ARI values are usually observed in patients with a higher degree of stenosis and particularly in patients with insufficient collateral compensation. ARI was significantly reduced in severe stroke patients (modified ranking scale≥1), as compared with asymptomatic or TIA patients (p<0.05). After MCA stent angioplasty was performed, there was a significant improvement in ARI in 11 subjects, which caused a mean increase in ARI from 2.08 ± 1.10 to 3.80 ± 1.36 (p=0.008).

Conclusions: Dynamic cerebral autoregulation is impaired in patients with middle cerebral artery stenosis. Assessing dynamic cerebral autoregulation may allow a subgroup of patients with MCA stenosis who are at risk of hemodynamic stroke to be identified. Dynamic cerebral disautoregulation in patients with severe MCA stenosis is mostly remedied by stent angioplasty.     

Detection of impaired cerebral autoregulation improves by increasing arterial blood pressure variability

Although the assessment of dynamic cerebral autoregulation (CA) based on measurements of spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CBF) is a convenient and much used method, there remains uncertainty about its reliability. We tested the effects of increasing ABP variability, provoked by a modification of the thigh cuff method, on the ability of the autoregulation index to discriminate between normal and impaired CA, using hypercapnia as a surrogate for dynamic CA impairment. In 30 healthy volunteers, ABP (Finapres) and CBF velocity (CBFV, transcranial Doppler) were recorded at rest and during 5% CO₂ breathing, with and without pseudo-random sequence inflation and deflation of bilateral thigh cuffs. The application of thigh cuffs increased ABP and CBFV variabilities and was not associated with a distortion of the CBFV step response estimates for both normocapnic and hypercapnic conditions (P=0.59 and P=0.96, respectively). Sensitivity and specificity of CA impairment detection were improved with the thigh cuff method, with the area under the receiver–operator curve increasing from 0.746 to 0.859 (P=0.031). We conclude that the new method is a safe, efficient, and appealing alternative to currently existing assessment methods for the investigation of the status of CA.     

Assessment of aspiration risk in stroke patients with quantification of voluntary cough

BACKGROUND: Dysphagia and subsequent aspiration are serious complications of acute stroke that may be related to an impaired cough reflex. It was hypothesized that aspirating stroke patients would have impaired objective measures of voluntary cough as compared with both nonstroke control subjects and nonaspirating stroke patients. METHODS: Swallowing was evaluated by standard radiologic or endoscopic methods, and stroke patients were grouped by aspiration severity (severe, n = 11; mild, n = 17; no aspiration, n = 15). Airflow patterns and sound pressure level (SPL) of voluntary cough were measured in stroke patients and in a group of normal control subjects (n = 18). Initial stroke severity was determined retrospectively with the Canadian Neurological Scale. RESULTS: All cough measures were altered in stroke patients as a group relative to nonstroke control subjects. Univariate analysis showed that peak flow of the inspiration phase (770.6 +/- 80.6 versus 1,120.1 +/- 148.4 mL/s), SPL (90.0 +/- 3.1 versus 100.2 +/- 1.6 dB), peak flow of the expulsive phase (875.1 +/- 122.7 versus 1,884.1 +/- 221.6 mL/s), expulsive phase rise time (0.34 +/- 0.1 versus 0.09 +/- 0.01 s), and cough volume acceleration (5.5 +/- 1.3 versus 27.8 +/- 3.9 mL/s/s) were significantly impaired in severe aspirators as compared with nonaspirators. Aspirating patients had more severe strokes than nonaspirators (mean Canadian Neurological Scale score 7.7 +/- 0.7 versus 9.8 +/- 0.3). Multivariate logistic regression found only expulsive phase rise time values during cough correlated with aspiration status. CONCLUSION: Objective analysis of cough may provide a noninvasive way to identify the aspiration risk of stroke patients.     

Metabolic changes in elderly patients with major depression: evidence for increased accumulation of visceral fat at follow-up

The accumulation of visceral fat is promoted by a specific endocrine syndrome, which is similarly found in major depression. The aim of this study was to investigate whether visceral fat depots increase in depressed patients during a follow-up period explaining the increased risk for cardiovascular disorders. Intraabdominal fat was measured in 29 depressed patients and 17 controls by computer tomography at the level of lumbar vertebra 4. In patients fat measurements were done initially during a major depressive episode and again after a follow-up period of 14 months; in controls the mean time interval between measurements was 28 months. In both groups, saliva was taken at 800 h over a period of seven days prior to each CT for the estimation of free cortisol. In patients only, an oral glucose tolerance test was also carried out. Compared to controls hyper- and normocortisolemic depressed patients showed a larger accumulation of visceral fat mass over time (hypercort.:132.0 +/- 45 vs. 144.7 +/- 47 cm(2), p = 0.07; normocort.: 115.5 +/- 53 vs. 135.0 +/- 51 cm(2), p = 0.002; controls: 130.1 +/- 66 vs. 137.3 +/- 76 cm(2), p = 0.4), despite similar weight gain (hypercort.: 2.1 +/- 5 kg, normocort.: 1.7 +/- 5 kg and controls: 2.3 +/- 4 kg). Further, normocortisolemic patients showed a trend for an higher percentile increase in visceral fat accumulation than controls (23.9 +/- 27 vs. 5.8 +/- 28%, p = 0.07). At follow-up, free cortisol concentrations were still above normal in patients who had been hypercortisolemic at first assessment (35.0 +/- 8 vs. 28.8 +/- 18 nmol/l, p = 0.1). Fasting and 2 h glucose concentrations were higher in hypercortisolemic compared to normocortisolemic patients at the index examination (6.2 +/- 1.1 vs. 5.0 +/- 0.05 mmol/l, p = 0.02; 11.5 +/- 2.7 vs. 7.8 +/- 1.9 mmol/l, p = 0.01). The larger proportion of visceral fat accumulation in patients may constitute a link for explaining the increased cardiovascular mortality in patients suffering from major depression.     

Peak systolic velocity Doppler index reflects most appropriately the dynamic time course of intact cerebral autoregulation

BACKGROUND: Transcranial Doppler sonography measures blood flow velocity in basal cerebral vessels with high accuracy and time resolution. Dynamic blood flow tests were used to investigate functional integrity of the cerebral autoregulation (CA) mechanism. It is known from cortical activation studies that velocity indices differ in their appropriateness to measure changes in blood flow velocity. We aimed to compare the peak systolic, end diastolic and time-averaged mean flow velocity indices for their use in measuring the effectiveness of the CA mechanism. METHODS: We performed the leg cuff test to induce in 15 healthy volunteers (aged 24.8 +/- 0.4 years, 9 males) CA due to a sudden arterial blood pressure decrease. Data from the middle and posterior cerebral arteries were measured continuously with transcranial Doppler ultrasound, and the arterial blood pressure with a noninvasive photoplethysmographic method. After transforming all variables to relative changes, velocity-pressure diagrams were calculated for each velocity-pressure index. Additionally, we calculated the autoregulation index. RESULTS: The step decrease in arterial blood pressure resulted in an initial drop, which is followed by a rapid recovery of cerebral blood flow velocity. The autoregulation index was 5.5 +/- 1. Efficacy of CA is illustrated more accurately by peak systolic velocity-pressure curves, which lie continuously above a passive velocity-pressure relationship assuming CA to be absent. CONCLUSIONS: Our data show peak systolic blood flow velocity index to be most accurate for measuring effectiveness of the dynamic CA mechanism. No differences in the CA were found between the vascular territory of the middle and posterior cerebral arteries.     

Pattern electroretinography and visual evoked potentials in optic nerve diseases.

BACKGROUND: To evaluate transient pattern electroretinography (PERG) and pattern visual evoked potential (VEP) for the diagnosis, differential diagnosis and follow-up of optic nerve diseases. METHODS: Twenty-nine consecutive patients (14 female, 15 male) with the diagnosis of ischaemic optic neuropathy (n=14) and optic neuritis (n=15) were included in this study. Mean age of the patients with ischaemic optic neuropathy was 63.3+/-3.3 (60-78) years and the mean age of the patients with optic neuritis was 28.3+/-8.4 (19-43) years. In each patient ophthalmological examination and systemic evaluation were done and VEP and PERG were recorded. As a control group, VEP recordings of 35 healthy subjects were included. RESULTS: In the ischaemic optic neuropathy group (group 1), mean VEP amplitude (+/-SD) (1.96+/-0.95 microV) was found to be decreased significantly in the affected eyes in comparison to the control group and the unaffected eyes. The delay in latency (116.3+/-20.14 msec in the affected eyes compared with 101.31+/-6.19 msec in unaffected eyes) was statistically significant when compared with the healthy subjects. In the optic neuritis group (group 2), VEP amplitude was decreased (4.13+/-4.04 microV vs 6.97+/-3.35 microV and 6.97+/-4.43 microV) and latency was increased (122.59+/-20.09 msec vs 101.31+/-6.19 msec and 108.76+/-13.57 msec) in affected eyes significantly in comparison to the unaffected eyes and control group, respectively. Even though there were no significant differences for P50 latency and N95/P50 ratios between affected and unaffected eyes in both groups, N95 amplitude decreased significantly in the affected eyes of the ischaemic optic neuropathy patients and N95 latency was found to be decreased in optic neuritis patients. There was no correlation between VEP and PERG findings in both groups. CONCLUSION: VEP amplitude decreased significantly in ischaemic optic neuropathies while latency delay was more significant in patients with optic neuritis. PERG findings showed decreased N95 amplitude in ischemic optic neuropathy without associated latency changes.     

Impairment of endothelial function in patients with spontaneous cervical artery dissection: evidence for a general arterial wall disease

BACKGROUND AND PURPOSE: Cervical artery dissection (CAD) accounts for 10-20% of ischemic strokes in young adults. Although trauma and preexisting disorders of the arterial wall are the main predisposing factors, most CADs are considered 'spontaneous'. We hypothesized that CAD could originate in systemic vascular disease bound to the intima-media interface without clinical signs. If this hypothesis is true, endothelium-dependent vasodilation would be impaired in response to a physiological stimulus such as an increase in blood flow. METHODS: Flow-mediated arterial dilation was studied in 65 consecutive patients with spontaneous CAD: 26 with carotid artery dissection (ICAD), and 39 with vertebral artery dissection (VAD). CAD patients with vascular risk factors, trivial or obvious cervical trauma, or connective tissue disease were excluded. Twenty-three patients with ischemic stroke of unknown cause were included as controls. Using high-resolution ultrasonography, brachial artery diameter was measured at rest, during post-ischemic hyperemia (flow-mediated endothelium-dependent dilation), and after sublingual glyceryl trinitrate spray (endothelium-independent dilation). RESULTS: The mean +/- SD values of the flow-mediated vasodilation index were 5.7 +/- 6.2% in ICAD, 5.0 +/- 9.3% in VAD and 13.2 +/- 6.5% in controls (p < 0.0005), without any difference between ICAD and VAD. Endothelium-independent dilation mean values were 21.5 +/- 9.5% in ICAD, 25.1 +/- 12.5% in VAD, and 20.8 +/- 8.4% in controls, without a significant difference between groups (p = 0.49). CONCLUSIONS: These results give evidence of impaired endothelium-dependent vasodilation in CAD patients that is not the result of stroke, and suggest that an underlying abnormality of the arterial wall layers may predispose to CAD.     

Visceral pain and public speaking stress: neuroendocrine and immune cell responses in healthy subjects

Whereas responses to psychological stressors are well-characterized, little is known regarding responses to painful visceral stimuli. We analyzed the emotional, cardiovascular, neuroendocrine, and cellular immune responses to painful rectal stimulation and psychological stress in healthy individuals. Eleven healthy subjects were studied in three conditions on separate days: painful rectal distension, public speaking stress, and rest. Blood was drawn for endocrinological and immunological analyses; heart rate and blood pressure were measured continuously; state anxiety was assessed with a questionnaire (STAI-S). Anxiety scores were highest in the rectal distension condition. This was evident following rectal distension (mean STAI-S scores: 44.2+/-3.5 post-distension vs. 36.6+/-3.8 post-speech, p<.05), but anxiety was also elevated at baseline (41.6+/-3.9 vs. 32+/-3.2 recovery, p<.01). This anticipatory effect was reflected by elevated baseline cortisol (p<.05) and baseline ACTH (p<.01) levels, as well as circulating lymphocytes and lymphocyte subsets, including decreased basal CD3+CD4+ cells (p<.05) and increased CD16+CD56+ cells (p=.06) compared to rest. Both public speech and rectal distension induced cardiovascular activation, but the effect was more pronounced following rectal distension (+63.8+/-9.4 mmHg in response to distension vs. +36.4+/-6.2 mmHg in response to speech for systolic BP, p<.05). Different response patterns were also observed in the distribution of circulating leukocytes and lymphocyte subsets, including CD16+CD56+ cells (p<.05). An acute visceral pain stimulus causes profound emotional, neuroendocrine, and immune cell responses, which are markedly affected by anticipatory anxiety. These findings may have implications for conditions associated with visceral hyperalgesia.     

Progression of dementia associated with lacunar infarctions

BACKGROUND: Lacunar stroke (L) is the most common stroke subtype associated with vascular dementia (VaD-L). OBJECTIVE: To evaluate the cognitive and behavioral course in patients with probable VaD-L. METHODS: We longitudinally measured rates of change on MMSE, digit span, logical memory, Controlled Oral Word Association, CERAD battery and neuropsychiatric inventory (NPI) in 77 patients (age at entry 69 +/- 8.1 years) with probable VaD-L for 25.75 +/- 11 months. RESULTS: The mean number of follow-up visits was 2.6 +/- 0.67 (range 2-4). Time interval between any two consecutive visits was at least 5 months (range 5-41). MMSE deteriorated by 1.44+/- 1.8 points annually and NPI increased by 6.01 +/- 13.7 points annually (p < 0.0001). The rates of cognitive and behavioral decline were predominantly influenced by the cognitive state at entry into the study and the occurrence of new vascular episodes during follow-up [(-0.95 +/- 1.7) MMSE and (+2.02 +/- 14.1) NPI points annually without vascular episodes vs. (-2.09 +/- 1.6) and (+11.3 +/- 11.4) points following vascular episodes (p < 0.0001)]. Impaired cognition was associated with impaired behavior (p < 0.001). VaD-L patients without additional vascular episodes at follow-up have a progressively deteriorating course as well (p < 0.0001). CONCLUSION: VaD-L is characterized by cognitive and behavioral decline. The rate of decline is determined mainly by the severity of the cognitive and behavioral impairment at baseline and by the occurrence of new vascular episodes.     

Intravenous administration of magnesium sulfate in acute stroke: a randomized double-blind study

A randomized, placebo-controlled, double-blind study was performed as a pilot study to examine the benefit of the administration of magnesium sulfate given intravenously as a protective substance during the first 24 hours following a stroke. Patients who had cortical infarction in the middle cerebral artery territory with moderate to severe neurologic deficits lasting for more than 15 minutes with onset less than 24 hours were included. The patients were treated with magnesium sulfate or placebo for 5 days and examined by a blinded investigator. Patients had follow-up for 30 days. The primary efficacy variable was the proportion of patients reaching mild to moderate neurologic deficit on the Orgogozo scale (80 points) and relative functional independence on the Barthel index (60 points). Orgogozo scale and Mathew scale values were obtained on admission and days 2, 4, 8, and 30 after stroke. Barthel activities of daily living index and Rankin disability score were obtained on day 30. Forty-one patients (22 given treatment and 19 given placebo) demonstrated significant beneficial effects on the Orgogozo scale (84 +/- 11 vs. 64 +/- 10, p < 0.0001) and (83 +/- 14 vs. 70 +/- 15, p < 0.009), respectively. At the end of 1-month follow-up, the Barthel ADL index was nonsignificantly higher and the Rankin disability score was marginally significantly lower in the magnesium-treated group (84 +/- 26 vs. 71.8 +/- 26, p < 0.143) than in control subjects (2.3 +/- 1.1 vs. 3 +/- 1.3, p < 0.077). Intravenous magnesium sulfate had significant positive effect on the outcome in patients with acute stroke. Further studies on a larger scale are needed to confirm these findings.     

Effect of perindopril on cerebral and renal perfusion on normotensives in mild early ischaemic stroke: a randomized controlled trial

BACKGROUND AND PURPOSE: Blood pressure reduction is central to secondary prevention after stroke, but the optimal time to start therapy is unknown. Cerebral autoregulation is impaired early after ischaemic insult, and any changes in systemic blood pressure may be reflected in cerebral perfusion. However, early initiation in hospital may better assure continued long-term treatment. We have investigated the effect of the angiotensin-converting enzyme inhibitor perindopril on blood pressure, global and focal cerebral blood flow (CBF) and glomerular filtration rate (GFR) in a normotensive acute stroke population. METHODS: Twenty-five patients within 4-8 days of mild ischaemic stroke/transient ischaemic attack and with diastolic blood pressure 70-90 mm Hg were randomized to receive perindopril 2 or 4 mg daily versus placebo according to estimated GFR. Mean arterial blood pressure (MABP), internal carotid artery (ICA) flow and middle cerebral artery velocity (MCAv) were measured prior to dosing, over the following 24 h and at 2 weeks. Brain hexamethyl propylene amino oxide single photon emission computed tomography (SPECT) was performed before dosing and at estimated time of peak drug effect (6-8 h after first dose). GFR measurement using a (51)Cr-ethylene diamine tetraacetic acid technique was undertaken prior to medication and repeated at 2 weeks. RESULTS: MABP was reduced throughout the first 24 h with a mean MABP reduction of 9.3 mm Hg (95% CI 7.4-11.3 mm Hg), maximal placebo corrected fall of 12.5 mm Hg at 10 h post-dose, p = 0.005. No significant change occurred in ICA flow, MCAv or CBF measured by SPECT: change from baseline in symptomatic hemisphere CBF was -0.02 (SD 3.11) ml/100 g/min (treated group) compared with 0 (SD 3.01) (placebo group). Similarly, no significant change was observed in cortical CBF. Mean within-group change in GFR was 2.7 +/- 10.1 in the treated group and -4.3 +/- 6.7 in the placebo group (p = NS). DISCUSSION: Antihypertensive therapy with perindopril may be introduced in the first week after mild ischaemic stroke in normotensive patients without affecting global or regional CBF or affecting GFR.