Cerebrovascular reactivity to L-arginine in patients with lacunar infarctions

BACKGROUND: It is well known that endothelial dysfunction plays an important role in the pathogenesis of many cardiovascular disorders. The aim of this study was to test the hypothesis that specific, marked endothelial dysfunction of cerebral arteries is present in patients with lacunar cerebral infarctions. METHODS: Cerebrovascular reactivity to L-arginine, which reveals the function of the cerebral endothelium, was investigated in patients with lacunar infarctions (20 patients, 11 male and 9 female, aged 60.9 +/- 7.3 years), 21 age- and gender-matched asymptomatic patients with similar cardiovascular risk factors (all patients had arterial hypertension) and 21 age- and gender-matched healthy controls. The mean arterial velocity (vm) in both middle cerebral arteries was measured by transcranial Doppler sonography during a 15-min baseline period, a 30-min intravenous infusion of L-arginine and a 15-min interval after L-arginine infusion. Arterial blood pressure, heart rate and CO2 were measured continuously. RESULTS: The measured vm increase during L-arginine infusion in the patients with lacunar infarctions (13.4 +/- 9.1%) was significantly lower compared to the healthy controls (20.5 +/- 9.9%) but similar to that obtained in the patients with cardiovascular risk factors (11.5 +/- 8.9%). CONCLUSIONS: Our results showed that cerebrovascular reactivity to L-arginine, which demonstrates cerebral endothelial function, is significantly impaired in patients with cardiovascular risk factors. Importantly, we found that patients with lacunar infarctions do not show any additional impairment of cerebral endothelial function.     

Large subcortical hemispheric infarctions. Presentation and prognosis

A specific form of large subcortical hemispheric infarction on computed tomography was identified in 24 of 2198 (1%) stroke registry patients. Combined with 13 cases from earlier literature reports, a characteristic neurologic picture developed. Severe face plus arm plus leg weakness at onset (76%), corticallike features of aphasia and/or contralateral neglect (68%), and premonitory transient ischemic attacks (24%) were frequent. Twenty-two patients (59%) had large vessel arterial occlusive disease. Eight patients (22%) had primary embolic occlusion in the middle cerebral artery territory. During an average follow-up of 16 months, five patients (14%) suffered recurrent stroke or death. The clinical presentation and prognostic features of this distinct stroke subtype are described.     

脑血管反应性与缺血性卒中

目的观察缺血性卒中患者脑血管反应性（CVR）变化,确定两者之间的相关性。方法采用经颅多普勒超声（TCD）结合屏气试验检测76例缺血性卒中患者及62例对照病例的屏气指数（BHI）。结果缺血性卒中患者组的BHI明显低于对照组（P〈0.001）,Logistic 回归显示,由BHI所表示的CVR是缺血性卒中的独立影响因素（P=0.000）。结论降低的CVR是缺血性脑卒中的独立危险因素,应该重视CVR在脑缺血发生、发展过程中的独立影响作用。     

单发皮质下小梗死部位与早期神经功能恶化的相关性

目的 探讨单发皮质下小梗死（SSSI）不同病变部位与早期神经功能恶化的关系。方法 回 顾性连续纳入2017年6月至2019年6月于北京市中关村医院神经内科住院的SSSI患者122例,根据病变部 位分为近端SSSI 组（52 例）和远端SSSI 组（70 例）。比较2 组患者临床资料和实验室资料、影像特征、早期 神经功能恶化发生率及预后,采用多因素Logistic 回归分析影响远端SSSI发生的影响因素。结果 与 近端SSSI 组比较,远端SSSI 组早期神经功能恶化发生率高［14.3（10/70）比０,χ2=8.092,P=0.005］,舒 张压［（94.14±17.29）mmHg（ 1 mmHg=0.133 kPa）比（88.35±13.16）mmHg,t=-2.201,P=0.046］、舒张压≥ 100 mmHg［ 40.0%（28/70）比19.2%（10/52）,χ2=6.001,P=0.018］、甘油三酯［（1.79±1.06）mmol/L 比 （1.39±0.78）mmol/Ｌ,t=-2.310,P=0.023］及不稳定斑块发生率［68.6%（48/70）比53.8%（28/52）,χ2=4.695, P=0.049］均高于近端SSSI组,差异有统计学意义。不稳定斑块（OR=3.345,95%CI：1.123～9.965,P=0.030） 及高水平低密度脂蛋白（OR=2.954,95%CI：1.492～5.848,P=0.002）是远端SSSI 的独立危险因素。 结论 SSSI患者梗死部位不同,临床特征及早期神经功能恶化发生率不同。积极控制血压、改善脂代 谢紊乱及稳定动脉粥样硬化斑块等治疗可有效预防远端SSSI。     

Cerebrovascular reactivity and dynamic autoregulation in nondemented patients with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)

Abstract Reduced cerebrovascular reactivity has been reported in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and the measurement has been suggested as a useful surrogate marker of disease progression. Previous studies have not determined whether cerebral autoregulation is also impaired. We measured dynamic cerebral autoregulation and carbon dioxide reactivity in 24 nondemented CADASIL patients and 20 controls, using transcranial Doppler ultrasound (TCD). No impairment in either measure was found in the CADASIL group. We conclude that either cerebrovascular reactivity and autoregulation are not impaired in early disease, or that TCD may not be a sufficiently sensitive tool to detect haemodynamic changes in early disease. TCD is unlikely to be useful for disease monitoring in patients without advanced disease.     

Cerebrovascular reactivity in multiple sclerosis patients

A close relationship between multiple sclerosis (MS) lesions and the cerebral vasculature has long been recognised. Some studies have suggested that vascular endothelial cell activation might be an early event in the evolution of MS, and demyelisation may have an ischemic basis in this condition. Hypoxia caused by breath holding (BH) results in autoregulatory vasodilatation, and an increase in CBF to the cortex. The increased CBF can be evaluated by transcranial Doppler (TCD), and can provide information about the vascular integrity. In this study, we aimed to examine the vascular integrity and assess the vasomotor reactivity of MS patients in response to BH in different activation phases of the disease by means of TCD. We studied 12 patients with clinically diagnosed relapsing remitting (RR) MS, according to the Poser criteria. The initial TCD examination was performed in the first two days of an acute exacerbation of disease and prior to any treatment. The second test was performed just after iv methylprednisolone (IVMP) treatment, and the third examination occurred one month later, when the patient was in the remission phase. A group of 11 healthy subjects was also examined by TCD as control. Blood flow velocities were recorded during 30 seconds of normal breathing and 15 seconds BH. Vasomotor reactivity was calculated as a ratio of difference of cerebral flow velocities during BH. There were no significant vasomotor reactivity differences between the controls (55.7%) and the patients during attacks (46.5%), as well as after treatment (48.3%) and during attack free periods (50.9%). There were also no significant changes amongst the patients groups throughout the study. In this study, in different disease activity stages, we observed non-significant cerebrovascular vasomotor reactivity difference between the RRMS patients and the healthy controls, although it was slightly lower in the MS patients. This observation suggests that cerebrovascular reactivity is normal in different disease activity levels.     

Acute small subcortical infarctions on diffusion weighted MRI: clinical presentation and aetiology

OBJECTIVE: To determine the clinical presentation and aetiology of small subcortical infarctions as found on diffusion weighted magnetic resonance imaging (DWI). DWI is both sensitive and specific in the early detection of acute ischaemic brain lesions irrespective of pre-existing vascular damage. METHODS: Ninety three patients were identified showing subcortical or brainstem DWI lesions <1.5 cm in diameter within a maximum of 7 days from the onset of stroke symptoms. The patients' clinical status on admission was reviewed according to the Oxfordshire Community Stroke Project (OCSP). The results of procedures searching for cerebrovascular risk factors, large artery disease, and potential sources of cardiac embolism were included to determine stroke aetiology. Magnetic resonance imaging scans were also reviewed for concomitant changes that could support the aetiologic classification. RESULTS: Only 41 (44.1%) patients presented clinically with a lacunar syndrome according to OCSP criteria. The nine (9.7%) patients who showed two or more DWI lesions in different vascular territories were also significantly more likely to have potential sources of cardiac embolism (5/9, 55.6% v 20/84, 23.8%). Hypertension was significantly more prevalent in the group of patients who showed a microangiopathy related imaging pattern, but this pattern did not exclude the presence of large artery disease or a possible cardioembolic source of stroke. CONCLUSION: Identification of small subcortical infarctions as the cause of stroke appears quite uncertain based on clinical characteristics only. DWI adds significant aetiologic information but does not obviate the search for other potentially causative mechanisms.     

Cerebrovascular reactivity over time course in healthy subjects

INTRODUCTION: Cerebrovascular reactivity (CVR) reflects the compensatory dilatory capacity of cerebral arterioles to a dilatory stimulus and is an important mechanism for maintaining constant cerebral blood flow. Many pathological conditions are associated with an impaired CVR thus contributing to a higher risk of cerebrovascular disease. Since an impaired CVR might contribute to a cerebrovascular disease if it lasts for a longer period of time, it is of importance to know what the time-course of CVR might be under healthy conditions. METHODS: We investigated CVR in 33 healthy subjects on baseline and on follow-up after 1 to 3 years. CVR was determined by calculating the difference between maximal blood flow velocity after stimulation with acetazolamide and during rest. Blood flow velocities were measured by transcranial Doppler ultrasound. RESULTS: CVR did not differ significantly in a group of healthy persons when reevaluated after 1 to 3 years. Possible influencing factors like age, gender, interval between testing, and smoking did not show a significant influence. DISCUSSION: This is the first study to investigate within-subject-differences in healthy subjects. CVR seems to remain constant under healthy conditions. Even this short period of life-span is of importance because an altered CVR can improve under treatment within weeks. Nevertheless further studies should follow-up longer periods of time.     

Cerebrovascular reactivity in patients under long-term acetazolamide treatment

BACKGROUND AND PURPOSE: The acetazolamide (AZA) test is a well-accepted method for measuring the vascular reactivity of the cerebral arteries. In order to investigate the nature of this reactivity after long-term daily AZA treatment, the cerebral blood velocity (CBV) was measured using transcranial Doppler in patients under continuous AZA treatment after a single AZA 1 g intravenous (IV) dose. METHODS: Thirteen patients (eight women, five men) on long-term daily AZA (750 mg/day, mean treatment duration 68 +/- 12+ months) were included in the study. The CBV of the middle cerebral artery (MCA) and the basilar artery (BA), including the values of peak velocity, mean velocity and pulsatility index (PI) were measured. The examination was performed twice - with the initial IV administration of AZA and 20 min later. The results were compared with those of 10 age matched volunteers. RESULTS: A consistent significant increase of CBV in the right and left MCA (P < 0.001 for both arteries) was found in all study participants. A highly significant decrease of peak CBV in the BA (P < 0.001) was found in the post-AZA velocities of the patient's group. In the control group, a consistent significant increase in all post-AZA tests was demonstrated (P < 0.001). CONCLUSIONS: A mild elevation of blood velocity in the MCAs concomitant with a highly significant decrease of velocity in the BA was present in all examined patients. These patterns of CBV changes indicate the presence of a 'steal phenomenon' from the posterior to the anterior circulation and stress the necessity for caution when evaluating the indications for performance of the AZA test in patients under continuous AZA therapy.     

Cerebrovascular reactivity in patients with mild head injury

Transcranial Doppler sonography (TCD) is a non-invasive method that can be repeated to measure blood flow velocity in intracranial arteries and to assess cerebrovascular reactivity in patients with a variety of neurological diseases. The aim of this study was Doppler sonography evaluation of blood flow and reactivity in the middle cerebral artery in patients at different stages after mild head injuries. The dynamic assessment of blood flow velocity and pulsatility index both at rest and after hyperventilation in 73 patients with mild head injuries was carried out on the day of injury, the third day, sixth day and after 6 months to 5 years. The control group consisted of 61 healthy volunteers. Obtained results indicate an increase in blood flow velocity in the middle cerebral artery on the day of injury and a decrease within the following days in younger patients (aged xleq 30 yrs). Also their cerebrovascular reactivity was significantly lower. In older persons (age > 30 yrs) and in patients with remotely suffered injuries, neither blood flow velocity in the middle cerebral arteries nor cerebrovascular reactivity differed significantly from the results of the respective age control groups. The findings justify a conclusion that mild head injury is followed by changes both in the blood flow and cerebrovascular reactivity. In younger patients with mild head injuries these haemodynamic disturbances seem to be connected with altered activity of the autonomic system.     

Cerebrovascular reactivity in depressed patients without vascular risk factors

INTRODUCTION: Cerebrovascular reactivity (CVR) seems to be gaining importance as a prognostic factor for stroke risk. CVR reflects the compensatory dilatory capacity of cerebral arterioles to a dilatory stimulus; this mechanism plays an important role in maintaining a constant cerebral blood flow. Evaluating factors that influence CVR will help prevention or early detection of cerebrovascular disease (CVD). In this study we aimed to measure the CVR in vascular-risk free depressed individuals so as to evaluate the effect depression has on CVR and hence its role as a stroke risk factor. METHODS: Using acetazolamid (ACZ) stimulation, CVR was assessed with a transcranial Doppler ultrasound in 25 non-smoking depressed patients (average age: 48.48 +/- 14.40) and in 25 healthy non-smoking controls (average age: 46.76 +/- 13.69) by calculating the difference between the maximal mean blood flow velocity at baseline and the maximal mean blood flow velocity after ACZ stimulation. RESULTS: Basal Cerebral Blood flow in Patients was 50.6 cm/s (SD: 11.6) versus controls 52.80 cm/s (SD: 12.70) whereas after stimulation maximal blood flow velocity was 72.64 cm/s (SD: 15.75) in patients versus 80.20 cm/s (SD: 18.43) in controls. In an analysis of covariance we found that cerebrovascular reactivity was significantly reduced in the vascular-risk free depressed sample. Age had a significant influence whereas gender did not. DISCUSSION: Major Depression appears to decrease cerebrovascular reactivity supporting the idea of increased risk for stroke in depressed patients. The mechanisms leading to this phenomenon and its subtle subgroup differences should be further investigated.     

Cerebrovascular acetazolamide reactivity and platelet function in asymptomatic cerebral thrombosis.

In order to find out the relationship between the cerebrovascular acetazolamide reactivity and platelet function in asymptomatic cerebral thrombosis, 10 cases of asymptomatic cerebral infarction and 10 age-matched control subjects were studied. The cerebrovascular acetazolamide reactivity was measured using xenon computed tomography method. As markers of platelet function, the plasma concentrations of platelet factor 4, beta-thromboglobulin, thromboxane B2, and 11-dehydrothromboxane B2 were determined. The cerebrovascular acetazolamide reactivity was significantly lower in the asymptomatic cerebral infarction group than in the control group. The plasma concentrations of platelet factor 4, beta-thromboglobulin, thromboxane B2, and 11-dehydrothromboxane B2 were higher in the asymptomatic cerebral infarction group than in the control group. There was a significant negative correlation between the cerebrovascular acetazolamide reactivity and the plasma concentrations of platelet factor 4, beta-thromboglobulin, thromboxane B2, and 11-dehydrothromboxane B2. The low cerebrovascular acetazolamide reactivity is considered to be related to platelet activation in asymptomatic cerebral thrombosis.     

Cerebrovascular reactivity in young and old patients with obstructive sleep apnea

ObjectiveImpaired cerebrovascular reactivity (CVR) in patients with obstructive sleep apnea syndrome (OSAS) increases the risk of ischemic stroke. CVR also decreases with age in normal individuals. However, it is unclear whether OSAS affects CVR differently in young and old patients. The aim of this study was to compare CVR in old and young patients with OSAS via transcranial Doppler (TCD) measurements of changes in cerebral blood flow velocity in the middle cerebral artery (MCAmv) during breath holding and hyperventilation.MethodsA total of 20 old patients (≥65 y) and 40 young patients (<65 y) with similar distributions of sex and OSAS severity were recruited for this study. The breath-holding index (BHI) and the hyperventilation index (HVI) were calculated to measure CVR.ResultsNo differences were found in MCAmv at baseline, apnea or hyperventilation between the two groups with different OSAS severities. However, reduced BHI (P < 0.01) and HVI (P < 0.01) were found in the young group with increasing severity of OSAS. Notably, the decline in BHI and HVI associated with OSAS severity was steeper in young patients than in old patients (P < 0.01).ConclusionsThese findings suggest that CVR in young patients is more impacted by OSAS severity than that in old patients, suggesting the existence of age-related cerebrovascular susceptibility to OSAS.     

Cerebrovascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) is a small vessel disease caused by TREX1 mutations. RVCL-S is characterized by retinal vasculopathy and brain white matter lesions with and without contrast enhancement. We aimed to investigate cerebrovascular reactivity (CVR) in RVCL-S. In this cross-sectional observational study, 21 RVCL-S patients, 23 mutation-negative family members, and 31 healthy unrelated controls were included. CVR to a hypercapnic challenge was measured using dual-echo arterial spin labeling magnetic resonance imaging. Stratified analyses based on age were performed. We found that CVR was decreased in gray and white matter of RVCL-S patients compared with family members and healthy controls (ANCOVA; P < 0.05 for all comparisons). This was most noticeable in RVCL-S patients aged ≥40 years (ANCOVA, P < 0.05 for all comparisons). In RVCL-S patients aged < 40 years, only CVR in white matter was lower when compared to healthy controls (P < 0.05). Gray matter CVR was associated with white matter lesion volume in RVCL-S patients (r = –0.527, P = 0.01). In conclusion, impaired cerebrovascular reactivity may play an important role in the pathophysiology of RVCL-S and may be an useful early biomarker of cerebrovascular disease severity.