Long-Term Adverse Effects of Neck Radiotherapy in Childhood on the Carotid Arteries in Survivors of Hodgkin Lymphoma.

INTRODUCTION: Survivors of Hodgkin lymphoma are recognized to have an increased risk of stroke and carotid artery disease owing to neck irradiation (RT). However, it remains unclear whether the vascular modifications induced by the treatment of Hodgkin lymphoma during childhood persist over the long term. METHODS: Our matched study involved 79 survivors of Hodgkin lymphoma in childhood who received neck RT and 57 healthy controls. Parameters of arterial stiffness (AS), intima-media thickness (IMT), and flow-mediated dilation (FMD) of carotid arteries were assessed using ultrasound. RESULTS: Our patient cohort demonstrated a significant increase in AS compared to controls (p < 0.05), though no such disparity was observed for FMD (p = 0.111). Neck RT intensified AS (B = 0.037, p = 0.000), while anthracyclines attenuated it (B = -0.803, p = 0.000). Multivariate analysis revealed a positive correlation between neck RT (p < 0.001) and AS. However, we found no significant association between neck RT and FMD (p = 0.277). We identified a substantial positive correlation between the dose of neck RT and AS. CONCLUSIONS: Vascular changes in survivors of childhood Hodgkin lymphoma after neck RT seem to be long-term. Therefore, these patients may have an increased risk of stroke. We suggest refinement of international guidelines according to our results.

The Responses to CGRP in the Territory of the Posterior Cerebral Artery in Migraine.

Calcitonin gene-related peptide (CGRP) is important in trigeminovascular (TMV) sensitization with neurogenic inflammation which might be involved in CGRP-induced headache (CGRP-IH). Distribution of white matter lesions, migraine aura, and functional neuroimaging indicate that posterior circulation is especially exposed to TMV sensitization. The transcranial Doppler (TCD) is able to detect changes in the posterior cerebral artery (PCA) during CGRP stimulation. Thus, we studied CGRP-induced hemodynamic changes in PCA and frequency of CGRP-IH. Twenty healthy subjects and 20 patients with migraine participated in our study. TCD was used to monitor mean arterial velocity in posterior cerebral artery (vmPCA). Simultaneously, end-tidal carbon dioxide (Et-CO2), mean arterial pressure (MAP), and heart rate (HR) were measured. During the experiment, we monitored the frequency of CGRP-IH. We determined the values of vmPCA, Et-CO2, MAP, and HR and calculate the response of vmPCA, Et-CO2, MAP, and HR to CGRP. To test the differences and relationships, statistical methods were applied using SSPS. We found significant decrease in vmPCA in migraine and control groups and found the vmPCA response to be significantly lower in migraine (p = 0.018). Et-CO2 decreases in both groups, and it is significantly lower in migraine (p < 0.001). MAP is significantly higher in migraine (p = 0.001), while HR is not significantly higher in migraine (p = 0.570). CGRP-IH is significantly associated with vmPCA responses (p = 0.003) and migraine (p < 0.001). We concluded that hemodynamic changes in PCA are significantly related to CGRP-IH. The TMV sensitization might be pronounced in posterior circulation explaining clinical and morphologic issues in migraine.

The Vasodilatory Response to CGRP of the Anterior and Posterior Cerebral Circulation in Migraine.

Introduction: Migraine aura can be associated with headache or it may occur without one, which suggests an independent mechanism for the aura and for migraine headache. The role of CGRP in migraine headache is well established, but the connection between CGRP and the aura is still lacking an explanation. Exogenous CGRP can induce CGRP headaches and migraine auras in patients with migraine. The results of our recent study suggest differences in the vascular response to CGRP stimulation between migraine without aura and migraine with aura. Therefore, we hypothesized that the magnitude of the posterior cerebral circulation response in migraine with aura is greater than in migraine without aura and that CGRP stimulation has different effects on the anterior and posterior circulation in migraine with aura and migraine without aura. Methods: By using transcranial doppler, we studied the hemodynamic effects of CGRP intravenous infusion at a rate of 1.5 mcg/min in 20 min on the mean arterial velocity in the middle cerebral artery and in the posterior cerebral artery in twenty patients with migraine and in a control group of twenty healthy subjects. The same CGRP effects on cerebral hemodynamics were analyzed separately for the group of patients with migraine with aura and the group of patients with migraine without aura. Fifteen patients with migraine (75%) had migraine without aura and 5 patients (25%) had migraine with aura. Results: We found that migraine has a significant impact on the vasodilatory response of the anterior (B = 4,249, SE = 1.023, r = 0.363, p < 0.001) and posterior cerebral circulation (B = 3.634, SE = 1.461, r = 0.227, p = 0.014). Migraine with aura was significantly associated with changes in the anterior (B = 2.558, SE = 0.880, r = 0.275, p = 0.005) and posterior cerebral circulation (B = 7.565, SE = 2,368, r = 0.359, p = 0.002), while migraine without aura was only significantly associated with changes in the anterior circulation. In addition, we established a significant impact of migraine with aura on VR PCA (B = 5.901, SE = 2,546, r = 0.291, p = 0.024). Conclusion: We conclude that TVR in the posterior cerebral circulation might be enhanced in MA and that aura might be a consequence of TVR enhancement.

Calcitonin gene-related peptide-induced hemodynamic changes in migraine with and without aura.

OBJECTIVES: Exogenous calcitonin gene-related peptide (eCGRP) can induce CGRP-induced headaches (CGRP-IH) and aura in migraine with aura (MA). This implies a common pathophysiological mechanism of trigeminovascular sensitization (TVS) in migraine headaches and aura. The aim was to assess hemodynamic changes in cerebral circulation induced by eCGRP. We predicted that cerebral hemodynamic changes may differ between migraine without aura (MO) and MA. MATERIALS AND METHODS: We included twenty participants with migraine, of whom 15 (75%) had MO, and 5 (25%) had MA. An intravenous infusion of eCGRP was administered. Polymodal recording of mean arterial velocity in MCA (vm MCA) and PCA (vm PCA), end-tidal carbon dioxide partial pressure (Et-CO2 ), mean arterial pressure (MAP), and heart rate (HR) was employed using transcranial Doppler sonography (TCD). The parameters were determined at different time points with single responses vm MCAtot , vm PCAtot , Et-CO2tot , MAPtot , and HRtot . RESULTS: The CGRP-IH appeared in five participants with MA (100%) and in 11 participants with MO (73.3%) (p = .530). The difference of changes in vm MCAtot (p = .014) and vm PCAtot (p = .004) was significant, whereas in Et-CO2tot (p = .658), MAPtot (p = .392), and HRtot (p = .686), it appeared to be non-significant. We found significant associations between vm MCAtot and MA (p = .023; OR = 0.88; 95%C.I. 0.78-0.98), and vm PCAtot and MA (p = .018; OR = 0.85; 95%C.I. 0.74-0.97). CONCLUSIONS: Cerebral hemodynamics differs between MO and MA, indicating a pronounced vasodilatation and TVS in MA, which could induce aura.

The Influence of Calcitonin Gene-Related Peptide on Cerebral Hemodynamics in Nonmigraine Subjects with Calcitonin Gene-Related Peptide-Induced Headaches.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is regarded as an important molecule in trigeminovascular sensitization (TVS). CGRP-induced headaches (CGRP-IH) are evoked by intravascular administration of CGRP in nonmigraine and migraine subjects. CGRP might be associated with vasodilatation of the middle cerebral artery (MCA). It is unclear whether CGRP-induced hemodynamic changes relate to CGRP-IH in nonmigraine subjects. METHODS: Twenty healthy subjects participated in our study. Polymodal recording of mean arterial velocity in MCA (vm MCA), end-tidal carbon dioxide partial pressure (Et-CO2), mean arterial pressure (MAP), and heart rate (HR) was employed using transcranial Doppler (TCD) sonography. During the experiment, we administered intravenous infusion of CGRP at a rate of 1.5 mcg/min. The vm MCA, Et-CO2, HR, and MAP were determined at time points T 0, T 1, T 2, and T 3. We calculated the responses at different time points and combined them into a single response vm MCAtot, Et-CO2tot, HRtot, and MAPtot. RESULTS: We found significant differences along the time points in vm MCA (p = <0.001), Et-CO2 (p = 0.003), MAP (p < 0.001), and HR (p < 0.001). The relationship between vm MCAtot and Et-CO2tot was significant and positive (p = 0.005). The t-test showed significant differences between CGRP-IH and non-CGRP-IH subjects in vm MCAtot (p = 0.021) but not in Et-CO2tot (p = 0.838), MAPtot (p = 0.839), and HRtot (p = 0.198). Only vm MCAtot showed a significant relationship with CGRP-IH (p = 0.028). CONCLUSIONS: Our study provides evidence for vasodilatation of MCA in relation to CGRP-IH due to intravascular CGRP detected by multimodal TCD. In the context of TVS induced by CGRP, MCA vasodilatation seems to represent an epiphenomenon of the underlying TVS.

Enhanced Hemodynamic and Clinical Response to αCGRP in Migraine Patients-A TCD Study.

Introduction: Sensitisation of the nervous system in a patient with migraine is supposed to be associated with calcitonin gene-related peptide (CGRP) activity. Therefore, the vascular response to human αCGRP (hαCGRP) could be a surrogate marker for the sensitization. We hypothesize that vascular response to hαCGRP is augmented in a patient with migraine. Methods: Twenty healthy subjects and 20 patients with migraine participated in our study. TCD was used to monitor mean arterial velocity in the middle cerebral artery (vm MCA). Simultaneously, end-tidal CO2 (Et-CO2), mean arterial pressure (MAP), and heart rate (HR) were measured. The reconstruction of the signals was made for basal conditions, during and after CGRP infusion which were compared using statistics. Results: In both groups, we found significant decrease between measurement points of vm MCA and Et-CO2 during and after hαCGRP infusion. MAP did not show significant trends during the infusion, but it was significantly increased after the infusion in migraine patients only. Responses to hαCGRP, defined as differences between two measurement points, were significantly higher for vm MCA and Et-CO2 in patients with migraine. A significant difference between groups was found in MAP response. Significant relationships were found between migraine and vm MCA, Et-CO2, and MAP. Conclusion: In patients with migraine, vm MCA responses to hαCGRP are significantly higher and are associated with CGRP-induced headache which indicates that patients with migraine are more prone to sensitization.

αCGRP-Induced Changes in Cerebral and Systemic Circulation; A TCD Study.

It is known that perivascular application of CGRP induces cerebral vasodilatation. However, it is unclear whether intravenous alfa CGRP (αCGRP) induces changes in cerebral and systemic hemodynamics. Therefore, we studied the influence of an αCGRP intravenous infusion at a rate of 1.5 mcg/min in 20 min on mean arterial velocity in the middle cerebral artery (vm MCA) and in the posterior cerebral artery (vm PCA) in twenty healthy subjects using transcranial Doppler (TCD). We found out that αCGRP decreased vm MCA (p < 0.001), vm PCA (p < 0.001), mean arterial pressure (MAP) (p < 0.001) and end-tidal CO2 (Et-CO2) (p = 0.030). The heart rate (HR) increased during αCGRP infusion (p < 0.001). In addition, we found a positive relationship between Et-CO2 and vm MCA (p = 0.001) as well as vm PCA (p = 0.043). In our view, αCGRP induces changes in cerebral and systemic circulation in healthy volunteers. It might cause vasodilatation of MCA and PCA and a compensatory decrease of Et-CO2 to αCGRP related hemodynamic changes.

Estimation of the Impact of Migraine on Self-rated Health: A Cross-sectional Study in Slovenia.

AIM: With the aim of providing a foundation for evidence-based public health actions, as well as the more individualised clinical treatment of migraine in Slovenia, the objective of our study was to assess the association between poor self-rated health (PSRH) and migraine, adjusted for selected comorbidity and socioeconomic factors. METHODS: The survey, conducted between August and December 2014, involved included 6,262 adults aged 15 years and over. Binary logistic regression was used in univariate as well as multivariate analysis. Three multivariate models were defined: MODEL 1 (migraine and comorbidities related to the physical dimension of health); MODEL 2 (comorbidities related to the mental dimension of health); MODEL 3 (demographic and socioeconomic factors). RESULTS: In univariate as well as all three multivariate models, the odds of PSRH were statistically significantly higher in migraine sufferers in comparison to non-sufferers (univariate model: ORmigraine=yes vs. migraine=no=2.22 (p<0.001); MODEL 1: ORmigraine=yes vs. migraine=no=2.27 (p<0.001); MODEL 2: ORmigraine=yes vs. migraine=no=1.51 (p=0.002); MODEL 3: ORmigraine=yes vs. migraine=no=1.56 (p=0.001)). CONCLUSION: Migraine is an important PSRH-related factor. Comorbidities related to the physical dimension of health do not reduce the power of association between migraine and PRSH, while comorbidities related to the mental dimension reduce the power of association of migraine and other health conditions. The power of the association between migraine and PRSH is also independent of demographic/socioeconomic factors. We can also conclude that migraine seems to be a phenomenon that is in a bi-directional relationship with mental states (thus having an impact on PSRH) and is itself a stressor.

Enhancement of Intravenous Thrombolysis by Nationwide Telestroke Care in Slovenia: A Model of Care for Middle-Income Countries.

Background:Stroke expertise is critical for timely and appropriate intravenous thrombolysis (IVT) and affects IVT use.Introduction:In Slovenia, IVT is administered in general hospitals, which often lack on-site neurologic expertise. To overcome this obstacle, a national telestroke network, TeleKap, has been implemented. The aim of the study was to determine whether TeleKap is associated with enhanced IVT use.Materials and Methods:This investigation was a retrospective observational study comparing the number of acute ischemic stroke (AIS) patients and the use of IVT during the first 3 consecutive years. TeleKap, a decentralized hub-and-spoke telestroke model covering the entire nation, consists of one comprehensive stroke center and 12 spokes classified according to the availability of on-site neurologic expertise.Results:During the observation period, we treated a total of 1,316 patients with AIS, of which 508 (38.6%) received IVT. We found statistically significant positive trends in the number of IVT patients (142 in 2015, 158 in 2016, and 208 in 2017; B = 4.39, standard error (SE) = 1.59, p = 0.01) and the number of AIS patients (326 in 2015, 424 in 2016, and 566 in 2017; B = 14.42, SE = 5.19, p = 0.01) for all spokes. The trend in the IVT rate was numerically negative but did not reach statistical significance (43.5% in 2015, 37.3% in 2016, and 36.7% in 2017; p = 0.30).Discussion:TeleKap enhanced IVT use regardless of on-site neurologic expertise.Conclusions:TeleKap proved to be efficient. It could serve as a model of telestroke care for other similar countries.

Stroke and antiphospholipid syndrome-antiphospholipid antibodies are a risk factor for an ischemic cerebrovascular event.

Testing for antiphospholipid antibodies could be an important part in determining the cause of a cerebrovascular event (CVE). Currently, it is also unknown whether antiphospholipid antibodies represent a risk factor for the development of a CVE and whether the selected therapy options are efficacious. So, this study aimed at (1) determining the frequency of patients experiencing a CVE and fulfilling the laboratory criterion for an antiphospholipid syndrome (APS), (2) investigating whether the persistent presence of antiphospholipid antibodies represented a risk factor for a CVE, and (3) focusing on the efficacy of the selected treatment strategy in the first year after the CVE. Eighty-nine patients with an acute CVE were prospectively followed for 1 year. At least two sera from each were tested for lupus anticoagulants, anticardiolipin, anti-ß2-glycoprotein I, anti-phosphatidylserine/prothrombin and anti-annexin V antibodies. Twenty out of eighty-nine (22%) of CVE patients fulfilled the criteria for APS (17/20 for definitive and 3 for probable APS). There was a significant association between persistently present antiphospholipid antibodies and the CVE (OR, 4.62). No statistically significant difference was found in the CVE recurrence rate between APS-CVE and non-APS-CVE patients being treated mainly with acetyl salicylic acid. Antiphospholipid antibodies represent an independent risk factor for a CVE. In the first year after the CVE, antiplatelet therapy seemed to be sufficient in secondary CVE thromboprophylaxis in most APS patients.

Is Carotid Stiffness a Possible Surrogate for Stroke in Long-term Survivors of Childhood Cancer after Neck Radiotherapy?

BACKGROUND: The risk for cerebrovascular late effects among childhood cancer survivors is considerable. According to recent studies it is not clear which marker could be reliable for the screening of cerebrovascular diseases among the long-term survivors of childhood cancer. The purpose of this study is to analyse arterial stiffness and intima-media thickness as possible early markers of later occurring stroke in long-term survivors of childhood cancer after neck radiotherapy. PATIENTS AND METHODS: Twenty-three patients, treated for Hodgkin disease (HD) in childhood, were included. They had received radiation therapy to the neck with 20-65 (median 30) Gy. Twenty-six healthy controls, matched in age, sex, body mass index, arterial hypertension, smoking history and total cholesterol levels were compared. Highresolution colour-coded duplex sonography and power Doppler sonography of the carotid arteries were performed and intima-media thickness, number and quality of plaques were measured. Arterial stiffness indices were calculated. RESULTS: Plaque deposits and/or arterial wall calcinations were found in 24 out of 43 (55.8%) irradiated vessels in cancer survivors group and 0 out of 52 vessels in the group of healthy controls (p < 0.01). We found significant group differences for all the stiffness parameters we used (P < 0.05), but there was no difference in intima-media thickness between cases and controls (p = 0.92). In a multivariate model, carotid pulse wave velocity was positively associated with smoking. CONCLUSIONS: The arterial stiffness has appeared as a possible surrogate marker for stroke in long-term survivors of childhood cancer. Smoking habit might have an additional negative influence on vascular aging in the group of patients after neck radiotherapy.

Functional impairment of precerebral arteries in Huntington disease.

BACKGROUND: Cardiovascular pathology of Huntington disease (HD) appears to be complex; while microvascular dysfunction seems to appear early, deaths from cardiomyopathy and stroke might occur in the late phase of HD. METHODS: Our study evaluated global risk factors for coronary heart disease (CHD), structure and function of precerebral arteries in 41 HD subjects and 41 matched controls. HD subjects were divided into groups by the United Huntington disease rating scale (presymptomatic-PHD, early-EHD, midstage-MHD and late-LHD). CHD risk factors assessment and Doppler examination of precerebral arteries were performed, including measurements of the carotid artery intima-media thickness (IMT), and parameters indicating local carotid artery distensibility (stiffness index ß, pulse wave velocity, pressure strain elasticity module and carotid artery compliance). RESULTS: In the HD and controls we identified a comparable number of non-obstructive plaques (<50% lumen narrowing). No obstructive plaques (>50% lumen narrowing) were found. There was significantly increased IMT in MHD. In PHD and EHD the parameters of arterial stiffness were significantly higher and the carotid artery compliance was significantly lower. CONCLUSIONS: Our results reveal functional vascular pathology in PHD, EHD, and MHD. Precerebral arteries dysfunction in HD therefore appears to be mostly functional and in agreement with recently described autonomic nervous system changes in HD.

Persons with Epilepsy: Between Social Inclusion and Marginalisation.

BACKGROUND: Epilepsy is a chronic neurological disorder that can lead to complex psychosocial consequences. Epilepsy can change the social status of persons with epilepsy (PWE) and has an effect on their social inclusion as well as their perception of social inclusion. This study aims to explore subjective experiences with social inclusion of PWE in Slovenia. METHODS: This study takes a qualitative approach. Eleven semistructured interviews were conducted with eleven participants. Interviews were analysed using thematic analysis. RESULTS: Epilepsy has physical, emotional, and social consequences. Physical consequences of epilepsy are mainly tiredness and exhaustion following an epileptic episode, frequently accompanied by headaches. Emotional consequences are different forms of fear. The main social consequence identified is a negative effect on PWE's social network, which leads to (self-)isolation and social distrust. CONCLUSION: PWE experience of social inclusion depends on various psychosocial factors and differs from person to person. The consequences of epilepsy are shown in PWE social contacts and their sense of social inclusion and autonomy.

Characteristics of Cerebral Hemodynamics in Patients with Ischemic Leukoaraiosis and New Ultrasound Indices of Ischemic Leukoaraiosis.

OBJECTIVE: The diagnosis of ischemic leukoaraiosis (ILA) is based on head magnetic resonance imaging (MRI) and exclusion of other causes of white matter hyperintensities (WMHs). Recent studies have shown increased arterial stiffness and diminished carotid flow in ILA patients. So far, there are very little data on intracerebral hemodynamic parameters in ILA. Due to the specific structure of the intracranial arteries, our aim was to investigate intracerebral hemodynamic parameters in ILA patients and, possibly, to find a reliable ultrasound index of combined intra- and extracranial cerebral arteries. METHODS: We compared different hemodynamic parameters in the middle cerebral artery (MCA) and local carotid stiffness parameters in 53 ILA patients to 40 gender and risk factor-matched controls with normal head MRI. The ILA diagnosis was based on head MRI and exclusion of other causes of WMH. In addition, we introduced new ischemic leukoariosis indices (ILAi) that are ratios of carotid stiffness parameters and MCA mean blood flow velocity. The diagnostic significance of ILAi for the prediction of ILA was analyzed. RESULTS: We found significantly lower diastolic, systolic, and mean MCA blood flow velocities and increased carotid stiffness in the ILA group (P ≤ .05). All ILAi significantly differed between the groups (P < .05), were significantly associated with ILA (P < .01), and were sensitive and specific for predicting ILA (P < .05). CONCLUSION: MCA blood flow velocities in ILA patients are lower compared to risk factor-matched controls. A combination of lower velocities and increased carotid stiffness represented as ILAi could have a potential diagnostic value for ILA.

Ratio between carotid artery stiffness and blood flow - a new ultrasound index of ischemic leukoaraiosis.

BACKGROUND: Ischemic leukoaraiosis (ILA) is associated with cognitive decline and aging. Its pathophysiology is believed to be ischemic in origin due to its association with cerebrovascular risk factors and similarity in location to lacunar infarctions. ILA diagnosis is still based on magnetic resonance imaging (MRI) as well as exclusion of other causes of white matter hyperintensities. So far, there are no known confirming diagnostic tests of ILA. Ultrasound studies have recently shown increased large artery stiffness, increased cerebrovascular resistance, and lower cerebral blood flow in patients with ILA. Increased arterial stiffness and decreased blood flow could have a synergistic effect, and their ratio could be a useful diagnostic index of ILA. METHODS: In this post hoc analysis, we introduced new ILA indices (ILAi) that are ratios of the carotid stiffness parameters (pulse wave velocity beta [PWVß], pressure-strain elasticity modulus [Ep], ß index), and diastolic and mean blood flows in the internal carotid artery: Q-ICAd and Q-ICAm. We compared the ILAi of 52 patients with ILA and 44 sex- and risk factor-matched controls with normal MRI of the head. ILA diagnosis was based on MRI and exclusion of other causes of white matter hyperintensities. The diagnostic significance of ILAi for the prediction of ILA was analyzed. RESULTS: All ILAi significantly differed between the groups; the most significant were PWVß/Q-ICAd (ILA group: 1.96±0.64 vs control group: 1.56±0.40, P=0.001) and PWVß/Q-ICAm (ILA group: 1.13±0.32 vs control group: 0.94±0.25, P=0.003). All ILAi were significantly associated with ILA (P<0.01) and were significant independent predictors of ILA. All ILAi were also sensitive and specific for predicting ILA (area under the curve: 0.632-0.683, P<0.05). CONCLUSION: The new ultrasound indices significantly differed between patients with ILA and the control group and were significant predictors of ILA. A combination of lower carotid blood flow and increased carotid stiffness represented as ILAi probably has a diagnostic value in patients with ILA.

The presence of cerebral and/or systemic endothelial dysfunction in patients with leukoaraiosis--a case control pilot study.

BACKGROUND: In spite of high prevalence and clinical relevance of leukoaraiosis (LA), its pathophysiology is still incompletely understood. Theories of ischaemic genesis and a leaky blood-brain barrier are contradictory yet could share a common denominator-endothelial dysfunction (cerebral, systemic or both), which has not been studied thoroughly in LA. METHODS: Thirty patients with LA (58 years (SD 7)) and 30 gender- and age-matched controls without LA (55 years (SD 6)) were recruited. The vascular risk factors (VRF) were identical in both groups. Cerebral endothelial function was determined by cerebrovascular reactivity to L-arginine (CVR). Systemic endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery after hyperaemia. All participants underwent a brain MRI to search for radiological signs of LA that was classified according to the Fazekas score. Linear regression was used to explore the correlation between CVR and FMD in patients with LA. A 95 % confidence interval was used. For any statistical test used in the study, p ≤ 0.050 was regarded as statistically significant. RESULTS: We found a marked and significant decrease in both CVR (9.6 % (SD 3.2) vs. 15.8 % (SD 6.1), p < 0.001) and FMD (4.8 % (SD 3.1) vs. 7.4 % (SD 3.8), p = 0.004) in LA patients compared to controls. Both CVR (7.4 % (SD 3.1) vs. 12.2 % (SD 2.6), p = 0.001) and FMD (3.0 % (SD 2.2) vs. 6.4 % (SD 3.1), p = 0.011) were significantly decreased in LA subgroup Fazekas 3 compared to subgroup Fazekas 1. CVR and FMD significantly positively correlated (b = 0.192, 95 % CI = 0.031-0.354, p = 0.02). CONCLUSIONS: The results of our pilot study suggest that patients with LA have a significant impairment of both cerebral and systemic endothelial function that is larger than could be expected based on present VRF. Endothelial dysfunction increases in parallel with LA severity and correlates between cerebral and systemic arterial territory. Overall, our results suggest a so far unknown "intrinsic" generalised endothelial dysfunction in patients with LA that could be involved in LA pathophysiology. This interesting issue needs to be confirmed in larger samples since it could help better understand the mechanisms underlying LA.

Carotid Arterial Hemodynamic in Ischemic Levkoaraiosis Suggests Hypoperfusion Mechanism.

BACKGROUND: Leukoaraiosis (ILA) is believed to be ischaemic in origin due to its similar location as that of lacunar infarctions and its association with cerebrovascular risk factors. However, its pathophysiology is not well understood. The ischaemic injuries may be a result of increased pulsatility or cerebral hypo-perfusion. We used carotid duplex ultrasound to prove that the underlying mechanism is hypo-perfusion. METHODS: We compared 55 ILA patients to 44 risk factor-matched controls with normal magnetic resonance imaging (MRI) of the head. ILA diagnosis was based on MRI and was further categorised according to the Fazekas scale. We measured carotid artery blood flow velocity and diameter and calculated carotid blood flow and resistance indexes. RESULTS: Blood flow velocities and blood flows were significantly lower in the ILA group, including diastolic, systolic and mean pressures (p ≤ 0.05). The resistance indices were higher in the ILA group, but the differences were not statistically significant. All the velocities and blood flows showed a decreasing trend with higher Fazekas score, whereas resistance indexes showed an increasing trend. CONCLUSIONS: Lower blood flow and higher resistance of carotid arteries are consistent with the hypo-perfusion theory of ILA. Carotid ultrasound could have a diagnostic and prognostic role in ILA patients.

Endovascular therapy for acute stroke is a safe and efficient evolving method: a single-center retrospective analysis.

PURPOSE: To determine the clinical outcome in patients undergoing endovascular therapy for acute stroke. MATERIALS AND METHODS: During the period 2009-2012, 134 patients with acute stroke and normal computed tomography (CT) findings were treated with endovascular therapy at a single center. Based on CT perfusion and CT angiography findings, all patients had large vessel occlusions. Intravenous thrombolysis was used in eligible patients. The recanalization rate, time to recanalization, periprocedural complications, and clinical outcome at discharge from the hospital (National Institutes of Health score, modified Rankin Scale [mRS]) were analyzed. RESULTS: The recanalization rate during the study interval increased from 70% (2008-2009) to 94% (2011-2012) (P ≤ .01). The procedure time was reduced from 124 minutes (2009) to 43 minutes (2012) (P ≤ .01), and the periprocedural complication rate decreased from 21% (2009) to 2% (2012) (P ≤ .01). Patients in 2009-2010 had a 2.21 times greater probability for an mRS score ≥ 2 after the procedure compared with patients in 2011-2012 (95% confidence interval, 1.0-5.0). If the procedure lasted 15 minutes longer, the prospect for an mRS score ≥2 after the procedure was 1.30 times greater (P = .02). CONCLUSIONS: High recanalization rates, low procedural complications, and improved clinical outcomes were achieved using endovascular therapy in selected patients with acute stroke during a 4-year period. Endovascular therapy is an evolving safe and effective treatment for intracranial large vessel occlusion.

Is there a persistent dysfunction of neurovascular coupling in migraine?

Changes in cerebral blood flow are one of the main features of migraine attack and have inspired the vascular theory of migraine. This traditional view has been reshaped with recent experimental data, which gave rise to the neural theory of migraine. In this review, we speculate that there might be an important link between the two theories, that is, the dysfunction of neurovascular coupling.

Study of neurovascular coupling during cold pressor test in patients with migraine.

BACKGROUND: Altered neurovascular coupling in migraineurs could be a consequence of impaired function of modulatory brainstem nuclei. The cold pressor test (CPT) should activate brainstem structures. We measured visually evoked cerebral blood flow velocity response (VEFR) to CPT in migraine. METHODS: Twenty-three healthy volunteers and 29 migraineurs participated in the study. We measured arterial blood pressure, end-tidal CO2, heart rate and cerebral blood flow velocity in posterior and middle cerebral artery using transcranial Doppler. VEFR was calculated as cerebrovascular reactivity to photic stimulation before, during and after CPT. RESULTS: In healthy individuals, there was a significant decrease in peak systolic VEFR from CPT phase to recovery phase (p < 0.05). There was an increase in mean VEFR from basal to CPT phase and a decrease from CPT to recovery phase, both significant (p < 0.05). End-diastolic VEFR increased from basal to CPT phase and decreased in recovery phase below the basal phase values, all changes significant (p < 0.05). In migraine, no statistically significant changes in peak systolic, mean or end-diastolic VEFRs were observed between phases (p > 0.05). The differences in phases in mean and end-diastolic VEFRs between the basal phase and the CPT phase and between the CPT phase and the recovery phase were significantly higher in healthy individuals (p < 0.05). CONCLUSIONS: The absence of the effect of CPT on VEFR in migraine is likely to be a consequence of impaired subcortical modulation of neurovascular coupling.