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.

Productivity Losses Due to Migraine in Slovenia: An Analysis of Absenteeism and Presenteeism Costs Based on Administrative and Self-Reported Data.

INTRODUCTION: Migraine is associated with significant morbidity and a significantly negative impact on the quality of life. A better understanding of the economic impact of migraine is becoming increasingly important. This paper aims to shed light on absenteeism and presenteeism costs of migraine in Slovenia. METHODS: We use the administrative national-level database on sick leave due to migraine for 2016. The absenteeism cost estimate is based on the number of patients with migraine on physician-determined sick leave and average daily labour costs. We calculate productivity costs from a social perspective regardless of who incurs them. Data from the national registry on sick leave are coupled with data from a web-based self-reported survey to also include the cost of presenteeism. MIDAS and WPAI presenteeism items were used and several different scenarios were designed to assess presenteeism costs. RESULTS: We estimated annual absenteeism costs per absentee due to migraine at the amount of EUR 531 in 2016 using the NIPH's administrative data on sick leave. Annual absenteeism costs per absentee due to migraine based on self-reported data amounted to EUR 626. The estimated annual presenteeism costs per patient range from EUR 344 - 900. CONCLUSION: Estimating the economic burden of a disease is becoming increasingly important. This paper is an insight into the absenteeism and presenteeism costs of migraine in Slovenia.

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.

Recommendations on telestroke in Europe.

Lack of stroke specialists determines that many European rural areas remain underserved. Use of telemedicine in stroke care has shown to be safe, increase use of evidence-based therapy and enable coverage of large areas of low population density. The aim of this article is to summarise the following recommendations of the Telestroke Committee of the European Stroke Organisation on the setup of telestroke networks in Europe: Hospitals participating in telestroke networks should be chosen according to criteria that include population density, transportation distance, geographic specifics and in-hospital infrastructure and professional resources. Three hospital categories are identified to be part of a hub-and-spoke network: (1) the Telemedicine Stroke Centre (an European Stroke Organisation stroke centre or equivalent with specific infrastructure and setup for network and telemedicine support), (2) the telemedicine-assisted stroke Unit (equivalent to an European Stroke Organisation stroke unit but without 24 h onsite stroke expertise) and (3) the telemedicine-assisted stroke ready hospital (only covering hyperacute treatment in the emergency department and transferring all patients for further treatment).

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.

In-tunnel closure of patent foramen ovale with a FlatStent EF™.

BACKGROUND: Devices for percutaneous closure of patent foramen ovale (PFO) are traditionally based on two opposing discs, leaving significant surface areas exposed in the left and right atrium. The FlatStent EF™ PFO Closure System (Coherex Inc., Salt Lake City, USA) represents a major departure from these devices because it is designed to focus primarily on the PFO tunnel, leaving minimal foreign material behind. AIM: To investigate the patient selection, effectiveness, and safety of in-tunnel closure with a FlatStent EF™ in patients with PFO of ≥ 4 mm tunnel length and < 12 mm diameter at preprocedural transoesophageal echocardiography (TEE). RESULTS: Among 46 consecutive patients undergoing PFO closure, a FlatStent EF™ could be implanted and resulted in initial successful closure (< 5 bubbles during Valsalva manoeuvre) in 21 (46%) patients. TEE at 162 ± 40 and 317 ± 162 days after implantation demonstrated functional closure in 90% and 95% of cases, respectively. No device or air embolisation, pericardial effusion, or thrombus formation was documented. Small in-tunnel peri-device colour Doppler left to right flow was documented in 10% and 2-6 mm protrusion of FlatStent EF™ along right atrial septum without any residual flow/bubble shunting in 14%. Patients with suboptimal closure (> 5 bubbles during Valsalva manoeuvre and/or in-tunnel colour flow) had shorter tunnel on preprocedural TEE (5.3 ± 1.5 vs. 10.8 ± 3.5 mm; p = 0.003). There was no difference in TEE diameter (1.8 ± 0.5 vs. 2.0 ± 0.5 mm; p = 0.38) and stretched diameter by sizing balloon (6.3 ± 2.5 vs. 6.3 ± 1.0 mm; p = 1.00). CONCLUSIONS: In-tunnel PFO closure with a FlatStent EF™ represents an effective and safe option only in carefully selected patients with long tunnel (> 4 mm) regardless of the diameter if it is < 12 mm. These criteria are fulfilled in < 50% of consecutive candidates for PFO closure. The new phenomenon of in-tunnel peri-device flow and FlatStent EF™ protrusion along the right atrial septum were documented during systematic TEE follow up.

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.

Ultrasound diagnosis of carotid artery stiffness in patients with ischemic leukoaraiosis.

The pathophysiology of ischemic leukoaraiosis (ILA) is unknown. It was recently found that ILA patients have increased aortic stiffness. Carotid stiffness is a more specific parameter and could have value as a non-invasive diagnostic value for ILA. Therefore, using color-coded duplex sonography, we compared local carotid stiffness parameters of 59 patients with ILA with those of 45 well-matched controls. The diagnosis of ILA was based on exclusion of other causes of white matter changes seen on magnetic resonance imaging. Pulse wave velocity ß (PWVß, m/s), pressure-strain elasticity modulus (Ep, kPa), ß index and augmentation index (Aix, %) values were higher and arterial compliance (AC, mm(2)/kPa) values were lower in the ILA group; however, only Ep and PWVß reached statistical significance (p ≤ 0.05). ß, Ep and PWVß exhibited an increasing trend with higher Fazekas score, though only Ep reached significance (p = 0.05). The main conclusion was that Ep and PWVß could have a diagnostic role in patients with ILA.

Chorea-acanthocytosis presenting as dystonia.

The aim of this article is to present two Slovenian chorea-acanthocytosis (ChAc) siblings with an unusual predominantly dystonic ChAc phenotype. For diagnostic purposes, the genomic DNA was screened for VPS13A mutations. Movement disorder was evaluated and scored according to the Dystonia Movement and Disability Scale (DMDS) in order to evaluate the effects of L-dopa on dystonia. Brain imaging was performed with the use of magnetic resonance imaging scan and 99m Tc-ethyl cysteinate dimmer single photon emission computed tomography (Tc-ECD SPECT). Clinical neurological examination disclosed gait dystonia. Marked swallowing difficulty due to tongue and feeding dystonia was observed. Both siblings were found to be heterozygous for a substitution in exon 22 (c.2191C>T) and for a deletion in exon 35 (c.3995_3996delinsA) leading to mutation in VPS13A. After being administered L-dopa for three months, both subjects showed significant symptomatic improvement documented by reduced DMDS scores. It is concluded that VPS13A mutation testing may improve diagnosis of dystonia and recognition of atypical ChAc phenotypes. It seems that L-dopa could be effective in the treatment of dystonia due to VPS13A mutations.

Associations between cerebral and systemic endothelial function in migraine patients: a post-hoc study.

BACKGROUND: There is a growing interest in the role of the endothelium in migraine. Recently, our group showed differences in endothelial function between the anterior and posterior cerebral circulation in healthy subjects, reduced vasodilatatory capacity of the posterior cerebral circulation and unimpaired systemic endothelial function in migraine patients without comorbidities. However, the relationship between cerebral and systemic endothelial function and the anterior and posterior cerebral endothelial function in migraine patients is still not clear. METHODS: We compared cerebral and systemic endothelial function through post-hoc linear regression analysis of cerebrovascular reactivity (CVR) to L-arginine between the middle cerebral artery (MCA) and flow-mediated vasodilatation (FMD) of the right brachial artery and the posterior cerebral artery (PCA) and FMD in migraine patients without comorbidities and in healthy subjects. The anterior and posterior cerebral endothelial function was also compared using post-hoc linear regression analysis between CVR to L-arginine in the MCA and the PCA. RESULTS: No significant correlation was found between CVR to L-arginine in the MCA and FMD and in the PCA and FMD in migraine patients with aura (p = 0.880 vs. p = 0.682), without aura (p = 0.153 vs. p = 0.179) and in healthy subjects (p = 0.869 vs. p = 0.662). On the other hand, we found a significant correlation between CVR to L-arginine in the MCA and PCA in migraine patients with aura (p = 0.004), without aura (p = 0.001) and in healthy subjects (p = 0.002). Detailed analysis of the linear regression between all migraine patients and healthy subjects did not show any difference in the regression coefficient (slope) (p = 0.382). However, a significant difference in curve elevation (intercept) was found (p = 0.002). CONCLUSIONS: Our study suggests that the endothelial function in the cerebral and systemic circulation might be different in migraine patients without comorbidities, while that of the anterior and posterior cerebral circulation might be coupled. These results could improve understanding of endothelial function in migraine patients without comorbidities.

Moyamoya syndrome with arteriovenous dural fistula after head trauma.

Moyamoya vascular pattern and dural arteriovenous fistula (dAVF) are rare vascular abnormalities and both can be secondary to head trauma. The role of dural angiogenesis in the pathophysiology of vascular malformation is rather unclear. We report a unique case of moyamoya vasculopathy simultaneously associated with dAVF after heavy head trauma. It seems that both moyamoya syndrome and dAVFs are associated with dural angiogenesis induced by head trauma. The interrelationship between vascular abnormalities is complex and unclear.

Endothelium-dependent vasodilatation in migraine patients.

BACKGROUND: Endothelial dysfunction could be involved in the pathophysiology of migraine. The results obtained from a few studies on endothelial dysfunction in migraine are controversial. We investigated brachial flow-mediated dilatation (FMD), which reflects systemic endothelial dysfunction, in migraine patients without comorbidities. By employing strict inclusion criteria we avoided the possible changes to FMD from confounding factors. METHODS: Forty migraine patients without comorbidities (20 with and 20 without aura) and 20 healthy subjects were included. FMD of brachial arteries and carotid intima-media thickness were measured by using standard procedures. RESULTS: We did not find any difference in FMD between migraine patients and healthy subjects (p = .96). Also, no differences were found among healthy subjects, migraine patients with aura and without aura (p = .99). CONCLUSION: Our study showed that systemic endothelial function is not impaired in migraine patients without comorbidities, neither in those with or without aura. Considering these findings, the investigation of cerebral endothelial function would be useful in a further investigation of the role of endothelial (dys)function in migraine pathophysiology.