Hyperechogenic intimal lesions and wall thickness of the temporal and facial arteries in elderly patients with arterial occlusions of the eye

ObjectiveTo determine the association of arteriosclerosis, characterised by hyperechogenic intimal lesions (HIL), with wall thickness of the temporal and facial arteries in elderly patients with ocular arterial occlusions.MethodsPatients suffering from non-arteritic ocular perfusion disorders were included. High-resolution compression sonography (18 MHz) images of the temporal arteries (frontal and parietal branch at the upper margin of the auricle) and facial arteries (at the crossing point of the artery over the mandible) were analysed for the presence of HIL (grade 0: absent; grade 1: moderate; grade 2: severe). Characteristics of patients with and without evidence of HIL >grade 1 were compared.ResultsIn total, 330 cranial artery segments of 55 patients were analysed. HIL ≥grade 1 was present in 13.0% of all artery segments and in 38.1% of all patients. Patients with HIL ≥grade 1 in at least one arterial segment displayed significantly increased maximum wall thickness of the temporal arteries (0.62±0.23 mm vs 0.50±0.13 mm; p<0.01) and facial arteries (0.71±0.20 mm vs 0.54±0.19 mm; p=0.01). Patients with at least one temporal or facial artery segment with HIL were older, more often male and more frequently suffered from diabetes mellitus.ConclusionThe presence of HIL goes along with a significantly increased wall thickness of the temporal and facial arteries. These findings should be considered when interpreting the results of sonography of the cranial arteries in the diagnostic workup of suspected giant cell arteritis.

Two-hour infusion of vasoactive intestinal polypeptide induces delayed headache and extracranial vasodilation in healthy volunteers

Background In recent years, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) have gained special interest in headache science. VIP and PACAPs (two isoforms, PACAP27 and PACAP38) are related in structure and function, as are their receptors, but they show differences in vasodilating- and headache-inducing properties. Intravenous infusion of PACAP27 or PACAP38, but not VIP, induces a long-lasting dilation of cranial arteries and delayed headache. The relationship between the long-lasting cranial vasodilation and headache development is not fully clarified. Methods In a double-blinded, placebo-controlled, crossover study in 12 healthy volunteers, diameter changes of cranial arteries, occurrence of headache and the parasympathetic system were examined before, during and after a 2-hour continuous intravenous infusion of VIP and placebo. Primary endpoints were the differences in area under the curve for the superficial temporal artery diameter and headache intensity scores, as well as in headache incidence, between VIP and placebo. Results The superficial temporal artery diameter was significantly larger on the VIP day compared to placebo ( p < 0.001) and the dilation lasted for more than 2 h. The incidence of headache was higher ( p = 0.003) on the VIP day compared to the placebo day. The difference in headache intensity scores was more evident in the post-infusion period (120–200 min, p = 0.034) and in the post-hospital phase (4–12 h, p = 0.025). Cranial parasympathetic activity, measured through the production of tears, was higher during VIP compared to placebo ( p = 0.033). Conclusion Continuous intravenous infusion of VIP over 2 h induced a long-lasting cranial vasodilation, activation of the cranial parasympathetic system, and delayed mild headaches in healthy volunteers. Trial Registration: The study is registered at ClinicalTrials.gov (NCT03989817).

Oxytocin as a regulatory neuropeptide in the trigeminovascular system: Localization, expression and function of oxytocin and oxytocin receptors

Background Recent clinical findings suggest that oxytocin could be a novel treatment for migraine. However, little is known about the role of this neuropeptide/hormone and its receptor in the trigeminovascular pathway. Here we determine expression, localization, and function of oxytocin and oxytocin receptors in rat trigeminal ganglia and targets of peripheral (dura mater and cranial arteries) and central (trigeminal nucleus caudalis) afferents. Methods The methods include immunohistochemistry, messenger RNA measurements, quantitative PCR, release of calcitonin gene-related peptide and myography of arterial segments. Results Oxytocin receptor mRNA was expressed in rat trigeminal ganglia and the receptor protein was localized in numerous small to medium-sized neurons and thick axons characteristic of A∂ sensory fibers. Double immunohistochemistry revealed only a small number of neurons expressing both oxytocin receptors and calcitonin gene-related peptide. In contrast, double immunostaining showed expression of the calcitonin gene-related peptide receptor component receptor activity-modifying protein 1 and oxytocin receptors in 23% of the small cells and in 47% of the medium-sized cells. Oxytocin immunofluorescence was observed only in trigeminal ganglia satellite glial cells. Oxytocin mRNA was below detection limit in the trigeminal ganglia. The trigeminal nucleus caudalis expressed mRNA for both oxytocin and its receptor. K+-evoked calcitonin gene-related peptide release from either isolated trigeminal ganglia or dura mater and it was not significantly affected by oxytocin (10 µM). Oxytocin directly constricted cranial arteries ex vivo (pEC50 ∼ 7); however, these effects were inhibited by the vasopressin V1A antagonist SR49059. Conclusion Oxytocin receptors are extensively expressed throughout the rat trigeminovascular system and in particular in trigeminal ganglia A∂ neurons and fibers, but no functional oxytocin receptors were demonstrated in the dura and cranial arteries. Thus, circulating oxytocin may act on oxytocin receptors in the trigeminal ganglia to affect nociception transmission. These effects may help explain hormonal influences in migraine and offer a novel way for treatment.

Giant cell arteritis and primary central nervous system vasculitis as causes of headache

Giant cell arteritis (GCA) is a granulomatous vasculitic disorder that affects cranial arteries, as well as large arteries, including the aorta. The possibility of GCA should always be considered in headache developing in elderly people. Temporal artery biopsy is usually required to establish the diagnosis. Prompt institution of steroid therapy reduces the risk of complications, such as visual loss and major ischaemic events. Primary central nervous system vasculitis (PCNSV), or primary angiitis of the central nervous system (PACNS), causes headache and neurological symptoms. Patients affected by PCNSV can exhibit thunderclap headache. In such cases, scrutiny for subarachnoid haemorrhage, pituitary apoplexy, and venous thrombosis is warranted. Differential diagnosis between PCNSV and reversible cerebral vasoconstriction syndrome can be challenging. However, this differentiation is important, because they require distinct therapeutic strategies. Steroid and cyclophosphamide are used to treat PCNSV.

Feasibility of Ultrafast Doppler technique for cranial ultrasound in neonates

Aims: The aim of this study was to compare the performances of Ultrafast Doppler ultrasound (US) with classic Doppler US, for cranial ultrasound in neonates.Materials and methods: We measured the peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI) of the anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior cerebral artery (PCA) in neonates using both conventional and Ultrafast Doppler US and acquisition times were compared. Distal ACA branches were assessed with Ultrafast Doppler US.Results: A total of 138 neonates were included. The PSV and EDV of the cranial arteries were comparable between the two Doppler methods (PSV, 64.6-85.5 cm/s vs. 63.4-84.1 cm/s, p=0.100-0.510; EDV, 19.1-26.5 cm/s vs. 17.8-24.2 cm/s, p=0.100-0.981). The RIs of the ACA and PCA were not significantly different (0.69-0.73 vs 0.68-0.74, p=0.174-0.810). Ultrafast Doppler US required shorter acquisition times than conventional Doppler US (6.7 s vs. 11.0 s, p=0.003). The PSV and EDV of the distal ACA were higher than the proximal ACA (20.1-63.3 cm/s vs. 9.4-36.7, p<0.001) although the RI was similar (0.69 vs. 0.68, p=0.251).Conclusions: Ultrafast Doppler US provides comparable values to conventional Doppler US with shorter acquisition times. This novel imaging technique provides quantitative information and is suitable for distal cranial artery evaluation.

Erenumab (AMG 334), a monoclonal antagonist antibody against the canonical CGRP receptor, does not impair vasodilatory or contractile responses to other vasoactive agents in human isolated cranial arteries

Background Calcitonin gene-related peptide (CGRP) is a neuronal transmitter present in intracranial sensory nerves, where it is involved in migraine pathophysiology as well as other biological functions. Recently, the fully human monoclonal antibody erenumab (AMG 334), which targets the canonical calcitonin gene-related peptide receptor, showed significant prophylactic efficacy and favourable safety in phase II and III clinical trials for episodic and chronic migraine and is now approved for migraine prevention in several countries. Objective Given that calcitonin gene-related peptide can mediate vasodilation, we investigated the effect of erenumab on vasoactive responses in the presence or absence of various vasodilatory and vasocontractile mediators in a model using isolated human cerebral and meningeal arteries. Methods Ring segments of human isolated cerebral and meningeal arteries were mounted in a sensitive myograph. On arterial segments pre-contracted with 30 mM potassium chloride, vasoactive responses to calcitonin gene-related peptide were studied in the presence of different concentrations of erenumab. At the maximal tested inhibitory concentration of erenumab (100 nM), functional arterial relaxation in response to nicardipine or substance P, and the contractile responses to sumatriptan and dihydroergotamine were examined. Results 30 mM potassium chloride produced a stable contraction of the vessel segments and calcitonin gene-related peptide induced a concentration-dependent relaxation. We observed that (i) erenumab had no direct contractile or relaxant effects per se (by itself), (ii) pre-treatment with erenumab antagonized the calcitonin gene-related peptide-induced relaxation in a competitive manner, (iii) the relaxant responses to nicardipine or substance P were unaffected in the presence of erenumab and (iv) the contraction induced by sumatriptan or dihydroergotamine was not modified by erenumab. Conclusion Our findings demonstrate that erenumab, while not associated with vasoactive properties per se, specifically inhibits calcitonin gene-related peptide-induced relaxation of cranial arteries without impacting vasodilatory responses or contractile responses of endogenous or pharmacological vasoactive compounds.

The vascular effect of glibenclamide: A systematic review

Objective: To systematically review the vascular effects of glibenclamide. Background: Infusion of adenosine triphosphate (ATP)-sensitive potassium (KATP) channel opener (KCO) levcromakalim dilates cranial arteries and induces headache and migraine attacks. Recent data show that levcromakalim-induced vasodilation is associated with headache. Glibenclamide is a KATP channel blocker that may alter the vascular tone and thus has an impact on headache or migraine prevention. Methods: A search through PubMed was undertaken for studies investigating the vascular effects of glibenclamide in vitro as well as in vivo published until July 2019. Results: We identified 58 articles; 31 in vitro studies, 24 in vivo studies and 3 studies with both. The main findings were that glibenclamide inhibited levcromakalim-induced and other KCOs-induced vasodilation, while the basal vascular tone remained unchanged. Conclusion: Glibenclamide could inhibit vasodilation by KCOs, and further studies are needed to clarify the vascular effect of glibenclamide on human cranial arteries.