Comparison of gepant effects at therapeutic plasma concentrations: connecting pharmacodynamics and pharmacokinetics.

BACKGROUND: Orally administered second-generation gepants are effective for the treatment of migraine. The intranasal administration of the third-generation gepant zavegepant might have additional benefits including a rapid onset of action, but it is not clear yet to which extent this has clinical relevance. METHODS: We examined the effect of zavegepant on the relaxations induced by calcitonin gene-related peptide (CGRP) in human isolated middle meningeal arteries. Furthermore, we connected the pharmacodynamics and pharmacokinetics of gepants by combining data from clinical and basic research. RESULTS: We showed that 10 nM zavegepant potently antagonized the functional response to CGRP. We also showed that all gepants are effective at inhibiting functional responses to CGRP at their therapeutic plasma concentrations. CONCLUSIONS: The relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients.

Letter to the editor: "Therapeutic efficacy of drilling drainage combined with intraoperative middle meningeal artery occlusion in the management of chronic subdural hematoma: a clinical study".

This letter addresses the research presented by Sun et al. on the integration of digital subtraction angiography (DSA) with conventional surgical drainage for chronic subdural hematoma (CSDH), focusing on precision in targeting the middle meningeal artery (MMA). The study demonstrates a reduction in hematoma recurrence and drainage tube indwelling times, highlighting the procedural benefits without added complications. The letter suggests further research directions, including the potential for personalized surgical approaches based on MMA anatomy variations, and emphasizes the importance of this technique in enhancing neurosurgical outcomes.

Oral bacterial genic expression detection in aneurysm wall of a French population sample - preliminary monocentric study.

INTRODUCTION: The etiology of brain aneurysms remains poorly understood. Finnish research suggests that oral bacteria might contribute to the development and rupture of brain aneurysms. Previous studies by our team have not confirmed these findings, likely due to methodological differences. We aimed to replicate the Finnish study with a French population, using the same primers and comparing the results to internal controls. METHODS: We used RT-qPCR to retrospectively analyze the expression of oral bacterial genes in eight patients. During surgical procedures, four tissue types were consistently sampled from each patient: the aneurysmal wall, the superficial temporal artery (STA), the middle meningeal artery (MMA), and the dura mater (DM). Results were expressed as fold differences employing the 2-∆∆Ct method, and statistical analyses were performed accordingly. RESULTS: Our cohort included eight patients, evenly split into ruptured and unruptured groups. The sex distribution was balanced (4 females, 4 males). We observed DNA expression from oral bacteria in all sampled tissues; however, there were no significant differences between the ruptured and unruptured groups. CONCLUSION: We detected oral bacterial gene expression in the aneurysmal wall, STA, MMA, and DM in a sample of French patients. Although limited by the small sample size, our results suggest a potential role for bacterial involvement in vascular invasiveness related to bacteremia. These findings do not definitively link oral bacteria to the pathogenesis of aneurysm development and rupture.

Sex differences in CGRP-induced vasodilation of human middle meningeal arteries but not human coronary arteries: implications for migraine.

BACKGROUND: Migraine prevalence and levels of calcitonin gene-related peptide (CGRP), a peptide involved in migraine pathophysiology, differ between men and women, and appear to be affected by changes in sex hormones. The present study investigated the sex-specific responses to CGRP in human isolated arteries. METHODS: CGRP-induced relaxation of 62 (28 men and 34 women) human isolated middle meningeal arteries (HMMA) and 139 (69 men and 70 women) human isolated coronary arteries (HCA) was compared between men and women in groups <50 years and ≥50 years of age as a proxy for pre- and postmenopausal status in women, as well as matched-age groups for men. RESULTS: In HCA, no differences were observed between male and female tissue, or between the different age groups. However, in HMMA, the maximum response was significantly smaller and CGRP was less potent in females <50 compared with males <50 years of age. No differences were observed between the older age groups. CONCLUSIONS: Sex differences were observed for CGRP-induced relaxation of HMMA, but not HCA. These differences could arise from differential receptor expression in the vascular beds combined with the effect of sex hormones on CGRP and subsequent receptor desensitization.

Facial nerve palsy after middle meningeal artery embolization for chronic subdural hematoma: a case report.

Middle meningeal artery embolization (MMAE) has emerged as a safe and efficacious alternative to surgery for the treatment of new or recurrent chronic subdural hematoma (CSDH). Several complications such as facial palsy may suddenly occur even in the absence of evident dangerous anastomoses in the angiogram. We herein present a case-report of left facial nerve palsy after MMAE.

Middle Meningeal Arterial Embolization Combined With Drilling in the Treatment of Acute Epidural Hematoma.

OBJECTIVE: The purpose of this study was to determine the technical feasibility and safety of middle meningeal arterial (MMA) embolization combined with drilling drainage in the treatment of acute epidural hematoma (AEDH) by comparing it with traditional craniotomy in the treatment. METHODS: One hundred seventeen patients with AEDH treated for MMA embolization combined with drilling and drainage or craniotomy hematoma removal from January 2017 to September 2020 were retrospectively analyzed and divided into a craniotomy group (n=85) and a minimally invasive group (n=32). Hematoma removal was performed in the craniotomy group, and MMA embolization combined with drilling and drainage was performed in the minimally invasive group. The general clinical data, imaging data, surgery, and follow-up of the 2 groups were compared and analyzed. RESULTS: Compared with the craniotomy group, the residual hematoma volume in the minimally invasive group was higher than in the craniotomy group. The average postoperative drainage duration in the minimally invasive group was longer than in the craniotomy group. Compared with the craniotomy group, the minimally invasive group was associated with shorter operative time, less intraoperative bleeding, and lower rates of postoperative rebleeding. In addition, the incidence of postoperative complications and length of hospitalization in the minimally invasive group were significantly shortened. CONCLUSION: Middle meningeal arterial embolization combined with drilling and drainage in the treatment of AEDH caused by MMA active bleeding is safe, effective, and more minimally invasive, and can be promoted and applied.

Therapeutic efficacy of drilling drainage combined with intraoperative middle meningeal artery occlusion in the management of chronic subdural hematoma: a clinical study.

BACKGROUND: The bone holes in the skull during surgical drainage were accurately located at the site of the MMA. The MMA was severed, and the hematoma was removed intraoperatively; furthermore, surgical drainage removed the pathogenic factors of CSDH. This study aimed to describe and compare the results of the new treatment with those of traditional surgical drainage, and to investigate the relevance of this approach. METHODS: From December 2021 to June 2023, 72 patients were randomly assigned to the observation group and the control group. The control group was treated with traditional surgical drainage, while the observation group was treated with DSA imaging to accurately locate the bone holes drilled in the skull on the MMA trunk before traditional surgical drainage. The MMA trunk was severed during the surgical drainage of the hematoma. The recurrence rate, time of indwelling drainage tube, complications, mRS, and other indicators of the two groups were compared, and the changes of cytokine components and imaging characteristics of the patients were collected and analyzed. RESULTS: Overall, 27 patients with 29-side hematoma in the observation group and 45 patients with 48-side hematoma in the control group were included in the study. The recurrence rate was 0/29 in the observation group and 4/48 in the control group, indicating that the recurrence rate in the observation group was lower than in the control group (P = .048). The mean indwelling time of the drainage tube in the observation group was 2.04 ± 0.61 days, and that in the control group was 2.48 ± 0.61 days. The indwelling time of the drainage tube in the observation group was shorter than in the control group (P = .003). No surgical complications were observed in the observation group or the control group. The differences in mRS scores before and after operation between the observation group and the control group were statistically significant (P < .001). The concentrations of cytokine IL6/IL8/IL10/VEGF in the hematoma fluid of the observation and control groups were significantly higher than those in venous blood (P < .001). After intraoperative irrigation and drainage, the concentrations of cytokines (IL6/IL8/IL10/VEGF) in the subdural hematoma fluid were significantly lower than they were preoperatively. In the observation group, the number of MMA on the hematoma side (11/29) before STA development was higher than that on the non-hematoma side (1/25), and the difference was statistically significant (P = .003). CONCLUSION: In patients with CSDH, accurately locating the MMA during surgical trepanation and drainage, severing the MMA during drainage, and properly draining the hematoma, can reduce the recurrence rate and retention time of drainage tubes, thereby significantly improving the postoperative mRS Score without increasing surgical complications.

Modified craniotomy procedures and virtual reality technology for accurate localization of the frontal branch of MMA in revascularization surgery.

The frontal branch of middle meningeal artery (MMA) can easily be damaged during revascularization surgery. To precise locate it and minimize its injury, we propose a set of modified craniotomy procedures combined with simple virtual reality (VR) technology based on three-dimensional (3D) Slicer simply, economically, and efficiently. Patients with Moyamoya disease (MMD) and internal carotid artery occlusion (ICAO) who received revascularization from January 2015 to December 2022 were divided into two groups based on the methods used to locate the MMA: traditional methods and precise MMA locating with VR technology. Patient demographics and clinical characteristics were analyzed to compare the preservation rates of MMA. The distances between this artery and bony anatomical landmarks were also measured to better understand its localization. There was no significant difference in baseline characteristics between the two groups. The precise MMA locating group exhibited a significantly higher preservation rate of the frontal branch of MMA (p = 0.037, 91.7% vs. 68.2%). Over 77% of patients had their frontal branch of MMA partially or completely surrounded by bony structures to varying degrees. Therefore, the combination of modified craniotomy procedures, 3D Slicer, and simple VR technology represents an economical, efficient, and operationally simple strategy.

[Az arteria meningea media embolisatio szerepe a krónikus subduralis haematoma kezelési algoritmusában, legújabb evidenciák és saját tapasztalataink]. / Az arteria meningea media embolisatio szerepe a krónikus subduralis haematoma kezelési algoritmusában, legújabb evidenciák és saját tapasztalataink.

Chronic subdural hematoma is one of the most common diseases requiring a neurosurgical operation that affect elderly and fragile patients. In addition to standard neurosurgical operations (trepanation and craniotomy), embolization of the meningeal artery media is an alternative solution. Several review aerticles have confirmed the very high rate of success and safety of the endovascular treatment. We present the technical details and results of our 10 consecutive selective media meningeal artery embolization procedures for residual chronic subdural hematomas. Our interventions were performed without complications and all resulted in complete recovery. 

Angiographic classification of chronic subdural hematoma.

Background and purpose:

Chronic subdural hematoma (cSDH) is a challenging pathology with high recurrence rate after surgical treatment and may seriously affect the patient’s quality of life. Membrane formation with angiogenesis plays an important role in the evolution of the disease, providing a promising target for endovascular therapy. Our goal is to categorize angiographic patterns of chronic subdural hematoma for standardized reporting purposes.

In our retrospective analysis of prospective data collection, we analyzed angiographic properties of all high recurrence risk patients with cSDH, who were treated by embolization in our hospital between February 2019 and June 2020. Altogether 17 patients were included in the analysis. 

Based on superselective angiography of the middle meningeal artery (MMA) in the two standard, AP and lateral views, three distinct categories of dural supply were defined: normal vascular pattern (Grade I), cottonwool appearance without enlargement of the MMA branches (Grad II) and strong cottonwool like staining with dilatative remodelling of the MMA branches (Grade III).

The proposed grading system of the angiographic appearance of cSDH, representing the pathophysiological evolution of the disease should be correlated to therapeutic success rates and could be applied in future clinical studies.

Absence and Duplicate Foramen Spinosum in the Same Patient: An Extremely Rare Variation.

The foramen spinosum, one of the important openings at the base of the cranium, is the opening through which the middle meningeal artery enters the cranium. The variations of the foramen spinosum should be well known to be an important landmark in middle fossa surgeries and to understand better the clinical conditions related to the middle meningeal artery passing through it. A total of 35 bones (32 cranial base and 3 separate sphenoid bones) of individuals of unknown age, sex, and ethnicity in the Laboratory of the Department of Anatomy, Gaziantep University, Faculty of Medicine were examined bilaterally in this study. One of the 35 bones was found to have a duplicated foramen spinosum on the left side and an absence foramen spinosum on the right side. Foramen spinosum variations should be considered in middle fossa approaches and procedures involving the middle meningeal artery.

Initial experience using middle meningeal artery embolisation for patients with recurrent and high-recurrence-risk chronic subdural haematoma.

Recurrence rates following surgical management of chronic subdural haematoma (CSDH) range from 5 to 33 %. There is growing evidence which suggests middle meningeal artery embolisation (MMAe) may reduce recurrence rates when used as surgical adjunct or standalone treatment. In this study we described our experience of this new procedure in the our UK institution. Patients with recurrent CSDH or CSDH at high risk of recurrence were selected for MMAe on a case-by-case basis following MDT discussion. A departmental database was used to identify patients treated. 26 CSDH were embolised in 20 patients; 9 CSDH were de-novo and 17 were recurrent. 10/26 CSDH were treated with MMAe only. No procedural mortality, access site or thrombo-embolic complications occurred. One patient experienced symptomatic collection growth 12 h following MMAe and required surgical drainage. 15 (75 %) of patients were living at home at follow-up (mean 14 months). On imaging follow-up 15/18 showed CSDH volume reduction or resolution, 1/18 remained stable requiring no further treatment, 2/18 patients suffered recurrent CSDH requiring treatment. In both recurrent cases incomplete embolisation was noted on procedural imaging (posterior division of MMA not embolised). Persistent posterior MMA division filling was significantly associated with collection recurrence (p = 0.002). Our results suggest MMAe as a stand-alone or adjuvant therapy can be performed safely in a UK neuroscience setting and is associated with high rates of symptomatic CSDH size reduction or resolution in problematic CSDH that have either recurred or are prone to recurrence.

Occult middle meningeal artery to middle cerebral artery anastomosis associated with prior trauma.

The report describes a patient who presented with traumatic right temporoparietal calvarial fracture with chronic right subdural haematoma who underwent right middle meningeal artery embolisation with n-BCA during which direct filling of an anterior temporal branch of the middle cerebral artery was observed.

[External Carotid Artery:Essential Knowledge of the External Carotid Artery Required for Neuroendovascular Surgery, with a Focus on the Middle Meningeal Artery and Occipital Artery].

The perfusion territory of the external carotid artery is often underestimated; however, this blood vessel forms abundant "dangerous anastomoses" with the internal carotid and vertebral arteries. An understanding of these vascular anastomoses is crucial to ensure safe cerebrovascular interventions. There are several important aspects of the middle meningeal artery that should be considered, including anastomoses with the anterior(frontal)branch and ophthalmic artery through the sphenoidal artery(recurrent meningeal artery)and meningolacrimal artery. Additionally, the blood supply to the facial nerve via branches of the petrosal branch, such as the superior tympanic artery, and the formation of the facial arcade by the superior tympanic and stylomastoid arteries, which often originate from the posterior auricular artery, is significant. The occipital artery demonstrates rich anastomoses with vessels, such as the ascending pharyngeal and vertebral arteries, forming what is known as the pharyngo-occipital system.