Formulation and In Vitro-Ex vivo Evaluation of Cannabidiol and Cannabidiol-Valine-Hemisuccinate Loaded Lipid-Based Nanoformulations for Ocular Applications.

The goal of this investigation is to develop stable ophthalmic nanoformulations containing cannabidiol (CBD) and its analog cannabidiol-valine-hemisuccinate (CBD-VHS) for improved ocular delivery. Two nanoformulations, nanoemulsion (NE) and nanomicelles (NMC), were developed and evaluated for physicochemical characteristics, drug-excipient compatibility, sterilization, thermal analysis, surface morphology, ex-vivo transcorneal permeation, corneal deposition, and stability. The saturation solubility studies revealed that among the surfactants tested, Cremophor EL had the highest solubilizing capacity for CBD (23.3 ± 0.1 mg/mL) and CBD-VHS (11.2 ± 0.2 mg/mL). The globule size for the lead CBD formulations (NE and NMC) ranged between 205 and 270 nm while CBD-VHS-NMC formulation had a particle size of about 78 nm. The sterilized formulations, except for CBD-VHS-NMC at 40 °C, were stable for three months of storage (last time point tested). Release, in terms of CBD, in the in-vitro release/diffusion studies over 18 h, were faster from the CBD-VHS nanomicelles (38 %) compared to that from the CBD nanoemulsion (16 %) and nanomicelles (33 %). Transcorneal permeation studies revealed improvement in CBD permeability and flux with both formulations; however, a greater improvement was observed with the NMC formulation compared to the NE formulation. In conclusion, the nanoformulations prepared could serve as efficient topical ocular drug delivery platforms for CBD and its analog.

Formulation and evaluation of inhaled Sildenafil-loaded PLGA microparticles for treatment of pulmonary arterial hypertension (PAH): A novel high drug loaded formulation and scalable process via hot melt extrusion technology (Part â ).

In recent years, several techniques were employed to develop a local sustained pulmonary delivery of sildenafil citrate (SC) as an alternative for the intravenous and oral treatment of pulmonary arterial hypertension (PAH). Most of these methods, however, need to be improved due to limitations of scalability, low yield production, low drug loading, and stability issues. In this study, we report the use of hot-melt extrusion (HME) as a scalable process for making Poly (lactic-co-glycolic acid) (PLGA) microparticles with high SC load. The prepared particles were tested in vitro for local drug delivery to the lungs by inhalation. Sodium bicarbonate was included as a porogen in the formulation to make the particles more brittle and to impart favorable aerodynamic properties. Six formulations were prepared with different formulation compositions. Laser diffraction analysis was used to estimate the geometric particle size distribution of the microparticles. In-vitro aerodynamic performance was evaluated by the next-generation cascade impactor (NGI). It was reported in terms of an emitted dose (ED), an emitted fraction (EF%), a respirable fraction (RF%), a fine particle fraction (FPF%), a mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD). The formulations have also been characterized for surface morphology, entrapment efficiency, drug load, and in-vitro drug release. The results demonstrated that PLGA microparticles have a mean geometric particle size between 6 and 14 µm, entrapment efficiency of 77 to 89 %, and SC load between 17 and 33 % w/w. Fifteen percent of entrapped sildenafil was released over 24 h from the PLGA microparticles, and seventy percent over 7 days. The aerodynamic properties included fine particle fraction ranging between 19 and 33 % and an average mass median aerodynamic diameter of 6-13 µm.

3D printing in vaginal drug delivery: a revolution in pharmaceutical manufacturing.

INTRODUCTION: The Food and Drug Administration's approval of the first three-dimensional (3D) printed tablet, Spritam®, led to a burgeoning interest in using 3D printing to fabricate numerous drug delivery systems for different routes of administration. The high degree of manufacturing flexibility achieved through 3D printing facilitates the preparation of dosage forms with many actives with complex and tailored release profiles that can address individual patient needs. AREAS COVERED: This comprehensive review provides an in-depth look into the several 3D printing technologies currently utilized in pharmaceutical research. Additionally, the review delves into vaginal anatomy and physiology, 3D-printed drug delivery systems for vaginal applications, the latest research studies, and the challenges of 3D printing technology and future possibilities. EXPERT OPINION: 3D printing technology can produce drug-delivery devices or implants optimized for vaginal applications, including vaginal rings, intra-vaginal inserts, or biodegradable microdevices loaded with drugs, all custom-tailored to deliver specific medications with controlled release profiles. However, though the potential of 3D printing in vaginal drug delivery is promising, there are still challenges and regulatory hurdles to overcome before these technologies can be widely adopted and approved for clinical use. Extensive research and testing are necessary to ensure safety, effectiveness, and biocompatibility.

Graphene quantum dots based on cannabis seeds for efficient wound healing in a mouse incisional wound model: Link with stress and neurobehavioral effect.

Graphene quantum dots (GQDs) are promising biomaterials with potential applicability in several areas due to their many useful and unique features. Among different applications, GQDs are photodynamic therapy agents that generate single oxygen and improve antimicrobial activity. In the present study, and for the first time, GQD were isolated from the Cannabis sativa L. seeds to generate C-GQDs as a new biomaterial for antibacterial and wound healing applications. Detailed characterization was performed using FTIR, UV-vis, Raman spectra, photoluminescence, TEM examination, HRTEM, ζ-potential, and XRD. Our results revealed in vitro and in vivo antibacterial activity of C-GQDs against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with reduced minimal inhibitory concentration of 236 µg/mL for both strains. In addition, the C-GQDs confirmed the in vitro analysis and exhibited anti-inflammatory activity by reducing the level of neutrophils in blood and skin tissue. C-GQDs act by accelerating re-epithelization and granulation tissue formation. In addition, C-GQDs restored neurobehavioral alteration induced by incisional wounds by reducing oxidative stress, decreasing cortisol levels, increasing anxiolytic-like effect, and increasing vertical locomotor activity. The wound-healing effects of C-GQDs support its role as a potential therapeutic agent for diverse skin injuries.

Arthroplasty-Related Pseudotumor of the Scapula: Case Report and Review of the Literature.

Arthroplasty-related pseudotumors are nonneoplastic and noninfectious inflammatory masses that are typically associated with adverse reaction to metal debris. Pseudotumors most commonly occur in the setting of metal-on-metal joint replacements at the hip. However, the presentation of pseudotumor at the shoulder is exceedingly rare. In this article, we reported a case of arthroplasty-related pseudotumor of the scapula. Clinical history, radiologic signs, and tissue analysis are described. Knowledge of this rare diagnosis will support clinical decision making for teams of radiologists, pathologists, oncologists, and orthopaedic surgeons who provide care for patients presenting with suspicious shoulder masses.

Ultrasound-assisted adsorption of organic dyes in real water samples using zirconium (IV)-based metal-organic frameworks UiO-66-NH2 as an adsorbent.

The utilization of dye adsorption through metal-organic frameworks represents an eco-friendly and highly effective approach in real water treatment. Here, ultrasound assisted adsorption approach was employed for the remediation of three dyes including methylene blue (MB), malachite green (MG), and congo red (CR) from real water samples using zirconium(IV)-based adsorbent (UiO-66-NH2). The adsorbent was characterized for structural, elemental, thermal and morphological features through XRD, XPS, FTIR, thermogravimetric analysis, SEM, BET , and Raman spectroscopy. The adsorption capacity of adsorbent to uptake the pollutants in aqueous solutions was investigated under different experimental conditions such as amount of UiO-66-NH2 at various contact durations, temperatures, pH levels, and initial dye loading amounts. The maximum removal of dyes under optimal conditions was found to be 938, 587, and 623 mg g-1 towardMB, MG, and CR, respectively. The adsorption of the studied dyes on the adsorbent surface was found to be a monolayer and endothermic process. The probable mechanism for the adsorption was chemisorption and follows pseudo-second-order kinetics. From the findings of regeneration studies, it was deduced that the adsorbent can be effectively used for three consecutive cycles without any momentous loss in its adsorption efficacy. Furthermore, UiO-66-NH2 with ultrasound-assisted adsorption might help to safeguard the environment and to develop new strategies for sustainability of natural resources.

Formulation development and in Vitro-Ex vivo characterization of hot-melt extruded ciprofloxacin hydrochloride inserts for ocular applications: Part I.

This study developed, optimized, characterized, and evaluated bioadhesive, hot-melt extruded (HME), extended-release ocular inserts containing ciprofloxacin hydrochloride (CIP-HCL) to improve the therapeutic outcomes of ocular bacterial infections. The inserts were fabricated with FDA-approved biocompatible, biodegradable, and bioadhesive polymers that were tuned in different ratios to achieve a sustained release profile. The results revealed an inverse relationship between the Klucel™ hydroxypropyl cellulose (HPC, 140,000 Da) concentration and drug release and extended-release profile over 24 h. The CIP-HCL-HME inserts presented stable drug content, thermal behavior, surface pH, and release profiles over three months of room-temperature storage and demonstrated adequate mucoadhesive strength. SEM micrographs revealed a smooth surface. Bacterial growth was not observed on the samples during the in vitro release experiment (0.5-24 h), indicating that a minimum inhibitory concentration (MIC) of 90 against Pseudomonas aeruginosa was achieved. Ex vivo transcorneal permeation studies using excised rabbit corneas revealed that the prepared ocular inserts prolonged the transcorneal flux of the drug compared to commercial eye drops and immediate-release inserts and could reduce the administration frequency to once daily. Therefore, the inserts could increase patient compliance and exhibited prolonged antibacterial activity and thus could provide better therapeutic outcomes against ocular bacterial infections.

Fabrication of a shell-core fixed-dose combination tablet using fused deposition modeling 3D printing.

Fixed-dose combinations (FDCs) achieve optimal goals for treatment with minimal side effects, decreased administration of large number of tablets, thus, greater convenience, and improved patient compliance. However, conventional FDCs do not have a guaranteed place in the future of patient-centered drug development because of the difficulty in achieving dose titration of each drug for individualized specific health needs and desired therapeutic outcomes. In the current study, FDCs of two antihypertensive drugs were fabricated with two distinct compartments using fused deposition modeling three-dimensional printing (FDM-3DP). Atorvastatin calcium and Amlodipine besylate loaded filaments were prepared by hot-melt extrusion. Shell-core FDC tablets were designed to have different infills for individualized dosing. Differential scanning calorimetry and powder X-ray diffraction revealed that both drugs were transformed into amorphous forms within the polymeric carriers. The fabricated tablets met the United States Pharmacopeia acceptance criteria for friability, content uniformity, and dissolution testing. The fabricated tablets were stable at room temperature with respect to drug content and thermal behavior over six months. This dynamic dosage form provides flexibility in dose titration and maintains the advantages of FDCs, thus achieving optimal therapeutic outcomes in different healthcare facilities.

Spinal meningiomas, from biology to management - A literature review.

Meningiomas arise from arachnoidal cap cells of the meninges, constituting the most common type of central nervous system tumors, and are considered benign tumors in most cases. Their incidence increases with age, and they mainly affect females, constituting 25-46% of primary spinal tumors. Spinal meningiomas could be detected incidentally or be unraveled by various neurological symptoms (e.g., back pain, sphincter dysfunction, sensorimotor deficits). The gold standard diagnostic modality for spinal meningiomas is Magnetic resonance imaging (MRI) which permits their classification into four categories based on their radiological appearance. According to the World Health Organization (WHO) classification, the majority of spinal meningiomas are grade 1. Nevertheless, they can be of higher grade (grades 2 and 3) with atypical or malignant histology and a more aggressive course. To date, surgery is the best treatment where the big majority of meningiomas can be cured. Advances in surgical techniques (ultrasonic dissection, microsurgery, intraoperative monitoring) increase the complete resection rate. Operated patients have a satisfactory prognosis, even in those with poor preoperative neurological status. Adjuvant therapy has a growing role in treating spinal meningiomas, mainly in the case of subtotal resection and tumor recurrence. The current paper reviews the fundamental epidemiological and clinical aspects of spinal meningiomas, their histological and genetic characteristics, and their management, including the various surgical novelties and techniques.

Day and night changes in energy expenditure of patients on automated peritoneal dialysis.

RATIONALE: Automated peritoneal dialysis (APD) treatment for end-stage kidney disease affords patients a degree of autonomy in everyday life. Clinical investigations of their energy expenditure (EE) are usually based on resting EE, which could mask day and night variations in EE. The aim of this study, therefore, was to compare the components of EE in APD patients and healthy control (C) subjects. MATERIAL AND METHOD: Patients treated with APD for more than 3 months were compared with C volunteers matched for age and lean body mass (LBM). Biochemical analyses were performed and body composition was determined by DEXA to adjust EE to LBM. Total EE, its different components and respiratory quotients (RQ) were measured by a gas exchange method in calorimetric chambers. Spontaneous total and activity-related EE (AEE) were also measured in free-living conditions over 4 days by a calibrated accelerometer and a heart rate monitor. RESULTS: APD (n = 7) and C (n = 7) patients did not differ in age and body composition. REE did not differ between the two groups. However, prandial increase in EE adjusted for dietary energy intake was higher in APD patients (+57.5 ± 12.71 kcal/h) than in C subjects (+33.8 ± 10.5 kcal/h, p = 0.003) and nocturnal decrease in EE tended to be lower in APD patients undergoing dialysis sessions (- 4.53 ± 8.37 kcal/h) than in subjects (- 11.8 ± 7.69 kcal/h, p = 0.059). Resting RQ (0.91 ± 0.09 vs 0.81 ± 0.04, p = 0.032) and nocturnal RQ (0.91 ± 0.09 vs 0.81 ± 0.04, p = 0.032) were significantly higher in APD patients, indicating a preferential use of glucose substrate potentially absorbed across the peritoneum. AEE was lower in APD patients (595.9 ± 383.2 kcal/d) than in C subjects (1205.2 ± 370.5 kcal/d, p = 0.011). In contrast, energy intakes were not significantly different (1986 ± 465 vs 2083 ± 377 kcal/d, p = 0.677). CONCLUSION: Although the two groups had identical resting EE, APD patients had a higher prandial increase in EE, a lower activity-related EE and higher resting and nocturnal RQ than healthy subjects.

Colloidal lipid nanodispersion enriched hydrogel of antifungal agent for management of fungal infections: Comparative in-vitro, ex-vivo and in-vivo evaluation for oral and topical application.

Ketoconazole (KZ) is broad spectrum antifungal drug, used for the treatment of fungal infections. KZ's clinical topical use has been associated with some adverse effects in healthy adults particularly local reactions, such as stinging, severe irritation, and pruritus. However, bioavailability of KZ after oral administration is low from tablets due to its low aqueous solubility. The objective of this investigation was development and characterization of KZ-containing solid lipid nanoparticles (KZ-SLNs) and SLN-containing hydrogel (KZ-SLN-H) for oral and topical delivery of KZ. KZ-SLNs were prepared using homogenization-sonication method. Optimal KZ-SLN formulation was selected based on physicochemical and in-vitro release studies. Optimized KZ-SLN converted to KZ-SLN hydrogel (KZ-SLN-H) using gelling polymers and optimized with rheological and in-vitro studies. Further, optimized KZ-SLN and KZ-SLN-H formulations evaluated for crystallinity, morphology, stability, ex-vivo and in-vivo pharmacokinetic (PK) studies in rats, comparison with KZ suspension (KZ-S) and KZ-S hydrogel (KZ-SH). Optimized KZ-SLN formulation showed desirable characters. KZ-SLN and KZ-SLN-H formulations exhibited spherical shape, converted to amorphous, sustained release behaviour and enhanced permeability (p < 0.05). Moreover, both formulations were stable for three months at 4 °C and 25 °C. PK studies revealed 1.9 and 1.5-folds, 3.5 and 2.8-folds enhancement of bioavailability of optimized KZ-SLN and KZ-SLN-H formulations (p < 0.05) compared with KZ-S and KZ-SH formulations, respectively. Overall, SLN and SLN-H formulations could be considered as an efficient delivery vehicles for KZ through oral and topical administration for better control over topical and systemic fungal infections.

Effect of lipid and edge activator concentration on development of aceclofenac-loaded transfersomes gel for transdermal application: in vitro and ex vivo skin permeation.

The present investigation focused mainly on the development of aceclofenac (AF) loaded transfersomal gel (AF-TG) to minimize the frequency of oral dosing during the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. AF-loaded transfersomes (AF-TS) were prepared by using the film hydration method. The effect of drug loading, pH of hydration medium, edge activator (EA) and lipid concentration on the properties of the AF-TS were studied and optimized. Optimized AF-TS converted into AF-TG by the addition of carbopol 934. Morphology and compatibility studies of AF-TS were observed with scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). AT-TG formulation was evaluated further for ex vivo skin permeation studies compared with marketed Hifenac 30 g gel. Optimized AF-TS showed vesicle size, PDI, and zeta potential of 111.1 ± 3.2 nm, 0.19 ± 0.02, and -29.6 ± 1.2 mV, respectively. Entrapment efficiency of 74.1 ± 1.8% with pH 5.8 phosphate buffer as a hydration medium and 17.1 ± 0.9 elasticity at 0.15%w/v EA and 1%w/v lipid concentration were observed. SEM and DSC studies revealed the spherical shape and no incompatibilities in the AF-TS formulation. The permeability of the AF from AF-TG was enhanced by 14-folds with similar rheological properties compared with marketed gel. Overall, TG containing AF was superior to marketed AF gel formulation for enhanced skin delivery. Therefore, TS and TG formulation could be considered as an alternative delivery approach for the enhanced transdermal application of AF.

CKD complications in kidney-transplanted patients going back to dialysis: impact on patients outcomes.

AIMS: The management of chronic kidney disease (CKD) complications is not always adequate in patients with a failed kidney transplant. We aimed to evaluate the frequency of CKD complications and assess whether they may lead to worse outcomes in this patient population. METHOD: We analyzed 49 kidney transplant recipients with a failed transplant (T+) and matched non-transplanted patients (T-) starting dialysis between 2000 and 2010 in five dialysis centers in France. CKD complications at dialysis initiation, hospitalizations and death were recorded and compared between the two groups. RESULTS: At dialysis initiation, T+ patients were more likely to have bicarbonate < 22 mmol/l (77.6 vs. 22.0%, p < 0.01), phosphate > 1.5 mmol/l (77.6 vs. 59.2%, p = 0.03), arterial blood pressure > 130/80 mmHg (75.5 vs. 93.9%, p = 0.01), body mass index < 23 (59.2 vs. 32.7%, p = 0.01) and albumin < 38 g/l (69.4 vs. 36.7%) than T- patients. T+ patients were hospitalized more frequently in the year following dialysis initiation (40.8 ± 7.0 vs. 16.3 ± 5.3%, log rank p = 0.01) and 5-year survival rate was lower than in T- patients (82.1 ± 6.2 vs. 64.0 ± 7.4%, log rank p = 0.02). However risk of hospitalization and mortality was lesser after adjustments for CKD complications. CONCLUSION: Despite regular follow-up by nephrologists, CKD complications before initiation of dialysis are more frequent in T+ patients than in T- patients. A better management of CKD complications in T+ patients could improve outcomes after dialysis initiation.

Symptomatic extensive thoracolumbar epidural hematoma following lumbar disc surgery treated by single level laminectomy.

Spinal epidural hematomas (SEHs) are rare complications following spine surgery, especially for single level lumbar discectomies. The appropriate surgical management for such cases remains to be investigated. We report a case of an extensive spinal epidural hematoma from T11-L5 following a L3-L4 discectomy. The patient underwent a single level L4. A complete evacuation of the SEH resulted in the patient's full recovery. When presenting symptoms limited to the initial surgical site reveal an extensive postoperative SEH, we propose: to tailor the surgical exposure individually based on preoperative findings of the SEH; and to begin the surgical exposure with a limited laminectomy focused on the symptomatic levels that may allow an efficient evacuation of the SEH instead of a systematic extensive laminectomy based on imaging.

Pathological effects and motor response threshold changes following radiofrequency application at various distances from the L-5 nerve root: an experimental study.

OBJECT: Radiofrequency (RF) ablation is a minimally invasive technique often used percutaneously in the treatment of many conditions such as spasticity, pain, and osteoid osteoma. The purpose of this study was to assess the value of motor response threshold (MRT) as an indirect indicator of the RF generator's electrode to nerve distance, and to evaluate the effects of RF at various distances from a nervous structure. METHODS: The L-5 nerve root was studied in 102 Sprague-Dawley rats (sham contralateral side). Motor response thresholds at 0, 2, 4, 5, and 6 mm from the nerve root were assessed before and after RF application for 2 minutes at 80° C on Days 0 and 7. Radiofrequency was applied 0, 2, 4, 5, and 6 mm away from L-5 and with the addition of interposed cortical bone. The effects of RF application on MRT were studied, and subsequent nerve injury was evaluated using light microscopy pathological examination. RESULTS: There is a significant correlation between MRT and the distance between the electrode tip and L-5, with MRT less than 0.5 V when the electrode was in direct contact with the root. Electrical and pathological changes following RF application were more pronounced at 0 mm, with worsening seen on Day 7. Radiofrequency at 2 and 4 mm produced fewer electrical and histological deleterious effects on the nerve on Days 0 and 7, with an obvious improvement on Day 7. At 5 mm, electrical and histological abnormalities were minimal on Day 0 and were fully reversible on Day 7. At 6 mm and with interposed cortical bone, MRT and pathological findings were unchanged on Days 0 and 7. CONCLUSIONS: The MRT proved to be a useful and reliable tool in decreasing nerve morbidity following RF ablation in animals and may be used in humans for the same purpose. It serves as an indirect indicator of the proximity of the RF generator's electrode tip to any adjacent motor nervous structure. A minimum safe distance of 5 mm between the electrode tip and the nerve is required to avoid irreversible nerve injury, unless a bony wall is interposed between them, thus serving as a nerve shield. In medical conditions that require RF ablation of the nerve, such as spasticity and pain, the MRT must be lower than 0.5 V. When a nerve lesion is to be avoided such as in cases of osteoid osteoma, an MRT higher than 2.5 V is considered safe, reflecting a distance greater than 5 mm.

[Brain tumors and epilepsy: postoperative evaluation of surgical procedures]. / Evolution postopératoire de l'epilepsie chez les patients opérés de tumeurs cérébrales.

OBJECTIVES: To study the efficacy of surgery on the postoperative control of epilepsy in patients operated for brain tumors. METHODS: Forty patients operated for supratentoriel cerebral tumors with epilepsy, at Hotel-Dieu de France (HDF) hospital center, between 1983 and 2005, were included in this study. Clinical, paraclinical and surgical information were collected. The extent of the tumor resection was based on the postoperative MRI results. RESULTS: The mean duration of the follow-up was 52 +/- 6 months (from 6 months to 10 years). 62.5% of our patients have had acute seizures (< 1 year) and 37% had experienced chronic seizures (> or = 1 year). The histopathologic exam revealed 2 DNET, 3 pilocytic astrocytomas, 2 diffuse astrocytomas, 6 A oligodendrogliomas, 7 B oligodendrogliomas, 7 anaplastic astrocytomas and glioblastomas and 13 meningiomas. Twenty-two patients had a complete resection, whereas the postoperative MRI of 18 patients have shown a tumoral remnant. After one year of follow-up, a complete remission was noted in 57.5% of the patients (Engel I). The prognostic factors of good outcome were: low-grade glial tumors (I +/- II), meningiomas, and complete tumor resection. CONCLUSION: The efficacy of surgery for epilepsy associated to cerebral tumors, established by the majority of articles, matched the results obtained for the patients operated at HDF, with complete seizures control in 57.5% of patients. This control depended essentially on the extent of tumor resection and on tumor's nature.

Multifocal meningeal melanocytoma: a new pathological entity or the result of leptomeningeal seeding?

Meningeal melanocytoma is a rare benign CNS tumor derived from the leptomeningeal melanocytes. Although unusual, malignant transformation with leptomeningeal seeding into the brain or spinal cord may occur years after the initial diagnosis. The authors report a unique case of multifocal benign meningeal melanocytoma involving both cerebellopontine angles and the thoracic spinal cord, with associated diffuse leptomeningeal hyperpigmentation. They review the literature relevant to this topic and discuss the radiological and pathological features of this disease as well as its treatment options.

Impact of the lunar cycle on the incidence of intracranial aneurysm rupture: myth or reality?

OBJECTIVE: To analyze the impact of the lunar cycle and season on the incidence of aneurysmal subarachnoid hemorrhage (SAH). PATIENTS AND METHODS: The medical records of 111 patients who were admitted over a 5-year period to our department because of aneurysmal SAH were retrospectively reviewed. The date of aneurysm rupture was matched with the corresponding season and moon phase. RESULTS: An incidence peak for aneurysm rupture (28 patients) was seen during the phase of new moon, which was statistically significant (p < 0.001). In contrast, no seasonal variation in the incidence of SAH was observed. CONCLUSION: The lunar cycle seems to affect the incidence of intracranial aneurysm rupture, with the new moon being associated with an increased risk of aneurysmal SAH.