The Importance of Early Intervention in Ruptured Cerebral Aneurysm: Biochemical and Pathophysiological Foundations Within the First 24 Hours

The Importance of Early Intervention in Ruptured Cerebral Aneurysm: Biochemical and Pathophysiological Foundations Within the First 24 Hours | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Importance of Early Intervention in Ruptured Cerebral Aneurysm: Biochemical and Pathophysiological Foundations Within the First 24 Hours Juan Armando Mejía, Andrés Felipe Bejarano-Ramírez, Luisa Figueredo, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9034232/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Severe vasospasm in cases of subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysms accounts for a high mortality rate ranging from 36% to 67%, as well as permanent neurological deficits. Biochemical changes involving neuropeptides such as Neuropeptide Y (NPY) and Calcitonin Gene-Related Peptide (CGRP) have been studied as regulators of vascular tone and protectors of cerebral perfusion. These peptides may become imbalanced during subarachnoid hemorrhage (SAH). Methods: This is an analytical descriptive case-control study with a 1:1 ratio, comparing patients diagnosed with subarachnoid hemorrhage secondary to ruptured aneurysms to those with incidental, unruptured aneurysms. A total of 46 patients were included, distributed equally into two groups: 23 in the case group and 23 in the control group. Cerebrospinal fluid (CSF) samples were collected from all participants during surgery, directly from the cerebral cisterns, ventricles, and through spinal catheters. The objective of this study was to analyze and correlate the levels of NPY and CGRP between patients with aneurysmal SAH and those with unruptured aneurysms. Results: A similarity in mean age was observed between both groups: cases = 57 ± 13.4 years vs. controls = 56.3 ± 12.4 years. Regarding NPY and CGRP values, the control group showed a median NPY level of 796 (P25 = 94, P75 = 903) versus 210 (P25 = 49, P75 = 901) in the aneurysmal rupture group. Although there was a trend toward increased NPY levels in the rupture group, the difference was not statistically significant (p = 0.62). For CGRP, the median level was 35.5 (P25 = 38.8, P75 = 61.9) in the control group versus 66.5 (P25 = 11.4, P75 = 88) in the case group, also without statistical significance (p = 0.39). In the control group, a negative correlation was found between NPY and CGRP levels, with a strong inverse relationship and statistical significance (Rho = –0.6; p = 0.001). Conclusions: In this study, we analyzed the levels of neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) in cerebrospinal fluid (CSF) collected from the basal cisterns, ventricles, and a spinal catheter in patients with subarachnoid hemorrhage (SAH) secondary to aneurysmal rupture, comparing them to patients without rupture. Although we observed a trend toward higher NPY levels in the rupture group, supporting the notion of early aneurysm intervention within the first 24 hours to prevent the development of vasospasm, and also noted differences in CGRP levels, these findings were not statistically significant. These results suggest that while these neuropeptides may play a role in vascular tone regulation and the pathophysiology of cerebral vasospasm, their specific function appears to be disrupted, representing one of the mechanisms of SAH that remains incompletely understood. Further studies with larger sample sizes and designs better suited to assessing the causal relationship between these biomarkers and clinical outcomes are required. Figures Figure 1 Figure 2 Figure 3 Introduction Subarachnoid hemorrhage (SAH) is defined as a complex, multifactorial neurological syndrome characterized by the sudden extravasation of high-pressure arterial blood into the subarachnoid space, with potential extension into the brain parenchyma and ventricles [ 1 ]. SAH can be classified as traumatic (being the most common form of presentation) however, the focus of this article is on non-traumatic SAH of aneurysmal origin [ 2 ]. It is the third most common subtype of stroke and poses a significant clinical challenge due to its high mortality rates, reported to range between 32% and 67%, although some authors have described mortality between 37% and 44%. It most commonly affects individuals with a mean age of 55 years [ 3 – 5 ]. The rupture of a cerebral aneurysm accounts for approximately 85% of SAH cases and may lead to delayed cerebral ischemia in up to 30% of these patients, with a pre-hospital mortality rate as high as 10% [ 4 , 6 , 7 ]. The risk of aneurysm rupture is influenced by several factors, including female sex, age ≥ 60 years, and aneurysm size ≥ 5 millimeters [ 7 ]. The leading cause of non-traumatic SAH is the rupture of an intracranial aneurysm, an event that can trigger cerebral vasospasm in 20–30% of cases. Among these, approximately 50% will develop cerebral infarction, and between 15% and 20% will experience permanent neurological deficits, significantly impacting quality of life, reducing productivity, and substantially increasing healthcare costs. Vasospasm is also the primary cause of death and long-term neurological disability among survivors [ 8 – 10 ]. The pathophysiology of vasospasm is complex and multifactorial, involving alterations in perivascular innervation, including dysfunction of neuropeptides such as calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and substance P. Although the exact mechanisms underlying this ischemic event have not been fully elucidated, proposed contributors include denervation, vascular hypersensitivity, and decreased levels of vasoactive substances such as catecholamines and neuropeptides [ 11 ]. Furthermore, elevated levels of NPY have been associated with cerebral vasospasm following aneurysmal SAH. Conversely, CGRP has been identified as one of the principal regulators of cerebral vascular tone, with a protective effect against severe vasoconstriction through its ability to induce relaxation of cerebral arteries [ 11 , 12 ]. This study aims to anticipate the pathophysiological events that occur during the first 24 hours following a subarachnoid hemorrhage by measuring the levels of the neuropeptides neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP). Both peptides are part of the perivascular innervation and play a regulatory role in cerebral vascular tone, independent of endothelial integrity which is often disrupted in the context of hemorrhage. Since cerebrospinal fluid (CSF) circulates through the basal cisterns and directly bathes the intracranial vessels, its analysis is proposed as an indirect method to assess intracranial neuropeptide levels during the acute phase of the hemorrhagic event [ 13 ]. To date, no studies have reported the collection of CSF samples obtained directly from the basal cisterns for the measurement of NPY and CGRP in patients with subarachnoid hemorrhage within the first 24 hours. Materials and Methods A prospective observational analytical study was conducted using a 1:1 case-control design, including a total of 23 cases and 23 controls. Data collection was carried out over a one-year period at a high-complexity hospital in Bogotá, Colombia, and included patients who required cranial surgical intervention. Cases were defined as patients between 18 and 80 years of age with a clinically and radiologically confirmed diagnosis of subarachnoid hemorrhage (SAH) secondary to aneurysmal rupture, from whom cerebrospinal fluid (CSF) samples were obtained from the basal cisterns during the surgical procedure. Controls consisted of patients within the same age range who were scheduled for posterior fossa tumor surgery or elective aneurysm clipping due to incidental findings, with no evidence of SAH. During the selection period, patients who did not meet the inclusion criteria or who met any exclusion criteria were excluded from the study (Table 1). All collected samples were analyzed using enzyme-linked immunosorbent assay (ELISA), employing the Human NPY (Neuropeptide Y) ELISA Kit (E-EL-H1893, Elabscience) and the Human CGRP1 (Calcitonin Gene-Related Peptide 1) ELISA Kit (E-EL-H0619, Elabscience), in order to identify and quantify the presence of the neuropeptides NPY and CGRP in cerebrospinal fluid (CSF). Samples were obtained intraoperatively, directly from the basal cisterns. Following collection, they were placed in sterile vials, temporarily stored in a portable refrigerator at –24°C, and subsequently frozen at –70°C for preservation. After one year, all samples from the 23 SAH patients and the 23 controls with incidental aneurysms were processed. Additionally, a review of medical records was conducted to collect relevant clinical variables, including age, sex, Hunt-Hess grade at admission, presence of vasospasm, past medical history, and Glasgow Coma Scale score at hospital discharge. For quantitative analysis, the samples were randomized and assessed in a blinded manner by the analyst. Six patients were excluded due to incomplete data, multiple measurements, or loss of biological material. Data Collection Patients were identified through the neurosurgery service database, and all clinical cases meeting the inclusion criteria were selected. Subsequently, controls were chosen from the same database, and a 1:1 randomization process was conducted, assigning one control for each case. Medical records of these patients were reviewed to extract data on age, sex, NPY and CGRP levels, surgical indication, type of surgical intervention, Hunt-Hess grade, presence of vasospasm, relevant medical history, and Glasgow Coma Scale score. Inclusion criteria Exclusion criteria Patients over 18 years of age. Patients under 18 years of age. Patients with clinically and radiologically confirmed subarachnoid hemorrhage who have no contraindications to cerebrospinal fluid or arterial blood sampling during hospitalization. Patients who do not require ventricular drainage. Patients undergoing posterior fossa tumor surgery or elective clipping of incidentally discovered, unruptured aneurysms, without contraindications to cerebrospinal fluid or arterial blood sampling. Patients with contraindications to cerebrospinal fluid sampling; those with chronic inflammatory or immunomodulatory diseases; subarachnoid hemorrhage associated with trauma, arteriovenous malformations, or dural arteriovenous fistulas. Table 1. Inclusion and exclusion criteria Objective The objective of this study is to analyze and correlate the levels of neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) in patients who experienced subarachnoid hemorrhage. Statistical Analysis All statistical analyses were performed using IBM SPSS version 25 and Jamovi version 2.3.28.0. Student’s t-tests and chi-square tests were used to compare the distribution of continuous and categorical variables, respectively, between cases and controls, as well as within clinical variable subgroups. In instances of non-normal distribution, the Shapiro-Wilk test and Fisher’s exact test were employed for comparing medians of continuous and categorical variables, respectively. The Mann-Whitney U test was used to assess the relationship between CGRP and NPY levels across both comparator groups (cases and controls). A descriptive analysis was also conducted for the following variables: age, day of admission, Hunt-Hess grade, presence and onset day of vasospasm, Glasgow Coma Scale at discharge, aneurysm location, type of treatment, site of sample collection, embolization, history of arterial hypertension, and whether the aneurysm was an incidental finding. CGRP and NPY levels were analyzed separately for each group. Results In the case group, the mean age for both sexes was 57 ± 13.4 years. A history of arterial hypertension was present in 60.1% of patients. All participants (100%) were diagnosed with subarachnoid hemorrhage secondary to ruptured cerebral aneurysm. Cerebrospinal fluid (CSF) samples for NPY and CGRP1 quantification were collected from the cisterns in all cases: 60% (14 patients) from the cerebral cisterns, 34.8% (8 patients) from the ventricles, and 4.3% (1 patient) from a spinal catheter. The Hunt-Hess scale classification revealed that 30.4% of patients (7 cases) were in grade IV (stupor, moderate to severe hemiparesis, possible decerebrate rigidity, or other neurological abnormalities). Vasospasm was documented in 80% of patients (20 cases) with ruptured aneurysms. Upon admission, Glasgow Coma Scale (GCS) scores were most frequently 3 points in 39% of patients (9 cases), followed by a score of 15 in 34.8% of cases (8 patients). In this study, the most commonly identified cerebral aneurysm location was the anterior communicating artery, present in 26% of cases (6 patients), with a 1:1 male-to-female ratio. Aneurysms of the right middle cerebral artery were observed in 13% (3 patients), followed by aneurysms in the left carotid artery, right posterior communicating artery, and left middle cerebral artery, each accounting for 8.7% of cases. Surgical clipping was performed in 79.6% of patients (16 cases), while 30.4% (7 patients) underwent ventriculostomy. Two patients (8.7%) with Hunt-Hess grades IV and V underwent endovascular embolization (Table 2). CASES Total Male Female 23 (100%) 9 (39.1%) 14 (60.9%) AGE (SD) 57 (13.4) 57.9 (14.8) 56.4 (12.9) ADMISSION DAY (SD) 3.3 (6.16) 2.4 (2.6) 3.86 (7.69) HUNT HESS (%) 1 5 (21.7%) 2 (40%) 3 (60%) 2 6 (26%) 2 (33.3%) 4 (66.6%) 3 4 (17.4%) 3 (75%) 1 (25%) 4 7 (30.4%) 2 (28.5%) 5(71.5%) 5 1 (4.3%) 0 (0%) 1 (100%) VASOSPASM (%) YES 20 (87%) 8 (40%) 12 (60%) NO 3 (13%) 1 (33.3%) 2 (66.6%) VASOSPASM DAY (SD) 1.9 (1.86) 1.8 (1.8) 1.9 (1.9) POST-SURGICAL VASOSPASM DAY (%) 1 3 (13%) 1 (33.3%) 2 (66.6%) 2 11 (47.8%) 5 (45.5%) 6 (54.5) 3 4 (17.4%) 1 (25%) 3 (75%) 4 1 (4.3%) 0 (0%) 1 (100%) 5 3 (13%) 2 (66.6%) 1 (33.3%) 7 1 (4.3%) 0 (0%) 1 (100%) GLASGOW outcome (%) 3 9 (39%) 5 (55.5%) 4 (44.5%) 8 1 (4.3%) 0 (0%) 1(100%) 11 1 (4.3%) 0 (0%) 1(100%) 13 3 (13%) 0 (0%) 3 (100%) 14 1 (4.3%) 1 (100%) 0 (0%) 15 8 (34.8%) 3 (37.5%) 5 (62%) TREATMENT (%) Clipping of aneurysm 16 (79.6%) 6 (37.5%) 10 (62.5%) Ventriculostomy 7 (30.4%) 3 (42.9%) 4 (57.1%) SITE OF ANEURISM (%) Left carotid artery 2 (8.7%) 2 (100%) 0 (0%) Posterior communicating artery 1 (4.3%) 1 (100%) 0 (0%) Anterior communicating artery 6 (26%) 3 (50%) 3 (50%) Middle cerebral artery 1 (4.3%) 1 (100%) 0 (0%) Left communicating artery 1 (4.3%) 0 (0%) 1 (100%) Left superior hypophyseal artery 1 (4.3%) 0 (0%) 1 (100%) Left posterior communicating artery 1 (4.3%) 0 (0%) 1 (100%) Right ophthalmic artery 1 (4.3%) 0 (0%) 1 (100%) Unspecified communicating artery 1 (4.3%) 0 (0%) 1 (100%) Right posterior communicating artery 2 (8.7%) 0 (0%) 2 (100%) Right middle cerebral artery 3 (13%) 1 (33.3%) 2 (66.6%) Left middle cerebral artery 2 (8.7%) 1 (50%) 1 (50%) Right carotid artery 1 (4.3%) 0 (0%) 1 (100%) SAMPLE SITE (%) Ventricle 8 (34.8%) 4 (50%) 4 (50%) Cistern 14 (60.1%) 5 (35.8%) 9 (64.2%) Spinal catheterd 1 (4.3%) 0 (0%) 1 (100%) EMBOLIZATION (%) YES 2 (8.7%) 1 (50%) 1 (50%) NO 21 (91.3%) 8 (38%) 13 (62%) HIGH BLOOD PRESSURE (%) YES 14 (60.1%) 6 (42.9%) 8 (57.1%) NO 9 (39%) 3 (33.3%) 6 (66.6%) Table 2. Characteristics of the “case” group population undergoing surgical intervention for subarachnoid hemorrhage secondary to aneurysmal rupture In the control group, the mean age for both sexes was 56.3 ± 12.4 years. All patients (100%) underwent surgical intervention by the neurosurgery service due to incidental findings of cerebral aneurysms. During the surgical procedures, cerebrospinal fluid (CSF) samples were obtained from the basal cisterns to determine levels of NPY and CGRP1. Surgical treatment was performed in 26.1% of cases for anterior communicating artery aneurysms, followed by 17.4% for aneurysms of the middle cerebral artery (unspecified laterality), and 8.7% for left middle cerebral artery aneurysms. The most frequent treatment in the control group was aneurysm clipping, performed in 78.2% (18 patients), and CSF sampling in this group was conducted during aneurysm clipping. Additionally, 8.7% of patients (2 cases) and 4.3% (1 case) underwent sampling during a right temporal craniotomy for a middle fossa tumor. In 4.3% of cases, the sample was obtained via lumbar puncture, and another 4.3% during endoscopic ventricular access (Table 3). CONTROLS Total Male Female 23 8 (34.8%) 15 (65.2%) AGE (SD) 56.3 (12.4) 58.7 (13.2) 54.9 (12.1) SITE OF ANEURISM (%) Posterior fossa tumor 1 (4.3%) 0 (0%) 1(100%) Right mesial glial tumor 1 (4.3%) 0 (0%) 1(100%) Aneurysm of the middle cerebral artery 4 (17.4%) 0 (0%) 4(100%) Cerebellar tumor 1 (4.3%) 0 (0%) 1(100%) Aneurysm of the anterior communicating artery 6 (26.1%) 4(66.6%) 2(33.3%) Aneurysm of the posterior communicating artery 1 (4.3%) 1(100%) 0 (0%) Meningioma 1 (4.3%) 0 (0%) 1(100%) Colloid cyst of the third ventricle 1 (4.3%) 0 (0%) 1(100%) Aneurysm of the left middle cerebral artery 2(8.7%) 0 (0%) 2(100%) Aneurysm of an unspecified carotid artery 1 (4.3%) 0 (0%) 1(100%) Secular aneurysm of the right pericallosal artery 1 (4.3%) 1(100%) 0 (0%) Aneurysm of the right middle cerebral artery 3 (13%) 2 (66.6%) 1 (33.3%) INCIDENTAL FINDING (%) YES 9(39.1%) 4(44.5%) 5(55.5%) NO 13(60.9%) 5(38.5%) 8 (61.5%) TREATMENT (%) Posterior fossa craniotomy 2 (8.7%) 1(50%) 1(50%) Right temporal craniotomy 1 (4.3%) 1(100%) 0 (0%) Clipping of aneurysm 18(78.2%) 7(38.9%) 11 (61.1%) Lumbar puncture 1 (4.3%) 0 (0%) 1(100%) Septostomy 1 (4.3%) 0 (0%) 1(100%) Table 3. Characteristics of the “control” group population undergoing surgical intervention for subarachnoid hemorrhage secondary to causes other than aneurysmal rupture For the case group, 23 NPY samples were obtained, with a median value of 796 (P25 = 94, P75 = 903), and a median CGRP1 value of 35.5 (P25 = 38.8, P75 = 61.9). In the control group, 23 samples were also collected, with NPY showing a median value of 210 (P25 = 49, P75 = 901), and CGRP1 a median of 66.5 (P25 = 11.4, P75 = 88). Although the case group exhibited higher NPY values, as illustrated in Figure 1, the difference between the two groups was not statistically significant (p = 0.62). As shown in Figure 2, CGRP values tended to be higher in the control group compared to the aneurysm rupture group; however, this difference was also not statistically significant (p = 0.39). FAs illustrated in Figure 3, CGRP initially peaks in response, but as NPY levels increase, CGRP levels decline. One hypothesis is that NPY may inhibit CGRP, thereby impairing its vasodilatory counterregulatory effect. Regarding age, an inverse relationship was observed: as age increases, CGRP levels decrease, suggesting reduced counterregulation in older patients and, consequently, a worse prognosis due to this intrinsic neuropeptidergic mechanism. Additionally, a negative correlation between NPY and CGRP levels was confirmed in the control group, showing a moderate-to-strong inverse association with statistical significance (Rho = –0.6; p = 0.001). Discussion Subarachnoid hemorrhage (SAH) is the third most common subtype of stroke, with a mean age of onset around 55 years [ 3 , 4 ]. The rupture of a cerebral aneurysm accounts for approximately 85% of SAH cases [ 4 ]. In the acute phase of this event, the involvement of various neuropeptides that modulate the neurovascular response has been identified. Among these, neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) stand out due to their pathophysiological roles in regulatory and counter-regulatory hemodynamic mechanisms, particularly at the level of vascular smooth muscle [ 14 , 15 ]. The present study analyzed the levels of NPY and CGRP in cerebrospinal fluid and the basal cisterns collected intraoperatively from patients with aneurysmal SAH compared to controls. Our understanding of the pathophysiology of cerebral vasospasm following SAH has advanced significantly in recent decades. It is now recognized that the phenomenon is not solely dependent on intraluminal alterations, but also involves inflammatory and neurovascular processes within the perivascular environment [ 16 ]. In this context, endothelial dysfunction plays a key role by disrupting nitric oxide production and increasing the permeability of the blood-brain barrier [ 17 ]. This process facilitates calcium influx into vascular smooth muscle cells, triggering sustained contraction and contributing to vasoconstriction [ 18 ]. Furthermore, endothelial injury promotes microthrombus formation, platelet dysfunction, and glycocalyx degradation, all of which exacerbate the vasospastic response [ 18 ]. Neuropeptide Y (NPY), discovered in 1982, is a 36-amino acid peptide found in perivascular innervation as well as in central regions such as the arcuate nucleus of the hypothalamus [ 19 ]. It is co-released with neurotransmitters including norepinephrine, acetylcholine, vasoactive intestinal peptide (VIP), neurokinin A, and substance P; however, NPY has been shown to be the most potent vasoconstrictor among them [ 20 ]. Its vasopressor action in the context of SAH is considered part of the acute neurogenic response to subarachnoid bleeding. Moreover, due to its involvement in multiple physiological processes, NPY has been proposed as a potential target for therapeutic modulation in vascular dysfunction settings, including SAH [ 15 , 20 – 22 ]. Conversely, CGRP is a neurosensory neuropeptide composed of 37 amino acids, with two known isoforms: αCGRP and βCGRP. αCGRP is the predominant form in the central nervous system and is localized in cerebral vasculature and enteric nerves [ 23 ]. Unlike NPY, CGRP functions as a potent vasodilator, exerting protective effects against ischemia and hypoxia. Its release has been proposed as part of a counter-regulatory response during acute cerebrovascular events such as SAH, aiming to counteract the vasoconstrictive effects of neuropeptides like NPY [ 24 , 25 ]. This duality between the two peptides suggests a vascular regulatory axis that may hold diagnostic and therapeutic implications in the early course of subarachnoid hemorrhage. In the literature, correlations between the levels of these peptides and various pathologies have been described; however, studies in humans remain limited. In patients with arterial hypertension (HTN), serum NPY concentrations have been found to be higher in individuals with hypertension secondary to overweight and obesity compared to those with primary hypertension. Moreover, a positive correlation has been observed between NPY levels and elevated body mass index (BMI) [ 26 ]. Despite the known vascular effects of CGRP, there is no consensus regarding its role in individuals with primary arterial hypertension, primarily due to heterogeneous findings in plasma-level studies [ 27 ]. In murine models, it has been observed that animals with hypertension exhibit an increased number of CGRP receptors, as well as a higher receptor-binding ratio. CGRP receptors are considered key cerebrovascular effectors in chronic hypertension, mediated through the regulation of RAMP2, suggesting that their role may be more organ-protective than counterregulatory toward hypertension itself [ 25 ]. In cardiovascular disease, elevated CGRP levels have also been found in autopsy specimens from patients who died of acute myocardial infarction, supporting the hypothesis that both ischemic and hypoxemic cardiovascular events trigger a compensatory response mediated by CGRP [ 28 ]. In the present study, an increase in NPY levels was observed in patients with aneurysmal SAH (median 796, P25 = 94, P75 = 903) compared to controls (median 210, P25 = 49, P75 = 901), although the difference did not reach statistical significance (p = 0.62). However, a statistically significant positive correlation was found between NPY levels and Hunt-Hess score (Rho = 0.4, p = 0.001). This finding suggests that elevated NPY levels may be associated with greater clinical severity in SAH patients, potentially due to its role in vasoconstriction and the development of vasospasm. This aligns with existing literature showing that increased CSF NPY levels are associated with cerebral vasospasm, with a persistent elevation beginning on the second day after SAH onset in patients who develop vasospasm, compared to those who do not [ 12 ]. The origin of the sample may also influence the measurement and predictive value of NPY levels for vasospasm, as serum NPY concentrations have not demonstrated correlation with cerebral vasospasm [ 29 ]. Although the strength of the correlation found in this study was moderate, the hypothesis that this association may become more robust with a larger sample size should be considered in future research. Conversely, CGRP levels tended to be higher in the control group (median 66.5, P25 = 11.4, P75 = 88) compared to the aneurysmal SAH group (median 35.5, P25 = 38.8, P75 = 61.9), although this difference was not statistically significant (p = 0.39). This finding is consistent with previous studies that have identified CGRP as a key vasodilator involved in the regulation of cerebral vascular tone and protection against vasospasm following SAH [ 12 , 25 ]. The trend toward lower CGRP levels in the aneurysmal SAH group may suggest an insufficient compensatory response to elevated NPY levels in these patients [ 12 , 24 ]. A negative correlation between NPY and CGRP levels was observed in both groups, although with differing magnitudes. In the case group, the correlation was weak and not statistically significant (Rho = − 0.33, p = 0.1), whereas in the control group, a statistically significant negative correlation was found between CGRP and NPY levels (Rho = − 0.6, p = 0.001), indicating that as NPY levels increased, CGRP levels decreased. This inverse relationship suggests a potential reciprocal regulatory mechanism between the two neuropeptides under physiological conditions. Given that NPY is involved in modulating the stress response, appetite regulation, and cardiovascular homeostasis, and that CGRP acts as a vasodilator and plays a key role in inflammatory and nociceptive processes, the correlation between these peptides may reflect a neurovascular and neuroimmune balance characteristic of healthy individuals. However, in the context of aneurysmal SAH, this regulatory mechanism may become disrupted, leading to an imbalance in the neurovascular unit that contributes to the development of vasospasm. Additionally, a relationship was found between NPY levels and age in patients with aneurysmal SAH. Although a positive correlation was observed (Rho = 0.36), it was weak and not statistically significant (p = 0.08). Nevertheless, these findings are consistent with the literature, which suggests that vascular reactivity may be influenced by age, with a possible decline in vasodilatory responsiveness (typically mediated by CGRP) leading to increased susceptibility to vasospasm in older patients [ 30 ]. Hunt-Hess grade IV scores and the presence of vasospasm in 80% of cases reinforce the hypothesis that elevated NPY levels may be involved in the neurological deterioration of these patients, potentially triggering delayed cerebral ischemia via vasospasm. As previously discussed, endothelial dysfunction and platelet-derived growth factors play key roles in the physiology of vasospasm. These changes begin with alterations to endothelial components and the vascular wall, initially leading to vasospasm, which may worsen over time. Therefore, early surgical intervention (ideally within the first 24 hours) is crucial to secure the aneurysm. This urgency is supported by the observed trend toward increased NPY levels and impaired CGRP response, particularly in hypertensive and elderly patients, as well as by the early inhibitory effect of NPY on CGRP activity. These pathophysiological mechanisms support the rationale for early surgical management [ 31 ]. However, no statistically significant association was found between these clinical factors and neuropeptide levels, suggesting that additional mechanisms (such as inflammation and oxidative stress) may also contribute to clinical outcomes in these patients. Among the limitations of this study, the small sample size stands out, which may have limited the ability to detect statistically significant differences. Additionally, variability in the site of sample collection (cisterns, ventricles, and spinal catheter) may have influenced the measured levels of NPY and CGRP, given the potential heterogeneity in the distribution of these neuropeptides within the central nervous system. Nonetheless, CSF samples were collected within the first 24 hours, the critical window during which perivascular peptide fluctuations are known to occur. This study provides evidence supporting the potential role of NPY and CGRP in the pathophysiology of aneurysmal subarachnoid hemorrhage (SAH), suggesting a neurovascular unit imbalance in these patients. Although NPY levels were higher in the aneurysmal SAH group and CGRP showed a negative correlation with NPY in controls, these findings did not reach statistical significance. This underscores the need for larger sample sizes and longitudinal analyses to better understand the role of these neuropeptides in vascular wall dynamics and the progression of cerebral vasospasm. It is proposed that early sampling of cerebrospinal fluid from the basal cisterns in surgically treated patients could serve as a future predictive test for vasospasm within the first 24 hours, particularly due to the significantly elevated NPY levels observed in female patients over the age of 60. While CGRP did not demonstrate statistical significance, a decreasing trend with age was noted in patients with aneurysmal SAH, which may facilitate greater reactivity and allow NPY to exert its vasoconstrictive effect during the critical early phase of the hemorrhagic event [ 32 ]. Declarations Authors Contributions J.A.M. and A.F.B.R. conceived the study and contributed to the methodological design. J.A.M., A.F.B.R., J.P., O.M., and C.N. contributed to data acquisition and intraoperative sample collection. D.U.L. and S.D.H. supported database organization and data curation. A.F.B.R., J.A.M., and L.F. performed the analysis and interpretation of the results. J.A.M., A.F.B.R., D.U.L., and S.D.H. prepared the final version of the manuscript. All authors reviewed and approved the final manuscript. Declarations None of the interventions presented required procedures beyond those already established in the standard protocol for the management of subarachnoid hemorrhage. Clinical trial number: not applicable. Trial registration: not applicable. Ethics approval: The research was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and complied with all applicable institutional, national, and international guidelines and regulations for research involving human subjects. The study protocol was reviewed and approved by the Institutional Review Board (IRB) of the Hospital Universitario Fundación Santa Fe de Bogotá, under communication CCEI-11935-2020 dated May 19, 2020. Consent to participate: Written informed consent to participate was obtained from all participants or their legally authorized representatives. Funding: This research received no external funding. Competing interests: The authors declare that they have no competing interests. References de Oliveira Manoel AL, Goffi A, Marotta TR, Schweizer TA, Abrahamson S, Macdonald RL. The critical care management of poor-grade subarachnoid haemorrhage. Crit Care [Internet]. 2016 Jan 23 [cited 2025 Feb 26];20(1):21. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4724088/ Sharma D. Perioperative Management of Aneurysmal Subarachnoid Hemorrhage: A Narrative Review. Anesthesiology [Internet]. 2020 Dec 1 [cited 2025 Feb 26];133(6):1283–305. 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Neuronal circuits involving neuropeptide Y in hypothalamic arcuate nucleus-mediated feeding regulation. Neuropeptides [Internet]. 2012 Dec 1 [cited 2025 May 27];46(6):285–9. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0143417912001035?via%3Dihub Calzada-León R, Altamirano-Bustamante N, De La M, Ruiz-Reyes L. Reguladores neuroendocrinos y gastrointestinales del apetito y la saciedad. Bol Med Hosp Infant Mex [Internet]. 2008 [cited 2025 Feb 25];65(6):468–87. Available from: http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-11462008000600007&lng=es&nrm=iso&tlng=es Ashina M. Migraine. Ropper AH, editor. New England Journal of Medicine [Internet]. 2020 Nov 5 [cited 2025 Feb 25];383(19):1866–76. Available from: https://www.nejm.org/doi/pdf/10.1056/NEJMra1915327 Bale R, Doshi G. Cross talk about the role of Neuropeptide Y in CNS disorders and diseases. Neuropeptides. 2023 Dec 1;102:102388. Hay DL, Walker CS. CGRP and its receptors. Headache: The Journal of Head and Face Pain [Internet]. 2017 Apr 1 [cited 2025 Feb 15];57(4):625–36. Available from: https://onlinelibrary-wiley-com.ezproxy.uniandes.edu.co/doi/full/10.1111/head.13064 Juul R, Edvinsson L, Fredriksen TA, Ekman R, Brubakk AO, Gisvold SE. Changes in the levels of neuropeptide Y-LI in the external jugular vein in connection with vasoconstriction following subarachnoid haemorrhage in man. Involvement of sympathetic neuropeptide Y in cerebral vasospasm. Acta Neurochir (Wien) [Internet]. 1990 Sep [cited 2025 Feb 15];107(3–4):75–81. Available from: https://pubmed.ncbi.nlm.nih.gov/2077856/ Wang Z, Martorell BC, Wälchli T, Vogel O, Fischer J, Born W, et al. Calcitonin Gene-Related Peptide (CGRP) Receptors Are Important to Maintain Cerebrovascular Reactivity in Chronic Hypertension. PLoS One [Internet]. 2015 Apr 10 [cited 2025 Feb 15];10(4):e0123697. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4393086/ Baltazi M, Katsiki N, Savopoulos C, Iliadis F, Koliakos G, Hatzitolios AI. Plasma neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (a-MSH) levels in patients with or without hypertension and/or obesity: a pilot study. Am J Cardiovasc Dis [Internet]. 2011 [cited 2025 Feb 25];1(1):48. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC3253505/ Kee Z, Kodji X, Brain SD. The role of calcitonin gene related peptide (CGRP) in neurogenic vasodilation and its cardioprotective effects. Front Physiol [Internet]. 2018 Sep 19 [cited 2025 Feb 25];9(SEP):405886. Available from: www.frontiersin.org Roudenok V, Gutjar L, Antipova V, Rogov Y. Expression of vasoactive intestinal polypeptide and calcitonin gene-related peptide in human stellate ganglia after acute myocardial infarction. Annals of Anatomy - Anatomischer Anzeiger. 2001 Jul 1;183(4):341–4. Rasmussen R, Stavngaard T, Jessing IR, Skjøth-Rasmussen J, Olsen N V., Ostrowski SR, et al. High plasma levels of neuropeptide y correlate with good clinical outcome but are not correlated to cerebral blood flow or vasospasm after subarachnoid hemorrhage. J Neurosurg Anesthesiol [Internet]. 2016 Jan 1 [cited 2025 Feb 25];28(1):65–70. Available from: https://journals.lww.com/jnsa/fulltext/2016/01000/high_plasma_levels_of_neuropeptide_y_correlate.10.aspx Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nature Reviews Neurology 2014 10:1 [Internet]. 2013 Dec 10 [cited 2025 Feb 15];10(1):44–58. Available from: https://www.nature.com/articles/nrneurol.2013.246 Xu S, Zhang W, Zhang Y, Xu Z, Wu T. Efficacy and Prognosis of Adjuvant Argatroban Treatment in Acute Ischemic Stroke Patients with Early Neurological Deterioration. Discov Med. 2023;35(175):185. Jabbarli R, Pierscianek D, Darkwah Oppong M, Sato T, Dammann P, Wrede KH, et al. Laboratory biomarkers of delayed cerebral ischemia after subarachnoid hemorrhage: a systematic review. Neurosurg Rev [Internet]. 2020 Jun 1 [cited 2025 Feb 15];43(3):825–33. Available from: https://openurl-ebsco-com.ezproxy.uniandes.edu.co/contentitem/doi:10.1007/s10143-018-1037-y?sid=ebsco:plink:crawler&id=ebsco:doi:10.1007/s10143-018-1037-y&crl=c Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9034232","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":609682400,"identity":"3d72f463-ec31-4214-8bad-ba185dbabe99","order_by":0,"name":"Juan Armando Mejía","email":"","orcid":"","institution":"Fundación Santa Fe de Bogotá","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"Armando","lastName":"Mejía","suffix":""},{"id":609682401,"identity":"ed4aeba9-055d-4f23-a774-095dc41040e3","order_by":1,"name":"Andrés Felipe Bejarano-Ramírez","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYDACCQYGAyjT8AGQkGFgYCNeizGQYcBDlBYYMJMgSgv/7OYDBT/32OXxix3eVvGx7Q8PP3tbAsOPim24LblzLMGw51lyseTstLKbM9sMeCR7jh1g7DlzG7c1N3IMDHgOMCduuJ1jdpsXqMXgRnoDM2Mbbi3yN/I/GP45UA/WUkyUFoMbOQzGPAcOg7UwQ7SkHcCrxfDOMQNjmQPHE2fOTiuWnHHOGOSXhIP4/CJ3u/mZ4ZsD1Yn90skbP3wok5MDhpjhgx8VeLwPjAYDDKED+NQDAfMDAgpGwSgYBaNgpAMAX9lYSuGRiRgAAAAASUVORK5CYII=","orcid":"","institution":"Fundación Santa Fe de Bogotá","correspondingAuthor":true,"prefix":"","firstName":"Andrés","middleName":"Felipe","lastName":"Bejarano-Ramírez","suffix":""},{"id":609682404,"identity":"d7698e6f-1576-49f2-baba-38bf69b70da6","order_by":2,"name":"Luisa Figueredo","email":"","orcid":"","institution":"New York University","correspondingAuthor":false,"prefix":"","firstName":"Luisa","middleName":"","lastName":"Figueredo","suffix":""},{"id":609682408,"identity":"b6a9fe3b-fa85-44d2-b986-c8315a3f08ed","order_by":3,"name":"Sebastián Dueñas-Hernandez","email":"","orcid":"","institution":"Universidad de Los Andes","correspondingAuthor":false,"prefix":"","firstName":"Sebastián","middleName":"","lastName":"Dueñas-Hernandez","suffix":""},{"id":609682409,"identity":"b006a8eb-f222-4550-8b63-1fa26d3befb1","order_by":4,"name":"David Uscategui-Lopez","email":"","orcid":"","institution":"Universidad de Los Andes","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Uscategui-Lopez","suffix":""},{"id":609682413,"identity":"97340ad1-916a-4a79-92d9-f66d35d18494","order_by":5,"name":"Jenny Perilla","email":"","orcid":"","institution":"Fundación Santa Fe de Bogotá","correspondingAuthor":false,"prefix":"","firstName":"Jenny","middleName":"","lastName":"Perilla","suffix":""},{"id":609682420,"identity":"a03bb403-b162-4c86-97c6-be4cfadf63c6","order_by":6,"name":"Oscar Martinez","email":"","orcid":"","institution":"Fundación Santa Fe de Bogotá","correspondingAuthor":false,"prefix":"","firstName":"Oscar","middleName":"","lastName":"Martinez","suffix":""},{"id":609682421,"identity":"7c4f77f0-7f91-4cba-966c-e09f0cda79e5","order_by":7,"name":"Claudia Niño","email":"","orcid":"","institution":"Fundación Santa Fe de Bogotá","correspondingAuthor":false,"prefix":"","firstName":"Claudia","middleName":"","lastName":"Niño","suffix":""}],"badges":[],"createdAt":"2026-03-04 23:23:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9034232/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9034232/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105291210,"identity":"5a83f660-39ed-43e0-b179-ac595351b412","added_by":"auto","created_at":"2026-03-24 12:21:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":45539,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of NPY values among patients who underwent surgical intervention for subarachnoid hemorrhage secondary to cerebral aneurysm rupture vs. controls\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9034232/v1/68336652bf66dcc8c40227b2.png"},{"id":105291209,"identity":"26f7a1e3-0bf3-4a15-a0ef-065a315d6b74","added_by":"auto","created_at":"2026-03-24 12:21:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":48677,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of CGRP values among patients who underwent surgical intervention for subarachnoid hemorrhage secondary to cerebral aneurysm rupture vs. controls\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9034232/v1/d05e8a7defea19a280baa532.png"},{"id":105291211,"identity":"29db7fdc-f65a-4247-9435-7a574e8e1597","added_by":"auto","created_at":"2026-03-24 12:21:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":146247,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of variables (CGRP and NPY values), case group (a) and control group (b). Figure 3 shows the correlation between variables in both the case and control groups. In the case group, a positive correlation was observed between NPY levels and age, indicating that higher NPY values were associated with older age in patients with subarachnoid hemorrhage (SAH) due to aneurysmal rupture. However, this was a weak correlation (Rho = 0.36) and was not statistically significant (p = 0.08). Additionally, a negative correlation was identified between NPY and CGRP values; that is, higher levels of NPY were associated with lower levels of CGRP. Nevertheless, this correlation was also weak (Rho = –0.33) and lacked statistical significance (p = 0.1). In the control group, a negative correlation was found between CGRP and NPY values; as NPY levels increased, CGRP levels decreased. This correlation was moderate to strong (Rho = –0.6) and statistically significant (p = 0.001).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9034232/v1/d61b289605b892556da22144.png"},{"id":109138929,"identity":"d6f8b505-e5ef-4b8f-9fba-c4bea40da638","added_by":"auto","created_at":"2026-05-13 01:56:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":619933,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9034232/v1/545fcacd-10fe-4670-a3f5-2efcda34e7e3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Importance of Early Intervention in Ruptured Cerebral Aneurysm: Biochemical and Pathophysiological Foundations Within the First 24 Hours","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSubarachnoid hemorrhage (SAH) is defined as a complex, multifactorial neurological syndrome characterized by the sudden extravasation of high-pressure arterial blood into the subarachnoid space, with potential extension into the brain parenchyma and ventricles [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. SAH can be classified as traumatic (being the most common form of presentation) however, the focus of this article is on non-traumatic SAH of aneurysmal origin [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It is the third most common subtype of stroke and poses a significant clinical challenge due to its high mortality rates, reported to range between 32% and 67%, although some authors have described mortality between 37% and 44%. It most commonly affects individuals with a mean age of 55 years [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The rupture of a cerebral aneurysm accounts for approximately 85% of SAH cases and may lead to delayed cerebral ischemia in up to 30% of these patients, with a pre-hospital mortality rate as high as 10% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The risk of aneurysm rupture is influenced by several factors, including female sex, age\u0026thinsp;\u0026ge;\u0026thinsp;60 years, and aneurysm size\u0026thinsp;\u0026ge;\u0026thinsp;5 millimeters [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe leading cause of non-traumatic SAH is the rupture of an intracranial aneurysm, an event that can trigger cerebral vasospasm in 20\u0026ndash;30% of cases. Among these, approximately 50% will develop cerebral infarction, and between 15% and 20% will experience permanent neurological deficits, significantly impacting quality of life, reducing productivity, and substantially increasing healthcare costs. Vasospasm is also the primary cause of death and long-term neurological disability among survivors [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The pathophysiology of vasospasm is complex and multifactorial, involving alterations in perivascular innervation, including dysfunction of neuropeptides such as calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), and substance P. Although the exact mechanisms underlying this ischemic event have not been fully elucidated, proposed contributors include denervation, vascular hypersensitivity, and decreased levels of vasoactive substances such as catecholamines and neuropeptides [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, elevated levels of NPY have been associated with cerebral vasospasm following aneurysmal SAH. Conversely, CGRP has been identified as one of the principal regulators of cerebral vascular tone, with a protective effect against severe vasoconstriction through its ability to induce relaxation of cerebral arteries [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aims to anticipate the pathophysiological events that occur during the first 24 hours following a subarachnoid hemorrhage by measuring the levels of the neuropeptides neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP). Both peptides are part of the perivascular innervation and play a regulatory role in cerebral vascular tone, independent of endothelial integrity which is often disrupted in the context of hemorrhage. Since cerebrospinal fluid (CSF) circulates through the basal cisterns and directly bathes the intracranial vessels, its analysis is proposed as an indirect method to assess intracranial neuropeptide levels during the acute phase of the hemorrhagic event [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. To date, no studies have reported the collection of CSF samples obtained directly from the basal cisterns for the measurement of NPY and CGRP in patients with subarachnoid hemorrhage within the first 24 hours.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eA prospective observational analytical study was conducted using a 1:1 case-control design, including a total of 23 cases and 23 controls. Data collection was carried out over a one-year period at a high-complexity hospital in Bogot\u0026aacute;, Colombia, and included patients who required cranial surgical intervention.\u003c/p\u003e\n\u003cp\u003eCases were defined as patients between 18 and 80 years of age with a clinically and radiologically confirmed diagnosis of subarachnoid hemorrhage (SAH) secondary to aneurysmal rupture, from whom cerebrospinal fluid (CSF) samples were obtained from the basal cisterns during the surgical procedure. Controls consisted of patients within the same age range who were scheduled for posterior fossa tumor surgery or elective aneurysm clipping due to incidental findings, with no evidence of SAH. During the selection period, patients who did not meet the inclusion criteria or who met any exclusion criteria were excluded from the study (Table 1).\u003c/p\u003e\n\u003cp\u003eAll collected samples were analyzed using enzyme-linked immunosorbent assay (ELISA), employing the Human NPY (Neuropeptide Y) ELISA Kit (E-EL-H1893, Elabscience) and the Human CGRP1 (Calcitonin Gene-Related Peptide 1) ELISA Kit (E-EL-H0619, Elabscience), in order to identify and quantify the presence of the neuropeptides NPY and CGRP in cerebrospinal fluid (CSF). Samples were obtained intraoperatively, directly from the basal cisterns. Following collection, they were placed in sterile vials, temporarily stored in a portable refrigerator at \u0026ndash;24\u0026deg;C, and subsequently frozen at \u0026ndash;70\u0026deg;C for preservation.\u003c/p\u003e\n\u003cp\u003eAfter one year, all samples from the 23 SAH patients and the 23 controls with incidental aneurysms were processed. Additionally, a review of medical records was conducted to collect relevant clinical variables, including age, sex, Hunt-Hess grade at admission, presence of vasospasm, past medical history, and Glasgow Coma Scale score at hospital discharge. For quantitative analysis, the samples were randomized and assessed in a blinded manner by the analyst. Six patients were excluded due to incomplete data, multiple measurements, or loss of biological material.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData Collection\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were identified through the neurosurgery service database, and all clinical cases meeting the inclusion criteria were selected. Subsequently, controls were chosen from the same database, and a 1:1 randomization process was conducted, assigning one control for each case. Medical records of these patients were reviewed to extract data on age, sex, NPY and CGRP levels, surgical indication, type of surgical intervention, Hunt-Hess grade, presence of vasospasm, relevant medical history, and Glasgow Coma Scale score.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"589\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eInclusion criteria\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eExclusion criteria\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"194\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 194px;\"\u003e\n \u003cp\u003ePatients over 18 years of age.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"6\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"202\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 202px;\"\u003e\n \u003cp\u003ePatients under 18 years of age.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"6\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003ePatients with clinically and radiologically confirmed subarachnoid hemorrhage who have no contraindications to cerebrospinal fluid or arterial blood sampling during hospitalization.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003ePatients who do not require ventricular drainage.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003ePatients undergoing posterior fossa tumor surgery or elective clipping of incidentally discovered, unruptured aneurysms, without contraindications to cerebrospinal fluid or arterial blood sampling.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 310px;\"\u003e\n \u003cp\u003ePatients with contraindications to cerebrospinal fluid sampling; those with chronic inflammatory or immunomodulatory diseases; subarachnoid hemorrhage associated with trauma, arteriovenous malformations, or dural arteriovenous fistulas.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTable 1.\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cem\u003eInclusion and exclusion criteria\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eObjective\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe objective of this study is to analyze and correlate the levels of neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) in patients who experienced subarachnoid hemorrhage.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical Analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using IBM SPSS version 25 and Jamovi version 2.3.28.0. Student\u0026rsquo;s t-tests and chi-square tests were used to compare the distribution of continuous and categorical variables, respectively, between cases and controls, as well as within clinical variable subgroups. In instances of non-normal distribution, the Shapiro-Wilk test and Fisher\u0026rsquo;s exact test were employed for comparing medians of continuous and categorical variables, respectively. The Mann-Whitney U test was used to assess the relationship between CGRP and NPY levels across both comparator groups (cases and controls).\u003c/p\u003e\n\u003cp\u003eA descriptive analysis was also conducted for the following variables: age, day of admission, Hunt-Hess grade, presence and onset day of vasospasm, Glasgow Coma Scale at discharge, aneurysm location, type of treatment, site of sample collection, embolization, history of arterial hypertension, and whether the aneurysm was an incidental finding. CGRP and NPY levels were analyzed separately for each group.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn the case group, the mean age for both sexes was 57 \u0026plusmn; 13.4 years. A history of arterial hypertension was present in 60.1% of patients. All participants (100%) were diagnosed with subarachnoid hemorrhage secondary to ruptured cerebral aneurysm. Cerebrospinal fluid (CSF) samples for NPY and CGRP1 quantification were collected from the cisterns in all cases: 60% (14 patients) from the cerebral cisterns, 34.8% (8 patients) from the ventricles, and 4.3% (1 patient) from a spinal catheter.\u003c/p\u003e\n\u003cp\u003eThe Hunt-Hess scale classification revealed that 30.4% of patients (7 cases) were in grade IV (stupor, moderate to severe hemiparesis, possible decerebrate rigidity, or other neurological abnormalities). Vasospasm was documented in 80% of patients (20 cases) with ruptured aneurysms.\u003c/p\u003e\n\u003cp\u003eUpon admission, Glasgow Coma Scale (GCS) scores were most frequently 3 points in 39% of patients (9 cases), followed by a score of 15 in 34.8% of cases (8 patients). In this study, the most commonly identified cerebral aneurysm location was the anterior communicating artery, present in 26% of cases (6 patients), with a 1:1 male-to-female ratio. Aneurysms of the right middle cerebral artery were observed in 13% (3 patients), followed by aneurysms in the left carotid artery, right posterior communicating artery, and left middle cerebral artery, each accounting for 8.7% of cases.\u003c/p\u003e\n\u003cp\u003eSurgical clipping was performed in 79.6% of patients (16 cases), while 30.4% (7 patients) underwent ventriculostomy. Two patients (8.7%) with Hunt-Hess grades IV and V underwent endovascular embolization (Table 2).\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"589\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 589px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCASES\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e23 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e9 (39.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e14 (60.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAGE (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e57 (13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e57.9 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e56.4 (12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eADMISSION DAY (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e3.3 (6.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e2.4 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e3.86 (7.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHUNT HESS (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e5 (21.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e2 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e3 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e6 (26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e2 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e4 (66.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e4 (17.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e3 (75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e7 (30.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e2 (28.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e5(71.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVASOSPASM (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eYES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e20 (87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e8 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e12 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e3 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e2 (66.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVASOSPASM DAY (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1.9 (1.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1.8 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1.9 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePOST-SURGICAL VASOSPASM DAY (%)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e3 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e2 (66.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e11 (47.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e5 (45.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e6 (54.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e4 (17.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e3 (75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e3 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e2 (66.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGLASGOW outcome (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e9 (39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e5 (55.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e4 (44.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e3 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e3 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e8 (34.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e3 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e5 (62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTREATMENT (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eClipping of aneurysm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e16 (79.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e6 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e10 (62.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eVentriculostomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e7 (30.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e3 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e4 (57.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSITE OF ANEURISM (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eLeft carotid artery\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e2 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003ePosterior communicating artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eAnterior communicating artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e6 (26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e3 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e3 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eMiddle cerebral artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eLeft communicating artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eLeft superior hypophyseal artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eLeft posterior communicating artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eRight ophthalmic artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eUnspecified communicating artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eRight posterior communicating artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e2 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eRight middle cerebral artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e3 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e2 (66.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eLeft middle cerebral artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eRight carotid artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSAMPLE SITE (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eVentricle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e8 (34.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e4 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e4 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eCistern\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e14 (60.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e5 (35.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e9 (64.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eSpinal catheterd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEMBOLIZATION (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eYES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e1 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e21 (91.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e8 (38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e13 (62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHIGH BLOOD PRESSURE (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eYES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e14 (60.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e6 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e8 (57.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 143px;\"\u003e\n \u003cp\u003e9 (39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e3 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 99px;\"\u003e\n \u003cp\u003e6 (66.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTable 2.\u003c/em\u003e\u003c/strong\u003e Characteristics of the \u0026ldquo;case\u0026rdquo; group population undergoing surgical intervention for subarachnoid hemorrhage secondary to aneurysmal rupture\u003c/p\u003e\n\u003cp\u003eIn the control group, the mean age for both sexes was 56.3 \u0026plusmn; 12.4 years. All patients (100%) underwent surgical intervention by the neurosurgery service due to incidental findings of cerebral aneurysms. During the surgical procedures, cerebrospinal fluid (CSF) samples were obtained from the basal cisterns to determine levels of NPY and CGRP1.\u003c/p\u003e\n\u003cp\u003eSurgical treatment was performed in 26.1% of cases for anterior communicating artery aneurysms, followed by 17.4% for aneurysms of the middle cerebral artery (unspecified laterality), and 8.7% for left middle cerebral artery aneurysms. The most frequent treatment in the control group was aneurysm clipping, performed in 78.2% (18 patients), and CSF sampling in this group was conducted during aneurysm clipping.\u003c/p\u003e\n\u003cp\u003eAdditionally, 8.7% of patients (2 cases) and 4.3% (1 case) underwent sampling during a right temporal craniotomy for a middle fossa tumor. In 4.3% of cases, the sample was obtained via lumbar puncture, and another 4.3% during endoscopic ventricular access (Table 3).\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"476\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 476px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCONTROLS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e8 (34.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e15 (65.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAGE (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e56.3 (12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e58.7 (13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e54.9 (12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSITE OF ANEURISM (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003ePosterior fossa tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eRight mesial glial tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eAneurysm of the middle cerebral artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e4 (17.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e4(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eCerebellar tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eAneurysm of the anterior communicating artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e6 (26.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e4(66.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2(33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eAneurysm of the posterior communicating artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eMeningioma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eColloid cyst of the third ventricle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eAneurysm of the left middle cerebral artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e2(8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eAneurysm of an unspecified carotid artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eSecular aneurysm of the right pericallosal artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eAneurysm of the right middle cerebral artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e3 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2 (66.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eINCIDENTAL FINDING (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eYES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e9(39.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e4(44.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e5(55.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e13(60.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e5(38.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e8 (61.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTREATMENT (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003ePosterior fossa craniotomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eRight temporal craniotomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eClipping of aneurysm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e18(78.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e7(38.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e11 (61.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eLumbar puncture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 260px;\"\u003e\n \u003cp\u003eSeptostomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTable 3.\u003c/em\u003e\u003c/strong\u003e Characteristics of the \u0026ldquo;control\u0026rdquo; group population undergoing surgical intervention for subarachnoid hemorrhage secondary to causes other than aneurysmal rupture\u003c/p\u003e\n\u003cp\u003eFor the case group, 23 NPY samples were obtained, with a median value of 796 (P25 = 94, P75 = 903), and a median CGRP1 value of 35.5 (P25 = 38.8, P75 = 61.9). In the control group, 23 samples were also collected, with NPY showing a median value of 210 (P25 = 49, P75 = 901), and CGRP1 a median of 66.5 (P25 = 11.4, P75 = 88). Although the case group exhibited higher NPY values, as illustrated in Figure 1, the difference between the two groups was not statistically significant (p = 0.62).\u003c/p\u003e\n\u003cp\u003eAs shown in Figure 2, CGRP values tended to be higher in the control group compared to the aneurysm rupture group; however, this difference was also not statistically significant (p = 0.39).\u003c/p\u003e\n\u003cp\u003eFAs illustrated in Figure 3, CGRP initially peaks in response, but as NPY levels increase, CGRP levels decline. One hypothesis is that NPY may inhibit CGRP, thereby impairing its vasodilatory counterregulatory effect. Regarding age, an inverse relationship was observed: as age increases, CGRP levels decrease, suggesting reduced counterregulation in older patients and, consequently, a worse prognosis due to this intrinsic neuropeptidergic mechanism. Additionally, a negative correlation between NPY and CGRP levels was confirmed in the control group, showing a moderate-to-strong inverse association with statistical significance (Rho = \u0026ndash;0.6; p = 0.001).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eSubarachnoid hemorrhage (SAH) is the third most common subtype of stroke, with a mean age of onset around 55 years [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The rupture of a cerebral aneurysm accounts for approximately 85% of SAH cases [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In the acute phase of this event, the involvement of various neuropeptides that modulate the neurovascular response has been identified. Among these, neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) stand out due to their pathophysiological roles in regulatory and counter-regulatory hemodynamic mechanisms, particularly at the level of vascular smooth muscle [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The present study analyzed the levels of NPY and CGRP in cerebrospinal fluid and the basal cisterns collected intraoperatively from patients with aneurysmal SAH compared to controls.\u003c/p\u003e \u003cp\u003eOur understanding of the pathophysiology of cerebral vasospasm following SAH has advanced significantly in recent decades. It is now recognized that the phenomenon is not solely dependent on intraluminal alterations, but also involves inflammatory and neurovascular processes within the perivascular environment [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In this context, endothelial dysfunction plays a key role by disrupting nitric oxide production and increasing the permeability of the blood-brain barrier [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This process facilitates calcium influx into vascular smooth muscle cells, triggering sustained contraction and contributing to vasoconstriction [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Furthermore, endothelial injury promotes microthrombus formation, platelet dysfunction, and glycocalyx degradation, all of which exacerbate the vasospastic response [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeuropeptide Y (NPY), discovered in 1982, is a 36-amino acid peptide found in perivascular innervation as well as in central regions such as the arcuate nucleus of the hypothalamus [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. It is co-released with neurotransmitters including norepinephrine, acetylcholine, vasoactive intestinal peptide (VIP), neurokinin A, and substance P; however, NPY has been shown to be the most potent vasoconstrictor among them [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Its vasopressor action in the context of SAH is considered part of the acute neurogenic response to subarachnoid bleeding. Moreover, due to its involvement in multiple physiological processes, NPY has been proposed as a potential target for therapeutic modulation in vascular dysfunction settings, including SAH [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConversely, CGRP is a neurosensory neuropeptide composed of 37 amino acids, with two known isoforms: αCGRP and βCGRP. αCGRP is the predominant form in the central nervous system and is localized in cerebral vasculature and enteric nerves [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Unlike NPY, CGRP functions as a potent vasodilator, exerting protective effects against ischemia and hypoxia. Its release has been proposed as part of a counter-regulatory response during acute cerebrovascular events such as SAH, aiming to counteract the vasoconstrictive effects of neuropeptides like NPY [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. This duality between the two peptides suggests a vascular regulatory axis that may hold diagnostic and therapeutic implications in the early course of subarachnoid hemorrhage.\u003c/p\u003e \u003cp\u003eIn the literature, correlations between the levels of these peptides and various pathologies have been described; however, studies in humans remain limited. In patients with arterial hypertension (HTN), serum NPY concentrations have been found to be higher in individuals with hypertension secondary to overweight and obesity compared to those with primary hypertension. Moreover, a positive correlation has been observed between NPY levels and elevated body mass index (BMI) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the known vascular effects of CGRP, there is no consensus regarding its role in individuals with primary arterial hypertension, primarily due to heterogeneous findings in plasma-level studies [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In murine models, it has been observed that animals with hypertension exhibit an increased number of CGRP receptors, as well as a higher receptor-binding ratio. CGRP receptors are considered key cerebrovascular effectors in chronic hypertension, mediated through the regulation of RAMP2, suggesting that their role may be more organ-protective than counterregulatory toward hypertension itself [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In cardiovascular disease, elevated CGRP levels have also been found in autopsy specimens from patients who died of acute myocardial infarction, supporting the hypothesis that both ischemic and hypoxemic cardiovascular events trigger a compensatory response mediated by CGRP [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the present study, an increase in NPY levels was observed in patients with aneurysmal SAH (median 796, P25\u0026thinsp;=\u0026thinsp;94, P75\u0026thinsp;=\u0026thinsp;903) compared to controls (median 210, P25\u0026thinsp;=\u0026thinsp;49, P75\u0026thinsp;=\u0026thinsp;901), although the difference did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.62). However, a statistically significant positive correlation was found between NPY levels and Hunt-Hess score (Rho\u0026thinsp;=\u0026thinsp;0.4, p\u0026thinsp;=\u0026thinsp;0.001). This finding suggests that elevated NPY levels may be associated with greater clinical severity in SAH patients, potentially due to its role in vasoconstriction and the development of vasospasm. This aligns with existing literature showing that increased CSF NPY levels are associated with cerebral vasospasm, with a persistent elevation beginning on the second day after SAH onset in patients who develop vasospasm, compared to those who do not [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The origin of the sample may also influence the measurement and predictive value of NPY levels for vasospasm, as serum NPY concentrations have not demonstrated correlation with cerebral vasospasm [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Although the strength of the correlation found in this study was moderate, the hypothesis that this association may become more robust with a larger sample size should be considered in future research.\u003c/p\u003e \u003cp\u003eConversely, CGRP levels tended to be higher in the control group (median 66.5, P25\u0026thinsp;=\u0026thinsp;11.4, P75\u0026thinsp;=\u0026thinsp;88) compared to the aneurysmal SAH group (median 35.5, P25\u0026thinsp;=\u0026thinsp;38.8, P75\u0026thinsp;=\u0026thinsp;61.9), although this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.39). This finding is consistent with previous studies that have identified CGRP as a key vasodilator involved in the regulation of cerebral vascular tone and protection against vasospasm following SAH [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The trend toward lower CGRP levels in the aneurysmal SAH group may suggest an insufficient compensatory response to elevated NPY levels in these patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA negative correlation between NPY and CGRP levels was observed in both groups, although with differing magnitudes. In the case group, the correlation was weak and not statistically significant (Rho = \u0026minus;\u0026thinsp;0.33, p\u0026thinsp;=\u0026thinsp;0.1), whereas in the control group, a statistically significant negative correlation was found between CGRP and NPY levels (Rho = \u0026minus;\u0026thinsp;0.6, p\u0026thinsp;=\u0026thinsp;0.001), indicating that as NPY levels increased, CGRP levels decreased. This inverse relationship suggests a potential reciprocal regulatory mechanism between the two neuropeptides under physiological conditions. Given that NPY is involved in modulating the stress response, appetite regulation, and cardiovascular homeostasis, and that CGRP acts as a vasodilator and plays a key role in inflammatory and nociceptive processes, the correlation between these peptides may reflect a neurovascular and neuroimmune balance characteristic of healthy individuals. However, in the context of aneurysmal SAH, this regulatory mechanism may become disrupted, leading to an imbalance in the neurovascular unit that contributes to the development of vasospasm.\u003c/p\u003e \u003cp\u003eAdditionally, a relationship was found between NPY levels and age in patients with aneurysmal SAH. Although a positive correlation was observed (Rho\u0026thinsp;=\u0026thinsp;0.36), it was weak and not statistically significant (p\u0026thinsp;=\u0026thinsp;0.08). Nevertheless, these findings are consistent with the literature, which suggests that vascular reactivity may be influenced by age, with a possible decline in vasodilatory responsiveness (typically mediated by CGRP) leading to increased susceptibility to vasospasm in older patients [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHunt-Hess grade IV scores and the presence of vasospasm in 80% of cases reinforce the hypothesis that elevated NPY levels may be involved in the neurological deterioration of these patients, potentially triggering delayed cerebral ischemia via vasospasm. As previously discussed, endothelial dysfunction and platelet-derived growth factors play key roles in the physiology of vasospasm. These changes begin with alterations to endothelial components and the vascular wall, initially leading to vasospasm, which may worsen over time. Therefore, early surgical intervention (ideally within the first 24 hours) is crucial to secure the aneurysm. This urgency is supported by the observed trend toward increased NPY levels and impaired CGRP response, particularly in hypertensive and elderly patients, as well as by the early inhibitory effect of NPY on CGRP activity. These pathophysiological mechanisms support the rationale for early surgical management [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, no statistically significant association was found between these clinical factors and neuropeptide levels, suggesting that additional mechanisms (such as inflammation and oxidative stress) may also contribute to clinical outcomes in these patients.\u003c/p\u003e \u003cp\u003eAmong the limitations of this study, the small sample size stands out, which may have limited the ability to detect statistically significant differences. Additionally, variability in the site of sample collection (cisterns, ventricles, and spinal catheter) may have influenced the measured levels of NPY and CGRP, given the potential heterogeneity in the distribution of these neuropeptides within the central nervous system. Nonetheless, CSF samples were collected within the first 24 hours, the critical window during which perivascular peptide fluctuations are known to occur.\u003c/p\u003e \u003cp\u003eThis study provides evidence supporting the potential role of NPY and CGRP in the pathophysiology of aneurysmal subarachnoid hemorrhage (SAH), suggesting a neurovascular unit imbalance in these patients. Although NPY levels were higher in the aneurysmal SAH group and CGRP showed a negative correlation with NPY in controls, these findings did not reach statistical significance. This underscores the need for larger sample sizes and longitudinal analyses to better understand the role of these neuropeptides in vascular wall dynamics and the progression of cerebral vasospasm.\u003c/p\u003e \u003cp\u003eIt is proposed that early sampling of cerebrospinal fluid from the basal cisterns in surgically treated patients could serve as a future predictive test for vasospasm within the first 24 hours, particularly due to the significantly elevated NPY levels observed in female patients over the age of 60. While CGRP did not demonstrate statistical significance, a decreasing trend with age was noted in patients with aneurysmal SAH, which may facilitate greater reactivity and allow NPY to exert its vasoconstrictive effect during the critical early phase of the hemorrhagic event [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors Contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJ.A.M. and A.F.B.R. conceived the study and contributed to the methodological design. J.A.M., A.F.B.R., J.P., O.M., and C.N. contributed to data acquisition and intraoperative sample collection. D.U.L. and S.D.H. supported database organization and data curation. A.F.B.R., J.A.M., and L.F. performed the analysis and interpretation of the results. J.A.M., A.F.B.R., D.U.L., and S.D.H. prepared the final version of the manuscript. All authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDeclarations\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone of the interventions presented required procedures beyond those already established in the standard protocol for the management of subarachnoid hemorrhage.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical trial number:\u003c/em\u003e\u003c/strong\u003e not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTrial registration:\u003c/em\u003e\u003c/strong\u003e not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and complied with all applicable institutional, national, and international guidelines and regulations for research involving human subjects. The study protocol was reviewed and approved by the Institutional Review Board (IRB) of the Hospital Universitario Fundaci\u0026oacute;n Santa Fe de Bogot\u0026aacute;, under communication CCEI-11935-2020 dated May 19, 2020.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent to participate:\u003c/em\u003e\u003c/strong\u003e Written informed consent to participate was obtained from all participants or their legally authorized representatives.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding:\u003c/em\u003e\u003c/strong\u003e This research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests:\u003c/em\u003e\u003c/strong\u003e The authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ede Oliveira Manoel AL, Goffi A, Marotta TR, Schweizer TA, Abrahamson S, Macdonald RL. 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Available from: https://www-tandfonline-com.ezproxy.uniandes.edu.co/doi/abs/10.1179/1743132813Y.0000000246\u003c/li\u003e\n\u003cli\u003eRomoli M, Giammello F, Mosconi MG, De Mase A, De Marco G, Digiovanni A, et al. Immunological Profile of Vasospasm after Subarachnoid Hemorrhage. Int J Mol Sci [Internet]. 2023 May 1 [cited 2025 May 27];24(10):8856. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10218712/\u003c/li\u003e\n\u003cli\u003eGao SQ, Shi JJ, Xue-Wang, Miao SH, Li T, Gao CC, et al. Endothelial NOX4 aggravates eNOS uncoupling by decreasing dihydrofolate reductase after subarachnoid hemorrhage. Free Radic Biol Med [Internet]. 2022 Nov 20 [cited 2025 May 27];193:499\u0026ndash;510. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0891584922009492?via%3Dihub\u003c/li\u003e\n\u003cli\u003eLenz IJ, Plesnila N, Terpolilli NA. Role of endothelial nitric oxide synthase for early brain injury after subarachnoid hemorrhage in mice. 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Available from: http://www.scielo.org.mx/scielo.php?script=sci_arttext\u0026amp;pid=S1665-11462008000600007\u0026amp;lng=es\u0026amp;nrm=iso\u0026amp;tlng=es\u003c/li\u003e\n\u003cli\u003eAshina M. Migraine. Ropper AH, editor. New England Journal of Medicine [Internet]. 2020 Nov 5 [cited 2025 Feb 25];383(19):1866\u0026ndash;76. Available from: https://www.nejm.org/doi/pdf/10.1056/NEJMra1915327\u003c/li\u003e\n\u003cli\u003eBale R, Doshi G. Cross talk about the role of Neuropeptide Y in CNS disorders and diseases. Neuropeptides. 2023 Dec 1;102:102388. \u003c/li\u003e\n\u003cli\u003eHay DL, Walker CS. CGRP and its receptors. Headache: The Journal of Head and Face Pain [Internet]. 2017 Apr 1 [cited 2025 Feb 15];57(4):625\u0026ndash;36. Available from: https://onlinelibrary-wiley-com.ezproxy.uniandes.edu.co/doi/full/10.1111/head.13064\u003c/li\u003e\n\u003cli\u003eJuul R, Edvinsson L, Fredriksen TA, Ekman R, Brubakk AO, Gisvold SE. 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High plasma levels of neuropeptide y correlate with good clinical outcome but are not correlated to cerebral blood flow or vasospasm after subarachnoid hemorrhage. J Neurosurg Anesthesiol [Internet]. 2016 Jan 1 [cited 2025 Feb 25];28(1):65\u0026ndash;70. Available from: https://journals.lww.com/jnsa/fulltext/2016/01000/high_plasma_levels_of_neuropeptide_y_correlate.10.aspx\u003c/li\u003e\n\u003cli\u003eMacdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nature Reviews Neurology 2014 10:1 [Internet]. 2013 Dec 10 [cited 2025 Feb 15];10(1):44\u0026ndash;58. Available from: https://www.nature.com/articles/nrneurol.2013.246\u003c/li\u003e\n\u003cli\u003eXu S, Zhang W, Zhang Y, Xu Z, Wu T. Efficacy and Prognosis of Adjuvant Argatroban Treatment in Acute Ischemic Stroke Patients with Early Neurological Deterioration. Discov Med. 2023;35(175):185. \u003c/li\u003e\n\u003cli\u003eJabbarli R, Pierscianek D, Darkwah Oppong M, Sato T, Dammann P, Wrede KH, et al. 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Available from: https://openurl-ebsco-com.ezproxy.uniandes.edu.co/contentitem/doi:10.1007/s10143-018-1037-y?sid=ebsco:plink:crawler\u0026amp;id=ebsco:doi:10.1007/s10143-018-1037-y\u0026amp;crl=c\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-9034232/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9034232/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003eSevere vasospasm in cases of subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysms accounts for a high mortality rate ranging from 36% to 67%, as well as permanent neurological deficits. Biochemical changes involving neuropeptides such as Neuropeptide Y (NPY) and Calcitonin Gene-Related Peptide (CGRP) have been studied as regulators of vascular tone and protectors of cerebral perfusion. These peptides may become imbalanced during subarachnoid hemorrhage (SAH).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This is an analytical descriptive case-control study with a 1:1 ratio, comparing patients diagnosed with subarachnoid hemorrhage secondary to ruptured aneurysms to those with incidental, unruptured aneurysms. A total of 46 patients were included, distributed equally into two groups: 23 in the case group and 23 in the control group. Cerebrospinal fluid (CSF) samples were collected from all participants during surgery, directly from the cerebral cisterns, ventricles, and through spinal catheters. The objective of this study was to analyze and correlate the levels of NPY and CGRP between patients with aneurysmal SAH and those with unruptured aneurysms.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eA similarity in mean age was observed between both groups: cases = 57 ± 13.4 years vs. controls = 56.3 ± 12.4 years. Regarding NPY and CGRP values, the control group showed a median NPY level of 796 (P25 = 94, P75 = 903) versus 210 (P25 = 49, P75 = 901) in the aneurysmal rupture group. Although there was a trend toward increased NPY levels in the rupture group, the difference was not statistically significant (p = 0.62). For CGRP, the median level was 35.5 (P25 = 38.8, P75 = 61.9) in the control group versus 66.5 (P25 = 11.4, P75 = 88) in the case group, also without statistical significance (p = 0.39). In the control group, a negative correlation was found between NPY and CGRP levels, with a strong inverse relationship and statistical significance (Rho = –0.6; p = 0.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e In this study, we analyzed the levels of neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) in cerebrospinal fluid (CSF) collected from the basal cisterns, ventricles, and a spinal catheter in patients with subarachnoid hemorrhage (SAH) secondary to aneurysmal rupture, comparing them to patients without rupture. Although we observed a trend toward higher NPY levels in the rupture group, supporting the notion of early aneurysm intervention within the first 24 hours to prevent the development of vasospasm, and also noted differences in CGRP levels, these findings were not statistically significant. These results suggest that while these neuropeptides may play a role in vascular tone regulation and the pathophysiology of cerebral vasospasm, their specific function appears to be disrupted, representing one of the mechanisms of SAH that remains incompletely understood. Further studies with larger sample sizes and designs better suited to assessing the causal relationship between these biomarkers and clinical outcomes are required.\u003c/p\u003e","manuscriptTitle":"The Importance of Early Intervention in Ruptured Cerebral Aneurysm: Biochemical and Pathophysiological Foundations Within the First 24 Hours","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-24 12:21:36","doi":"10.21203/rs.3.rs-9034232/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2e97c9f5-3db0-4a72-94d1-166291ede603","owner":[],"postedDate":"March 24th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-13T01:51:26+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-13T01:55:38+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-24 12:21:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9034232","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9034232","identity":"rs-9034232","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}