Subarachnoid Hemorrhage Research Articles

Elucidation of pathophysiology of intracranial aneurysms based on metagenome analyses of oral bacteria

When intracranial aneurysms occur in arteries, this can lead to weakening of the arterial wall and subarachnoid haemorrhage, which can result in death. Intracranial aneurysms can’t be diagnosed without cerebrovascular imaging tests and there are few clues to indicate their presence. Neurosurgeon Assistant Professor Hirokazu Koseki, Department of Neurosurgery, The Jikei University School of Medicine, Japan, is looking for novel ways to predict the presence of intracranial aneurysms before they rupture. He is investigating the role of oral bacteria, which have been associated with cerebral haemorrhage and dementia, in order to clarify the relationship between oral bacteria and aneurysms. In unprecedented work, he and the team want to map this relationship based on severity of periodontal disease and will utilise metagenomic analysis of saliva to identify the bacterial strains that might contribute to the neuropathology. They will also take samples from the walls of the aneurysms to precisely decipher which bacterial strains can be directly associated with them. The work will enable researchers to establish simple and inexpensive targeted treatment for intracranial aneurysms and is also anticipated to have knock-on effects, being used for the screening of inherent risk factors for the occurrence of intracranial aneurysms. Although there are known risk factors, patients without any of the risk factors can still develop intracranial aneurysms or subarachnoid haemorrhages. Building on existing research that points to association between oral microbiology and neuropathology, Koseki is working to identify further risk factors that might help in diagnosing intracranial aneurysms in patients.

Hospital and one-year outcomes following a hypertensive urgency or emergency: a major challenge

Abstract Introduction Hypertension is an important issue, and recommendations are constantly evolving based on the latest research findings and directions. Hypertensive emergencies are defined as a severe elevation of blood pressure associated with organ damage. End organ damage was defined as the presence of one of the following findings: encephalopathy, ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, acute heart failure, acute coronary syndrome, or aortic dissection. Furthermore, malignant hypertension is a HE characterized by small artery fibrinoid necrosis in the kidney, retina and brain. All these definitions are confusing, but what about their evolution? Objective:The present study aims to analyze the mortality in the short and long term (12months), the survival of the hypertensive patients, the frequency of malignant hypertension and hypertensive retinopathy. Methods For this purpose, we conducted a prospective study including all patients who followed or were diagnosed with hypertension and admitted to the emergency department for hypertensive urgency/emergency, from January to March 2023; after that, we studied the evolution of these patients for one year until January 2024. Demographic data, disease history, blood pressure, clinical presentation on admission, target organ involvement, ophthalmological examination and evolution during hospitalization were studied. Statistical analysis was performed using SPSS software. Preeclampsia and chronic renal failure were excluded.Result: Our work brought together 300 patients, mainly female, with an average age of 63.4. One hundred fifteen were admitted for HE and 185 for HU. The most common presenting symptoms at admission were headache, focal neurologic deficit and dyspnea. Malignant hypertension was identified in 9 patients based on optical coherence tomography angiography by identifying subclinical microvascular damage, and investigation is still in progress searching for hypertensive retinopathy grade III-IV Keith-Wagner in the second group. Patients were mainly hospitalized for hypertensive emergencies. Regarding their therapeutic management, except for the acute lowering of blood pressure in stroke, there was no consensus initially; ideally was to determine which organs are affected to assess the need for specific intervention other than lowering blood pressure. Overall, 49 had died from HE n=44/115(vs n=5/185 for HU). Of these, 33 have died at the Hospital (mortality was higher for HE and attributable to neurovascular emergencies rather than cardiovascular emergencies) and ten at 12 months. Conclusion Properly managing patients who come to the Emergency Department for BP elevation faces many difficulties. Can we still talk about hypertensive emergencies/urgency, discuss retinal lesions, and the importance of hypertension monitoring? However, all those definitions can be potentially life-threatening; these results justify better follow-up and treatment for these patients.

Spinal subarachnoid hematoma involving a thoracic ventral dural defect: illustrative case.

Spinal subarachnoid hematoma of unknown origin is rare. Superficial siderosis has been associated with chronic bleeding from spinal dural defects; however, the relationship between these defects and spinal subarachnoid hematoma remains unclear. A 32-year-old woman presenting with severe back pain and leg weakness exhibited an extensive thoracic spinal hematoma with spinal cord compression on magnetic resonance imaging. Emergency surgery was performed, which revealed a ventral subarachnoid hematoma that was evacuated. A ventral dural defect at the hematoma site and venous bleeding from the surrounding area were observed. Hemostasis was achieved and the defect closed. After surgery, her neurological symptoms quickly resolved. Postoperative spinal angiography showed no vascular lesions. Like superficial siderosis, ventral spinal subarachnoid hematoma can be caused by a spinal dural defect. https://thejns.org/doi/10.3171/CASE24435.

Role of clipping in aneurysmal subarachnoid hemorrhage: a post hoc analysis of the Earlydrain trial

The choice between clipping and coiling of ruptured cerebral aneurysms in subarachnoid hemorrhage (SAH) remains controversial. The recently published Earlydrain trial provides the opportunity to analyze the latest clip-to-coil ratio in German-speaking countries and to evaluate vasospasm incidence and explorative outcome measures in both treatment modalities. We performed a post hoc analysis of the Earlydrain trial, a multicenter randomized controlled trial investigating the use of an additional lumbar drain in aneurysmal SAH. The decision whether to clip or to coil the ruptured aneurysm was left to the discretion of the participating centers, providing a real-world insight into current aneurysm treatment strategies. Earlydrain was performed in 19 centers in Germany, Switzerland, and Canada, recruiting 287 patients with aneurysmal SAH of all severity grades. Of these, 140 patients (49%) received clipping and 147 patients (51%) coiling. Age and clinical severity based on Hunt-Hess/WFNS grades and radiological criteria were similar. Clipping was more frequently used for anterior circulation aneurysms (55%), whereas posterior circulation aneurysms were mostly coiled (86%, p < 0.001). In high-volume recruiting centers, 56% of patients were treated with clipping, compared to 38% in other centers. A per-year analysis showed a stable and balanced clipping/coiling ratio over time. Regarding vasospasm, 60% of clipped versus 43% of coiled patients showed elevated transcranial Doppler criteria (p = 0.007), reflected in angiographic vasospasm rates (51% vs. 38%, p = 0.03). In contrast to the Earlydrain main results establishing the superiority of an additional lumbar drain, explorative outcomes after clipping and coiling measured by secondary infarctions, mortality, modified Rankin Score, Glasgow Outcome Scale Extended, or Barthel-Index showed no significant differences after discharge and at six months. In clinical practice, aneurysm clipping is still a frequently used method in aneurysmal SAH. Apart from a higher rate of vasospasm in the clipping group, an exploratory outcome analysis showed no difference between the two treatment methods. Further development of periprocedural treatment modalities for clipped ruptured aneurysms to reduce vasospasm is warranted.

Stem Cells Treatment for Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) refers to bleeding in the subarachnoid space, which is a serious neurologic emergency. However, the treatment effects of SAH are limited. In recent years, stem cell (SC) therapy has gradually become a very promising therapeutic method and advanced scientific research area for SAH. The SCs used for SAH treatment are mainly bone marrow mesenchymal stem cells (BMSCs), umbilical cord mesenchymal stem cells (hUC-MSCs), dental pulp stem cells (DPSCs), neural stem cells (NSCs)/neural progenitor cell (NPC), and endothelial progenitor cell (EPC). The mechanisms mainly included differentiation and migration of SCs for tissue repair; alleviating neuronal apoptosis; anti-inflammatory effects; and blood-brain barrier (BBB) protection. The dosage of SCs was generally 106 orders of magnitude. The administration methods included intravenous injection, nasal, occipital foramen magnum, and intraventricular administration. The administration time is generally 1 hour after SAH modeling, but it may be as late as 24 hours or 6 days. Existing studies have confirmed the neuroprotective effect of SCs in the treatment of SAH. SC has great potential application value in SAH treatment, a few case reports have provided support for this. However, the relevant research is still insufficient and there is still a lack of clinical research on the SC treatment for SAH to further evaluate the effectiveness and safety before it can go from experiment to clinical application.

Time to Treatment and Outcomes of Hemorrhagic Stroke, Comparing Patients Entering Surgery before and after 120 Minutes Upon Arrival at the Emergency Department Pattani Hospital

Background: The duration between a patient’s hospital arrival and the point at which they enter surgery for hemorrhagic stroke affects survival, length of stay, health care costs, and outcome (Glasgow Outcome Scale). Therefore, a study to explore the effects of time on these outcomes is warranted. Objective: To compare treatment outcomes of patients with hemorrhagic stroke having entered surgery before and after 120 minutes upon arrival at the emergency department. Materials and Methods: A therapeutic and interventional study with a retrospective observational cohort design at Pattani Hospital in patients with hemorrhagic stroke who received treatment between October 2018 and April 2023. A retrospective review of medical records, which collected clinical characteristics and the time to treatment. Glasgow Outcome Scale was evaluated at 72 hours, two weeks, one month, and date of hospital discharge. Length of stay, health care costs, and survival status at date of hospital discharge were analyzed. Comparative analysis was performed by Fisher’s exact probability test and t-test, and prognostic analysis was performed by risk ratio. Results: Of all the patients in the present study, 49 and 182 received treatment before and after 120 minutes, respectively, upon arrival at the emergency department. Clinical characteristics of gender, age, underlying conditions, regular medications, and level of consciousness were not significantly different between the two groups. Patients who entered surgery within 120 minutes of arrival had more occurrences of basal ganglia hemorrhage compared with those who received surgery thereafter. Furthermore, patients who received surgery within 120 minutes had a 11.4% increased chance of survival. The number needed to treat (NNT) hemorrhagic stroke patients with a time to treatment of under 120 minutes is 9. However, there was an associated increase in complications, health care cost, and length of stay. The Glasgow Outcome Scale improvement was greater only in the two-week follow-up period. These results were similar when subarachnoid hemorrhage and anticoagulating medication used were excluded. Conclusion: Patients with hemorrhagic stroke who receive early surgical treatment have lower mortality rates. Adequate provision of personnel and facilities for delivering prompt care should be made available. Measures should be taken to reduce the complications of patients who receive surgical treatment after 120 minutes upon arrival at the emergency department.

Frictional forces in stent retriever procedures: The impact of vessel diameter, angulation, and deployment position.

Mechanical thrombectomy has improved the outcome of patients with acute ischemic stroke, but complications such as subarachnoid hemorrhage (SAH) can worsen the prognosis. This study investigates the frictional forces exerted by stent retrievers (SRs) on vessel walls, hypothesizing that these forces contribute to vascular stress and a risk of hemorrhage. We aimed to understand how vessel diameter, curvature, and stent deployment position influence these forces. Using a silicone vascular model simulating the middle cerebral artery, we created virtual vessels with diameters of 2.0 mm and 2.5 mm, each with branching angles of 60° and 120°. A Trevo NXT (4 × 28 mm) SR was deployed and retracted through these models, measuring the maximum static frictional force at the moment the SR began to move. The stent deployment position relative to the curvature (straight, distal 1/4, center, and proximal 1/4) was also varied to assess its impact on frictional forces. Each condition was tested 15 times, and the results were statistically analyzed. The highest frictional force was observed in the 2.0 mm/120° model, followed by the 2.0 mm/60°, 2.5 mm/120°, and 2.5 mm/60° models. Narrower and more sharply curved vessels exhibited significantly higher frictional forces. Friction also increased with more distal stent deployment, particularly in the narrower vessels. Smaller vessel diameters, greater curvature, and more distal stent deployment positions increase frictional forces during thrombectomy, potentially leading to SAH. These findings highlight the importance of selecting appropriately sized SRs and considering stent deployment positions to minimize vascular stress.

Association of serum lipidomic profiles with risk of intracranial aneurysm: A Mendelian randomization study.

A two-sample Mendelian randomization (MR) analysis was utilized to assess the causal relationship between lipidomic profiles and the risk of intracranial aneurysms (IAs). Genetic variants related to lipidomic profiles (227 components) and IA [IA, aneurysmal subarachnoid hemorrhage (aSAH) only, unruptured IA (uIA) only] were obtained from published genome-wide association studies (GWASs) or the IEU Open GWAS project and used as instrumental variables for MR analysis. The inverse-variance weighted method was used in the primary analyses to derive causality estimates and was expressed as odds ratio (OR) with 95% confidence interval (CI). Of these 227 lipidomic profiles, only genetically predicted high levels of cholesterol to total lipids ratio in very small very-low-density lipoproteins (VLDL) [OR = 0.629 (95% CI, 0.504-0.786)], cholesteryl esters to total lipids ratio in very small VLDL [OR = 0.637 (95% CI, 0.509-0.797)], ratio of docosahexaenoic acid to total fatty acids [OR = 0.691 (95% CI, 0.582-0.820)], and ratio of polyunsaturated fatty acids to monounsaturated fatty acids [OR = 0.630 (95% CI, 0.522-0.760)] reduced the risk of aSAH, whereas genetically predicted high ratio of monounsaturated fatty acids to total fatty acids [OR = 1.471 (95% CI, 1.215-1.781)] increased the risk of aSAH. Moreover, genetically predicted high levels of cholesterol to total lipids ratio in very small VLDL [OR = 0.657 (95% CI, 0.542-0.798)], cholesteryl esters to total lipids ratio in very small VLDL [OR = 0.663 (95% CI, 0.548-0.803)], free cholesterol to total lipids ratio in small VLDL [OR = 0.682 (95% CI, 0.560-0.832)], phospholipids to total lipids ratio in small VLDL [OR = 0.674 (95% CI, 0.548-0.830)], and ratio of polyunsaturated fatty acids to monounsaturated fatty acids [OR = 0.678 (95% CI, 0.569-0.808)] reduced the risk of IA. The results of multivariable MR demonstrated that these causal associations persisted after adjusting for systolic blood pressure and cigarettes smoked per day. The effect of serum lipids on IA and aSAH may be mainly caused by subclasses of lipids such as VLDL.

Vasospasm management: a meta-synthesis of current modalities used by different medical societies

Background: Cerebral vasospasm is a life-threatening complication of an aneurysmal subarachnoid hemorrhage (aSAH), with approximately 6 to 10 cases per 100,000 patients yearly. Despite the publication of numerous guidelines from various medical societies, there is a lack of standardized consensus on what the optimal management strategies for this severe complication truly are. This meta-synthesis aims to synthesize these endorsed recommendations to ultimately identify standardized care guidelines and improve patient outcomes after aSAH. Methods: A comprehensive database search of existing guidelines published by major medical societies in the past 10 years was performed. Results: The analysis included 28 relevant documents from 7 major medical societies. Key findings included: 1) Unanimous endorsement for oral nimodipine administration for 21 days post-aSAH. 2) Varying recommendations for alternative calcium channel blockers and hemodynamic management methods. 3) Targeted hypermagnesemia and routine statin therapy were not universally recommended due to insufficient evidence. 4) Use of antifibrinolytics was considered on a case-by-case basis. 5) Endovascular interventions were recommended for refractory cases, specifically. Conclusion: This meta-synthesis reveals consistencies and divergences in vasospasm management recommendations across medical societies, highlighting the need for more robust clinical trials, regular guideline updates, and increased medical society collaboration. Keywords: Vasospasm, cerebral vasospasm, aSAH, management, guidelines, meta-synthesis

Trajectory of mean platelet volume changes after aneurysmal subarachnoid hemorrhage in patients with or without delayed cerebral ischemia

The morbidity of aneurysmal subarachnoid hemorrhage (aSAH) remains high, particularly because of secondary cerebral lesions that significantly aggravate the primary lesions. The main type of secondary lesions is delayed cerebral ischemia (DCI), in which platelets (PLT) appear to play a key role. Mean platelet volume (MPV) is an indirect marker of platelet activation. We aimed to determine the individual trajectories of MPV over time in patients with and without DCI during the course of aSAH. This is a single-center, retrospective, longitudinal analysis of individual trajectories of MPV over time, in a cohort of aSAH patients included in the Prospective, Observational Registry of Patient with Subarachnoid Hemorrhage in Neurocritical Care Unit (ProReSHA). A mixed-effects linear regression model was used to compare the trajectories of MPV and MPV/PLT ratio between patients who developed a DCI and those who did not. A total of 3634 MPV values were collected in 587 patients. The analysis of MPV as a function of DCI occurrence showed a significant difference in the trajectory over time between patients with DCI and those without, with an estimate of 0.02 (95%CI 0.01, 0.04, p = 0.009). The analysis of the MPV/PLT ratio as a function of DCI occurrence and other covariates showed a significant difference in the trajectory over time only for patients with a modified Fisher score less than 3, with an estimate of -0.59 (95%CI: -0.94, -0.23, p = 0.001). The individual trajectories of MPV over time differ between patients with DCI and those without. However, MPV values vary greatly over time and between patients. Thus it does not appear as a reliable biomarker for stratifying patients based on their specific risk of developing DCI. ClinicalTrials.gov identifier: (NCT02890004), registered in August 2016.

Identifying Patients at Increased Risk for Poor Outcomes Among Poor-Grade Aneurysmal Subarachnoid Hemorrhage Patients: The IPOGRO Risk Model

Background: A subarachnoid hemorrhage due to an aneurysmal rupture (aSAH) is a serious condition with severe neurological consequences. The World Federation of Neurosurgical Societies (WFNS) classification is a reliable predictor of death and long-term disability in patients with aSAH. Poor-grade neurological conditions on admission in aSAH (PG-aSAH) are often linked to high mortality rates and unfavorable outcomes. However, more than one-third of patients with PG-aSAH may recover and have good functional outcomes if aggressive treatment is provided. We developed a risk model called Identifying POor GRade Outcomes (IPOGRO) to predict 6-month mRS outcomes in PG-aSAH patients as a secondary analysis of a previously published study. Methods: All consecutive patients in poor-grade neurological conditions (WFNS IV-V) admitted to our institute from 2010 to 2020 due to aSAH were considered. Clinical and neuroradiological parameters were employed in the univariable analysis to evaluate the relationship with a 6-month modified Rankin Scale (mRS). Then, a multivariable multinomial regression model was performed to predict 6-month outcomes. Results: 149 patients with PG-aSAH were included. Most patients were surgically treated, with only 33.6% being endovascularly treated. The 6-month mRS score was significantly associated with clinical parameters on admission, such as lowered Glasgow Coma Scale (GCS), leukocytosis, hyperglycemia, raised Systolic Blood Pressure (SBP), greater Simplified Acute Physiology Score (SAPS II score), increased initial serum Lactic Acid (LA) levels, and the need for Norepinephrine (NE) administration. Neuroradiological parameters on the initial CT scan showed a significant association with a worsening 6-month mRS. The IPOGRO risk model analysis showed an association between a WFNS V on admission and a poor outcome (mRS 4-5), while raised SBP was associated with mortality. Conclusions: Our IPOGRO risk model indicates that PG-aSAH patients with higher SBP at admission had an increased risk of death at 6-month follow-up, whereas patients with WFNS grade V at admission had an increased risk of poor outcome but not mortality.

Development and Validation of a Prechiasmatic Mouse Model of Subarachnoid Hemorrhage to Measure Long-Term Cognitive Deficits.

Controllable and reproducible animal models of aneurysmal subarachnoid hemorrhage (SAH) are crucial for the systematic study of the pathophysiology and treatment of this debilitating condition. However, current animal models have not been successful in replicating the pathology and disabilities seen in SAH patients, especially the long-term neurocognitive deficits that affect the survivor's quality of life. Therefore, there is an unmet need to develop experimental models that reliably replicate the long-term clinical ramifications of SAH - especially in mice where genetic manipulations are straightforward and readily available. To address this need, a standardized mouse SAH model is developed that reproducibly produced significant and trackable long-term cognitive deficits. SAH is induced by performing double blood injections into the prechiasmatic cistern - a simple modification to the well-characterized single prechiasmatic injection mouse model of SAH. Following SAH, mice recapitulated key characteristics of SAH patients, including cerebral edema measured by MRI - an indicator of early brain injury (EBI), neuroinflammation, apoptosis, and long-term cognitive impairment.This newly developed SAH mouse model is considered an ideal paradigm for investigating the complex SAH pathophysiology and identifying novel druggable therapeutic targets for treating SAH severity and SAH-associated long-term neurocognitive deficits in patients.

Clinical Development of the GluN2B-selective NMDA Receptor Inhibitor NP10679 for the Treatment of Neurologic Deficit after Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) may be associated with cerebral vasospasm, which can lead to delayed cerebral ischemia, infarction, and worsened functional outcomes. The delayed nature of cerebral ischemia secondary to SAH-related vasculopathy presents a window of opportunity for the evaluation of well-tolerated neuroprotective agents administered soon after ictus. Secondary ischemic injury in SAH is associated with increased extracellular glutamate, which can overactivate NMDA receptors (NMDARs), thereby triggering NMDAR-mediated cellular damage. In this study, we have evaluated the effect of the pH-sensitive GluN2B-selective NMDAR inhibitor, NP10679, on neurologic impairment after SAH. This compound demonstrates a selective increase in potency at the acidic extracellular pH levels that occur in the setting of ischemia. We found that NP10679 produced durable improvement of behavioral deficits in a well-characterized murine model of SAH, and these effects were greater than those produced by nimodipine alone, the current standard of care. In addition, we observed an unexpected reduction in SAH-induced luminal narrowing of the middle cerebral artery. Neither nimodipine nor NP10679 alter each other's pharmacokinetic profile, suggesting no obvious drug-drug interactions. Based on allometric scaling of both toxicological and efficacy data, the therapeutic margin in man should be at least 2. These results further demonstrate the utility of pH-dependent neuroprotective agents and GluN2B-selective NMDAR inhibitors as potential therapeutic strategies for the treatment of aSAH. Significance Statement This report describes the properties and utility of the GluN2B-selective pH-sensitive NMDA receptor inhibitor, NP10679, in a well-characterized rodent model of subarachnoid hemorrhage. We show that the administration of NP10679 improves long-term neurological function following subarachnoid hemorrhage, and that in rats there are no drug-drug interactions between NP10679 and nimodipine, the standard of care for this indication.

A review of intracranial aneurysm imaging modalities, from CT to state-of-the-art MR.

Traditional guidance for intracranial aneurysm (IA) management is dichotomized by rupture status. Fundamental to ruptured aneurysm management is the detection and treatment of subarachnoid hemorrhage, along with securing the aneurysm by the safest technique. On the other hand, unruptured aneurysms first require a careful assessment of natural history versus treatment risk, including an imaging assessment of aneurysm size, location, and morphology, along with additional evidence-based risk factors such as smoking, hypertension, and family history. Unfortunately, a large proportion of ruptured aneurysms are in the lower risk size category (<7mm), putting a premium on discovering a more refined non-invasive biomarker to detect and stratify aneurysm instability prior to rupture. In this review of aneurysm work-up, we cover the gamut of established imaging modalities (e.g., CT, CTA, DSA, FLAIR, 3D-TOF-MRA, CE-MRA) as well as more novel MR techniques (MR-VWI, DCE-MRI, CFD). Additionally, we evaluate the current landscape of AI software and their integration into diagnostic and risk stratification pipelines for IAs. These advanced MR techniques, increasingly complemented with AI models, offer a paradigm shift by evaluating factors beyond size and morphology, including vessel wall inflammation, permeability, and hemodynamics. Additionally, we provide our institution's scan parameters for many of these modalities as reference. Ultimately, this review provides an organized, up-to-date summary on the array of available modalities/sequences for IA imaging to help build protocols focused on IA characterization.ABBREVIATIONS: IA = intracranial aneurysm; LP = lumbar puncture; UIA = unruptured intracranial aneurysm; VWI = vessel wall imaging; 3DRA = 3D Rotational Angiography.

Significant individual variation in cardiac-cycle-linked cerebrospinal fluid production following subarachnoid hemorrhage

BackgroundSpontaneous subarachnoid hemorrhage (SAH) often results in altered cerebrospinal fluid (CSF) flow and secondary hydrocephalus, yet the mechanisms behind these phenomena remain poorly understood. This study aimed to elucidate the impact of SAH on individual CSF flow patterns and their association with secondary hydrocephalus.MethodsIn patients who had experienced SAH, changes in CSF flow were assessed using cardiac-gated phase-contrast magnetic resonance imaging (PC-MRI) at the Sylvian aqueduct and cranio-cervical junction (CCJ). Within these regions of interest, volumetric CSF flow was determined for every pixel and net CSF flow volume and direction calculated. The presence of acute or chronic hydrocephalus was deemed from ventriculomegaly and need of CSF diversion. For comparison, we included healthy subjects and patients examined for different CSF diseases.ResultsTwenty-four SAH patients were enrolled, revealing a heterogeneous array of CSF flow alterations at the Sylvian aqueduct. The cardiac-cycle-linked CSF net flow in Sylvian aqueduct differed from the traditional figures of ventricular CSF production about 0.30–0.40 mL/min. In 15 out of 24 patients (62.5%), net CSF flow was retrograde from the fourth to the third and lateral ventricles, while it was upward at the cranio-cervical junction in 2 out of 2 patients (100%). The diverse CSF flow metrics did not distinguish between individuals with acute or chronic secondary hydrocephalus. In comparison, 4/4 healthy subjects showed antegrade net CSF flow in the Sylvian aqueduct and net upward CSF flow in CCJ. These net CSF flow measures also showed interindividual variability among other patients with CSF diseases.ConclusionsThere is considerable inter-individual variation in net CSF flow rates following SAH. Net CSF flow in the Sylvian aqueduct differs markedly from the traditional ventricular CSF production rates of 0.30–0.40 mL/min in SAH patients, but less so in healthy subjects. Furthermore, the cardiac-cycle-linked net CSF flow rates in Sylvian aqueduct and CCJ suggest an important role of extra-ventricular CSF production.

Door-in-Door-Out Times at Referring Hospitals and Outcomes from Hemorrhagic Stroke

Interhospital transfer is often required in the care of patients with hemorrhagic stroke. Guidelines recommend a door-in-door-out (DIDO) time of ≤120 minutes at the transferring emergency department (ED); however, it is unknown whether DIDO times are related to clinical outcomes of hemorrhagic stroke. Retrospective, observational cohort study using US registry data from Get With The Guidelines-Stroke participating hospitals. Patients include those aged ≥18 years with intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) who were transferred from the ED to a Get With The Guidelines participating receiving hospital from January 1, 2019, to July 31, 2022. The primary outcome was ordinal discharge modified Rankin scale (mRS) score and secondary outcomes included dichotomous discharge mRS, ability to ambulate independently at discharge, and inhospital mortality at the receiving hospital. In all, 19,708 ICH and 7,757 patients with SAH were included. For patients with ICH, an increasing DIDO time was associated with greater odds of mRS 0 to 3 versus 4 to 6 at discharge in the unadjusted analyses (DIDO 91 to 180 minutes, odds ratio [OR] 1.15 [1.04 to 1.27]; DIDO 181 to 270 minutes, OR 1.51 [1.33, 1.71]; DIDO >270 minutes, OR 1.83 [1.58, 2.11]; versus DIDO ≤90 minutes). In the adjusted analyses, no associations were observed. Similar results were seen for mRS at discharge in patients with SAH. In both patients with ICH and SAH, longer DIDO times were associated with greater odds of independent ambulation at discharge and lower odds of inhospital mortality in the unadjusted analyses. After adjustment, the effect sizes of these associations were reduced, with some of the results based on quartiles becoming statistically nonsignificant. These findings suggest that EDs currently expedite the transfer of the sickest patients; however, prospective studies and more granular data are needed to understand the impact of early treatment and timing of transfer for patients with hemorrhagic stroke.

Association between estimated pulse wave velocity and the risk of mortality in patients with subarachnoid hemorrhage: a retrospective cohort study based on the MIMIC database

BackgroundThe estimated pulse wave velocity (ePWV) is a recently developed, simple and useful tool to measure arterial stiffness and to predict long-term cardiovascular mortality. However, the association of ePWV with mortality risk in patients with subarachnoid hemorrhage (SAH) is unclear. Herein, this study aims to assess the potential prediction value of ePWV on short- and long-term mortality of SAH patients.MethodsData of adult patients with no traumatic SAH were extracted from the Medical Information Mart for Intensive Care (MIMIC) III and IV database in this retrospective cohort study. Weighted univariate and multivariable Cox regression analyses were used to explore the associations of ePWV levels with 30-day mortality and 1-year mortality in SAH patients. The evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). In addition, subgroup analyses of age, the sequential organ failure assessment (SOFA) score, surgery, atrial fibrillation (AF), renal failure (RF), hepatic diseases, chronic obstructive pulmonary disease (COPD), sepsis, hypertension, and diabetes mellitus (DM) were also performed.ResultsAmong 1,481 eligible patients, 339 died within 30 days and 435 died within 1 year. After adjusting for covariates, ePWV ≥ 12.10 was associated with higher risk of both 30-day mortality (HR = 1.77, 95%CI: 1.17–2.67) and 1-year mortality (HR = 1.97, 95%CI: 1.36–2.85), compared to ePWV < 10.12. The receiver operator characteristic (ROC) curves showed that compared to single SOFA score, ePWV combined with SOFA score had a relative superior predictive performance on both 30-day mortality and 1-year mortality, with the area under the curves (AUCs) of 0.740 vs. 0.664 and 0.754 vs. 0.658. This positive relationship between ePWV and mortality risk was also found in age ≥ 65 years old, SOFA score < 2, non-surgery, non-hepatic diseases, non-COPD, non-hypertension, non-DM, and sepsis subgroups.ConclusionBaseline ePWV level may have potential prediction value on short- and long-term mortality in SAH patients. However, the application of ePWV in SAH prognosis needs further clarification.

Essential thrombocythemia complicated by multivessel intracranial dolichoectasia with subarachnoid hemorrhage and recurrent cerebral infarction

BackgroundPatients with essential thrombocythemia (ET) can develop systemic thrombotic and hemorrhagic vascular complications due to increased and dysfunctional platelets.Case presentationWe encountered a 49-year-old Japanese woman with a history of essential ET, cerebral infarction, hypertension, and hyperlipidemia. She had been taking anagrelide (2.5 mg/day) and aspirin (100 mg/day) and had vomited at home. At the time of admission to our hospital, she was in a deep stupor. We thought these symptoms were caused by intracranial hypertension. Head computed tomography showed severe subarachnoid hemorrhage (SAH) at the interhemispheric fissure, hematoma at the corpus callosum, and intraventricular hemorrhages. Digital subtraction angiography demonstrated multiple dilated, stenotic, tortuous intracranial arteries, and a dissecting aneurysm at the right anterior cerebral artery (ACA). The dissecting aneurysm measured 7.7 × 15.5 mm, and a bleb was observed. Our diagnosis was ruptured ACA dissecting aneurysm and diffuse intracranial arterial dolichoectasia (DIADE). We performed stent-assisted coil embolization of the aneurysm. She remained apathetic and manifested unilateral apraxia and alien limb syndrome due to a partial callosal disconnection. Two months thereafter her symptoms gradually improved, her consciousness level and limb function improved, and her modified Rankin scale (mRS) score was 2. However, when we tapered her antiplatelet therapy, she again developed an acute cerebral infarct.ConclusionsThis is the first presentation of a patient with ET complicated by DIADE, both of which can result in ischemic and hemorrhagic vascular complications including SAH. As antithrombotic therapy in patients with DIADE and ET may be associated with higher hemorrhage rates, its effects must be monitored carefully.

Electroencephalographic monitoring in detection and prediction of delayed cerebral ischemia due to non-traumatic subarachnoid hemorrhage

Intensive care of patients with acute non-traumatic subarachnoid hemorrhage primarily relies on diagnostics of delayed cerebral ischemia (DCI). The major difficulty in detecting DCI emerges upon suppression of wakefulness, when clinical assessment of growing neurological deficit becomes complicated. Widely used transcranial dopplerography allows solely to verify a vasospasm development not always leading to DCI exhibiting a multifactorial underlying mechanism. Electroencephalography (EEG) is the only broadly available instrumental tool ensuring a continuous monitoring of cerebral functional status including in subjects at intensive care unit. To date, non-specific EEG parameters pointing at development of acute cerebral injury were identified that provide varying diagnostic and predictive informative value in DCI. We reviewed publications aimed at assessing the data on visual and quantitative EEG parameters such as regional slowing, alpha rhythm spectral power and relative variability, alpha-to-delta power ratio, and detection of epileptiform activity. Having searched international and Russia-wide medical databases, we found only 7 publications quantitatively assessing diagnostic value of EEG monitoring, which showed that for DCI diagnosis its sensitivity ranged from 76% to 100%, and specificity – from 54% to 100%. We also present a clinical case with a 70-year-old female patient who underwent surgery for non-traumatic subarachnoid hemorrhage due to a ruptured aneurysm of the communicating segment of the right internal carotid artery. During the continuous videoEEG monitoring 2 days before clinical deterioration and appearance of ischemic changes in the right cerebral hemisphere on computed tomography scans, an ictal-interictal continuum pattern was noted to emerge. Future studies should be aimed at clarifying and validating the most informative DCI biomarkers including while recording EEG with intracranial electrodes that may contribute to development of automated algorithms for DCI detection.

Prescribed Drug Use and Aneurysmal Subarachnoid Hemorrhage Incidence: A Drug-Wide Association Study.

Prescribed Drug Use and Aneurysmal Subarachnoid Hemorrhage Incidence: A Drug-Wide Association Study.