Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.

Comparative diagnostic efficacy of cranial CT, CTA, and DSA in subarachnoid hemorrhage management: A systematic review and meta-analysis.

INTRODUCTION: Subarachnoid hemorrhage (SAH) is a critical medical condition associated with high morbidity and mortality rates. Timely and accurate diagnosis is crucial for optimal patient outcomes. Cranial computed tomography (CT), computed tomography angiography (CTA), and digital subtraction angiography (DSA) are commonly used imaging modalities for diagnosing SAH, but their comparative diagnostic efficacy remains debated. METHODS: A systematic review and meta-analysis was conducted to evaluate the diagnostic performance of cranial CT, CTA, and DSA in identifying SAH. PubMed, Google scholar, Cochrane Library databases were searched for relevant studies published up to January 2024. Pooled sensitivity, specificity, and the summary receiver operating characteristic (SROC) curve were calculated using Review Manager 5.4. RESULTS: A total of 31 studies involving 10,287 patients were included in the analysis. The pooled sensitivity of cranial CT for detecting SAH was 94.7 % (95 % Confidence Interval, CI) with a specificity of 98.3 % (95 % CI). CTA demonstrated a pooled sensitivity of 94.1 % (95 % CI) and specificity of 93.4 % (95 % CI). DSA showed a pooled sensitivity of 87.7 % (95 % CI) and specificity of 95.8 % (95 % CI). The SROC curve demonstrated discriminatory ability for all modalities. CONCLUSION: Cranial CT, CTA, and DSA are valuable imaging modalities for diagnosing SAH, with high sensitivity and specificity. Cranial CT serves as an initial screening tool, while CTA offers superior sensitivity in detecting aneurysmal SAH. DSA remains essential in specific clinical scenarios. Further prospective studies are needed to validate these findings and refine diagnostic guidelines for SAH.

Cerebrospinal fluid volume as an early radiological factor for clinical course prediction after aneurysmal subarachnoid hemorrhage. A pilot study.

BACKGROUND: The pathological mechanisms following aneurysmal subarachnoid hemorrhage (SAH) are poorly understood. Limited clinical evidence exists on the association between cerebrospinal fluid (CSF) volume and the risk of delayed cerebral ischemia (DCI) or cerebral vasospasm (CV). In this study, we raised the hypothesis that the amount of CSF or its ratio to hemorrhage blood volume, as determined from non-contrast Computed Tomography (NCCT) images taken on admission, could be a significant predictor for CV and DCI. METHODS: The pilot study included a retrospective analysis of NCCT scans of 49 SAH patients taken shortly after an aneurysm rupture (33 males, 16 females, mean age 56.4 ± 15 years). The SynthStrip and Slicer3D software tools were used to extract radiological factors - CSF, brain, and hemorrhage volumes from the NCCT images. The "pure" CSF volume (VCSF) was estimated in the range of [-15, 15] Hounsfield units (HU). RESULTS: VCSF was negatively associated with the risk of CV occurrence (p = 0.0049) and DCI (p = 0.0069), but was not associated with patients' outcomes. The hemorrhage volume (VSAH) was positively associated with an unfavorable outcome (p = 0.0032) but was not associated with CV/DCI. The ratio VSAH/VCSF was positively associated with, both, DCI (p = 0.031) and unfavorable outcome (p = 0.002). The CSF volume normalized by the brain volume showed the highest characteristics for DCI prediction (AUC = 0.791, sensitivity = 0.80, specificity = 0.812) and CV prediction (AUC = 0.769, sensitivity = 0.812, specificity = 0.70). CONCLUSION: It was demonstrated that "pure" CSF volume retrieved from the initial NCCT images of SAH patients (including CV, Non-CV, DCI, Non-DCI groups) is a more significant predictor of DCI and CV compared to other routinely used radiological biomarkers. VCSF could be used to predict clinical course as well as to personalize the management of SAH patients. Larger multicenter clinical trials should be performed to test the added value of the proposed methodology.

ß-hydroxybutyrate alleviates neurological deficits by restoring glymphatic and inflammation after subarachnoid hemorrhage in mice.

BACKGROUND: Both glymphatic system dysfunction and inflammatory response aggravate neurological dysfunction after subarachnoid hemorrhage (SAH). Studies have shown that ß-hydroxybutyrate (BHB) may mitigate painful diabetic neuropathy (PDN) by upregulating SNTA1 expression and reinstating AQP4 polarity. However, the potential of BHB to ameliorate glymphatic system function and inflammatory response in SAH mice remains uncertain. METHODS: The SAH models were constructed by injection of arterial blood into cisterna Magana. Three groups of C57 mice were randomly assigned: Sham, SAH, and BHB. All mice were subjected to neurological function assessment, western blot, immunofluorescence double staining, and RNA-seq. Glymphatic system function was examined with tracer and immunofluorescence double staining, and the differential genes were examined with RNA-seq. In addition, the expression of related inflammation was detected. RESULTS: Compared with the SAH group, BHB reinstated AQP4 polarization by upregulating SNTA1 protein to enhance the glymphatic system. According to RNA-seq, the different genes were primarily connected to microglia activation, astrocytes, and inflammation. Western blot and immunofluorescence further confirmed that the related inflammatory protein expression levels were upregulated. BHB attenuated neuroinflammation after SAH. Ultimately, it can mitigate the neurological deficits in SAH mice. CONCLUSION: The study reveals a novel mechanism that BHB treatment mitigates neurologic impairment in SAH mice. We propose that BHB may play a neuroprotective effect by enhancing glymphatic system function and attenuating neuroinflammatory subarachnoid hemorrhage.

[Management of SAH]. / Prise en charge de la HSA.

Every year, the neurosurgical intensive care unit at Grenoble's university hospital (CHU) receives a large number of cerebrovascular patients. Data collected in the department during 2023 show that subarachnoid hemorrhage (SAH) is one of the most frequent causes of the pathologies treated. In this article, we focus on the appropriate course of action.

A Rare Intersection of Septic Cavernous Sinus Thrombosis and Subarachnoid Hemorrhage: Insights from the Case of a 70-Year-Old Patient.

We describe a rare and complex case of septic cavernous sinus thrombosis (SCST) in a 70-year-old patient who initially presented with ocular symptoms that rapidly progressed to severe intracranial vascular complications, including subarachnoid hemorrhage (SAH). Despite the use of broad-spectrum antibiotics and anticoagulants, the patient's condition deteriorated. SCST, often caused by sinus infections, presents a significant diagnostic and therapeutic dilemma, with mortality rates exceeding 20%. This report underscores the diversity of clinical presentations, ranging from mild headaches to severe cranial nerve deficits, that complicate diagnosis and treatment. The inability to detect any aneurysms in our patient using magnetic resonance imaging (MRI) and computed tomography angiography (CTA) may indicate an alternative pathogenesis. This could involve venous hypertension and endothelial hyperpermeability. This case illustrates the need for personalized treatment approaches, as recommended by the European Federation of Neurological Societies, and the importance of a multidisciplinary perspective when managing such intricate neurological conditions. Our findings contribute to the understanding of SCST coexisting with SAH.

Inhibiting RIPK1-driven neuroinflammation and neuronal apoptosis mitigates brain injury following experimental subarachnoid hemorrhage.

RIPK1, a receptor-interacting serine/threonine protein kinase, plays a crucial role in maintaining cellular and tissue homeostasis by integrating inflammatory responses and cell death signaling pathways including apoptosis and necroptosis, which have been implicated in diverse physiological and pathological processes. Suppression of RIPK1 activation is a promising strategy for restraining the pathological progression of many human diseases. Neuroinflammation and neuronal apoptosis are two pivotal factors in the pathogenesis of brain injury following subarachnoid hemorrhage (SAH). In this study, we established in vivo and in vitro models of SAH to investigate the activation of RIPK1 kinase in both microglia and neurons. We observed the correlation between RIPK1 kinase activity and microglia-mediated inflammation as well as neuronal apoptosis. We then investigated whether inhibition of RIPK1 could alleviate neuroinflammation and neuronal apoptosis following SAH, thereby reducing brain edema and ameliorating neurobehavioral deficits. Additionally, the underlying mechanisms were also explored. Our research findings revealed the activation of RIPK1 kinase in both microglia and neurons following SAH, as marked by the phosphorylation of RIPK1 at serine 166. The upregulation of p-RIPK1(S166) resulted in a significant augmentation of inflammatory cytokines and chemokines, including TNF-α, IL-6, IL-1α, CCL2, and CCL5, as well as neuronal apoptosis. The activation of RIPK1 in microglia and neurons following SAH could be effectively suppressed by administration of Nec-1 s, a specific inhibitor of RIPK1. Consequently, inhibition of RIPK1 resulted in a downregulation of inflammatory cytokines and chemokines and attenuation of neuronal apoptosis after SAH in vitro. Furthermore, the administration of Nec-1 s effectively mitigated neuroinflammation, neuronal apoptosis, brain edema, and neurobehavioral deficits in mice following SAH. Our findings suggest that inhibiting RIPK1 kinase represents a promising therapeutic strategy for mitigating brain injury after SAH by attenuating RIPK1-driven neuroinflammation and neuronal apoptosis.

Nrf-2 modulates excitability of hippocampal neurons by regulating ferroptosis and neuroinflammation after subarachnoid hemorrhage in rats.

Excitability of hippocampal neurons in subarachnoid hemorrhage (SAH) rats has not been well studied. The rat SAH model was applied in this study to explore the role of nuclear factor E2-related factor (Nrf-2) in the early brain injury of SAH. The neural excitability of CA1 pyramidal cells (PCs) in SAH rats was evaluated by using electrophysiology experiments. Ferroptosis and neuroinflammation were measured by ELISA, transmission electron microscopy and western blotting. Our results indicated that SAH induced neurological deficits, brain edema, ferroptosis, neuroinflammation and neural excitability in rats. Ferrostatin-1 treatment significantly decreased the expression and distribution of IL-1ß, IL-6, IL-10, TGF-ß and TNF-α. Inhibiting ferroptosis by ferrostatin-1 can attenuate neural excitability, neurological deficits, brain edema and neuroinflammation in SAH rats. Inhibiting the expression of Nrf-2 significantly increased the neural excitability and the levels of IL-1ß, IL-6, IL-10, TGF-ß and TNF-α in Fer-1-treated SAH rats. Taken together, inhibiting the Nrf-2 induces early brain injury, brain edema and the inflammatory response with increasing of neural excitability in Fer-1-treated SAH rats. These results have indicated that inhibiting ferroptosis, neuroinflammation and neural excitability attenuates early brain injury after SAH by regulating the Nrf-2.

Netrin-1 Alleviates Early Brain Injury by Regulating Ferroptosis via the PPARγ/Nrf2/GPX4 Signaling Pathway Following Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a type of stroke with high morbidity and mortality. Netrin-1 (NTN-1) can alleviate early brain injury (EBI) following SAH by enhancing peroxisome proliferator-activated receptor gamma (PPARγ), which is an important transcriptional factor modulating lipid metabolism. Ferroptosis is a newly discovered type of cell death related to lipid metabolism. However, the specific function of ferroptosis in NTN-1-mediated neuroprotection following SAH is still unclear. This study aimed to evaluate the neuroprotective effects and the possible molecular basis of NTN-1 in SAH-induced EBI by modulating neuronal ferroptosis using the filament perforations model of SAH in mice and the hemin-stimulated neuron injury model in HT22 cells. NTN-1 or a vehicle was administered 2 h following SAH. We examined neuronal death, brain water content, neurological score, and mortality. NTN-1 treatment led to elevated survival probability, greater survival of neurons, and increased neurological score, indicating that NTN-1-inhibited ferroptosis ameliorated neuron death in vivo/in vitro in response to SAH. Furthermore, NTN-1 treatment enhanced the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and glutathione peroxidase 4 (GPX4), which are essential regulators of ferroptosis in EBI after SAH. The findings show that NTN-1 improves neurological outcomes in mice and protects neurons from death caused by neuronal ferroptosis. Furthermore, the mechanism underlying NTN-1 neuroprotection is correlated with the inhibition of ferroptosis, attenuating cell death via the PPARγ/Nrf2/GPX4 pathway and coenzyme Q10-ferroptosis suppressor protein 1 (CoQ10-FSP1) pathway.

Initial real-world experience of clazosentan for subarachnoid hemorrhage in Japan.

BACKGROUND: Cerebral vasospasm (CVS) is one of the most critical factors associated with clinical outcomes of patients with subarachnoid hemorrhage (SAH). Clazosentan has been investigated worldwide as a prophylactic agent to prevent CVS. We evaluated a new CVS management protocol which included clazosentan. METHODS: Consecutive 138 patients with SAH, hospitalized in our institution between January 2017 and December 2022, were included in this study. Baseline characteristics, clinical findings, and operative records were analyzed retrospectively. From May 2022, 10 mg/h clazosentan was co-administered with fasudil to all patients according to the indication in the Japanese label. Patients admitted before this date received the conventional combined protocol using the fasudil hydrochloride, nicardipine, and ozagrel. RESULTS: Eighteen (13.0%) patients received the new protocol during the CVS period (defined as day 1 up to day 14 after SAH onset). There were 54 (39.1%) elderly patients aged 75 years or older. Seventy-two (52.2%) patients underwent neurosurgical clipping, whereas 55 (39.9%) patients received endovascular coiling. Among the patients with new protocol, only one patient (5.6%) had symptomatic CVS, compared with 18 patients (15.0%) in those with conventional protocol. More patients who received the new protocol had fluid retention compared with control group (38.9% [7/18] vs. 8.3% [10/120]). Other results did not differ between the two groups. CONCLUSIONS: Clinical outcomes of the new protocol were comparable to those of conventional protocol. Clazosentan may simplify anti-vasospasm treatment. Fluid retention was a specific side-effect of clazosentan, which requires attention especially in the first half of the CVS period.

Wu-zhu-yu Decoction reduces early brain injury following subarachnoid hemorrhage in vivo and in vitro by activating the Nrf2 antioxidant system via SIRT6 targeting.

ETHNOPHARMACOLOGICAL RELEVANCE: Early brain damage (EBI) following subarachnoid hemorrhage (SAH) is a long-lasting condition with a high occurrence. However, treatment options are restricted. Wu-zhu-yu Decoction (WZYD) can treat headaches and vomiting, which are similar to the early symptoms of subarachnoid hemorrhage (SAH). However, it is yet unknown if WZYD can reduce EBI following SAH and its underlying mechanisms. AIM OF THE STUDY: This study aimed to investigate whether WZYD protects against EBI following SAH by inhibiting oxidative stress through activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling via Sirtuin 6 (SIRT6)-mediated histone H3 lysine 56 (H3K56) deacetylation. MATERIALS AND METHODS: In the current investigation, the principal components of WZYD were identified using high-performance liquid chromatography-diode array detection (HPLC-DAD). The SAH model in rats using the internal carotid artery plug puncture approach and the SAH model in primary neurons using hemoglobin incubation were developed. WZYD with different doses (137 mg kg-1, 274 mg kg-1, 548 mg kg-1) and the positive drug-Nimodipine (40 mg kg-1) were intragastrically administered in SAH model rats, respectively. The PC12 cells were cultured with corresponding medicated for 24h. In our investigation, neurological scores, brain water content, Evans blue leakage, Nissl staining, TUNEL staining, oxidative stress, expression of apoptosis-related proteins, and Nrf2/HO-1 signaling were evaluated. The interaction between SIRT6 and Nrf2 was detected by co-immunoprecipitation. SIRT6 knockdown was used to confirm its role in WZYD's neuroprotection. RESULTS: The WZYD treatment dramatically reduced cerebral hemorrhage and edema, and enhanced neurological results in EBI following SAH rats. WZYD administration inhibited neuronal apoptosis via reducing the expression levels of Cleaved cysteinyl aspartate specific proteinase-3(Cleaved Caspase-3), cysteinyl aspartate specific proteinase-3(caspase-3), and Bcl-2, Associated X Protein (Bax) and increasing the expression of B-cell lymphoma-2(Bal2). It also decreased reactive oxygen species and malondialdehyde levels and increased Nrf2 and HO-1 expression in the rat brain after SAH. In vitro, WZYD attenuated hemoglobin-induced cytotoxicity, oxidative stress and apoptosis in primary neurons. Mechanistically, WZYD enhanced SIRT6 expression and H3K56 deacetylation, activated Nrf2/HO-1 signaling, and promoted the interaction between SIRT6 and Nrf2. Knockdown of SIRT6 abolished WZYD-induced neuroprotection. CONCLUSIONS: WZYD attenuates EBI after SAH by activating Nrf2/HO-1 signaling through SIRT6-mediated H3K56 deacetylation, suggesting its therapeutic potential for SAH treatment.

Inhibition of USP30 Promotes Mitophagy by Regulating Ubiquitination of MFN2 by Parkin to Attenuate Early Brain Injury After SAH.

Subarachnoid hemorrhage (SAH) is a type of stroke with a high disability and mortality rate. Apoptosis caused by massive damage to mitochondria in neuron cells and inflammatory responses caused by high extracellular ATP lead to poor outcomes. USP30 is a deubiquitinating enzyme that inhibits mitophagy, resulting in a failure to remove damaged mitochondria in a timely manner after SAH; nevertheless, the pathway through which USP30 inhibits mitophagy is unknown. This study evaluated the neuroprotective role and possible molecular basis by which inhibiting USP30 to attenuate SAH-induced EBI by promoting neuronal mitophagy. We used an in vitro model of hemoglobin exposure and an in vivo model of intravascular perforation. Increased expression of USP30 was found after SAH in vivo and in vitro, and USP30 inhibition expression in SAH mice treated with MF094 resulted in significant improvement of neurological injury and inflammatory response and mediated good outcomes, suggesting a neuroprotective effect of USP30 inhibition. In cultured neurons, inhibition of USP30 promoted ubiquitination modification of mitochondrial fusion protein 2 (MFN2) by E3 ubiquitin ligase (Parkin), separating damaged mitochondria from the healthy mitochondrial network and prompting mitophagy, causing early clearance of damaged intracellular mitochondria, and reducing the onset of apoptosis. The high extracellular ATP environment was meliorated, reversing the conversion of microglia to a pro-inflammatory phenotype and reducing inflammatory injury. USP30 inhibition had no autophagy-promoting effect on structurally and functionally sound mitochondria and did not inhibit normal intracellular ATP production. The findings suggest that USP30 inhibition has a neuroprotective effect after SAH by promoting early mitophagy after SAH to clear damaged mitochondria.

Association between a four-parameter inflammatory index and all-cause mortality in critical ill patients with non-traumatic subarachnoid hemorrhage: a retrospective analysis of the MIMIC-IV database (2012-2019).

Background: Non-traumatic subarachnoid hemorrhage (SAH), primarily due to the rupture of intracranial aneurysms, contributes significantly to the global stroke population. A novel biomarker, pan-immune-inflammation value (PIV) or called the aggregate index of systemic inflammation (AISI), linked to progression-free survival and overall survival in non-small-cell lung cancer and mortality in Coronavirus Disease 2019 (COVID-19) patients, has surfaced recently. Its role in non-traumatic SAH patients, however, remains under-researched. This study aims to determine the relationship between PIV and all-cause mortality in non-traumatic SAH patients. Methods: A retrospective analysis was conducted using data from the Medical Information Mart for Intensive Care (MIMIC-IV) database to examine the association between PIV and all-cause mortality in critically ill patients with non-traumatic SAH. PIV measurements were collected at Intensive Care Unit (ICU) admission, and several mortality measures were examined. To control for potential confounding effects, a 1:1 propensity score matching (PSM) method was applied. The optimal PIV cutoff value was identified as 1362.45 using X-tile software that is often used to calculate the optimal cut-off values in survival analysis and continuous data of medical or epidemiological research. The relationship between PIV and short- and long-term all-cause mortality was analyzed using a multivariate Cox proportional hazard regression model and Kaplan-Meier (K-M) survival curve analysis. Interaction and subgroup analyses were also carried out. Results: The study included 774 non-traumatic SAH patients. After PSM, 241 pairs of score-matched patients were generated. The Cox proportional hazard model, adjusted for potential confounders, found a high PIV (≥ 1362.45) independently associated with 90-day all-cause mortality both pre- (hazard ratio [HR]: 1.67; 95% confidence intervals (CI): 1.05-2.65; P = 0.030) and post-PSM (HR: 1.58; 95% CI: 1.14-2.67; P = 0.042). K-M survival curves revealed lower 90-day survival rates in patients with PIV ≥ 1362.45 before (31.1% vs. 16.1%%, P < 0.001) and after PSM (68.9% vs. 80.9%, P < 0.001). Similarly, elevated PIV were associated with increased risk of ICU (pre-PSM: HR: 2.10; 95% CI: 1.12-3.95; P = 0.02; post-PSM: HR: 2.33; 95% CI: 1.11-4.91; P = 0.016), in-hospital (pre-PSM: HR: 1.91; 95% CI: 1.12-3.26; P = 0.018; post-PSM: 2.06; 95% CI: 1.10-3.84; P = 0.034), 30-day (pre-PSM: HR: 1.69; 95% CI: 1.01-2.82; P = 0.045; post-PSM: 1.66; 95% CI: 1.11-2.97; P = 0.047), and 1-year (pre-PSM: HR: 1.58; 95% CI: 1.04-2.40; P = 0.032; post-PSM: 1.56; 95% CI: 1.10-2.53; P = 0.044) all-cause mortality. The K-M survival curves confirmed lower survival rates in patients with higher PIV both pre- and post PSM for ICU (pre-PSM: 18.3% vs. 8.4%, P < 0.001; post-PSM:81.7 vs. 91.3%, P < 0.001), in-hospital (pre-PSM: 25.3% vs. 12.8%, P < 0.001; post-PSM: 75.1 vs. 88.0%, P < 0.001), 30-day (pre-PSM: 24.9% vs. 11.4%, P < 0.001; post-PSM:74.7 vs. 86.3%, P < 0.001), and 1-year (pre-PSM: 36.9% vs. 20.8%, P < 0.001; P = 0.02; post-PSM: 63.1 vs. 75.1%, P < 0.001) all-cause mortality. Stratified analyses indicated that the relationship between PIV and all-cause mortality varied across different subgroups. Conclusion: In critically ill patients suffering from non-traumatic SAH, an elevated PIV upon admission correlated with a rise in all-cause mortality at various stages, including ICU, in-hospital, the 30-day, 90-day, and 1-year mortality, solidifying its position as an independent mortality risk determinant. This study represents an attempt to bridge the current knowledge gap and to provide a more nuanced understanding of the role of inflammation-based biomarkers in non-traumatic SAH. Nevertheless, to endorse the predictive value of PIV for prognosticating outcomes in non-traumatic SAH patients, additional prospective case-control studies are deemed necessary.

Hounsfield unit as a predictor of symptomatic vasospasm and hydrocephalus in good-grade subarachnoid hemorrhage treated with endovascular coiling.

Background: Patients with good-grade subarachnoid hemorrhage (SAH) often expect favorable outcomes; however, several patients may experience secondary neurological deterioration. Hydrocephalus and vasospasm are significant complications affecting SAH prognosis. We aimed to evaluate the relationship between the incidence of symptomatic vasospasm or hydrocephalus and the Hounsfield unit (HU) value of the subarachnoid space on brain computed tomography (CT) in patients with good-grade SAH treated with endovascular coiling. Methods: We conducted a retrospective analysis of consecutive initially good-grade pure SAH patients (Hunt-Hess grade I or II, modified Fisher scale I or III) with ruptured anterior circulation aneurysms treated with endovascular coiling in a single tertiary neurosurgical center between January 2010 and December 2019. The HU value within each cisterns of enrolled patients was measured, and after setting an appropriate cutoff value, it was investigated whether it could be a predictor of the occurrence of vasospasm and hydrocephalus. Results: The study included 108 eligible patients (34 males, mean age 60.88±12.26 years): 26 (24.1%) showed symptomatic vasospasm and 31 (28.7%) developed hydrocephalus. Patients with symptomatic vasospasm had a greater proportion of those with Hunt-Hess grade II (77% vs. 51%, P=0.021) and modified Fisher scale III scores (58% vs. 22%, P=0.001). The hydrocephalus group presented an older mean age (65.90 vs. 58.86 years, P=0.006) and a greater proportion of Hunt-Hess grade II (74% vs. 51%, P=0.025) and modified Fisher scale III cases (45% vs. 25%, P=0.037). The mean HU values of the Sylvian cistern (53.23 vs. 43.99, P<0.001) and basal cisterns (47.04 vs. 40.18, P=0.003) were higher in the vasospasm group. In the hydrocephalus group, only the basal cistern HU value was significantly higher (45.60 vs. 40.32, P=0.016). The area under the receiver operating characteristic (ROC) curve to determine the best cut-off HU value for the prediction of patients with symptomatic vasospasm revealed a Sylvian cistern HU value of 50.375 (sensitivity: 0.692, specificity: 0.683) and basal cistern HU value of 44.875 (sensitivity: 0.615, specificity: 0.659). Multivariable logistic analysis showed that age >70 years and Sylvian cistern HU value were independent predictors of any neurological complication at 1 year. Conclusions: The HU value of the subarachnoid space on brain CT can predict vasospasm, hydrocephalus, and long-term prognosis in good-grade SAH patients.

An In-Depth Analysis of Medullary Strokes at a Tertiary Care Stroke Center: Incidence, Clinical and Radiological Characteristics, Etiology, Treatment, and Prognosis.

Introduction Medullary infarctions (MI) are a rare medical entity that is classified mainly as the more commonly lateral medullary infarcts (LMI) and the less common medial medullary infarcts (MMI). Lateral medullary syndrome, also known as Wallenberg syndrome, results when the medulla oblongata is affected and predominantly occurs secondary to atherosclerotic occlusion of the vertebrobasilar arteries. Previous studies have focused more on the anatomical, clinical, and topographical aspects of medullary infarcts. We describe the incidence of their presentation, radiological findings, etiology, treatment, and outcome at our comprehensive stroke center. Material and method This is a retrospective cohort study of 108 medullary stroke patients with confirmed clinical and radiological diagnoses of MI at Hamad General Hospital, Doha, between January 1, 2018 and December 31, 2020. We evaluated the electronic medical records of all stroke patients. Result During the selected period, a total of 2,912 ischemic strokes were reported. Of these, 843 (28.8%) were posterior circulation strokes. Only 108 (3.7%) patients had medullary strokes. Commonly encountered neurological features were dizziness (94.4%), limb ataxia (84.3%), dysarthria (44.4%), ipsilateral facial sensory loss (32.4%), headache (32.4%), contralateral limb sensory loss (25%), ipsilateral hemiparesis (24%), dysphagia (19.4%), and hiccups (13%). Most strokes reported were either minor (73% with National Institutes of Health Stroke Scale [NIHSS] 1-4) or moderate (26% with NIHSS 5-15). LMIs (87.9%) were the most common, followed by medial paramedian MI (10%). Twenty-five percent had extramedullary involvement, predominantly of the cerebellum (17.6%). Out of the total number of patients, 44 (40.7%) had large vessel atherosclerotic disease, followed by 41 (37.6%) whose stroke was due to small vessel disease, 15 (13.8 %) due to undetermined etiology, and 6 (5.5%) due to arterial dissection. Twenty-eight patients (25.4%) underwent 48-hour Holter monitoring, which detected atrial fibrillation in two patients (1.85%). The majority of patients (98.2%, or 106 patients) received antiplatelet therapy, while 68.5% (74 patients) received single antiplatelet therapy (SAPT), and 29.6% (32 patients) received dual antiplatelet therapy (DAPT). Noteworthy is that only 2.7% (three patients) received thrombolysis as an acute reperfusion therapy. Forty-seven percent (51 patients) were discharged home (mRS 0-2), and 51.9% (56 patients) were transferred to rehabilitation facilities. Follow-up assessments were performed at the stroke clinic for 57.4% (62) of the patients. The assessments found that 46 of the follow-up patients were functionally independent at that time (mRS 0-2). Conclusion This is the first large local study of medullary strokes to determine their frequency, presentation, etiology, treatment, and clinical outcome. Medullary strokes represent 3.7% of total ischemic strokes at our comprehensive stroke center. MI is rare and could present with a variety of neurological and non-specific symptoms that mimic common benign conditions. Prompt and early recognition with a high index of suspicion, the use of posterior NIHSS (POST-NIHSS), and urgent MRI-diffusion-weighted imaging (DWI) of the brain in acute settings can improve early diagnosis and the rate of reperfusion therapy. Further studies are needed to enable the early recognition and treatment of medullary infarcts.

StrokeNet: An automated approach for segmentation and rupture risk prediction of intracranial aneurysm.

Intracranial Aneurysms (IA) present a complex challenge for neurosurgeons as the risks associated with surgical intervention, such as Subarachnoid Hemorrhage (SAH) mortality and morbidity, may outweigh the benefits of aneurysmal occlusion in some cases. Hence, there is a critical need for developing techniques that assist physicians in assessing the risk of aneurysm rupture to determine which aneurysms require treatment. However, a reliable IA rupture risk prediction technique is currently unavailable. To address this issue, this study proposes a novel approach for aneurysm segmentation and multidisciplinary rupture prediction using 2D Digital Subtraction Angiography (DSA) images. The proposed method involves training a fully connected convolutional neural network (CNN) to segment aneurysm regions in DSA images, followed by extracting and fusing different features using a multidisciplinary approach, including deep features, geometrical features, Fourier descriptor, and shear pressure on the aneurysm wall. The proposed method also adopts a fast correlation-based filter approach to drop highly correlated features from the set of fused features. Finally, the selected fused features are passed through a Decision Tree classifier to predict the rupture severity of the associated aneurysm into four classes: Mild, Moderate, Severe, and Critical. The proposed method is evaluated on a newly developed DSA image dataset and on public datasets to assess its generalizability. The system's performance is also evaluated on DSA images annotated by expert neurosurgeons for the rupture risk assessment of the segmented aneurysm. The proposed system outperforms existing state-of-the-art segmentation methods, achieving an 85 % accuracy against annotated DSA images for the risk assessment of aneurysmal rupture.

Narrative review of roles of astrocytes in subarachnoid hemorrhage.

Background and Objective: Astrocytes play an important role in healthy brain function, including the development and maintenance of blood-brain barrier (BBB), structural support, brain homeostasis, neurovascular coupling and secretion of neuroprotective factors. Reactive astrocytes participate in various pathophysiology after subarachnoid hemorrhage (SAH) including neuroinflammation, glutamate toxicity, brain edema, vasospasm, BBB disruption, cortical spreading depolarization (SD). Methods: We searched PubMed up to 31 May, 2022 and evaluated the articles for screening and inclusion for subsequent systemic review. We found 198 articles with the searched terms. After exclusion based on the selection criteria, we selected 30 articles to start the systemic review. Key Content and Findings: We summarized the response of astrocytes induced by SAH. Astrocytes are critical for brain edema formation, BBB reconstruction and neuroprotection in the acute stage of SAH. Astrocytes clear extracellular glutamate by increasing the uptake of glutamate and Na+/K+ ATPase activity after SAH. Neurotrophic factors released by astrocytes contribute to neurological recovery after SAH. Meanwhile, Astrocytes also form glial scars which hinder axon regeneration, produce proinflammatory cytokines, free radicals, and neurotoxic molecules. Conclusions: Preclinical studies showed that therapeutic targeting the astrocytes response could have a beneficial effect in ameliorating neuronal injury and cognitive impairment after SAH. Clinical trials and preclinical animal studies are still urgently needed in order to determine where astrocytes stand in various pathway of brain damage and repair after SAH and, above all, to develop therapeutic approaches which benefit patient outcomes.

Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43.

Background: Cerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia. Purpose: This study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their efficacy in treating neurodegenerative diseases. Methods: Genes associated with subarachnoid hemorrhage and CV were acquired and screened for differentially expressed miRNAs (DEmiRNAs) associated with aneurysm rupture. A regulatory network of DEmiRNAs and mRNAs was constructed, and virtual screening was performed to evaluate possible binding patterns between Food and Drug Administration (FDA)-approved drugs and core proteins. Molecular dynamics simulations were performed on the optimal docked complexes. Optimally docked drugs were evaluated for efficacy in the treatment of neurodegenerative diseases through cellular experiments. Results: The study found upregulated genes (including WDR43 and THBS1) and one downregulated gene associated with aneurysm rupture. Differences in the expression of these genes indicate greater disease risk. DEmiRNAs associated with ruptured aortic aneurysm were identified, of which two could bind to THBS1 and WDR43. Cromolyn and lanoxin formed the best docking complexes with WDR43 and THBS1, respectively. Cellular experiments showed that cromolyn improved BV2 cell viability and enhanced Aß42 uptake, suggesting its potential as a therapeutic agent for inflammation-related disorders. Conclusion: The findings suggest that WDR43 and THBS1 are potential targets for preventing and treating CV-induced dementia in the elderly. Cromolyn may have therapeutic value in the treatment of Alzheimer's disease and dementia.

Neurocognitive Sequelae and Rehabilitation after Subarachnoid Hemorrhage: Optimizing Outcomes.

Subarachnoid hemorrhage (SAH) is a medical emergency that requires immediate intervention. The etiology varies between cases; however, rupture of an intracranial aneurysm accounts for 80% of medical emergencies. Early intervention and treatment are essential to prevent long-term complications. Over the years, treatment of SAH has drastically improved, which is responsible for the rapid rise in SAH survivors. Post-SAH, a significant number of patients exhibit impairments in memory and executive function and report high rates of depression and anxiety that ultimately affect daily living, return to work, and quality of life. Given the rise in SAH survivors, rehabilitation post-SAH to optimize patient outcomes becomes crucial. The review addresses the current rehabilitative strategies to combat the neurocognitive and behavioral issues that may arise following SAH.