Onset Of Subarachnoid Hemorrhage Research Articles

Power suppression in EEG after the onset of SAH is a significant marker of early brain injury in rat models

We analyzed the correlation between the duration of electroencephalogram (EEG) recovery and histological outcome in rats in the acute stage of subarachnoid hemorrhage (SAH) to find a new predictor of the subsequent outcome. SAH was induced in eight rats by cisternal blood injection, and the duration of cortical depolarization was measured. EEG power spectrums were given by time frequency analysis, and histology was evaluated. The appropriate frequency band and recovery percentage of EEG (defined as EEG recovery time) to predict the neuronal damage were determined from 25 patterns (5 bands × 5 recovery rates) of receiver operating characteristic (ROC) curves. Probit regression curves were depicted to evaluate the relationships between neuronal injury and duration of depolarization and EEG recovery. The optimal values of the EEG band and the EEG recovery time to predict neuronal damage were 10–15 Hz and 40%, respectively (area under the curve [AUC]: 0.97). There was a close relationship between the percentage of damaged neurons and the duration of depolarization or EEG recovery time. These results suggest that EEG recovery time, under the above frequency band and recovery rate, may be a novel marker to predict the outcome after SAH.

Nonconvulsive status epilepticus in patients with acute subarachnoid hemorrhage is associated with negative arterial spin labeling on peri-ictal magnetic resonance images

PurposeNon-convulsive status epilepticus (NCSE) is characterized by repetitive or continuous seizures without convulsions. Arterial spin labeling (ASL) is useful for assessing hyperperfusion due to neurovascular unit coupling in patients with NCSE; subarachnoid hemorrhage (SAH) impairs the neurovascular unit. We hypothesized that the sensitivity of ASL in detecting NCSE is low in patients with SAH during the acute phase. MethodsBased on ASL findings obtained within 48 h after the clinical suspicion of focal-onset NCSE, we divided 34 patients into ASL-negative (no hyperperfusion; n = 10) and ASL-positive (confirmed hyperperfusion; n = 24) groups. We further divided the two groups according to the NCSE etiology: patients who were diagnosed with NCSE within 14 days after SAH onset (acute SAH, n = 11) and patients with NCSE due to factors other acute SAH (n = 23) and compared their characteristics. ResultsIn 10 of the 34 patients (29.4 %) the ASL findings were normal. The rate of acute SAH was significantly higher in ASL-negative- (n = 8, 80.0 %) than ASL-positive patients (n = 3, 12.5 %). The rate of patients in aphasic status was significantly lower in ASL-negative patients (n = 1, 10 %) than in ASL-positive patients (n = 12, 50.0 %). ConclusionNormal ASL findings alone should not be used to exclude a diagnosis of NCSE particularly in patients in the acute phase of SAH with deterioration or no improvement in consciousness.

Increased plasma periostin concentration predicts angiographic vasospasm development in non-severe aneurysmal subarachnoid hemorrhage

It is unknown whether plasma concentrations of a matricellular protein periostin change in association with the development of angiographic vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In 113 patients with aneurysmal SAH of World Federation of Neurological Surgeons grades 1–3 at admission, plasma periostin concentrations were serially measured at days 1–3, 4–6, 7–9 and 10–12 after SAH onset. Measured periostin levels and clinical variables were compared between patients with and without angiographic vasospasm. Periostin concentrations were significantly higher in patients with angiographic vasospasm at days 4–6 and 7–9. Receiver operating characteristic curve analyses indicated that cutoff plasma periostin values of 54.3 ng/ml at days 4–6 and 58.1 ng/ml at days 7–9 predicted or diagnosed angiographic vasospasm development with a specificity of 66.0 % and a sensitivity of 72.7 %, and a specificity of 75.0 % and a sensitivity of 55.0 %, respectively. Multivariate analyses also revealed that increased plasma periostin concentrations at days 7–9 was independently associated with angiographic vasospasm development. This study showed for the first time that plasma periostin levels were increased in patients with angiographic vasospasm. These findings suggest that plasma periostin can serve as a biomarker and may be a new therapeutic target for angiographic vasospasm after SAH.

Preventive effect of intermittent cerebrospinal fluid drainage for secondary chronic hydrocephalus after aneurysmal subarachnoid hemorrhage

BackgroundThe efficacy of intermittent cerebrospinal fluid (CSF) drainage compared with that of continuous CSF drainage in patients with subarachnoid hemorrhage (SAH) remains undetermined to date. Therefore, we investigated whether intermittent CSF drainage is effective in reducing secondary chronic hydrocephalus (sCH) after aneurysmal SAH.MethodsOverall, 204 patients (69 men and 135 women) treated for aneurysmal SAH between 2007 and 2022 were included in this study. Following SAH onset, 136 patients were managed with continuous CSF drainage, whereas 68 were managed with intermittent CSF drainage. Logistic regression analyses were used to calculate the age-adjusted and multivariate odds ratios for the development of sCH. The Cox proportional hazards regression model were used to compare the effects of intermittent and continuous CSF drainage on sCH development.ResultsOverall, 96 patients developed sCH among the 204 patients with SAH. In total, 74 (54.4%) of the 136 patients managed with continuous CSF drainage developed sCH, whereas 22 (32.4%) of the 68 patients managed with intermittent CSF drainage developed sCH. This demonstrated that the rate of sCH development was significantly lower among patients managed with intermittent CSF drainage. Compared with continuous CSF drainage, intermittent CSF drainage exhibited a multivariate odds ratio (95% confidential interval) of 0.25 (0.11–0.57) for sCH development. Intermittent CSF drainage was more effective (0.20, 0.04–0.95) in patients with severe-grade SAH than in those with mild-grade SAH (0.33, 0.12–0.95). Intermittent CSF drainage was ineffective in patients with acute hydrocephalus (8.37, 0.56–125.2), but it was effective in patients without acute hydrocephalus (0.11, 0.04–0.31).ConclusionsCompared with continuous CSF drainage, intermittent drainage is more effective in reducing sCH after aneurysmal SAH. Although intermittent drainage was ineffective in cases of co-occurrence of acute hydrocephalus, it was effective in reducing sCH development regardless of the severity of initial symptoms at SAH onset.

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

BACKGROUNDCerebral 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. METHODSConsecutive 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. RESULTSEighteen (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. CONCLUSIONSClinical 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.

Regulatory T Cells Secrete IL10 to Suppress Neuroinflammation in Early Stage after Subarachnoid Hemorrhage.

Objective: Accumulating evidence supports neuroprotective effects of regulatory T cells (Tregs) in response to brain injury. However, the precise mechanisms underlying the beneficial effects of Tregs on suppressing neuroinflammation after subarachnoid hemorrhage (SAH) remain unclear. Methods: We performed flow cytometry to detect the infiltration of Tregs into the brain at different time points after SAH. Behavioral tests, including Adhesive and Rotarod, were performed to assess neurological deficits in mice after SAH. Bulk RNA sequencing was used to investigate the transcriptomic change of Tregs infiltrating into the brain after SAH. qPCR was performed to verify the variation of inflammatory cytokines expression in the brain after Tregs exogenous infusion. FoxP3-DTR mice and Il10 gene KO mice were used to explore the mechanism of Tregs inhibiting neuron apoptosis after infiltrating the brain following SAH onset. Results: Peripheral Tregs infiltrated into the brain one day after SAH and gradually accumulated in the hemorrhagic hemisphere. An exogenous infusion of Tregs significantly improved the neurological function of mice after SAH, while poor recovery of neurological function was observed in Tregs depletion mice. Transcriptome sequencing data suggested that the immunosuppressive function of brain-infiltrated Tregs was significantly upregulated. qPCR showed that the expression of pro-inflammatory cytokines decreased in the brain of SAH mice after exogenous Tregs infusion. Bioinformatic analysis revealed that IL-10 and other cytokines secreted by brain-infiltrated Tregs were upregulated after SAH. Moreover, exogenous infusion of Il10 gene KO Tregs did not totally improve neurological function in SAH mice. Conclusions: Tregs infiltrated into the brain in the early stage after SAH and exerted neuroprotective effect by secreting IL-10 to suppress neuroinflammation and reduce neuron apoptosis.

Determination of indications for early surgical treatment in patients with ruptured anterior communicating artery aneurysms

Aim. To analyze and determine the optimal indications for microsurgical operative interventions in the shortest possible time from the subarachnoid hemorrhage onset to prevent anterior communicating artery (AcomA) aneurysm re-rupture and bleeding. Materials and methods. 280 patients with brain aneurysms were examined at the Uzhhorod Regional Center of Neurosurgery and Neurology and the City Hospital of Urgent and Emergency Medical Care under Zaporizhzhia City Council. Among them, 98 patients (48 males and 50 females) were diagnosed with AcomA aneurysms. The age of patients with AcomA aneurysms was from 20 to 72 years (mean age 47.8 ± 11.0 years). Aneurysms were verified using head and neck computed tomography angiography (a Toshiba Astelion scanner, 2016, No. 4СС162106), selective cerebral angiography (an angiography system General Energy Optima IGS 330, 2019, No. 80071260314), and brain magnetic resonance angiography (an i_Open 0,36 T magnetic resonance tomograph, 2005, No. Toc102633006). Cerebral hemodynamics was assessed using transcranial dopplerography (“Philips HD7” ultrasound diagnostic system, 2014, No. 69935). Results. In the first three days after the onset of subarachnoid hemorrhage, 18 (18 %) patients were admitted with ruptured aneurysms of this location, 62 (62 %) within 4–8 days, 12 (12 %) patients within 9–14 days, later than 14 days – 6 (6 %). All 98 patients underwent microsurgical clipping of AcomA aneurysms. Due to severe cerebral edema, decompressive craniectomy was performed in two patients. The results of surgical treatment were evaluated according to the modified Rankin scale at the time of hospital discharge and were as follows: in 65 (65 %) patients – good; in 18 (18 %) – moderate disability; in 4 (4 %) – serious disability. 11 (11 %) patients died. Conclusions. The treatment outcomes in patients with ruptured AcomA aneurysms were significantly dependent on factors related to increased risk of re-rupture: the presence of large-sized intracerebral hematoma, the aneurysm index exceeding 2, and multi-chamber aneurysm.

Diagnosis and treatment approaches for simultaneous onset of subarachnoid hemorrhage and thyroid storm: a case report

BackgroundSubarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital.Case presentationThe patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient’s symptoms improved, and she became lucid.In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient’s condition.ConclusionIf a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient’s condition is critical, and early diagnosis will lead to a favorable outcome for the patient.

Peroxiredoxin 2 Is a Potential Objective Indicator for Severity and the Clinical Status of Subarachnoid Hemorrhage Patients.

We have demonstrated that peroxiredoxin 2 (Prx2) released from lytic erythrocytes and damaged neurons into the subarachnoid space could activate microglia and then result in neuronal apoptosis. In this study, we tested the possibility of using Prx2 as an objective indicator for severity of the subarachnoid hemorrhage (SAH) and the clinical status of the patient. SAH patients were prospectively enrolled and followed up for 3 months. Cerebrospinal fluid (CSF) and blood samples were collected 0-3 and 5-7 days after SAH onset. The levels of Prx2 in the CSF and the blood were measured by an enzyme-linked immunosorbent assay (ELISA). We used Spearman's rank coefficient to assess the correlation between Prx2 and the clinical scores. Receiver operating characteristic (ROC) curves were used for Prx2 levels to predict the outcome of SAH by calculating the area under the curve (AUC). Unpaired Student's t-test was used to analyze the differences in continuous variables across cohorts. Prx2 levels in the CSF increased after onset while those in the blood decreased. Existing data showed that Prx2 levels within 3 days in the CSF after SAH were positively correlated with the Hunt-Hess score (R = 0.761, P < 0.001). Patients with CVS had higher levels of Prx2 in their CSF within 5-7 days after onset. Prx2 levels in the CSF within 5-7 days can be used as a predictor of prognosis. The ratio of Prx2 in the CSF and the blood within 3 days of onset was positively correlated with the Hunt-Hess score and negatively correlated with Glasgow Outcome Scale (GOS; R = -0.605, P < 0.05). We found that the levels of Prx2 in the CSF and the ratio of Prx2 in the CSF and the blood within 3 days of onset can be used as a biomarker to detect the severity of the disease and the clinical status of the patient.

Epidemiology of Subarachnoid Hemorrhage in Isolated Islands in Japan: A Population-based Study in the Miyako Islands.

The Miyako Islands (with a population of approximately 50,000) are located in southwestern Japan, with a subtropical oceanic climate. This isolated location permitted a retrospective population-based epidemiological study of subarachnoid hemorrhage. We retrospectively enrolled 110 consecutive patients from 2010 to 2019 using the subarachnoid hemorrhage database at Okinawa Miyako Hospital, which is the only local facility with neurosurgeons. We calculated the incidence of subarachnoid hemorrhage standardized to the entire Japanese population. The seasonal distribution of subarachnoid hemorrhage onset and patients' epidemiological characteristics were also investigated. The standardized annual incidence of subarachnoid hemorrhage was 21.4 per 100,000 population, as reported previously in Japan. The patients' mean age was 62.1 ± 15.4 years, and women constituted 60.9%. Anterior communicating artery aneurysms were most common. The endovascular treatment for ruptured aneurysms was increasing as standard levels in Japan. The rates of symptomatic vasospasm and secondary hydrocephalus requiring additional neurosurgical treatment were 2.7% and 19.1%, respectively. The mortality rate was 23.6%. The percentage of patients with a modified Rankin scale score of 0-2 at discharge was 55.5%. There were no differences in the frequency of subarachnoid hemorrhage associated with seasonal distribution or climatic factors. The incidence, baseline characteristics, and clinical outcomes of subarachnoid hemorrhage in the Miyako Islands were similar to those in other regions of Japan. There are preferable epidemiological backgrounds for further practical clinical research.

Association of Gut Microbiome with Early Brain Injury After Subarachnoid Hemorrhage: an Experimental Study.

The occurrence of early brain injury (EBI) following subarachnoid hemorrhage (SAH) is crucial in the prognosis of SAH; however, no effective treatment for EBI has been developed. Gut microbiome (GM) composition influences the outcome of various diseases, including ischemic stroke. Here, we evaluated whether prior GM alteration could prevent EBI following SAH. We altered the GM of 7-week-old male rats by administering antibiotic-containing water for 2weeks and performing fecal microbiome transplantation after antibiotic induction. Composition of the GM was profiled using 16S rRNA. We induced SAH by injecting blood in the subarachnoid space of control rats and rats with altered GM. We evaluated EBI indicators such as neurological score, brain water content, Evans blue extravasation, and neuronal injury. Additionally, we studied inflammatory cells using immunohistochemistry, immunocytochemistry, quantitative PCR, and flow cytometry. EBI was significantly averted by alterations in GM using antibiotics. The altered GM significantly prevented neutrophil infiltration into the brain among inflammatory cells, and this anti-inflammatory effect was observed immediately following SAH onset. The altered GM also prevented neutrophil extracellular trap formation in the brain and blood, indicating the systemic protective effect. The cause of the protective effect was attributed to a significant decrease in aged neutrophils (CXCR4high CD62Llow) by the altered GM. These protective effects against EBI disappeared when the altered GM was recolonized with normal flora. Our findings demonstrated that EBI following SAH is associated with GM, which regulated neutrophil infiltration.

Impact of analgesic regimen on patient outcome following subarachnoid hemorrhage: positive adjuvant effects of metamizole

Introduction Various analgesics are used to control intense headaches in patients following subarachnoid hemorrhage. In addition to pain control, it has been shown that some analgesics can affect various pathophysiological cascades. Therefore, we devised a study to assess whether the use of metamizole has a significant impact on the development of ischemic complications, hydrocephalus, and the overall outcome in patients following aneurysmal subarachnoid hemorrhage in the context of the other non-opioids and opioids effects. Methods In our retrospective, single-center cohort study, we enrolled 192 patients diagnosed with subarachnoid hemorrhage. We recorded their initial clinical status, comorbidities, and the daily dosage of analgesics over 14 days of hospitalization after the onset of subarachnoid hemorrhage. Using univariate and subsequent multivariate logistic regression analysis, we assessed the influence of various factors, including analgesics, on the development of delayed cerebral ischemia and hydrocephalus, as well as on 2-week and 6-month outcomes. Results Although the administration of non-opioids, in general, had no effect on the development of delayed cerebral ischemia or hydrocephalus, the use of metamizole as the main analgesic was associated with a significantly lower chance of poor outcome at both 2-weeks and 6-months, as well as the development of delayed cerebral ischemia. As opioids were indicated primarily for analgosedation in mechanically ventilated patients with poor clinical status, their usage was associated with a significantly higher chance of poor outcome, delayed cerebral ischemia, and hydrocephalus. Conclusion Our results suggest that the prescription of metamizole may be associated with better outcomes and a lower chance of delayed cerebral ischemia development in patients after subarachnoid hemorrhage. Considering the retrospective nature of our study and the limited worldwide availability of metamizole due to its prohibition in some countries, our results do not demonstrate a clear benefit but rather justify the need for subsequent prospective studies.

Systematic review and meta-analysis of outcome-relevant anemia in patients with subarachnoid hemorrhage

Anemia is a common, treatable condition in patients with aneurysmal subarachnoid hemorrhage (SAH) and has been associated with poor outcome. As there are still no guidelines for anemia management after aneurysm rupture, we aimed to identify outcome-relevant severity of anemia in SAH. We systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library for publications before Oct 23rd, 2022, reporting on anemia in SAH patients. The presence and severity of anemia were assessed according to the reported hemoglobin values and/or institutional thresholds for red blood cells transfusion (RBCT). Out of 1863 original records, 40 full-text articles with a total of 14,701 patients treated between 1996 and 2020 were included in the final analysis (mean 445.48 patients per study). A substantial portion of patients developed anemia during SAH (mean pooled prevalence 40.76%, range 28.3–82.6%). RBCT was administered in a third of the cases (mean 32.07%, range 7.8–88.6%), with institutional threshold varying from 7.00 to 10.00 g/dL (mean 8.5 g/dL). Anemia at the onset of SAH showed no impact on SAH outcome. In contrast, even slight anemia (nadir hemoglobin < 11.0–11.5 g/dL) occurring during SAH was associated with the risk of cerebral infarction and poor outcome at discharge and follow-up. The strongest association with SAH outcome was observed for nadir hemoglobin values ranging between 9.0 and 10.0 g/dL. The effect of anemia on SAH mortality was marginal. The development of anemia during SAH is associated with the risk of cerebral infarction and poor outcome at discharge and follow-up. Outcome-relevant severity of post-SAH anemia begins at hemoglobin levels clearly above the thresholds commonly set for RBCT. Our findings underline the need for further studies to define the optimal management of anemia in SAH patients.

Predictive factors associated with outcome in patients six months after mild to moderate aneurysmal subarachnoid hemorrhage: Focus on neuropsychological tests conducted one month after the event

ObjectiveThe study aimed to investigate predictive factors associated with outcome six months after mild to moderate aneurysmal subarachnoid hemorrhage (SAH). MethodsWe divided 136 patients (51 men and 85 women) after SAH (Hunt & Kosnik [H&K] grade I to III) into groups with good and poor outcome according to scores on the modified Rankin Scale (mRS) at six months after SAH onset: good outcome (mRS score, 0–1; n = 105) and poor outcome (mRS score, 2–6; n = 31). At admission, we assessed age, sex, H&K grade, and Fisher grade, and one month after aneurysmal SAH, we evaluated aneurysm location, treatment modality (coil embolization, clipping, or no surgical treatment), proportion of patients who underwent shunt placement, proportion of patients with delayed cerebral ischemia, and scores on neuropsychological tests (Mini-Mental State Examination, Raven’s Colored Progressive Matrices, Kana-hiroi Test, Trail Making Test, and Rey-Osterrieth Complex Figure Test, immediate recall). ResultsH&K grade was associated with outcome (χ2 = 6.220, P = 0.005), and a significantly higher proportion of the good outcome group had an H&K grade II (P = 0.025). The good outcome group had significantly better scores on the Mini-Mental State Examination (U = 1251, P = 0.045), Raven’s Colored Progressive Matrices (U = 1224, P = 0.036), and Trail Making Test parts A (U = 1238, P = 0.043) and B (U = 1247, P = 0.048). However, we found no significant intergroup differences in the other patient demographic and disease characteristics, including age, treatment modality, and delayed cerebral ischemia, or in the other neuropsychological assessments. Binary logistic regression analysis identified H&K grade I and II as predictive factors associated with good outcome. ConclusionBesides severity at admission as indicated by H&K grade, neuropsychological tests explicitly performed one month after mild to moderate aneurysmal SAH may help nursing staff to predict patient outcome, including possible symptoms after discharge.

Effect of early stellate ganglion block in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (BLOCK-CVS): study protocol for a randomized controlled trial

IntroductionStellate ganglion block has been reported to expand cerebral vessels and alleviate vasospasm after aneurysmal subarachnoid hemorrhage. However, the causal relationship between early stellate ganglion block and cerebral vasospasm prevention has not yet been established. The purpose of this study was to explore the effectiveness and safety of early stellate ganglion block as a preventive treatment for cerebral vasospasm and delayed cerebral ischemia.Methods/designThis is a single-center, prospective, randomized, controlled, blinded endpoint assessment superiority trial. A total of 228 patients will be randomized within 48 h of aneurysmal subarachnoid hemorrhage onset in a 1:1 ratio into two groups, one group receiving an additional e-SGB and the other group receiving only a camouflaging action before anesthesia induction in the operating room. The primary outcome is the incidence of symptomatic vasospasm within 14 days after aSAH. Further safety and efficacy parameters include the incidence of radiographic vasospasm, new cerebral infarction, postoperative delirium, and complications up to 90 days after surgery; postoperative cerebral hemodynamics; Mini-Mental State Examination score; modified Rankin scale score; and all-cause mortality up to 90 days after surgery.DiscussionThis is a randomized controlled trial to explore the effectiveness and safety of early stellate ganglion block as a preventive treatment to reduce cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. If the results are positive, it may provide a new direction for the prevention and treatment of cerebral vasospasm and delayed cerebral ischemia.Trial registrationThe study was registered on Clincaltrials.gov on December 13, 2020 (NCT04691271).

ODP279 A Case of Nephrogenic Diabetes Insipidus Diagnosed at an Advanced Age in a Female Patient with an AVPR2 Gene Mutation and Skewed×Inactivation

Abstract Background Arginine vasopressin receptor 2 (AVPR2) gene mutationsare the most common cause of congenital nephrogenic diabetes insipidus (CNDI), and they are inherited in an X-linked recessive manner. Women are generally asymptomatic or mildly affected, but atypically severe cases have been reported. Skewed X inactivation, in which the X chromosome is unevenly active, is a cause of this atypical severe case.×chromosome inactivation is a developmental compensation mechanism that results in equal doses of X-linked genes between XX females and XY males and has been reported to be accentuated by aging. Clinical Case A 69-year-old woman had no family history of diabetes insipidus. Immediately after undergoing a craniotomy for subarachnoid hemorrhage in July, she showed marked polyuria of approximately 8000 mL/day and hypernatremia of 161 mEq/L. The use of desmopressin (15mcg/kg/day) did not improve herpolyuria. She was referred to our department in September for further investigation and treatment. Her urine osmolality remained hypotonic at approximately 60–80 mOsm/kg/H 2 O (50–1300 mOsm/kg/H 2 O) according to a water restriction test. Her urine osmolality increased slightly to 106 mOsm/kg/H 2 O in a desmopressin test. These results indicated that desmopressin was ineffective, and the patient was diagnosed with nephrogenic diabetes. Her urine output decreased to approximately 2500 mL/day with trichlormethiazide treatment. There was no significant anterior pituitary hypofunction. Genetic examination revealed a heterozygous mutation of the AVPR2 gene (c.656T&amp;gt;G, p. Leu219Arg) in her X chromosome, and her X chromosome activity ratio was 79: 21 in a human androgen receptor assay, indicating skewed X inactivation. Conclusion We observed a case of CNDI in an elderly woman with no family history of the disease. In this case, a combination of the skewed X inactivation, presumably accentuated by aging, and the onset of subarachnoid hemorrhage, reduced her drinking water and led to the diagnosis of CNDI.

Emergent Subarachnoid Clot Removal with Aneurysm Repair for Subarachnoid Hemorrhage Might Improves Clinical Outcome

The goal in treating patients with subarachnoid hemorrhage (SAH) is shifting to preventing early brain injury. Intracranial pressure must be controlled to manage such an injury. We retrospectively analyzed the impact of aggressive removal of cisternal subarachnoid clots with simultaneous aneurysm repair for all grades ofSAH. Our study included 260 consecutive patients with SAH treated through aggressive subarachnoid clot removal with simultaneous aneurysm repair. Baseline patient characteristics, history, radiographic findings, and time of SAH onset to arrival in the operating room were retrospectively collected. Factors related to poor outcome (modified Rankin Scale score >2) were analyzed. Multivariate analysis revealed several characteristics were significantly associated with poor outcome: advanced age (adjusted odds ratio [aOR] 1.07, 95% confidence interval [CI] 1.04-01.10); time of SAH onset to operating room per 1-hour increments (aOR 1.03, 95% CI 1.01-01.05; postoperative hematoma volume (aOR 1.04, 95% CI 1.01-01.06); and poorer World Federation of Neurosurgical Societies grade (aOR 2.18, 95% CI 1.63-02.92). According to a receiver operating characteristic analysis, the cut-off time of SAH onset to operating room was 6.0 hours (area under the curve 0.61, P= 0.01, 95% CI 0.52-0.69, sensitivity= 0.79, specificity= 0.43) as the threshold between modified Rankin Scale scores of 0-2 and 3-6. Prognostic factors of SAH in patients undergoing emergent aneurysm repair with simultaneous removal of a cisternal subarachnoid clot are advanced age, poorer World Federation of Neurosurgical Societies grade, postoperative hematoma volume, and a longer time from SAH onset to operating room. The clinical outcome may improve with emergent reduction of intracranial pressure through removal of the subarachnoid clot as soon as possible.

Predictors of thromboembolic complications after stent-assisted coiling of acutely ruptured intracranial aneurysms: A retrospective multicenter study.

BackgroundStent-assisted coiling (SAC) has been reported to safely and effectively treat wide-necked unruptured intracranial aneurysms. However, SAC of acutely ruptured aneurysms is controversial because of perioperative thromboembolic complications. We aimed to investigate the predictors of the thromboembolic complications after SAC of acutely ruptured aneurysms.MethodsWe performed a retrospective multicenter analysis of 110 consecutive patients with ruptured intracranial aneurysms treated with SAC within 72 h of the onset of subarachnoid hemorrhage. Thromboembolic complications were defined as any angiographic filling defects at the aneurysms base or the distal artery during the stent treatment and the new onset of symptomatic ischemia and a new hypo-density in a vascular distribution confirmed by CT scan within 24 h of treatment. These patients were grouped into patients with thromboembolic complications and those without thromboembolic complications. A multivariate logistic regression analysis was performed to identify predictors of thromboembolic complications.ResultsOne hundred and one patients with 101 ruptured aneurysms were included in this study. 9 (8.9%) patients experienced thromboembolic complications. Patients with thromboembolic complications had a higher rate of unfavorable outcomes at discharge (P < 0.001) and at the last follow-up (p = 0.017). Of these patients, four patients presented with intraprocedural thrombus formation, and 5 experienced postprocedural ischemia. There was a trend toward thromboembolic complications in patients with a higher Fisher grade (p = 0.076) and those treated with intravenous tirofiban (p = 0.052). Patients with thromboembolic complications more often presented with poor grade clinical conditions (p = 0.005) and aneurysms with a large dome to neck ratio (p = 0.031). In the multivariate analysis, a worse World Federation World Federation of Neurological Societies (WFNS) grade (OR = 8.241; 95% CI 1.686–40.292; P = 0.009) and a larger dome to neck ratio (OR = 5.385; 95% CI 1.023–28.337; P = 0.047) were independent predictors of thromboembolic complications.ConclusionPatients with thromboembolic complications are more likely to have an unfavorable outcome. A worse clinical condition before the treatment and a larger dome to neck ratio were independent predictors of thromboembolic complications after SAC of acutely ruptured intracranial aneurysms.

Longitudinal ventricular cerebrospinal fluid profile in patients with spontaneous subarachnoid hemorrhage.

BackgroundSpontaneous subarachnoid hemorrhage (SAH) is a severe neurological disease that frequently requires placement of external ventricular drainage (EVD). Cerebrospinal fluid (CSF) obtained via the drain is used to detect potential complications of SAH.ObjectiveThis study aimed to describe the longitudinal profile of routine CSF parameters in patients with SAH and to identify associations with neurological complications.MethodsA total of thirty-three patients with spontaneous SAH who required an EVD and had at least three consecutive CSF samples collected over a period of more than 7 days were included in this study.ResultsA median of 6 longitudinally collected CSF samples per patient were available within 1–22 days after SAH onset. Overall, red blood cells (RBC) steadily decreased over time, whereas white blood cells (WBC) and total protein (TP) increased until days 6 and 13, respectively, and decreased thereafter. The estimated decay rates of RBC, WBC, and TP were 28, 22, and 6% per day. Distinct CSF patterns over time were linked to known complications after SAH. Patients with rebleeding showed increased RBC, TP, and phagocytosing cells compared to patients without re-bleeding. For ventriculitis, an elevated cell index with a higher proportion of granulocytes was characteristic. CSF of patients with delayed cerebral ischemia showed increased RBC and WBC compared to patients without DCI. Early CSF WBC and cell index were predictive for the occurrence of DCI and ventriculitis later during the disease course. The amount of daily CSF drainage via EVD had no impact on routine CSF parameters.ConclusionLongitudinal CSF characteristics are associated with SAH-related complications.

The impact of hormonal dynamics and serum sodium fluctuations on symptomatic vasospasm after subarachnoid hemorrhage

BackgroundSymptomatic vasospasm (SVS) is a major cause of morbidity and mortality in aneurysmal subarachnoid hemorrhage (SAH), and serum sodium frequently decreases before SVS. Serum sodium changes might be regulated by sodium metabolism-related hormones. This multi-institutional prospective cohort study therefore investigated the measurement of sodium metabolism-related hormones to elucidate the pathophysiology of serum sodium changes in SAH. MethodsSAH patients were treated with clipping or coiling from September 2017 to August 2020 at five hospitals. The laboratory data of 133 SAH patients were collected over 14 days and correlations between changes in serum sodium, sodium metabolism-related hormones (plasma adrenocorticotropic hormone (ACTH), serum cortisol, plasma arginine vasopressin (AVP)), and SVS were determined. Serum sodium concentrations were measured every day and serum sodium levels >135 mEq/L were maintained until day 14. ResultsOf the 133 patients, 18 developed SVS within 14 days of subarachnoid hemorrhage onset (SVS group) and 115 did not suffer from SVS (non-SVS group). Circulating AVP, ACTH, and cortisol concentrations were significantly higher on day 1 in the SVS group compared with the non-SVS group. Fluctuations in serum sodium in the SVS group were significantly higher than those in the non-SVS group. There were antiparallel fluctuations in serum sodium and potassium from days 2 to 14. ConclusionsElevated levels of ACTH/cortisol and AVP on day 1 may be predictive markers for the occurrence of SVS. Multiple logistic regression analysis showed that serum sodium fluctuations were associated with SVS occurrence. Serum sodium fluctuations were associated with stress-related hormonal dynamics. (249 words)