Days Of Subarachnoid Hemorrhage Research Articles

Impact of ventriculo-cisternal irrigation on prevention of delayed cerebral infarction in aneurysmal subarachnoid hemorrhage: a single-center retrospective study and literature review

ObjectiveThe aim of this study was to evaluate the effectiveness of ventriculo-cisternal irrigation (VCI) in preventing vasospasms and delayed cerebral infarction (DCI) by washing out subarachnoid clots earlier after aneurysm surgery.MethodsWe retrospectively identified 340 subarachnoid hemorrhage (SAH) patients with ruptured intracranial aneurysms treated with postoperative VCI at our institution between December 2010 and January 2020. As VCI therapy, a ventricular drain/cisternal drain was placed during aneurysm surgery, and lactated Ringer’s solution was used for irrigation until day 4 of SAH, followed by intracranial pressure control at 5–10 cmH2O until day 14.ResultsThe median age was 65 years (interquartile range 52–75), with 236 female patients (69%). The World Federation of Neurosurgical Societies grade distribution was as follows: grade I or II, 175 patients (51%); grade III or IV, 84 (25%); and grade V, 81 (24%). With VCI management in all patients, total vasospasm occurred in 162 patients (48%), although the DCI incidence was low (23 patients [6.8%]). Major drainage-related complications were observed in five patients (1.5%). Early surgery, performed on SAH day 0 or 1, was identified as a preventive factor against DCI occurrence (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.07–0.67; P = 0.008), while additional surgery (4.76, 1.62–13.98; P = 0.005) and dyslipidemia (3.27, 1.24–8.63; P = 0.017) were associated with DCI occurrence.ConclusionManaging vasospasms with VCI after SAH is considered a safe and effective method to prevent DCI. Early surgery after SAH may be associated with a decreased risk of DCI with VCI therapy.

Vasodilatory effects of tadalafil in an animal model of cerebral vasospasm: Comparative analysis with oral nimodipine

ObjectivesCerebral vasospasm is one of the most fatal complications after spontaneous aneurysmal subarachnoid hemorrhage. Although various treatments have been tried for the treatment of cerebral vasospasm so far, the effect is insignificant or temporary except for oral nimodipine. Phosphodiesterase isozyme type 5 inhibitor, which is used to treat erection dysfunction, recently has been known to have a cerebrovascular vasodilation. It is thought that this will be effective in cerebral vasospasm, and the effect will be compared and analyzed with oral nimodipine through an animal model of cerebral vasospasm. Material and MethodsA total of 40 rabbits were used to make subarachnoid hemorrhage model and were divided into three groups - a control group, nimodipine group, and tadalafil group. The cerebral vessels were angiographically measured before and on the third day of subarachnoid hemorrhage. Then vertebrobasilar arteries were harvested and evaluated. Under the microscope, lumen area and media area were measured for each group and were compared. ResultsAngiographically, tadalafil group showed significant vasodilation compared with the control group (p < 0.01). Histologically, tadalafil showed a similar effect on lumen and on media area to that of nimodipine group compared with the control group. ConclusionsCerebral vasospasm could leave neurologic deficit or sequelae even after proper treatment. Therefore, prevention is important. Tadalafil showed preventive effect against cerebral vasospasm and vasodilative effect similar to that of nimodipine. Therefore, tadalafil could be considered an alternative preventive treatment of cerebral vasospasm.

A timeline of oligodendrocyte death and proliferation following experimental subarachnoid hemorrhage.

AimsWhite matter (WM) injury is a critical factor associated with worse outcomes following subarachnoid hemorrhage (SAH). However, the detailed pathological changes are not completely understood. This study investigates temporal changes in the corpus callosum (CC), including WM edema and oligodendrocyte death after SAH, and the role of lipocalin‐2 (LCN2) in those changes.MethodsSubarachnoid hemorrhage was induced in adult wild‐type or LCN2 knockout mice via endovascular perforation. Magnetic resonance imaging was performed 4 hours, 1 day, and 8 days after SAH, and T2 hyperintensity changes within the CC were quantified to represent WM edema. Immunofluorescence staining was performed to evaluate oligodendrocyte death and proliferation.ResultsSubarachnoid hemorrhage induced significant CC T2 hyperintensity at 4 hours and 1 day that diminished significantly by 8 days post‐procedure. Comparing changes between the 4 hours and 1 day, each individual mouse had an increase in CC T2 hyperintensity volume. Oligodendrocyte death was observed at 4 hours, 1 day, and 8 days after SAH induction, and there was progressive loss of mature oligodendrocytes, while immature oligodendrocytes/oligodendrocyte precursor cells (OPCs) proliferated back to baseline by Day 8 after SAH. Moreover, LCN2 knockout attenuated WM edema and oligodendrocyte death at 24 hours after SAH.ConclusionsSubarachnoid hemorrhage leads to T2 hyperintensity change within the CC, which indicates WM edema. Oligodendrocyte death was observed in the CC within 1 day of SAH, with a partial recovery by Day 8. SAH‐induced WM injury was alleviated in an LCN2 knockout mouse model.

Values of blood copeptin level as a marker of unfavorable forecast in subarachnoid haemorrhage of the brain of atraumatic origin

Objective – to evaluate of diagnostic informativeness of сopeptin serum values in determining the risk of complications in patients with subarachnoid hemorrhage.Materials and methods. A prospective cohort study of 82 patients (40 men and 42 women) with spontaneous (non-traumatic) subarachnoid hemorrhage (SAH) from the age of 23 to 72 years (average age – (49,6 ±1,3) year) was conducted.Results. Complications were recorded in 31 (74.20 %) patients with a serum level of copeptin ≥ 0.605 ng/ml on the third day of the SAH, which was in 9.49 times higher (95 % CI 3.60–24.80, р ˂0.0001) than in patients with a serum level of copeptin &lt; 0.605 ng/ml. When determining the cumulative risk of developing complications of SAH, the values ​​of positive and negative predictive values ​​of serum levels of copeptin on third day of SAH were 74.19 % and 92.20 % respectively, the accuracy of prediction (the sum of correctly classified observations) was 85.39 %.Conclusions. ROC-analysis suggests that the serum level of copeptin on third day of SAH ≥ 0.605 ng/ml is characterized by an optimal ratio of sensitivity and specificity in assessing the cumulative risk of developing such SAH complications as secondary ischemia combined with cerebral angiospasm.

Flow Diversion for Treatment of Acutely Ruptured Intracranial Aneurysms

BackgroundReports about the use of flow diverter stents (FDS) in the acute setting of subarachnoid hemorrhage (SAH) are limited. This article presents a single center experiences based on 45 consecutive cases with emphasis on complication rates and clinical and radiologic outcomes.MethodsA prospectively maintained database of all cases treated with FDS as a stand-alone or adjunct device was retrospectively reviewed. All patients treated within 30 days of SAH were included. Records were made of clinical presentation, details of endovascular treatment, procedural complications, clinical outcome, and degree of occlusion on follow-up.ResultsIn this study 45 patients (48.9% females; mean age 58.8 ± 12.4 years) were included. Flow diversion was performed after a median of 4 days. The procedural complication rate was 13.3% resulting in 2.2% permanent morbidities and 4.4% mortalities. No major hemorrhagic complications related to antiplatelet therapy were recorded. Immediate complete occlusion was achieved in 13.3%. Among survivors, complete occlusion was achieved in 94.6%. Excellent clinical outcome was recorded in 68.9% and 81.6% of the total population and survivors, respectively. There were no records of rebleeding from the target lesions.ConclusionFlow diversion is an attractive alternative strategy for management of acutely ruptured aneurysms with high rates of delayed complete occlusion and acceptable complication rates.

Serum glutamine and hospital-acquired infections after aneurysmal subarachnoid hemorrhage.

To understand nutritional and inflammatory factors contributing to serum glutamine levels and their relationship to hospital-acquired infections (HAIs) after aneurysmal subarachnoid hemorrhage (SAH). A prospective observational study of patients with SAH who had measurements of daily caloric intake and C-reactive protein, transthyretin, tumor necrosis factor α receptor 1a (TNFαR1a), glutamine, and nitrogen balance performed within 4 preset time periods during the 14 days after SAH. Factors associated with glutamine levels and HAIs were analyzed with multivariable regression. HAIs were tracked daily for time-to-event analyses. Outcome 3 months after SAH was assessed by the Telephone Interview for Cognitive Status and modified Rankin Scale. There were 77 patients with an average age of 55 ± 15 years. HAIs developed in 18 (23%) on mean SAH day 8 ± 3. In a multivariable linear regression model, negative nitrogen balance (p = 0.02) and elevated TNFαR1a (p = 0.04) were independently associated with higher glutamine levels during the study period. The 14-day mean glutamine levels were lower in patients who developed HAI (166 ± 110 vs 236 ± 81 μg/mL, p = 0.004). Poor admission Hunt and Hess grade (p = 0.04) and lower glutamine levels (p = 0.02) predicted time to first HAI. Low 14-day mean levels of glutamine were associated with a poor recovery on the Telephone Interview for Cognitive Status score (p = 0.03) and modified Rankin Scale score (p = 0.04) at 3 months after injury. Declining glutamine levels in the first 14 days after SAH are influenced by inflammation and associated with an increased risk of HAI.

Factors Predicting Ventricle Volume Increase After Aneurysmal Clipping in Patients with Subarachnoid Hemorrhage.

Although many studies have evaluated risk factors associated with hydrocephalus after aneurysmal subarachnoid hemorrhage, specific ventricle volume changes after subarachnoid hemorrhage have not been evaluated. We sought to evaluate factors predicting ventricle volume enlargement in patients with aneurysmal subarachnoid hemorrhage by measuring ventricle volume with a validated, semiautomated tool. Uni- and multivariable linear regression analyses were conducted with the follow-up ventricle volume as the dependent variable and the duration between subarachnoid hemorrhage occurrence and follow-up imaging as the independent variable, classified by the use of various predictive factors. A logistic regression model was used to calculate the odds ratio for the greater ventricle volume group compared with the lower ventricle volume group based on predictive factors. We included 173 participants with a mean age of 55.5 years. Overall, an approximate increase in ventricle volume of 1.1 mL was observed daily within 60 days of clipping due to subarachnoid hemorrhage. In the multivariate logistic regression analysis, patients in the first and second tertile groups for body mass index showed approximately a 5.9- and 4.1-fold increased risk of greater follow-up ventricle volume, respectively, compared with the third tertile group for body mass index within 60 days of subarachnoid hemorrhage. We found that greater body mass index independently predicted suppression of ventricle volume growth, owing to maintenance of subarachnoid trabeculae structures after subarachnoid hemorrhage. Further studies are needed to confirm our findings.

Follow-up of Vasospasm by Transcranial Doppler Sonography (TCD) in Subarachnoid Hemorrhage (SAH).

Introduction:Subarachnoid hemorrhage (SAH)represents hemorrhage in the space between arachnoidea and pia mater, due to aneurysm burst, spontaneously or as a consequence of trauma. It is condition that occurs more common in women than men, and its most common complications are rebleeding and vazospasm. As a result of vasospasm, develops ischemia in the portion of brain tissue that can cause additional neurological deficit. Transcranial Doppler Sonography (TCD) is a noninvasive ultrasound diagnostic method that allows monitoring of the state of intracerebral hemodynamics.Goal:The goal is to follow the occurrence of vasospasm after SAH, by the TCD method.Material and methods:We have analyzed 47 patients with SAH, by analyzing the presence of aneurysm, hypertension and smoking, and by the TCD method monitor the state of intracerebral hemodynamics during the first four days, then in the second and third week.Results:SAH was more common in women (61.7%) than men (38.3%), and in the age range from 22 to 64 years. Aneurism was demonstrated in 61.7% of patients, more common in women, with hypertension 68.1% also more common in women and smoking in 87.2% of patients, also more common in women. By TCD method are recorded milder, elevated blood flow velocities at a quarter of patients in the first measurement, during the second measurement at all and it had significantly greater value, and the third measurement also more increased in about a quarter of patients, so that there is a statistically significant difference in the first and second, second and third measurement for each vessel separately, but not between the first and third measurement.Conclusion:Predilection factors for SAH are aneurysms, hypertension and smoking. By using TCD method were recorded milder elevated blood flow velocity in the first days of SAH, with about a quarter of patients, significantly greater increase in blood flow velocity during the second week in all patients and also milder increase blood flow velocity in the third week of the start of SAH is a quarter of patients. TCD is the method of choice in the evaluation and management of vasospasm after SAH, which allows the prevention of delayed cerebral ischemia.

Expression of high-mobility group box-1 (HMGB1) in the basilar artery after experimental subarachnoid hemorrhage

It has been suggested that inflammatory damage may be involved in the pathogenesis of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). High-mobility group box-1 protein (HMGB1) has been identified as a potent proinflammatory mediator, and may trigger increases in other inflammatory cytokines. However, little is known about the role of HMGB1 in SAH-induced cerebrovascular inflammation. In this study, 48 male rats were assigned randomly to four groups: a control group, or SAH day 3, day 5, or day 7 groups. The animals in SAH day 3, day 5, and day 7 groups were subjected to injection of autologous blood into the cisterna magna twice, on day 0 and day 2, and were killed on days 3, 5, and 7, respectively. Cross-sectional area of the basilar artery was measured and the HMGB1 expression was assessed by immunohistochemistry and western blot analysis. The mRNA level of HMGB1 was also determined by reverse transcription polymerase chain reaction. The basilar arteries exhibited vasospasm after SAH which was most severe on day 3 and 5. Elevated expression of HMGB1 was detected after SAH and was highest on day 3 and 5. HMGB1 is increasingly expressed in parallel to the development of CVS in this rat experimental model of SAH. These results suggest that HMGB1 may be related to the CVS observed after SAH and HMGB1 may play a key role in the inflammatory response in CVS after SAH.

Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage.

Statins may promote vasodilation following subarachnoid hemorrhage (SAH) and improve the response to blood pressure elevation. We sought to determine whether simvastatin increases cerebral blood flow (CBF) and alters the response to induced hypertension after SAH. Statin-naïve patients admitted <72h after WFNS ≥2 aneurysmal SAH were randomly assigned to 80mg simvastatin/day or placebo for 21days. Regional CBF was measured with quantitative (15)O PET on SAH day 7-10 before and after raising mean arterial pressure (MAP) 20-25%. Autoregulatory index (AI) was calculated as the ratio of % change in resistance (MAP/CBF) to % change in MAP. Angiography was performed within 24h of PET. Results are presented as simvastatin vs. placebo. Thirteen patients received simvastatin and 12 placebo. Clinical characteristics were similar. Moderate or severe angiographic vasospasm occurred in 42 vs. 45% and delayed cerebral ischemia in 14 vs. 55% (p=0.074). During PET studies, MAP (110±10 vs. 111±12), global CBF (41±12 vs. 43±13), and CVR (2.95±1.0 vs. 2.81±1.0) did not differ at baseline. When MAP was raised to 135±7mm Hg vs. 137±15, global CBF did not change. Global AI did not differ (107±59 vs. 0. 89±52%, p=0.68). CBF did not change in regions with low baseline flow or in regions supplied by vessels with angiographic vasospasm in either group. Six-month modified Rankin Scale scores did not differ. Our data indicate that initiation of therapy with high-dose simvastatin does not alter baseline CBF or response to induced hypertension.

Abstract T P400: Subarachnoid Hemorrhage-Induced Reactive Astrogliosis Is Correlated With Inversion of Neurovascular Coupling

Poor patient outcome following aneurysmal subarachnoid hemorrhage (SAH) has been linked to delayed cerebral ischemia (DCI), presenting several days following aneurysm rupture. Enhanced constriction of the brain vasculature, including intracerebral (parenchymal) arterioles contribute to SAH-induced DCI. Activity-dependent blood flow through parenchymal arterioles is controlled by local neuronal and astrocytic activity, a process known as neurovascular coupling. In response to numerous types of brain insults (e.g. tumors, trauma, and strokes), astrocytes undergo a transformation to a reactive phenotype, reactive astrogliosis, characterized by hypertrophy and hyperplasia. Here, we examined the hypothesis that SAH-induced reactive gliosis of perivascular astrocytes contribute to enhanced parenchymal arteriolar constriction. Astrocyte and vascular changes were assessed in a mouse endovascular perforation SAH model. Glial fibrillary acidic protein (GFAP), an astrocyte-specific intermediate filament that is upregulated during reactive astrogliosis, was assessed by immunohistochemistry in brain cortex of the middle cerebral artery territory. We observed increased GFAP staining at Day 2 and Day 4 following induction of SAH when compared to brain sections from control and sham-operated animals (all p values &lt;.05). In separate animals, neurovascular coupling was examined using two-photon and infrared-differential interference contrast microscopy. In brain slices from control and sham-operated animals, neuronal activation caused the anticipated neurovascular response-an increase in astrocyte endfoot Ca2+ followed by parenchymal arteriole dilation. In marked contrast, brain slices from SAH animals exhibited an inverted neurovascular response (i.e. vasoconstriction rather than vasodilation) in ≈ 80% of brain slices from day 1 and day 2 SAH mice and ≈ 60% of slices from SAH day 4 mice. In conclusion, we demonstrate changes in astrocyte structure, the development of reactive astrogliosis, correlate to a polarity shift in neurovascular coupling after SAH. These data indicates that SAH-induced reactive astrogliosis may play an important role in DCI development.

Safety and tolerability of gabapentin for aneurysmal subarachnoid hemorrhage (sah) headache and meningismus.

Headache after aneurysmal subarachnoid hemorrhage (SAH) is very common and is often described as the "worst headache imaginable." SAH-associated headache can persist for days to weeks and is traditionally treated with narcotics. However, narcotics can have significant adverse effects. We hypothesize that gabapentin (GBP), a non-narcotic neuropathic pain medication, would be safe and tolerable and would reduce narcotic requirements after SAH. We retrospectively reviewed the clinical, radiographic, and laboratory data of SAH patients at the neuroscience intensive care unit at Mayo Clinic in Jacksonville, Florida, from January 2011 through February 2013. Headache intensity was quantified by a visual analog scale score. Total opioid use per day was tabulated using an intravenous morphine equivalents scale. Cerebrospinal fluid was also reviewed when available. There were 53 SAH patients who were treated with GBP along with other analgesics for headache. Among these SAH patients, 34 (64 %) were women, with a mean age of 54 years (SD 12.3). Severe headache was observed in all SAH patients. GBP dosing was rapidly escalated within days of SAH up to a median of 1,200 mg/day, with a range of 300 mg three times a day to 900 mg three times a day. Approximately 6 % of patients treated with GBP had nausea (95 % CI 1-16 %), and only one patient (1.8 %) had to discontinue GBP. GBP appears to be relatively safe and tolerable in SAH patients with headache and may be a useful narcotic-sparing agent to prevent narcotics-associated complications, such as gastrointestinal immobility, ileus, and constipation.

In vivo and ex vivo dysfunction of neurovascular coupling in a mouse model of subarachnoid hemorrhage (676.3)

Neurovascular coupling (NVC) represents activity‐dependent focal increases in cerebral blood flow (CBF) crucial for the enhanced delivery of nutrients to maintain brain function in regions of high metabolic demand. We have previously reported inversion of NVC, with neuronal activation causing vasoconstriction rather than vasodilation, in brain slices from subarachnoid hemorrhage (SAH) model rats (Koide et al, 2012). Here, we examined ex vivo NVC, in vivo functional hyperemia and sensory motor function using a mouse endovascular perforation SAH model. In brain slices, astroctyic endfoot Ca2+ and adjoining parenchymal arteriolar diameter were measured using two‐photon and infrared‐differential interference contrast microscopy. Neuronal activation caused increased endfoot Ca2+ that was followed by an inverted neurovascular response (i.e. vasoconstriction rather than vasodilation) in ~ 80% of brain slices from day 1 and day 2 SAH mice and ~ 30% of slices from SAH day 4 mice. In vivo functional hyperemia (whisker stimulation‐induced CBF increases) measured by laser Doppler flowmetry in SAH day 1 mice was also significantly attenuated. Consistent with impaired NVC, SAH mice showed a decreased ability to perform sensory motor tasks. These data demonstrate dysfunction of neurovascular coupling occurs both ex vivo and in vivo following SAH, which may contribute to the development of neuronal deficits. Grant Funding Source: Supported by Totman Research Trust, P. Martin Endowment, NIH P01HL095488, P30RR032135 &amp; P30GM103498.

Heart Rate Variability for Preclinical Detection of Secondary Complications After Subarachnoid Hemorrhage

We sought to determine if monitoring heart rate variability (HRV) would enable preclinical detection of secondary complications after subarachnoid hemorrhage (SAH). We studied 236 SAH patients admitted within the first 48 h of bleed onset, discharged after SAH day 5, and had continuous electrocardiogram records available. The diagnosis and date of onset of infections and DCI events were prospectively adjudicated and documented by the clinical team. Continuous ECG was collected at 240 Hz using a high-resolution data acquisition system. The Tompkins-Hamilton algorithm was used to identify R-R intervals excluding ectopic and abnormal beats. Time, frequency, and regularity domain calculations of HRV were generated over the first 48 h of ICU admission and 24 h prior to the onset of each patient's first complication, or SAH day 6 for control patients. Clinical prediction rules to identify infection and DCI events were developed using bootstrap aggregation and cost-sensitive meta-classifiers. The combined infection and DCI model predicted events 24 h prior to clinical onset with high sensitivity (87 %) and moderate specificity (66 %), and was more sensitive than models that predicted either infection or DCI. Models including clinical and HRV variables together substantially improved diagnostic accuracy (AUC 0.83) compared to models with only HRV variables (AUC 0.61). Changes in HRV after SAH reflect both delayed ischemic and infectious complications. Incorporation of concurrent disease severity measures substantially improves prediction compared to using HRV alone. Further research is needed to refine and prospectively evaluate real-time bedside HRV monitoring after SAH.

Ischemia modified albumin increase indicating cardiac damage after experimental subarachnoid hemorrhage

BackgroundCardiac complications are often developed after subarachnoid hemorrhage (SAH) and may cause sudden death of the patient. There are reports in the literature addressing ischemia modified albumin (IMA) as an early and useful marker in the diagnosis of ischemic heart events. The aim of this study is to evaluate serum IMA by using the albumin cobalt binding (ACB) test in the first, second, and seventh days of experimental SAH in rats.Twenty-eight Wistar albino rats were divided into four groups each consisting of seven animals. These were classified as control group, 1st, 2nd and 7th day SAH groups. SAH was done by transclival basilar artery puncture. Blood samples were collected under anesthesia from the left ventricles of the heart using the cardiac puncture method for IMA measurement. Histopathological examinations were performed on the heart and lung tissues. Albumin with by colorimetric, creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were determined on an automatic analyser using the enzymatic method. IMA using by ACB test was detected with spectrophotometer.ResultsSerum IMA (p = 0.044) in seventh day of SAH were higher compared to the control group. Total injury scores of heart and lung tissue, also myocytolysis at day 7 were significantly higher than control group (p = 0.001, p = 0.001, p = 0.001), day 1 (p = 0.001, p = 0.001, p = 0.001) and day 2 (p = 0.001, p = 0.007, p = 0.001). A positive correlation between IMA - myocytolysis (r = 0.48, p = 0.008), and between IMA – heart tissue total injury score (r = 0.41, p = 0.029) was found.ConclusionThe results revealed that increased serum IMA may be related to myocardial stress after SAH.

The impact of surgical timing on the management of aneurysms with acute hydrocephalus after aneurysmal subarachnoid hemorrhage.

To explore the feasibility and effectiveness of early microsurgical therapy for acute hydrocephalus resulting from a ruptured intracranial aneurysm. Forty patients with Hunt-Hess grades II-III were assigned to group A; 27 patients with grades IV-V formed group B. The patients were also divided into 2 groups based on the time interval between the hemorrhage and surgery. Subjects in the early surgery group underwent aneurysm clipping within 3 days of subarachnoid hemorrhage (SAH), followed by intraoperative lateral ventricle puncture and third ventriculostomy. Subjects in the late surgery group underwent aneurysm clipping within 10 days of SAH, after initial treatment with lateral ventricular drainage. Three months after surgery, we used the Glasgow Outcome Scale (GOS) to compare the differences between the early and late surgery groups. More patients benefited from early surgery than from late surgery in both groups: GOS4-5 was achieved by 75% and 73.3% of early-surgery patients compared to 37.5% and 25% of late-surgery patients from Groups A and B, respectively (both p < 0.05). Analysis of the relationship between surgical timing and outcomes with the Ridit method showed that outcomes of early surgery were better than those of late surgery (p < 0.05). Aneurysmal SAH with acute hydrocephalus requires early surgery.

Multicenter Prospective Cohort Study on Volume Management After Subarachnoid Hemorrhage

Systemic circulation management has not been established for patients with poor grade aneurysmal subarachnoid hemorrhage (SAH) or delayed cerebral ischemia (DCI) after SAH. The aims of the study were to examine hemodynamic variables in these patients and to establish treatment strategies. A multicenter prospective cohort study of hemodynamic variables from days 1 to 14 was performed using a transpulmonary thermodilution system (PiCCO Plus). Parameters were analyzed by Mann-Whitney test. Multivariate analysis was performed to identify parameters involved in onset of DCI. The subjects were 204 patients, including 138 with poor grade SAH (World Federation of Neurological Surgeons grades IV and V) and 52 who developed DCI. The extravascular lung water index, pulmonary vascular permeability index, and systemic vascular resistance index were significantly greater in patients with poor grade SAH compared with those with good grade SAH (World Federation of Neurological Surgeons I-III) on day 2 (P=0.049, P=0.039, and P=0.038). Cardiac index was significantly lower in patients with poor grade SAH on days 1 and 2 (P=0.027 and P=0.011). In patients with DCI, the global end-diastolic volume index was significantly lower than in those without DCI on days 3 to 5 (P=0.0053; P=0.048; and P=0.048). In multivariate analysis, median global end-diastolic volume index, cardiac index, and systemic vascular resistance index at an early stage of SAH (days 3-6) were independently related to onset of DCI (P=0.023, P=0.013, and P=0.003). Patients with poor grade SAH developed heart failure-like afterload mismatch at an early stage, and those with DCI had decreased global end-diastolic volume index (hypovolemia) in the early stage of SAH. http://www.clinicaltrials.gov. Unique identifier: UMIN000003794.

Prediction of Cerebral Vasospasm Using Early Stage Transcranial Doppler

Transcranial Doppler (TCD) is widely used to monitor vasospasm after subarachnoid hemorrhage (SAH), but its ability to predict the future occurrence of the symptomatic vasospasm (SVS) remains controversial. We investigated the utility of TCD for predicting the future occurrence of SVS after SAH in 45 patients with aneurysmal SAH. TCD was performed on days 1, 3, 5, 7, 10, and 14 after SAH. The mean flow velocity (MFV) of the horizontal portion of the middle cerebral artery (M1) was recorded. SVS occurred in 24.4% of patients (n = 11). MFV of M1 increased progressively in patients with SVS, but did not increase in patients without SVS. The mean MFV values were significantly higher in patients with SVS than in patients without SVS (p = 0.031). The mean MFV value on day 3 was already significantly higher in patients with SVS than in patients without SVS (88.5 cm/sec versus 62.7 cm/sec, respectively) (p = 0.018). The receiver operating characteristic curve of MFV on day 3 showed the threshold of 72.5 cm/sec for predictive value of SVS in the future (sensitivity 71.4%, specificity 68.1%, and accuracy 82.3%). Increased MFV of M1 during the early stage of SAH may predict the future occurrence of SVS. The threshold value of 72.5 cm/sec MFV of M1 on SAH day 3 was one of the best predictor of future SVS. To prevent delayed cerebral ischemia, aggressive treatment for vasospasm is needed for patients with increased MFV in the early stages of SAH.

Acute postoperative neurological deterioration associated with surgery for ruptured intracranial aneurysm: incidence, predictors, and outcomes.

Subarachnoid hemorrhage (SAH) results in significant morbidity and mortality, even among patients who reach medical attention in good neurological condition. Many patients have neurological decline in the perioperative period, which contributes to long-term outcomes. The focus of this study is to characterize the incidence of, characteristics predictive of, and outcomes associated with acute postoperative neurological deterioration in patients undergoing surgery for ruptured intracranial aneurysm. The Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) was a multicenter randomized clinical trial that enrolled 1001 patients and assesssed the efficacy of hypothermia as neuroprotection during surgery to secure a ruptured intracranial aneurysm. All patients had a radiographically confirmed SAH, were classified as World Federation of Neurosurgical Societies (WFNS) Grade I-III immediately prior to surgery, and underwent surgery to secure the ruptured aneurysm within 14 days of SAH. Neurological assessment with the National Institutes of Health Stroke Scale (NIHSS) was performed preoperatively, at 24 and 72 hours postoperatively, and at time of discharge. The primary outcome variable was a dichotomized scoring based on an IHAST version of the Glasgow Outcome Scale (GOS) in which a score of 1 represents a good outcome and a score > 1 a poor outcome, as assessed at 90-days' follow-up. Data from IHAST were analyzed for occurrence of a postoperative neurological deterioration. Preoperative and intraoperative variables were assessed for associations with occurrence of postoperative neurological deterioration. Differences in baseline, intraoperative, and postoperative variables and in outcomes between patients with and without postoperative neurological deterioration were compared with Fisher exact tests. The Wilcoxon rank-sum test was used to compare variables reported as means. Multiple logistic regression was used to adjust for covariates associated with occurrence of postoperative deficit. Acute postoperative neurological deterioration was observed in 42.6% of the patients. New focal motor deficit accounted for 65% of postoperative neurological deterioration, while 60% was accounted for using the NIHSS total score change and 51% by Glasgow Coma Scale score change. Factors significantly associated with occurrence of postoperative neurological deterioration included: age, Fisher grade on admission, occurrence of a procedure prior to aneurysm surgery (ventriculostomy), timing of surgery, systolic blood pressure during surgery, ST segment depression during surgery, history of abnormality in cardiac valve function, use of intentional hypotension during surgery, duration of anterior cerebral artery occlusion, intraoperative blood loss, and difficulty of aneurysm exposure. Of the 426 patients with postoperative neurological deterioration at 24 hours after surgery, only 46.2% had a good outcome (GOS score of 1) at 3 months, while 77.7% of those without postoperative neurological deterioration at 24 hours had a good outcome (p < 0.05). Neurological injury incurred perioperatively or in the acute postoperative period accounts for a large percentage of poor outcomes in patients with good admission WFNS grades undergoing surgery for aneurysmal SAH. Avoiding surgical factors associated with postoperative neurological deterioration and directing investigative efforts at developing improved neuroprotection for use in aneurysm surgery may significantly improve long-term neurological outcomes in patients with SAH.

Abstract 2834: Elevated Blood and Cerebrospinal Fluid Matrix Metalloproteinase-9 is Associated with Poor 3-month Outcome Following Subarachnoid Hemorrhage

Background There is growing evidence supporting the role of inflammation in early brain injury (EBI) and cerebral vasospasm following subarachnoid hemorrhage (SAH). Matrix Metalloproteinases (MMP) are released by inflammatory cells and can mediate EBI via disruption of the extracellular matrix. MMPs also cleave endothelin-1 (ET-1) into strongly vasoactive fragments and may thereby mediate vasospasm, which can further worsen SAH outcome. We hypothesize that elevated MMP-9 in human cerebrospinal fluid (CSF) is associated with vasospasm and SAH outcome, and therefore a potential clinical biomarker. Methods We prospectively enrolled consecutive SAH subjects, banked serial blood and CSF samples, and evaluated their 3- and 6-month modified Rankins scores (mRS) via telephone follow-up. Angiographic vasospasm was defined as &gt;50% reduction in vessel caliber on angiography on post-SAH day 6-8. Poor outcome was defined as mRS&gt;2. We compared blood and CSF MMP-9 by ELISA on post SAH days 0-1, 2-3, 4-5, 6-8, and 10-14 in a cohort of SAH subjects (N=35) with respect to vasospasm and to 3-month outcome. Continuous variables were compared using student t-test or Wilcoxan rank sum test depending on data normality. Repeated measurements were analyzed using longitudinal regression. Results The study population had a mean age of 53 years and has 54% female. Sixty percent of subjects presented with Hunt and Hess grade of 3 and above. Fifty-four percent developed vasospasm and 32% achieved poor 3-month outcome. Elevation of CSF MMP-9 throughout post SAH days 0-14 was associated with poor 3-month outcome (p=0.008). Specifically, elevated CSF MMP-9 on post SAH day 2-3 (p=0.05) and blood MMP-9 on post SAH day 4-5 (p=0.045) were associated with poor 3-month outcome ( Figure 1 ). Blood MMP-9 correlated strongly with blood leukocyte count (r=0.56, p=0.007). Neither CSF nor blood MMP-9 correlated with vasospasm. Conclusion Early elevation of CSF and blood MMP-9 are associated with poor 3-month outcome but not with vasospasm in SAH. Leukocytes are likely a significant source of blood but not CSF MMP-9. Blood and CSF MMP-9 may mediate neuronal death in SAH via mechanisms independent of angiographic vasospasm. Further studies are necessary to determine the source of CSF MMP-9 and the mechanism by which it mediates poor outcome in SAH. Larger prospective studies are necessary to validate CSF MMP-9 as a predictive biomarker for SAH outcome.