Delayed Cerebral Ischemia Onset Research Articles

Value of Glycemic Indices for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Retrospective Single-Center Study

Delayed cerebral ischemia (DCI) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH), linked to poor functional outcomes and prolonged intensive care unit (ICU) stays. Timely DCI diagnosis is crucial but remains challenging. Dysregulated blood glucose, commonly observed after aSAH, may impair the constant glucose supply that is vital for brain function, potentially contributing to DCI. This study aimed to assess whether glucose indices could help identify at-risk patients and improve DCI detection. This retrospective, single-center observational study examined 151 aSAH patients between 2016 and 2019. Additionally, 70 of these (46.4%) developed DCI and 81 did not (no-DCI). To determine the value of glycemic indices for DCI, they were analyzed separately in patients in the period before (pre-DCI) and after DCI (post-DCI). The time-weighted average glucose (TWAG, p = 0.024), mean blood glucose (p = 0.033), and novel time-unified dysglycemic rate (TUDR140, calculated as the ratio of dysglycemic to total periods within a glucose target range of 70–140 mg/dL, p = 0.042), showed significantly higher values in the pre-DCI period of the DCI group than in the no-DCI group. In the time-series analysis, significant increases in TWAG and TUDR140 were observed at the DCI onset. In conclusion, DCI patients showed elevated blood glucose levels before and a further increase at the DCI onset. Prospective studies are needed to confirm these findings, as this retrospective, single-center study cannot completely exclude confounders and limitations. In the future blood glucose indices might become valuable parameters in multiparametric models to identify patients at risk and detect DCI onset earlier.

Temporal Immune Profiling in the CSF and Blood of Patients with Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is a significant complication of aneurysmal subarachnoid hemorrhage (aSAH). This study profiled immune responses after aSAH and evaluated their association with DCI onset. Twelve aSAH patients were enrolled. Leukocyte populations and cytokine levels were analyzed in cerebrospinal fluid (CSF) and peripheral blood (PB) on days 3, 5, 7, 10, and 14 post-aSAH. Peripheral blood mononuclear cells (PBMCs) were collected and their cytokine production quantified following stimulation. Mixed-effects models revealed distinct immune cell dynamics in CSF compared to blood. Natural killer T cell frequency increased over time in CSF only, while monocyte/macrophage numbers increased in both CSF and PBMCs. CD4+ HLA II+ T cells increased in circulation. Unstimulated PBMCs showed increased IL-1β, IL-6, and TNFα production, peaking at 7 days post-aSAH, coinciding with typical DCI onset. Ex vivo stimulation of PBMCs showed that only IL-6 significantly changed over time. In CSF, cytokines peaked 5 days post-injury, preceding immune cell profile alterations. Our findings reveal a time-dependent immune response following aSAH, with distinct within-patient patterns in CSF and PB. The early CSF cytokine peak preceding immune cell changes suggests a potential mechanistic link and identifies the cytokine response as a promising therapeutic target. This cytokine surge may drive immune cell expansion and prime PBMCs for increased inflammatory activity, potentially contributing to DCI risk. Future studies should explore the importance and sources of specific cytokines in driving immune activation. These insights may inform the development of targeted immunomodulatory strategies for preventing or managing DCI in aSAH patients.

Association of ABO Blood Group with Delayed Cerebral Ischemia and Clinical Outcomes Following Aneurysmal Subarachnoid Hemorrhage in Pakistan.

Background The ABO blood type, due to its various hemostaseologic properties, has been associated with several vascular diseases, including aneurysmal subarachnoid hemorrhage (aSAH). However, the role of ABO blood type in delayed cerebral ischemia (DCI) onset and other clinical outcomes after aSAH is largely unexplored. This study aimed to investigate the association between ABO blood type and outcomes after aSAH, primarily DCI. Methods A retrospective analysis was made on the data collected from 175 aSAH patients at a tertiary supraregional neurosurgery department over 5 years. Socio-demographic factors, clinical variables (DCI, mFG, WFNS grade, and Glasgow Outcome Scale at discharge), EVD placement, and aneurysm size were analyzed for their association with ABO blood type. Results DCI was reported in 25% of patients with 'O' blood type and 9.6% with 'non-O' blood type. A stepwise logistic regression model showed that after adjusting for BMI, mFG, WFNS grade, and EVD placement, 'O' type blood group was an independent risk factor for DCI, greatly increasing the risk of DCI as compared to 'non-O' type groups (OR = 3.27, 95% CI: 1.21-8.82). Conclusion This study provides evidence that individuals with 'O' blood type may have a higher risk of DCI onset after aSAH. However, further studies are essential to address the limitations of our work and confirm our findings.

High epileptiform discharge burden predicts delayed cerebral ischemia after subarachnoid hemorrhage

ObjectiveTo investigate whether epileptiform discharge burden can identify those at risk for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). MethodsRetrospective analysis of 113 moderate to severe grade SAH patients who had continuous EEG (cEEG) recordings during their hospitalization. We calculated the burden of epileptiform discharges (ED), measured as number of ED per hour. ResultsWe find that many SAH patients have an increase in ED burden during the first 3–10 days following rupture, the major risk period for DCI. However, those who develop DCI have a significantly higher hourly burden from days 3.5–6 after SAH vs. those who do not. ED burden is higher in DCI patients when assessed in relation to the onset of DCI (area under the receiver operator curve 0.72). Finally, specific trends of ED burden over time, assessed by group-based trajectory analysis, also help stratify DCI risk. ConclusionsThese results suggest that ED burden is a useful parameter for identifying those at higher risk of developing DCI after SAH. The higher burden rate associated with DCI supports the theory of metabolic supply-demand mismatch which contributes to this complication. SignificanceED burden is a novel biomarker for predicting those at high risk of DCI.

Dynamic Detection of Delayed Cerebral Ischemia

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage negatively impacts long-term recovery but is often detected too late to prevent damage. We aim to develop hourly risk scores using routinely collected clinical data to detect DCI. A DCI classification model was trained using vital sign measurements (heart rate, blood pressure, respiratory rate, and oxygen saturation) and demographics routinely collected for clinical care. Twenty-two time-varying physiological measures were computed including mean, SD, and cross-correlation of heart rate time series with each of the other vitals. Classification was achieved using an ensemble approach with L2-regularized logistic regression, random forest, and support vector machines models. Classifier performance was determined by area under the receiver operating characteristic curves and confusion matrices. Hourly DCI risk scores were generated as the posterior probability at time t using the Ensemble classifier on cohorts recruited at 2 external institutions (n=38 and 40). Three hundred ten patients were included in the training model (median, 54 years old [interquartile range, 45-65]; 80.2% women, 28.4% Hunt and Hess scale 4-5, 38.7% Modified Fisher Scale 3-4); 101 (33%) developed DCI with a median onset day 6 (interquartile range, 5-8). Classification accuracy before DCI onset was 0.83 (interquartile range, 0.76-0.83) area under the receiver operating characteristic curve. Risk scores applied to external institution datasets correctly predicted 64% and 91% of DCI events as early as 12 hours before clinical detection, with 2.7 and 1.6 true alerts for every false alert. An hourly risk score for DCI derived from routine vital signs may have the potential to alert clinicians to DCI, which could reduce neurological injury.

Role of ABO blood type in delayed cerebral ischemia onset and clinical outcomes after aneurysmal subarachnoid hemorrhage in an ethnic minority urban population.

Background: In recent years, the role of ABO blood type moved into focus through the discovery of different hemostaseologic properties with importance in many diseases including subarachnoid hemorrhage (SAH). However, the role of ABO blood type in delayed cerebral ischemia (DCI) onset, clinical progress, and outcome after SAH is to date largely unexplored. Our aim was to explore the role of ABO blood group in DCI and clinical outcomes after aneurysmal SAH (aSAH).Methods: A retrospective analysis was made with data collected from patients who presented aSAH at our single- academic center from 2015 to 2018. We included demographic, clinical, and imaging variables in the univariate analysis and in the subsequent multivariate analysis.Results: A total of 204 patients were included in this study. About 17.9% of “O” type patients developed a DCI while DCI was reported in only 8.2% of non-O type patients (P = 0.04). “O” type was an independent risk after in the logistic regression after adjusting for significant factors in the univariate analysis (OR=2.530, 95% CI: 1.040- 6.151, P = 0.41). Compared to “non-O” type patients, “O” type patients had a trend to have poorer outcomes at discharge (25.5% vs. 21.3%, P = 0.489) and at 12–18 months (21.1% vs. 19.5%, P = 0.795). However, there were no significant differences.Conclusion: Our study evidenced that patients with “O” blood type have higher risk of DCI onset after aSAH. Although these findings need to be confirmed, they may aid to improve DCI prevention and outcome predictions.

Heart rate variability monitoring for the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Delayed cerebral ischemia (DCI) is a major cause of impaired outcome after aneurysmal subarachnoidal hemorrhage (aSAH). In this observational cohort study we investigated whether changes in heart rate variability (HRV) that precede DCI could be detected. Sixty-four patients with aSAH were included. HRV data were collected for up to 10days and analyzed offline. Correlation with clinical status and/or radiologic findings was investigated. A linear mixed model was used for the evaluation of HRV parameters over time in patients with and without DCI. Extended Glasgow outcome scale score was assessed after 1year. In 55 patients HRV data could be analyzed. Fifteen patients developed DCI. No changes in HRV parameters were observed 24hours before onset of DCI. Mean of the HRV parameters in the first 48hours did not correlate with the development of DCI. Low/high frequency (LF/HF) ratio increased more in patients developing DCI (β -0.07 (95% confidence interval, 0.12-0.01); P=.012). Lower STDRR (standard deviation of RR intervals), RMSSD (root mean square of the successive differences between adjacent RR intervals), and total power (P=.003, P=.007 and P=.004 respectively) in the first 48hours were seen in patients who died within 1year. Impaired HRV correlated with 1-year mortality and LF/HF ratio increased more in patients developing DCI. Even though DCI could not be detected by the intermittent analysis of HRV used in this study, continuous HRV monitoring may have potential in the detection of DCI after aSAH using different methods of analysis.

Extracellular Mitochondrial Dysfunction in Cerebrospinal Fluid of Patients with Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage.

Mitochondrial dysfunction is related to brain ischemic injury and neural cell death. However, little is known about the association between mitochondrial dysfunction of cerebrospinal fluid (CSF) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). The objective of this study was to investigate whether extracellular CSF mitochondria might serve as a potential biomarker for DCI. CSF samples were serially collected at 1, 3, and 5days following SAH in 33 patients (DCI, n = 12; and non-DCI, n = 21) who underwent coil embolization. To monitor mitochondrial membrane potentials, JC-1 dye was used. The ratio (red/green) of JC-1 was considered as an indicator of intact mitochondrial membrane potential. Flow cytometry was done to analyze extracellular mitochondria particles and their possible cellular origins. DCI patients had lower JC-1 red/green ratios than non-DCI patients at 1day (3.35 [3.20-3.75] vs. 3.70 [3.40-3.95] in non-DCI) and 3days (4.65 [4.45-5.00] vs. 5.10 [4.65-5.30] in non-DCI) after SAH. At 5days after SAH, JC-1 red/green ratio was significantly lower in DCI than that in non-DCI (3.05 [2.90-3.35] vs. 4.20 [4.10-4.50]; p < 0.01) patients. DCI patients had a higher percentage of vWF-positive mitochondria (40.10% [38.25%-44.90%] vs. 30.20% [25.70%-36.68%]) and a lower percentage of GLAST-positive mitochondria particles (26.85% [17.10%-30.00%] vs. 31.60% [26.70%-35.00%]) than non-DCI patients. However, there was no significant difference in CD45-positive (p = 0.369) or CD41/61-positive mitochondrial particles (p = 0.155) between the two groups of patients. Mitochondrial membrane potential could be a marker of DCI. JC-1 ratios seemed to be able to predict future DCI onset. Further studies are needed to determine detailed mechanisms of extracellular mitochondria-mediated cell-to-cell signals in DCI.

Hippocampal Atrophy Following Subarachnoid Hemorrhage Correlates with Disruption of Astrocyte Morphology and Capillary Coverage by AQP4.

Despite successful management of ruptured intracranial aneurysm following subarachnoid hemorrhage (SAH), delayed cerebral ischemia (DCI) remains the main cause of high mortality and morbidity in patients who survive the initial bleeding. Astrocytes play a key role in neurovascular coupling. Therefore, changes in the neurovascular unit including astrocytes following SAH may contribute to the development of DCI and long-term complications. In this study, we characterized morphological changes in hippocampal astrocytes following experimental SAH, with special emphasis on glia-vascular cross-talk and hippocampal volume changes. Four days after induction of SAH or sham-operation in mice, their hippocampal volumes were determined by magnetic resonance imaging (MRI) and histological/stereological methods. Glial fibrillary acid protein (GFAP) immunostained hippocampal sections were examined by stereological techniques to detect differences in astrocyte morphology, and global spatial sampling method was used to quantify the length density of Aquaporin-4 (AQP4) positive capillaries. Our results indicated that hippocampal volume, as measured both by MRI and by histological approaches, was significantly lower in SAH animals than in the sham-operated group. Accordingly, in this animal model of SAH, hippocampal atrophy existed already at the time of DCI onset in humans. SAH induced retraction of GFAP positive astrocyte processes, accompanied by a significant reduction in the length density of AQP4 positive capillaries as well as narrowing of hippocampal capillaries. Meanwhile, astrocyte volume was higher in SAH mice compared with the sham-operated group. Morphological changes in hippocampal astrocytes seemingly disrupt glia-vascular interactions early after SAH and may contribute to hippocampal atrophy. We speculate that astrocytes and astrocyte-capillary interactions may provide targets for the development of therapies to improve the prognosis of SAH.

Abstract 38: Soluble ST2 Predicts Delayed Cerebral Ischemia and Outcome After Subarachnoid Hemorrhage

Introduction: Soluble ST2 (sST2) is a member of the Toll-like receptor superfamily implicated in pro-inflammatory signaling. We investigated whether sST2 predicts delayed cerebral ischemia (DCI) and 90-day clinical outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods: Soluble ST2 was measured in plasma samples from 182 patients who presented to a single institution with SAH. Blood samples were collected between days 1 and 5 after onset of SAH, and prior to the onset of DCI. Functional outcome was assessed at 3 months using the modified Rankin Scale (mRS) with good and poor outcome defined as mRS 0-2 and 3-6, respectively. Using a consensus definition, DCI was defined as a 2-point drop in GCS over a sustained period in patients whose clinical deterioration could not be explained by another cause. The relationships between sST2 level, DCI and outcome were assessed in univariable analysis. Multivariable logistic regression, Kaplan-Meier survival analysis, and receiver operating characteristic curves were used to determine the ability of sST2 to predict outcome and mortality. These findings were tested for replication in an independent cohort of 51 SAH patients recruited from a separate institution. Results: The discovery cohort consisted of 182 subjects (mean age 56±12 years, 61% women). Elevated plasma sST2 predicted the development of DCI (OR 2.10, 95% 1.06-4.18 CI, P=0.0295), which remained an independent predictor after adjustment for age, World Federation of Neurological Surgeons (WFNS) grading score, modified Fisher score, intra-arterial vasodilator therapy and hydrocephalus (OR 2.78, 95% CI 1.00-7.97, p=0.0453). Elevated sST2 was also independently associated with poor 90-day functional outcome (OR 2.65, 95%CI 1.07-6.59, P =0.0304), and mortality (OR 5.36, 95% CI 1.48-19.39, p=0.0039) when adjusted for age, WFNS score, modified Fisher score and hydrocephalus. In the replication cohort (N=51, 88% women), sST2 level was an independent predictor of DCI (OR 5.02, 95% CI 1.46-17.20, p=0.0034) and outcome at 90 days (OR 4.24, 95% CI 1.31-13.74, p=0.0072). Conclusion: Plasma sST2 level predicted risk of DCI, outcome, and mortality after SAH. Further study of the potential link between sST2 and brain injury after SAH is warranted.

The Role of Thromboinflammation in Delayed Cerebral Ischemia after Subarachnoid Hemorrhage

Delayed cerebral ischemia (DCI) is a major determinant of patient outcome following aneurysmal subarachnoid hemorrhage. Although the exact mechanisms leading to DCI are not fully known, inflammation, cerebral vasospasm, and microthrombi may all function together to mediate the onset of DCI. Indeed, inflammation is tightly linked with activation of coagulation and microthrombi formation. Thromboinflammation is the intersection at which inflammation and thrombosis regulate one another in a feedforward manner, potentiating the formation of thrombi and pro-inflammatory signaling. In this review, we will explore the role(s) of inflammation and microthrombi in subarachnoid hemorrhage (SAH) pathophysiology and DCI, and discuss the potential of targeting thromboinflammation to prevent DCI after SAH.

Biomarkers of Glycocalyx Injury are Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Case Series Supporting a New Hypothesis.

Delayed cerebral ischemia (DCI) contributes to morbidity following aneurysmal subarachnoid hemorrhage; however, its etiology remains poorly understood. DCI is not only a consequence of angiographic vasospasm, but also involves microthrombosis and neuroinflammation, two events with unexplained phenomenology. The vascular endothelial glycocalyx mediates platelet aggregation and endothelial cell-leukocyte interactions and may play an important role in DCI pathogenesis. We present a case series in which we conducted multiplex and singlet enzyme-linked immunosorbent assays of endothelial, glycocalyx, inflammatory, and neuroinjury proteins in both CSF and plasma in three patients during active DCI following SAH. Samples were obtained at baseline following surgical repair of SAH, and again at DCI onset. CSF was sampled at the same time points from in situ external ventricular drains. DCI was associated with significant elevations of soluble markers of endotheliopathy, including vascular adhesion protein-1, soluble fractions of endothelial cell adhesion molecules (CAMs), procoagulant tissue factor, and specific markers of glycocalyx injury, including syndecan-1, and CD44. These phenomena were also associated with an elevation of both circulating and CSF matrix metalloproteinases, which are known to cleave components of the glycocalyx. Elevation of vascular CAM-1 in the CSF with DCI indicated these events were possibly associated with the breakdown of brain microvasculature integrity. These preliminary data support the hypothesis that glycocalyx injury occurs in SAH, and might contribute to DCI by regulating cerebral microthrombosis and delayed neuroinflammation.

Cerebral Perfusion Pressure and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Whether delayed cerebral ischemia (DCI) mediates the relationship between Hunt and Hess grade and outcomes after aneurysmal subarachnoid hemorrhage remains unknown. To investigate the relationship between cerebral perfusion pressure, DCI, Hunt and Hess grade, and outcomes after aneurysmal subarachnoid hemorrhage. DCI was defined as neurological deterioration due to impaired cerebral blood flow. Relationships between minimum cerebral perfusion pressure and onset and occurrence of DCI were tested by using logistic regression and the accelerated failure time model. The mediation effect of DCI on relationships between Hunt and Hess grade and outcomes was tested by using the bootstrap confidence interval. Outcomes at 3 and 12 months included mortality and neuropsychological, functional, and physical outcomes. DCI occurred in 211 patients (42%). About one-third of the patients had poor functional outcome at 3 (32%) and 12 (30%) months. Impaired neuropsychological outcome was observed in 33% of patients at 3 months and 17% at 12 months. For every increase of 10 mm Hg in cerebral perfusion pressure, odds for DCI increased by 2.78 (95% CI, 2.00-3.87). High perfusion pressure was associated with earlier onset of DCI (P < .001). DCI does not mediate the relationship of Hunt and Hess grade to functional outcome or death. The relationship between cerebral perfusion pressure and DCI was most likely due to induced hypertension and hypervolemia. Clinical guidelines may need to include limits for induced hypertension.

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.

Changes in Cerebral Perfusion around the Time of Delayed Cerebral Ischemia in Subarachnoid Hemorrhage Patients

Background: Because the pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is unclear, we studied cerebral perfusion at different time points around the occurrence of DCI. Methods: We prospectively enrolled 53 patients admitted to the University Medical Center Utrecht who underwent CT perfusion (CTP) scans on admission, and within 2 weeks after hemorrhage on 2 scheduled time points or during clinical deterioration. The occurrence of DCI was assessed according to predefined criteria by 2 neurological observers blinded to perfusion results. Clinically stable patients (no-DCI) served as reference, and patients with other causes of deterioration (n = 11) were excluded. In DCI patients, the day of DCI onset and in no-DCI patients the median day of DCI onset was taken as t = 0. Scans made before and after DCI were clustered into 5 additional time points. At each time point, cerebral blood volume (CBV) and flow (CBF), and mean transit time (MTT) were measured, and absolute and relative (interhemispheric asymmetry) values were compared between DCI and no-DCI patients. Results: Absolute CBF was lower and MTT was higher in the 18 DCI patients than in the 24 no-DCI patients before, during and after DCI. MTT asymmetry increased during DCI and partially recovered afterwards in DCI patients while it remained constant in no-DCI patients. Absolute and relative CBV remained constant in both groups. Conclusions: Our findings suggest that DCI patients already have diffusely worse perfusion (absolute values) than no-DCI patients before focal worsening (increased asymmetry) occurs and becomes symptomatic. The partial recovery in the measured areas suggests that DCI can be partly reversible.

Association of Platelet and Leukocyte Counts with Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Background and Purpose: A proinflammatory prothrombotic state may increase the risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). We studied the relationship of levels of leukocytes, platelets, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) with the development of DCI and with clinical outcome in patients with aneurysmal SAH. Methods: In 125 patients admitted within 72 h after aneurysmal SAH, we dichotomized initial blood levels at their median values and investigated the prediction of DCI with Cox proportional hazard analysis and of poor clinical outcome with logistic regression analysis. We also analyzed concentrations before and after onset of DCI with the paired-samples t test and compared changes with those in patients without DCI. Results: During the development of DCI (unrelated to treatment), patients had a larger increase in counts of platelets (difference 49 × 10⁹/l; 95% CI: 2–98) and leukocytes (difference 2.6 × 10⁹/l; 95% CI: 0.4–5.0) than patients without DCI during the same period. CRP increased during DCI and decreased in patients without DCI (difference 14 mg/l; 95% CI: –29 to 58). ESR increased slightly in both groups (difference 3 mm/h; 95% CI: –15 to 20). None of the determinants at baseline predicted the development of DCI. An increased risk of poor outcome predicted by a high initial leukocyte count (OR 2.5; 95% CI: 1.1–5.7) decreased after adjustment for clinical variables (OR 2.1; 95% CI: 0.8–5.5). Conclusion: Counts of platelets and leukocytes disproportionally increase during the occurrence of DCI after aneurysmal SAH. Drugs with anti-thrombotic or anti-inflammatory properties should be studied for prevention and treatment of DCI.

TRANSCRANIAL DOPPLER FOR PREDICTING DELAYED CEREBRAL ISCHEMIA AFTER SUBARACHNOID HEMORRHAGE

Transcranial Doppler (TCD) is widely used to monitor the temporal course of vasospasm after subarachnoid hemorrhage (SAH), but its ability to predict clinical deterioration or infarction from delayed cerebral ischemia (DCI) remains controversial. We sought to determine the prognostic utility of serial TCD examination after SAH. We analyzed 1877 TCD examinations in 441 aneurysmal SAH patients within 14 days of onset. The highest mean blood flow velocity (mBFV) value in any vessel before DCI onset was recorded. DCI was defined as clinical deterioration or computed tomographic evidence of infarction caused by vasospasm, with adjudication by consensus of the study team. Logistic regression was used to calculate adjusted odds ratios for DCI risk after controlling for other risk factors. DCI occurred in 21% of patients (n = 92). Multivariate predictors of DCI included modified Fisher computed tomographic score (P = 0.001), poor clinical grade (P = 0.04), and female sex (P = 0.008). After controlling for these variables, all TCD mBFV thresholds between 120 and 180 cm/s added a modest degree of incremental predictive value for DCI at nearly all time points, with maximal sensitivity by SAH day 8. However, the sensitivity of any mBFV more than 120 cm/s for subsequent DCI was only 63%, with a positive predictive value of 22% among patients with Hunt and Hess grades I to III and 36% in patients with Hunt and Hess grades IV and V. Positive predictive value was only slightly higher if mBFV exceeded 180 cm/s. Increased TCD flow velocities imply only a mild incremental risk of DCI after SAH, with maximal sensitivity by day 8. Nearly 40% of patients with DCI never attained an mBFV more than 120 cm/s during the course of monitoring. Given the poor overall sensitivity of TCD, improved methods for identifying patients at high risk for DCI after SAH are needed.

Hypomagnesemia after aneurysmal subarachnoid hemorrhage.

Hypomagnesemia frequently occurs in hospitalized patients, and it is associated with poor outcome. We assessed the frequency and time distribution of hypomagnesemia after aneurysmal subarachnoid hemorrhage (SAH) and its relationship to the severity of SAH, delayed cerebral ischemia (DCI), and outcome after 3 months. Serum magnesium was measured in 107 consecutive patients admitted within 48 hours after SAH. Hypomagnesemia (serum magnesium <0.70 mmol/L) at admission was related to clinical and initial computed tomographic characteristics by means of the Mann-Whitney U test. Hypomagnesemia at admission and during the DCI onset period (Days 2-12) was related to the occurrence of DCI and hypomagnesemia at admission, and hypomagnesemia that occurred any time during the first 3 weeks after SAH was related to outcome. Hypomagnesemia at admission was found in 41 patients (38%) and was associated with more cisternal (P = 0.006) and ventricular (P = 0.005) blood, a longer duration of unconsciousness (P = 0.007), and a worse World Federation of Neurosurgical Societies scale score at admission (P = 0.001). The crude hazard ratio for DCI with hypomagnesemia at admission was 2.4 (95% confidence interval, 1.0-5.6), and after multivariate adjustment it was 1.9 (95% confidence interval, 0.7-4.7). The hazard ratio of hypomagnesemia from Days 2 to 12 for patients with DCI was 3.2 (range, 1.1-8.9) after multivariate adjustment. The crude odds ratio for poor outcome (Glasgow Outcome Scale score, 1-3) with hypomagnesemia at admission was 2.5 (range, 1.1-5.5). Hypomagnesemia at admission did not contribute to the prediction of outcome in the multivariate model. Hypomagnesemia is frequently present after SAH and is associated with severity of SAH. Hypomagnesemia occurring between Days 2 and 12 after SAH predicts DCI.