Occurrence and impact of delayed cerebral ischemia after coiling and after clipping in the International Subarachnoid Aneurysm Trial (ISAT)

Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). We studied differences in incidence and impact of DCI as defined clinically after coiling and after clipping in the International Subarachnoid Aneurysm Trial. We calculated odds ratios (OR) for DCI for clipping versus coiling with logistic regression analysis. With coiled patients without DCI as the reference group, we calculated ORs for poor outcome at 2 months and 1 year for coiled patients with DCI and for clipped patients without, and with DCI. With these ORs, we calculated relative excess risk due to Interaction (RERI). Clipping increased the risk of DCI compared to coiling in the 2,143 patients OR 1.24, 95% confidence interval (95% CI 1.01–1.51). Coiled patients with DCI, clipped patients without DCI, and clipped patients with DCI all had higher risks of poor outcome than coiled patients without DCI. Clipping and DCI showed no interaction for poor outcome at 2 months: RERI 0.12 (95% CI −1.16 to 1.40) or 1 year: RERI −0.48 (95% CI −1.69 to 0.74). Only for patients treated within 4 days, coiling and DCI was associated with a poorer outcome at 1 year than clipping and DCI (RERI −2.02, 95% CI −3.97 to −0.08). DCI was more common after clipping than after coiling in SAH patients in ISAT. Impact of DCI on poor outcome did not differ between clipped and coiled patients, except for patients treated within 4 days, in whom DCI resulted more often in poor outcome after coiling than after clipping.     

Achieved serum magnesium concentrations and occurrence of delayed cerebral ischaemia and poor outcome in aneurysmal subarachnoid haemorrhage

Background

Magnesium therapy probably reduces the frequency of delayed cerebral ischaemia (DCI) in subarachnoid haemorrhage (SAH) but uncertainty remains about the optimal serum magnesium concentration. We assessed the relationship between serum magnesium concentrations achieved with magnesium sulphate therapy 64 mmol/day and the occurrence of DCI and poor outcome in patients with SAH.

Methods

Differences in magnesium concentrations between patients with and without DCI and with and without poor outcome were calculated. Quartiles of last serum magnesium concentrations before the onset of DCI, or before the median day of DCI in patients without DCI, were related to the occurrence of DCI and poor outcome at 3 months using logistic regression.

Results

Compared with the lowest quartile of serum magnesium concentration (1.10–1.28 mmol/l), the risk of DCI was decreased in each of the higher three quartiles (adjusted odds ratio (OR) in each quartile 0.2; lower 95% CI 0.0 to 0.1; upper limit 0.8 to 0.9). The OR for poor outcome was 1.8 (95% CI 0.5 to 6.9) in the second quartile, 1.0 (95% CI 0.2 to 4.5) in the third quartile and 4.9 (95% CI 1.2 to 19.7) in the highest quartile.

Discussion

Magnesium sulphate 64 mmol/day results in a stable risk reduction of DCI over a broad range of achieved serum magnesium concentrations, and strict titration of the dosage therefore does not seem necessary. However, concentrations ⩽1.28 mmol/l could decrease the effect on DCI while concentrations ⩾1.62 might have a negative effect on clinical outcome.Aneurysmal subarachnoid haemorrhage (SAH) has a poor prognosis: half of patients die and one out of every five survivors remains dependent.¹ In patients who survive the initial hours after the haemorrhage and undergo early aneurysm treatment, delayed cerebral ischaemia (DCI) is the most important cause of poor outcome. DCI occurs in approximately one‐third of patients and develops mostly between the fourth and tenth day after SAH.^2,3Magnesium is a neuroprotective agent with a well established clinical profile, and is commonly used in obstetric medicine.^4,5 Hypomagnesaemia occurs in more than half of patients with SAH and is related to the occurrence of DCI.⁶ Recently, we conducted a randomised, placebo controlled phase II trial with magnesium sulphate in patients with SAH.⁷ Magnesium therapy reduced the occurrence of DCI by 34% (95% CI −14 to 62) and of poor outcome by 23% (95% CI −9 to 46). In this trial, magnesium sulphate was given in a standard dose of 64 mmol/day. With this dosage, 85% of patients had serum magnesium levels between 1.0 and 2.0 mmol/l.⁸ Whether there is an optimal serum magnesium concentration within this range is unclear.In this study, we assessed whether there is a relationship between achieved serum magnesium levels and the occurrence of DCI and poor outcome in patients with aneurysmal SAH treated with continuous magnesium sulphate infusion at a fixed dose.     

Magnesium and aspirin treatment in patients with subarachnoid haemorrhage

Objective   Aneurysm treatment with endovascular coiling is associated with a better outcome than neurosurgical clipping in patients with subarachnoid haemorrhage (SAH). The better outcome after coiling may decrease the risk reduction from other treatments in these patients, and thus may increase sample sizes for current or future neuroprotective trials. The influence of the method of aneurysm treatment was studied in our randomised MASH trial, which assessed in a factorial design the efficacy of magnesium and aspirin in preventing delayed cerebral ischaemia (DCI) and poor outcome. Methods   Between November 2000 and January 2004 315 patients were enrolled in the trial; 55 of them had no aneurysm treatment and were excluded for the current analysis, 176 underwent neurosurgical and 84 endovascular treatment. The effect of treatment on the risk of DCI was assessed by means of Cox proportional hazards modelling and that of poor outcome by means of logistic regression analysis. Results   The hazard ratio of DCI with aspirin was 1.4 (95 % CI 0.3 – 1.7) after coiling and 1.9 (0.8 – 4.4) after clipping, and with magnesium 0.4 (0.1 – 1.2) after coiling and 0.8 (0.4 – 1.7) after clipping. The odds ratio of poor outcome with aspirin was 0.7 (0.2 – 2.9) after coiling and 0.8 (0.3 – 2.3) after clipping, and with magnesium 0.3 (0.1 – 1.0) after coiling and 0.8 (0.4 – 1.6) after clipping. Conclusion   This post hoc analysis does not suggest that medical treatments are less effective after endovascular than after neurosurgical treatment in patients with SAH, and thus do not support a need for adjusting sample size calculations in future trials. Magnesium and Acetylsalicylic acid in Subarachnoid Haemorrhage (MASH) Study Group: W. M. van den Bergh,A. Algra, S. M. Dorhout Mees,J. van Gijn,G. J. E. Rinkel,Dept. of Neurology,University Medical Centre Utrecht,Utrecht, The Netherlands Ale Algra,Julius Centre for Health Sciences and Primary Care,University Medical Centre Utrecht,Utrecht, The Netherlands Fop van Kooten,Dept. of Neurology,Erasmus Medical Centre,Rotterdam, The Netherlands Clemens M.F. Dirven,Dept. of Neurology,VU University Medical Centre,Amsterdam, The Netherlands Marinus Vermeulen,Dept. of Neurology,Academic Medical CentreUniversity of Amsterdam,Amsterdam, The Netherlands W. M. van den Bergh, MD, PhD ✉, Dept. of Intensive Care, Room Q04.460,University Medical Centre Utrecht,P.O. Box 85500,3508 GA, Utrecht, The Netherlands,Tel.: +31-30/2508350,Fax: +31-30/2522782,E-Mail: w.m.vandenbergh@umcutrecht.nl     

Relation of Serum TNF-α and TNF-α Genotype with Delayed Cerebral Ischemia and Outcome in Subarachnoid Hemorrhage

Introduction  

The pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) remains obscure. The authors assessed the relationship of tumor necrosis factor alpha (TNF-α) and TNF-α gene polymorphisms with occurrence of DCI and poor outcome at 3 months.     

Interobserver agreement and predictive value for outcome of two rating scales for the amount of extravasated blood after aneurysmal subarachnoid haemorrhage

Background In patients with SAH the amount of extravasated blood on the initial CT scan is related with delayed cerebral ischemia and clinical outcome. We investigated the interobserver variation of the Hijdra and Fisher scales for the amount of extravasated blood and the predictive values of these scales for delayed cerebral ischemia and outcome. Methods For 132 patients admitted within 48 hours after SAH three observers assessed the amount of blood on the initial CT scan by means of the Hijdra and Fisher scale. We analyzed interobserver agreement with kappa statistics and used multivariate logistic regression for the association with delayed cerebral ischemia and clinical outcome. Results The interobserver agreement of all three pairs of observers was good for the Hijdra scale (kappas for total sum scores ranging from 0.67 to 0.75) and mild to moderate for the Fisher scale (kappas ranging from 0.37 to 0.55). For the Hijdra scale the risk of DCI was higher for intermediate (OR 4.2; 95% CI 1.1–16.3) and large (OR 3.6; 95% CI 0.8–16.4) amounts of blood with small amount as reference. Fisher grade III (OR 1.0; 95% CI 0.2–5.2) and IV (OR 0.3; 95% CI 0.02–4.0) were not related with DCI. For the Hijdra scale and clinical outcome we found an increasing risk for poor outcome with intermediate (OR 3.9; 95% CI 1.0–15.9) and large (OR 10.7; 95% CI 2.3–50.1) amounts of blood. Such a relation was not found for Fisher grade III (OR 1.2; 95% CI 0.2–7.0) and IV (OR 0.2; 95% CI 0.01–3.4). Conclusions For the Hijdra scale we found a distinct better interobserver agreement than for the Fisher score. Moreover, the Hijdra scale was an independent prognosticator for DCI and clinical outcome, which was not the case for the Fisher score. Received in revised form: 9 February 2006     

国际蛛网膜下腔出血动脉瘤试验:栓塞与夹闭后迟发性脑缺血的发生与影响(英文)

Delayed cerebral ischemia(DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage(SAH).We studied differences in incidence and impact of DCI as defined clinically after coiling and after clipping in the International Subarachnoid Aneurysm Trial.We calculated odds ratios(OR) for DCI for clipping versus coiling with logistic regression analysis.With coiled patients without DCI as the reference group,we calculated ORs for poor outcome at 2 months and 1 year for coiled patients with DCI and for clipped patients without,and with DCI.With these ORs,we calculated relative excess risk due to Interaction(RERI).Clipping increased the risk of DCI compared to coiling in the 2,143 patients OR 1.24,95% confidence interval(95% CI 1.01-1.51).Coiled patients with DCI,clipped patients without DCI,and clipped patients with DCI all had higher risks of poor outcome than coiled patients without DCI.Clipping and DCI showed no interaction for poor outcome at 2 months: RERI 0.12(95% CI-1.16 to 1.40) or 1 year: RERI-0.48(95% CI-1.69 to 0.74).Only for patients treated within 4 days,coiling and DCI was associated with a poorer outcome at 1 year than clipping and DCI(RERI-2.02,95% CI-3.97 to-0.08).DCI was more common after clipping than after coiling in SAH patients in ISAT.Impact of DCI on poor outcome did not differ between clipped and coiled patients,except for patients treated within 4 days,in whom DCI resulted more often in poor outcome after coiling than after clipping.     

Amount of blood during the subacute phase and clot clearance rate as prognostic factors for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Delayed cerebral ischemia (DCI) is a poorly predictable complication occurring after aneurysmal subarachnoid hemorrhage (SAH) that can have dramatic functional consequences. Identifying the patients with the highest risk of DCI may help to institute more suitable monitoring and therapy. Early brain injuries and aneurysm-securing procedure complications could be regarded as confounding factors leading to severity misjudgment. After an early resuscitation phase, a subacute assessment may be more relevant to integrate the intrinsic SAH severity.A retrospective analysis was performed upon patients prospectively included in the registry of SAH patients between July 2015 to April 2020. The amount of cisternal and intraventricular blood were assessed semi-quantitatively on acute and subacute CT scans performed after early resuscitation. A clot clearance rate was calculated from their comparison. The primary endpoint was the occurrence of a DCI.A total of 349 patients were included in the study; 80 (22.9%) experienced DCI. In those patients, higher Fisher grades were observed on acute (p = 0.026) and subacute (p = 0.003) CT scans. On the subacute CT scan, patients who experienced DCI had a higher amount of blood, either at the cisternal (median Hijdra sum score: 11 vs 5, p < 0.001) or intraventricular (median Graeb score: 4 vs 2, p < 0.001) level. There was a negative linear relationship between the cisternal clot clearance rate and the risk of DCI.The assessment of the amount of subarachnoid blood and clot clearance following resuscitation after aneurysmal SAH can be useful for the prediction of neurological outcome.     

Effect of pharmaceutical treatment on vasospasm,delayed cerebral ischemia,and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

As it is often assumed that delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is caused by vasospasm, clinical trials often focus on prevention of vasospasm with the aim to improve clinical outcome. However, the role of vasospasm in the pathogenesis of DCI and clinical outcome is possibly smaller than previously assumed. We performed a systematic review and meta-analysis on all randomized, double-blind, placebo-controlled trials that studied the effect of pharmaceutical preventive strategies on vasospasm, DCI, and clinical outcome in SAH patients to further investigate the relationship between vasospasm and clinical outcome. Effect sizes were expressed in pooled risk ratio (RR) estimates with corresponding 95% confidence intervals (CI). A total of 14 studies randomizing 4,235 patients were included. Despite a reduction of vasospasm (RR 0.80 (95% CI 0.70 to 0.92)), no statistically significant effect on poor outcome was observed (RR 0.93 (95% CI 0.85 to 1.03)). The variety of DCI definitions did not justify pooling the DCI data. We conclude that pharmaceutical treatments have significantly decreased the incidence of vasospasm, but not of poor clinical outcome. This dissociation between vasospasm and clinical outcome could result from methodological problems, sample size, insensitivity of clinical outcome measures, or from mechanisms other than vasospasm that also contribute to poor outcome.     

Fluid Balance and Blood Volume Measurement after Aneurysmal Subarachnoid Hemorrhage

Background  Patients with aneurysmal subarachnoid hemorrhage (SAH) are at risk for circulatory volume depletion, which is a risk factor for delayed cerebral ischemia (DCI). In a prospective observational study we assessed the effectiveness of fluid administration based on regular evaluation of the fluid balance in maintaining normovolemia. Methods  A total of 50 patients with aneurysmal SAH were included and were treated according to a standard protocol aimed at maintaining normovolemia. Fluid intake was adjusted on the basis of the fluid balance, which was calculated at 6-h intervals. Circulating blood volume (CBV) was measured by means of pulse dye densitometry (PDD) on alternating days during the first 2 weeks after SAH. Results  Of the 265 CBV measurements, 138 (52%) were in the normovolemic range of 60–80 ml/kg; 76 (29%) indicated hypovolemia with CBV < 60 ml/kg; and 51 (19%) indicated hypervolemia with CBV > 80 ml/kg. There was no association between CBV and daily fluid balance (regression coefficient β = −0.32; 95% CI: −1.81 to 1.17) or between CBV and a cumulative fluid balance, adjusted for insensible loss through perspiration and respiration (β = 0.20; 95% CI: −0.31 to 0.72). Conclusion  Calculations of fluid balance do not provide adequate information on actual CBV after SAH, as measured by PDD. This raises doubt whether fluid management guided by fluid balances is effective in maintaining normovolemia.     

Relationship Between Hemoglobin Concentrations and Outcomes Across Subgroups of Patients with Aneurysmal Subarachnoid Hemorrhage

Objective  Anemia predicts poor outcome following aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that this association would be stronger among patients with more severe SAH, since these patients are likely to be more vulnerable to secondary brain injury in the form of reduced cerebral oxygen delivery. Methods  Daily nadir hemoglobin (Hb) concentrations over 2 weeks following SAH were retrieved in 245 consecutive patients, and compared between those with a favorable versus unfavorable outcome. The analysis was repeated with patients dichotomized as follows: WFNS score 4–5 vs. 1–3; modified Fisher score (MFS) 4 vs. 0–3; and vasospasm present vs. absent. Mixed effect models and multivariable analysis using the generalized estimating equation were employed to assess correlated data with repeated measures. Results  Patients with an unfavorable outcome consistently had lower Hb concentrations, especially between days 6–11 following SAH (P ranging from <0.001 to 0.009), as well as a greater fall in Hb over time (β = −0.07, P < 0.001). This was true regardless of WFNS score, MFS, or the presence or absence of vasospasm. However, the effect was somewhat more pronounced among patients with higher WFNS and modified Fisher scores. Conclusion  Lower Hb levels are associated with worse outcomes regardless of SAH severity or the development of vasospasm. This finding may imply that a lower Hb concentration is largely a marker for a greater degree of systemic illness, rather than necessarily causing direct harm. However, the association is somewhat stronger among patients with more severe SAH. Thus, if there is a benefit for maintaining higher Hb levels with transfusions or erythropoietin, it may be more pronounced among these patients. Supported in part by the Louise Nerancy endowment of The University of Virginia.     

Increased Cortisol Levels are Associated with Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Background  

Physiological reactions of the stress hormone cortisol include hyperglycemia, hypertension, and endothelium dysfunction. In patients with aneurysmal subarachnoid hemorrhage (SAH), hyperglycemia, hypertension, and endothelium dysfunction are associated with the occurrence of delayed cerebral ischemia (DCI). Therefore, the purpose of the present study was to investigate whether increased serum cortisol levels after aneurysmal SAH are associated with DCI occurrence.     

Massive intraventricular haemorrhage from aneurysmal rupture: patient proportions and eligibility for intraventricular fibrinolysis

Massive intraventricular haemorrhage (IVH) complicating aneurysmal subarachnoid haemorrhage (SAH) is associated with a poor prognosis. Small observational studies suggest favourable results from fibrinolysis of the intraventricular blood. We performed an observational study on IVH in a large series of patients with SAH to assess the proportion of patients that may benefit from fibrinolytic treatment. From our prospective database we retrieved patients with aneurysmal SAH admitted between January 2000 and January 2005. We calculated the proportion of patients with massive IVH and the proportion of patients that are eligible for fibrinolysis on basis of clinical and CT-scan characteristics and assessed neurological outcome in a treatment strategy without fibrinolysis. Poor neurological condition was defined as World Federation of Neurological Surgeons scale 4 and 5, poor outcome as death or dependence 3 months after SAH. Of the 573 patients admitted with aneurysmal SAH, 59 (10%; 95% confidence interval CI 8–13%) had massive IVH, of which 55 were in poor clinical condition. For these 55 patients, the case-fatality rate was 78% (95% CI 66–88%) and the proportion with poor outcome 91% (95% CI 81–97%). Of the 55 patients, 31 (56%, and 5% of all patients SAH within the study period) fulfilled our eligibility criteria and were considered suitable for intraventricular fibrinolysis. At 3 months, 30 of these 31 eligible patients (97%; 95% CI 85–100%) had a poor outcome. Massive IVH occurs in 10% of patients with aneurysmal SAH. Half of these patients may benefit from intraventricular fibrinolysis. Without fibrinolysis outcome is almost invariably poor in these patients.     

A case control study of statin and magnesium administration in patients after aneurysmal subarachnoid hemorrhage: incidence of delayed cerebral ischemia and mortality

Abstract

Objective: To analyse the effect of the implementation of statin and magnesium treatment on delayed cerebral ischemia (DCI) and 14 day mortality in patients with subarachnoid hemorrhage (SAH).

Methods: Retrospective, single-center, observational case control study. One hundred SAH patients received either simvastatin and magnesium, solely statin or no treatment.

Results: Eighteen percent (n=5) of patients receiving statin and magnesium treatment developed a DCI whereas 24% (n=5) in the statin group and 16% (n=8) in the control group had DCI. Dead by day 14 was registered in 18% (n=5) of patients in the statin and magnesium group, in 10% (n=2) in the statin group and in 27% (n=14) in the control group. None of the results reached a statistical significance level of 0.05.

Conclusion: A trend towards a lower mortality within 14 days in patients receiving solely simvastatin and those receiving statin and magnesium as compared with the control group was found. A higher incidence for DCI was found in the statin group, whereas patients without statin and magnesium tended to have less often DCI. None of the results was statistically significant.     

蛛网膜下腔出血后迟发性脑缺血的病理生理机制探讨

蛛网膜下腔出血（subarachnoid hemorrhage,SAH）是一种十分凶险的脑血管病,具有高死亡 率、高致残率及高治疗难度的特点。迟发性脑缺血（delayed cerebral ischemia,DCI）是SAH后一种常见 的并发症,一旦发生将严重影响患者预后。因此,明确DCI的病理生理机制对其预防和治疗具有至关 重要的作用。既往认为,脑血管痉挛是SAH后导致DCI的唯一原因,但近年来这一观点受到广泛质疑。 目前认为DCI是一个由多种病理生理机制共同参与的复杂病理过程,本文旨在探讨DCI的病理生理机 制,以期帮助找到早期识别DCI高风险人群的方法,探索新的防治方式,从而改善患者预后。     

Early circulating levels of endothelial cell activation markers in aneurysmal subarachnoid haemorrhage: associations with cerebral ischaemic events and outcome

OBJECTIVE: To investigate the relation of endothelial cell activation with delayed cerebral ischaemia (DCI) and outcome after subarachnoid haemorrhage (SAH). METHODS: Concentrations of soluble (s) intercellular adhesion molecule-1, sE-selectin, sP-selectin, ED1-fibronectin, von Willebrand Factor (vWf), and vWf propeptide were measured within three days of SAH onset. The associations with poor outcome were investigated at three months in 106 patients. In 90 patients in whom the occurrence of cerebral ischaemia could be dated accurately, two analyses were undertaken: one for all ischaemic events (n = 32), including those related to treatment, and another for spontaneous DCI (n = 11). Concentrations of markers were dichotomised at their medians. The associations of endothelial cell activation markers with outcome were expressed as odds ratios (OR) from logistic regression and those with ischaemic events as hazard ratios (HR) derived from Cox regression. RESULTS: Early vWf concentrations were associated with poor outcome (crude OR = 4.6 (95% CI, 2.0 to 10.9; adjusted OR = 3.3 (1.1 to 9.8). Early levels of vWf were also positively related to occurrence of all ischaemic events (crude HR = 2.3 (1.1 to 4.9); adjusted HR = 1.8 (0.8 to 3.9) and with occurrence of spontaneous DCI (crude HR = 3.5 (0.9 to 13.1); adjusted HR = 2.2 (0.5 to 9.8). None of the other markers showed any associations. CONCLUSIONS: Concentrations of sICAM-1, sP-selectin, sE-selectin, and ED1-fibronectin do not predict the occurrence of DCI or outcome. The positive associations of raised early vWf concentrations with ischaemic events and poor outcome after SAH may reflect a predisposition to further ischaemic injury through formation of microthrombi in the cerebral circulation.     

Cardiac Troponin-I: A Predictor of Prognosis in Subarachnoid Hemorrhage

Background  Release of cardiac biomarkers is reported in patients with subarachnoid hemorrhage (SAH). Data addressing the impact of cardiac injury on outcome in these patients is sparse. This study was conducted to ascertain the association of elevation of serum cardiac Troponin-I (cTnI) with mortality and neurological outcome in patients with SAH. Methods  Medical records of all patients admitted with a diagnosis of SAH and at least one measured cTnI were reviewed. Demographic and clinical variables including admission neurological status were collected. Conservative and non-parametric statistics were used to assess association between cTnI and death or neurological outcome at discharge. Results  The study group comprised of 83 patients with a mean age of 59 years. There was a female (60%) and African-American (60%) preponderance. At admission, the median Glasgow Coma Scale (GCS) was 9, and 47% had a severe Hunt–Hess grade (HHG) of ≥4. Elevation of cTnI was found in 31 (37%) patients and was associated with worse baseline Fisher grade (p=0.01) and neurological status: GCS score (p=0.006) and HHG (p=0.007). Patients with abnormal cTnI were more likely to die (55% vs.27%; odds ratio 1.3–8.4, p = 0.01) and had a worse GCS score (p = 0.008) and HHG (p = 0.004) on discharge. On multivariate analysis, peak cTnI (p = 0.04) and admission GCS score of <12 (p = 0.02) were independent predictors of death at discharge. Conclusion  Patients with subarachnoid hemorrhage and elevated cTnI are found to have worse neurological status at admission. These patients have a worse neurological outcome and in-hospital mortality.     

Predictors of left ventricular regional wall motion abnormalities after subarachnoid hemorrhage

Introduction  Cardiac abnormalities that have been reported after subarachnoid hemorrhage (SAH) include the release of cardiac biomarkers, electrocardiographic changes, and left ventricular (LV) systolic dysfunction. The mechanisms of cardiac dysfunction after SAH remain controversial. The aim of this study was to determine the prevalence of LV regional wall motion abnormalities (RWMA) after SAH and to quantify the independent effects of specific demographic and clinical variables in predicting the development of RWMA. Methods  Three hundred patients hospitalized with SAH were prospectively studied with serial echocardiography. The primary outcome measure was the presence of RWMA. The predictor variables included the admission Hunt & Hess grade, age, gender, cardiac risk factors, aneurysm location, plasma catecholamine levels, cardiac troponin I (cTi) level, heart rate (HR), blood pressure, and phenylephrine dose. Univariate and multivariate logistic regression was performed with adjustment for serial measurements, reporting olds ratios (OR) and 95% confidence intervals (CI). Results  In this study, 817 echocardiograms were analysed. RWMA were detected in 18% of those studied. The prevalence of RWMA in patients with Hunt & Hess grades 3–5 was 35%. Among patients with a peak cTi level grater than 1.0 μg/L, 65% had RWMA. Multivariate analysis demonstrated that high Hunt & Hess grade (OR 4.22 for grade 3–5 versus grade 1–2, p=0.046), a cTi level greater than 1.0 μg/L (OR 10.47, p=0.001), a history of prior cocaine or amphetamine use (OR 5.50, p=0.037), and higher HR (OR 1.34 per 10 bpm increase, p=0.024) were predictive of RWMA. Conclusions  RWMA were frequent after SAH. High-grade SAH, an elevation in cTi levels, a history of prior stimulant drug use, and tachycardia are independent predictors of RWMA.     

Acute hyponatremia after aneurysmal subarachnoid hemorrhage: Frequency,treatment, and outcome

We retrospectively examined the course of serum sodium levels in 180 patients with acute aneurysmal subarachnoid hemorrhage (SAH) who had been admitted to the anesthesiologic-neurosurgical intensive care unit of the University Medical Center Regensburg, Germany, between January 2014 and December 2018. Each patient file was analyzed regarding the frequency and intensity of hyponatremic episodes and the administered medication. At admission to the intensive care unit (ICU), 18 patients had shown initial hyponatremia (<135 mmol/L) and 4 patients hypernatremia (greater than145 mmol/L). 88 (48.9%) of the 158 patients with normal serum sodium levels developed at least one hyponatremic episode during ICU treatment. The number of hyponatremic episodes was similar between patients with higher-grade and lower-grade aneurysmal SAH (P = 0.848). At the end of ICU treatment, outcome did not differ between patients with and without hyponatremia (40/88, 45.5% vs. 38/70, 54.3%, P = 0.270). At 6 months after SAH, however, good outcome (Glasgow outcome scale, GOS 4–5) was more frequently observed in patients with hyponatremia (26/88, 29.5% vs. 32/70, 45.7%, P = 0.036). Medication with sodium chloride, fludrocortisone, or tolvaptan was initiated in 75.4% patients with mild hyponatremia (130–134 mmol/L) and in 92.9% with moderate hyponatremia (125–129 mmol/L). At 6 months after SAH, patients treated with tolvaptan had a lower rate of poor outcome than patients who had not received tolvaptan (1/14, 7.1% vs. 25/74, 33.8%, P = 0.045). In patients with acute aneurysmal SAH and hyponatremic episodes, consequent treatment of hyponatremia prevented impaired outcome. Because administration of tolvaptan rapidly normalized serum sodium levels, this therapy seems to be a promising treatment approach.     

Low serum magnesium is associated with poor functional outcome in acute ischemic stroke or transient ischemic attack patients

Aim

The association between magnesium and outcomes after stroke is uncertain. We aimed to investigate the association of serum magnesium with all-cause mortality and poor functional outcome.

Methods

We included patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) from the China National Stroke Registry III. We used Cox proportional hazards model for all-cause mortality and logistic regression model for poor functional outcome (modified Rankin Scale [mRS] 2–6/3–6) to examine the relationships.

Results

Among the 6483 patients, the median (interquartile range) magnesium was 0.87 (0.80–0.93) mmol/L. Patients in the first quartile had a higher risk of mRS score 3–6/2–6 at 3 months (adjusted odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.02, 1.64; adjusted OR: 1.29; 95% CI: 1.04–1.59) compared with those in the fourth quartile. Similar results were found for mRS score 26 at 1 year. The age- and sex-adjusted hazard ratio (HR) with 95% CI in first quartile magnesium was 1.40 (1.02–1.93) for all-cause mortality within 1 year, but became insignificant (HR: 1.03; 95% CI: 0.71–1.50) after adjusting for potential variables.

Conclusions

Low serum magnesium was associated with a high risk of poor functional outcome in patients with AIS or TIA.     

Can vitamin D<Subscript>3</Subscript> supplementation prevent bone loss in persons with MS? A placebo-controlled trial

Multiple sclerosis (MS) is a possible cause of secondary osteoporosis. In this phase II trial we assessed whether a weekly dose of 20,000 IU vitamin D₃ prevents bone loss in ambulatory persons with MS age 18–50 years. ClinicalTrials.gov ID NCT00785473. All patients managed at the University Hospital of North Norway who fulfilled the main inclusion criteria were invited to participate in this double-blinded trial. Participants were randomised to receive 20,000 IU vitamin D₃ or placebo once a week and 500 mg calcium daily for 96 weeks. The primary outcome was the effect of the intervention on percentage change in bone mineral density (BMD) at the hip, the spine, and the ultradistal radius over the study period. Of 71 participants randomised, 68 completed. Mean serum 25-hydroxyvitamin D [25(OH)D] levels in the intervention group increased from 55 nmol/L at baseline to 123 nmol/L at week 96. After 96 weeks, percentage change in BMD did not differ between groups at any site. BMD decreased at the hip, by 1.4% in the placebo group (95% CI −2.3 to −0.4, SD 2.7, p = 0.006) and by 0.7% in the treatment group (−1.6 to 0.2, 2.7, p = 0.118), difference 0.7% (−1.9 to 0.7, p = 0.332). Findings were not altered by adjustment for sex or serum 25(OH)D. Supplementation with 20,000 IU vitamin D₃ a week did not prevent bone loss in this small population. Larger studies are warranted to assess the effect of vitamin D on bone health in persons with MS.