Backpack palsy and other brachial plexus neuropathies in the military population.

Brachial plexus neuropathy is often seen in the military population, especially due to pressure (backpack palsy, BPP) or idiopathic (neuralgic amyotrophy, NA). We aimed to gain insight in the disease characteristics of soldiers with brachial plexus neuropathies in the Dutch military population and to compare disease characteristics between patients with BPP and NA. In this retrospective chart review study we aimed to include all patients with brachial plexus neuropathy, who presented in the Joint Military Hospital between 1 January, 2011 and 31 December, 2016. We calculated the incidence of NA and BPP and Chi-square tests or Student t tests were performed for differences in patient characteristics between NA and BPP. We included 127 patients, 63 with BPP, 45 with NA, 10 with traumatic brachial plexus neuropathy, and 9 with other plexopathy. The incidence of brachial plexus neuropathy was 50/100 000 person years overall, 25/100 000 person years for BPP, and 18/100 000 person years for NA. Patients in the BPP group differed from the NA with regard to pain (BPP 41% vs NA 93%, P = .000), atrophy (13% BPP vs 29% NA, P = .049), and sensory symptoms (83% BPP vs 44% NA, P = .000). In the BPP group 90% had incomplete recovery and in the NA group 78%. Our study showed a high incidence of BPP and NA in the military population and suggests recovery is not so benevolent as previously thought. Future research is necessary to improve insight and outcome of military patients with brachial plexus neuropathies.

Preventive Antibiotics and Delayed Cerebral Ischaemia in Patients with Aneurysmal Subarachnoid Haemorrhage Admitted to the Intensive Care Unit.

INTRODUCTION: Delayed cerebral ischemia (DCI) is an important contributor to poor outcome after aneurysmal subarachnoid haemorrhage (aSAH). Development of DCI is multifactorial, and inflammation, with or without infection, is one of the factors independently associated with development of DCI and poor outcome. We thus postulated that preventive antibiotics might be associated with a reduced risk of DCI and subsequent poor outcome in aSAH patients. METHODS: We performed a retrospective cohort-study in intensive care units (ICU) of three university hospitals in The Netherlands. We included consecutive aSAH patients with minimal ICU stay of 72 h who received either preventive antibiotics (SDD: selective digestive tract decontamination including systemic cefotaxime or SOD: selective oropharyngeal decontamination) or no preventive antibiotics. DCI was defined as a new hypodensity on CT with no other explanation than DCI. Hazard ratio's (HR) for DCI and risk ratio's (RR) for 28-day case-fatality and poor outcome at 3 months were calculated, with adjustment (aHR/aRR) for clinical condition on admission, recurrent bleeding, aneurysm treatment modality and treatment site. RESULTS: Of 459 included patients, 274 received preventive antibiotics (SOD or SDD) and 185 did not. With preventive antibiotics, the aHR for DCI was 1.0 (95% CI 0.6-1.8), the aRR for 28-day case-fatality was 1.1 (95% CI 0.7-1.9) and the aRR for poor functional outcome 1.2 (95% CI 1.0-1.4). CONCLUSIONS: Preventive antibiotics were not associated with reduced risk of DCI or poor outcome in aSAH patients in the ICU.

Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS: Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS: We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS: This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.

Aneurysm treatment <24 versus 24-72 h after subarachnoid hemorrhage.

INTRODUCTION: In patients with aneurysmal subarachnoid hemorrhage (aSAH), it is unclear whether aneurysm treatment <24 h after ictus results in better outcomes than treatment 24-72 h after aSAH. We studied whether aneurysm occlusion <24 h is associated with better outcomes than occlusion 24-72 h after aSAH. METHODS: We used two cohorts of patients with aSAH: (1) the UMC Utrecht cohort with patients admitted between 2008 and 2012 and (2) the International Subarachnoid Aneurysm Trial cohort. Aneurysm treatment was categorized into <24 h and 24-72 h after ictus. We calculated adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) using Poisson regression analyses for poor functional outcome (death or dependency) for both cohorts separately, and performed a pooled analysis based on individual patient data. We also performed a worst-case scenario analysis wherein all patients with rebleeding >3 h after admission were re-categorized into the group with aneurysm treatment 24-72 h after aSAH. RESULTS: We included 1,238 patients (UMC Utrecht cohort: n = 330; ISAT: n = 908). The aRR for poor outcome after treatment <24 h was in the UMC Utrecht cohort 1.84 (95% CI: 1.25-2.70), in ISAT 1.14 (95% CI 0.84-1.55), in the pooled analysis 1.37 (95% CI 1.11-1.68), and in the worst-case scenario pooled analysis 1.24 (95% CI 1.01-1.52). CONCLUSION: Our results suggest that aneurysm occlusion can be performed in day time within 72 h after ictus, instead of on an emergency basis. However, due to the retrospective, non-randomized design of our study, our results cannot be considered as definitive evidence.

Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial.

BACKGROUND: Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage. METHODS: We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome-defined as a score of 4-5 on the modified Rankin Scale-3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36). FINDINGS: 1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85-1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86-1·08). INTERPRETATION: Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended. FUNDING: Netherlands Heart Foundation, UK Medical Research Council.

Timing of aneurysm treatment after subarachnoid hemorrhage: relationship with delayed cerebral ischemia and poor outcome.

BACKGROUND AND PURPOSE: The ideal timing of coiling or clipping after aneurysmal subarachnoid hemorrhage is unknown. Within the International Subarachnoid Aneurysm Trial we assessed differences in incidence of delayed cerebral ischemia and clinical outcome between different timings of treatment. METHODS: The treated 2106 patients randomized to coiling or clipping were divided into 4 categories: treatment <2 days, on days 3 to 4, on days 5 to 10, and >10 days after the hemorrhage. ORs with 95% CI were calculated with logistic regression analysis for delayed cerebral ischemia, poor outcome at 2 months, and 1 year for the different timing categories, with treatment <2 days as reference. Analyses were performed for all patients, and for coiled and clipped patients separately, and were adjusted for baseline characteristics. RESULTS: Adjusted ORs of delayed cerebral ischemia for treatment on days 5 to 10 were 1.18 (95% CI, 0.91-1.53) for all patients, 1.68 (95% CI, 1.17-2.43) after coiling, and 0.79 (95% CI, 0.54-1.16) after clipping. ORs for poor outcome at 2 months were 1.16 (95% CI, 0.89-1.50) for treatment (clipping and coiling combined) at 3 to 4 days, 1.39 (95% CI, 1.08-1.80) for treatment at 5 to 10 days, and 1.84 (95% CI, 1.36-2.51) for treatment >10 days. ORs for coiled and clipped patients separately were in the same range. Results for outcome at 1 year were similar. CONCLUSIONS: Our results support the current practice for early aneurysm treatment in subarachnoid hemorrhage patients. The risk for poor outcome was highest when treatment was performed after day 10; postponing treatment in patients who are eligible for treatment between days 5 to 10 after subarachnoid hemorrhage is not recommended.

Interobserver variability of grading scales for aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Worldwide, different scales are used to assess the clinical condition on admission after aneurysmal subarachnoid hemorrhage. In addition to the prognostic value, the inter-rater variability should be taken into account when deciding which scale preferably should be used. We assessed the interobserver agreement of the commonly used World Federation of Neurological Surgeons, the Hunt and Hess, and the Prognosis on Admission of Aneurysmal Subarachnoid Hemorrhage scales. METHODS: In a cohort of 50 subarachnoid hemorrhage patients, 103 paired assessments were performed on the 3 admission scales by 2 independent observers per assessment with a total of 57 different raters. Patients were assessed during the first week after the hemorrhage. The interobserver agreement was calculated using quadratic (weighted) kappa statistics. RESULTS: The weighted kappa value of the Prognosis on Admission of Aneurysmal Subarachnoid Hemorrhage scale was 0.64 (95% CI, 0.49-0.79), of the World Federation of Neurological Surgeons scale was 0.60 (95% CI, 0.48-0.73), and of the Hunt and Hess scale was 0.48 (95% CI, 0.36-0.59). CONCLUSIONS: The Hunt and Hess scale showed the lowest interobserver agreement, whereas agreement of the World Federation of Neurological Surgeons and Prognosis on Admission of Aneurysmal Subarachnoid Hemorrhage scales was similar with overlapping CI.

Brain natriuretic peptide concentrations after aneurysmal subarachnoid hemorrhage: relationship with hypovolemia and hyponatremia.

BACKGROUND: Hyponatremia and hypovolemia occur often after aneurysmal subarachnoid hemorrhage (SAH) and are associated with poor outcome. The authors investigated whether brain natriuretic peptide (BNP) is related to hypovolemia and hyponatremia after SAH and whether it can differentiate between hypovolemic and non-hypovolemic hyponatremia. METHODS: In 58 SAH patients, the authors daily measured serum BNP and sodium concentrations, and circulating blood volume by means of pulse dye densitometry, during the initial 10 days. For each patient, mean BNP concentrations were calculated until occurrence of the following events: hyponatremia (Na <130 mmol/l), hypovolemia (blood volume <60 ml/kg), and severe hypovolemia (blood volume <50 ml/kg). The median day of onset of each event was calculated. In patients without an event, the authors calculated and used for comparison the mean BNP concentration until the median day of onset of the particular event. Odds Ratio's (OR) for high versus low mean BNP concentrations (dichotomized on median values per event) were calculated for the occurrence of each event and adjusted for relevant baseline characteristics. RESULTS: Patients with BNP above median more often had severe hypovolemia (adjusted OR 4.2, 95% confidence interval, CI 1.2-15.0) and showed a trend toward hyponatremia (adjusted OR 3.3, 95% CI 0.7-9.2). In the 12 hyponatremic patients, BNP could not differentiate between hypovolemic and non-hypovolemic hyponatremia. CONCLUSIONS: High BNP concentrations are related to the occurrence of severe hypovolemia and possibly hyponatremia. These data do not support a role for BNP measurements to differentiate between hypovolemic and non-hypovolemic hyponatremia in SAH patients.

Comparison of telephone and face-to-face assessment of the modified Rankin Scale.

BACKGROUND: A structured interview improves the reliability of the modified Rankin Scale (mRS), a commonly used functional outcome scale in stroke trials. Telephone interview is a fast and convenient way to assess the mRS grade, but its validity is unknown. We assessed the validity of a telephone interview in patients who had had an aneurysmal subarachnoid haemorrhage (SAH) by comparing it with a face-to-face assessment. METHODS: Eighty-three SAH patients were interviewed twice, once face-to-face and once by telephone, by 2 of 5 observers who used a structured interview to assess the mRS grade. Intermodality agreement was measured using weighted kappa statistics. To check for systematic differences between face-to-face and telephone assessment the Wilcoxon test for matched pairs was used. RESULTS: Agreement between telephone and face-to-face assessment was perfect in 47 (57%) patients. A difference of 1 level occurred in 31 (37%) patients and this was almost equally distributed over the grades of the mRS. Weighted kappa was 0.71 (95% CI 0.59-0.82). Telephone assessment did not result in a consistently more or less favourable grade than face-to-face assessment (Wilcoxon test for matched pairs, p = 0.33). CONCLUSIONS: Telephone assessment of the mRS with a structured interview has a good agreement with face-to-face assessment and can thus be used reliably in the setting of a clinical trial.

Validation of a prognostic subarachnoid hemorrhage grading scale derived directly from the Glasgow Coma Scale.

BACKGROUND AND PURPOSE: A new Glasgow Coma Scale-based scale has been developed to predict patient outcome in subarachnoid hemorrhage by calculating cut-off points by which 2 consecutive categories corresponded to a statistically significant different outcome. We assessed the external validity of this Prognosis on Admission of Aneurysmal Subarachnoid Hemorrhage (PAASH) scale and compared it to the commonly used World Federation of Neurological Surgeons scale. METHODS: From our database of subarachnoid hemorrhage patients we retrieved data on all patients admitted between November 2000 and March 2006. By means of logistic regression, we calculated OR with corresponding 95% CI for poor outcome at 3 months for each category in comparison with the lowest category of both scales. Areas under the curve of the corresponding receiver operator characteristic curve were calculated. RESULTS: We included 537 patients. For the PAASH scale, OR ranged from 3.9 (95% CI, 2.4 to 6.2) to 84 (95% CI, 25 to 287) and increased more evenly than for the World Federation of Neurological Surgeons (WFNS) scale, with OR ranging from 2.3 (95% CI, 1.3 to 4.1) to 69 (95% CI, 31 to 157). Areas under the curve were 0.81 (95% CI, 0.77 to 0.84) for the PAASH and 0.82 (95% CI, 0.79 to 0.86) for the WFNS scale. CONCLUSIONS: Both PAASH and WFNS scales have a good discriminatory ability for patient prognosis. Because the OR of the PAASH increase more gradually, it is slightly preferable to the WFNS scale.

Fever after aneurysmal subarachnoid hemorrhage: relation with extent of hydrocephalus and amount of extravasated blood.

BACKGROUND AND PURPOSE: Fever after aneurysmal subarachnoid hemorrhage is associated with poor outcome. Because hydrocephalus and extravasated blood may influence thermoregulation, we determined whether these factors increase the risk for fever after subarachnoid hemorrhage. METHODS: Fever within 14 days (subdivided into infectious and noninfectious) was defined as a mean daily body temperature above 38.0 degrees C for at least 2 consecutive days in a prospectively collected cohort of 194 patients with subarachnoid hemorrhage. Hazard ratios were calculated to assess the impact of hydrocephalus (bicaudate index) and cisternal and intraventricular blood (Hijdra score) on the occurrence of fever. Adjusted hazard ratios were calculated in one multivariate model, including other possible confounding factors. RESULTS: Infectious fever occurred in 34% of patients and noninfectious fever in 9%. Adjusted hazard ratios of intraventricular blood were 2.2 (95% CI, 1.3 to 3.8) for any fever, 2.4 (95% CI, 1.3 to 4.4) for infectious fever, and 2.0 (95% CI, 0.7 to 5.9) for noninfectious fever. Adjusted hazard ratios of cisternal blood and hydrocephalus for infectious and noninfectious fever ranged from 0.6 to 1.5, all with wide CIs. CONCLUSIONS: Intraventricular blood is an independent risk factor for the development of fever. In this study, noninfectious fever was rare and not related to extravasated blood or hydrocephalus.

Extent of acute hydrocephalus after aneurysmal subarachnoid hemorrhage as a risk factor for delayed cerebral infarction.

BACKGROUND AND PURPOSE: Delayed cerebral infarction (DCI) is an important cause of poor outcome after subarachnoid hemorrhage. Cerebral perfusion is a predictor for DCI. Because acute hydrocephalus may impair cerebral perfusion, we evaluated the predictive value of the extent of acute hydrocephalus on the development of DCI. METHODS: We retrieved data on 321 patients admitted within 4 days after aneurysmal subarachnoid hemorrhage from our prospectively collected database. Ventricular enlargement was quantified by measuring the bicaudate index and the width of the third ventricle. Ventricular sizes were analyzed as continuous variables and after categorization into quartiles. The relationship between these variables and the development of DCI was analyzed by means of the Cox proportional hazards model. RESULTS: DCI occurred in 76 patients (23.7%). Hazard ratios for occurrence of DCI of the continuous variables were 1.01 (95% CI: 0.97 to 1.06) for the bicaudate index, 1.00 (95% CI: 1.00 to 1.01) for the age-adjusted bicaudate index, and 0.99 (95% CI: 0.92 to 1.06) for the width of the third ventricle in univariable analysis. The adjusted hazard ratio for the highest quartile of the bicaudate index versus the lowest quartile was 0.9 (95% CI: 0.5 to 1.8). No linear trend could be recognized in consecutive quartiles. CONCLUSIONS: Acute hydrocephalus is not a risk factor for occurrence of DCI, even when the extent of hydrocephalus is taken into account. However, we cannot exclude the possibility that extensive hydrocephalus leading to coma does increase the risk for DCI if no therapeutic intervention were done.

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 < or = 1.28 mmol/l could decrease the effect on DCI while concentrations > or = 1.62 might have a negative effect on clinical outcome.

Effect of magnesium treatment and glucose levels on delayed cerebral ischemia in patients with subarachnoid hemorrhage: a substudy of the Magnesium in Aneurysmal Subarachnoid Haemorrhage trial (MASH-II).

BACKGROUND: Magnesium treatment did not improve outcome in patients with aneurysmal subarachnoid haemorrhage in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. We hypothesized that high glucose levels may have offset a potential beneficial effect to prevent delayed cerebral ischemia. We investigated if magnesium treatment led to less delayed cerebral ischemia and if glucose levels interacted with magnesium treatment in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. AIM: To investigate the effect of magnesium treatment on occurrence of delayed cerebral ischemia and the interaction between glucose levels and magnesium treatment in subarachnoid hemorrhage patients. METHODS: The Magnesium in Aneurysmal Subarachnoid Haemorrhage was a phase III randomized placebo-controlled trial assessing the effect of magnesium sulphate on clinical outcome in aneurysmal subarachnoid hemorrhage patients. For the current study, we included only the patients admitted to the University Medical Centre-Utrecht. We calculated hazard ratios for occurrence of delayed cerebral ischemia in patients treated with magnesium vs. placebo for the entire study population, and separately in the subgroups of patients with high and low mean fasting and mean daily glucose levels until onset of delayed cerebral ischemia. We used the cross-product of magnesium and glucose in the regression analysis to evaluate whether an interaction between magnesium and glucose existed. RESULTS: We included 616 patients: 307 received magnesium and 309 placebo; 156 patients had delayed cerebral ischemia. Hazard ratio for magnesium on occurrence of delayed cerebral ischemia was 1·0 (95% confidence interval: 0·7-1·4). Results were similar in patients with low or high fasting or daily glucose levels. We found no interactions between magnesium treatment and high fasting (P = 0·54) and daily glucose (P = 0·60). CONCLUSIONS: Magnesium treatment did not reduce the risk of delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage, nor was there an interaction with glucose levels. It is therefore unlikely that glucose levels explain the failure of magnesium to prevent delayed cerebral ischemia and poor outcome after aneurysmal subarachnoid hemorrhage.

Antiplatelet therapy in aneurysmal subarachnoid hemorrhage: a systematic review.

BACKGROUND AND PURPOSE: Observational studies suggest that platelet inhibitors reduce the risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage and thereby have a beneficial effect on clinical outcome. Robust evidence, however, is lacking. We performed a systematic meta-analysis to determine whether antiplatelet therapy has a beneficial effect after SAH. METHODS: We searched Medline and the Cochrane Library to identify all randomized controlled trials of antiplatelet drugs versus control and calculated relative risks with corresponding 95% confidence intervals (CIs) for poor outcome (dependence or death), the occurrence of DCI, and the occurrence of any intracranial hemorrhage. RESULTS: We included 5 trials totaling 699 patients. The overall relative risk for poor outcome was 0.87 (95% CI, 0.65 to 1.17); for the occurrence of DCI (reported in 3 of the 5 studies), 0.65 (95% CI, 0.47 to 0.89); and for the occurrence of intracranial hemorrhage, 1.19 (reported in 4 of the 5 studies) (95% CI, 0.76 to 1.85). CONCLUSIONS: Our data indicate that antiplatelet drugs reduce the risk of DCI in patients with subarachnoid hemorrhage. A randomized clinical trial is warranted to assess the effect on overall outcome.

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.

Magnesium in aneurysmal subarachnoid hemorrhage (MASH II) phase III clinical trial MASH-II study group.

RATIONALE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Magnesium is a neuroprotective agent that acts as an NMDA-receptor antagonist and a calcium channel blocker. In a phase II randomized clinical trial of 283 patients, magnesium treatment reduced the risk of DCI by 34% and of poor outcome by 23%. AIMS: To determine whether magnesium improves clinical outcome in patients with aneurysmal SAH. DESIGN: The MASH-II study is a phase III randomized, clinical international multicenter trial. Magnesium sulfate 64 mmol/day (equals 16 g/day) or placebo is started intravenously within 4 days after the SAH and is continued until 20 days after the hemorrhage. The primary outcome measure is poor outcome, defined as death or dependence (Rankin score >3) after 3 months. We aim to include 1200 patients in 5 years. STUDY OUTCOMES: Primary outcome will be poor clinical outcome as measured by the modified Rankin scale at 3 months.