Summary 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 0·84–1·10). 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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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