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Effect of magnesium on cognition after aneurysmal subarachnoid haemorrhage in a randomized trial.

ABSTRACT: BACKGROUND AND PURPOSE:In randomized trials magnesium supplementation did not improve clinical outcome after aneurysmal subarachnoid haemorrhage (aSAH) on handicap scales. After aSAH, many patients have cognitive problems that may not translate into handicap. The effect of magnesium on cognitive outcome after aSAH was studied. METHODS:In total, 209 patients who had been included in the Magnesium for Aneurysmal Subarachnoid Haemorrhage (MASH-2) trial in the University Medical Centre of Utrecht were studied. Patients had been randomized to 64 mmol magnesium sulfate daily or placebo during hospitalization. Three months after aSAH patients underwent a neuropsychological examination (NPE) consisting of six neuropsychological tests or a brief cognitive assessment. Poisson and linear regression analyses were used to analyse the effect of magnesium on cognition. RESULTS:In the magnesium group 53 (49.5%) of the 107 patients and in the placebo group 51 (50.0%) of the 102 patients scored lower than the median cognitive score [relative risk 0.99, 95% confidence interval (CI) 0.76-1.30]. Linear regression analyses showed no significant relationship between intervention and cognition (B = 0.05, 95% CI -0.15 to 0.33). CONCLUSIONS:Treatment with magnesium has no effect on cognitive outcome after aSAH.

SUBMITTER: Huenges Wajer IMC

PROVIDER: S-EPMC6282849 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Effect of magnesium on cognition after aneurysmal subarachnoid haemorrhage in a randomized trial.

Huenges Wajer I M C IMC Dorhout Mees S M SM van den Bergh W M WM Algra A A Visser-Meily J M A JMA Rinkel G J E GJE van Zandvoort M J E MJE

European journal of neurology 20180903 12

<h4>Background and purpose</h4>In randomized trials magnesium supplementation did not improve clinical outcome after aneurysmal subarachnoid haemorrhage (aSAH) on handicap scales. After aSAH, many patients have cognitive problems that may not translate into handicap. The effect of magnesium on cognitive outcome after aSAH was studied.<h4>Methods</h4>In total, 209 patients who had been included in the Magnesium for Aneurysmal Subarachnoid Haemorrhage (MASH-2) trial in the University Medical Centr ...[more]

PMID: 30048027

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Project description: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.

Project description:The prognosis of patients with aneurysmal subarachnoid haemorrhage requiring decompressive craniectomy is usually poor. Proper selection and early performing of decompressive craniectomy might improve the patients' outcome. We aimed at developing a risk score for prediction of decompressive craniectomy after aneurysmal subarachnoid haemorrhage. All consecutive aneurysmal subarachnoid haemorrhage cases treated at the University Hospital of Essen between January 2003 and June 2016 (test cohort) and the University Medical Center Freiburg between January 2005 and December 2012 (validation cohort) were eligible for this study. Various parameters collected within 72 h after aneurysmal subarachnoid haemorrhage were evaluated through univariate and multivariate analyses to predict separately primary (PrimDC) and secondary decompressive craniectomy (SecDC). The final analysis included 1376 patients. The constructed risk score included the following parameters: intracerebral ('Parenchymal') haemorrhage (1 point), 'Rapid' vasospasm on angiography (1 point), Early cerebral infarction (1 point), aneurysm Sac > 5 mm (1 point), clipping (' S urgery', 1 point), age U nder 55 years (2 points), Hunt and Hess grade ≥ 4 ('Reduced consciousness', 1 point) and External ventricular drain (1 point). The PRESSURE score (0-9 points) showed high diagnostic accuracy for the prediction of PrimDC and SecDC in the test (area under the curve = 0.842/0.818) and validation cohorts (area under the curve = 0.903/0.823), respectively. 63.7% of the patients scoring ≥6 points required decompressive craniectomy (versus 12% for the PRESSURE < 6 points, P < 0.0001). In the subgroup of the patients with the PRESSURE ≥6 points and absence of dilated/fixed pupils, PrimDC within 24 h after aneurysmal subarachnoid haemorrhage was independently associated with lower risk of unfavourable outcome (modified Rankin Scale >3 at 6 months) than in individuals with later or no decompressive craniectomy (P < 0.0001). Our risk score was successfully validated as reliable predictor of decompressive craniectomy after aneurysmal subarachnoid haemorrhage. The PRESSURE score might present a background for a prospective randomized clinical trial addressing the utility of early prophylactic decompressive craniectomy in aneurysmal subarachnoid haemorrhage.

Project description:ObjectiveThe objective of the study was to assess the long-term self-reported health status and quality of life (QoL) of patients following an aneurysmal subarachnoid haemorrhage (ASAH) using a self-completed questionnaire booklet.DesignA two-cohort study.SettingA regional tertiary neurosurgical centre.Participants2 cohorts of patients with ASAH treated between 1998 and 2008 and followed up at approximately 1 year.InterventionsRoutine care.Primary and secondary outcomesA range of standardised scales included: AKC Short Sentences Test, the Barthel Index, the Self-Report Dysexecutive Questionnaire, the Everyday Memory Questionnaire, Stroke Symptom Checklist, Wimbledon Self-Report Scale, Modified Rankin Score (MRS) and a new Stroke-QoL. The data from summated scales were fit to the Rasch measurement model to validate the summed score.Results214 patients (48%) returned the questionnaires; the majority (76%) had a World Federation of Neurosurgeons grade of 1 or 2. The most frequent aneurysm type was that of the anterior communicating artery (28%) with approximately 90% of aneurysms of the anterior circulation. Of those previously in full or part-time employment, 48.9% were unemployed at follow-up. All summated scales satisfied the Rasch measurement model requirements, such that their summed scores were a sufficient statistic. Given this, one-third of patients were noted to have a significant mood disorder and 25% had significant dysexecutive function. Patients with an MRS of 3, 4 or 5 had significantly worse scores on most outcome measures, but a significant minority of those with a score of zero had failed to return to work and displayed significant mood disorder.ConclusionsA range of self-reported cognitive and physical deficits have been highlighted in a cohort of patients with ASAH. While the MRS has been shown to provide a reasonable indication of outcome, in routine clinical follow-up it requires supplementation by instruments assessing dysexecutive function, memory and mood.

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Effect of magnesium on cognition after aneurysmal subarachnoid haemorrhage in a randomized trial.

Publications

Effect of magnesium on cognition after aneurysmal subarachnoid haemorrhage in a randomized trial.

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