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      Magnesium Protects in Episodes of Critical Perfusion after Aneurysmal SAH

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          Abstract

          Background

          To analyze whether magnesium has a neuroprotective effect during episodes that indicate a critical brain perfusion after aneurysmal subarachnoid hemorrhage (SAH).

          Methods

          107 patients with aSAH were randomized to continuously receive intravenous magnesium sulfate with target serum levels of 2.0 – 2.5 mmol/l (n = 54) or isotonic saline (n = 53). Neurological examination and transcranial Doppler sonography (TCD) were performed daily, Perfusion-CT (PCT) was acquired in 3-day intervals, angiography in case of suspected vasospasm. The primary endpoint was the development of secondary infarction following episodes of delayed ischemic neurological deficit (DIND), elevated mean flow velocity (MFV) in TCD or pathological findings in PCT.

          Results

          In the magnesium group, 9 episodes of DIND were registered, none was followed by secondary infarction. In the control group, 23 episodes of DIND were registered, 9 were followed by secondary infarction (p < 0.05). In the magnesium group, 114 TCD-measurements showed an elevated MFV(> 140 cm/s). 7 were followed by new infarction. In control patients, 135 measurements showed elevated MFV, 32 were followed by new infarction (p < 0.05). 10 of 117 abnormal PCT-findings were followed by new infarction, compared to 30 of 122 in the control-group (p < 0.05).

          Conclusion

          DIND, elevated MFV in TCD and abnormal PCT are findings which are associated with an increased risk to develop delayed secondary infarction. The results of this analysis suggest that magnesium-treatment may reduce the risk to develop infarction in a state of critical brain perfusion.

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          Most cited references34

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          Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition?

          Vasospasm is an important complication of subarachnoid hemorrhage, but is variably defined in the literature. We studied 580 patients with subarachnoid hemorrhage and identified those with: (1) symptomatic vasospasm, defined as clinical deterioration deemed secondary to vasospasm after other causes were eliminated; (2) delayed cerebral ischemia (DCI), defined as symptomatic vasospasm, or infarction on CT attributable to vasospasm; (3) angiographic spasm, as seen on digital subtraction angiography; and (4) transcranial Doppler (TCD) spasm, defined as any mean flow velocity >120 cm/sec. Logistic regression analysis was performed to test the association of each definition of vasospasm with various hospital complications, and 3-month quality of life (sickness impact profile), cognitive status (telephone interview of cognitive status), instrumental activities of daily living (Lawton score), and death or severe disability at 3 months (modified Rankin scale score 4-6), after adjustment for covariates. Symptomatic vasospasm occurred in 16%, DCI in 21%, angiographic vasospasm in 31%, and TCD spasm in 45% of patients. DCI was statistically associated with more hospital complications (N=7; all P<0.05) than symptomatic spasm (N=4), angiographic spasm (N=1), or TCD vasospasm (N=1). Angiographic and TCD vasospasm were not related to any aspect of clinical outcome. Both symptomatic vasospasm and DCI were related to reduced instrumental activities of daily living, cognitive impairment, and poor quality of life (all P<0.05). However, only DCI was associated with death or severe disability at 3 months (adjusted OR, 2.2; 95% CI, 1.2-3.9; P=0.007). DCI is a more clinically meaningful definition than either symptomatic deterioration alone or the presence of arterial spasm by angiography or TCD.
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            Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought.

            Delayed cerebral vasospasm has long been recognized as an important cause of poor outcome after an otherwise successful treatment of a ruptured intracranial aneurysm, but it remains a pathophysiological enigma despite intensive research for more than half a century. Summarized in this review are highlights of research from North America, Europe and Asia reflecting recent advances in the understanding of delayed ischemic deficit. It will focus on current accepted mechanisms and on new frontiers in vasospasm research. A key issue is the recognition of events other than arterial narrowing such as early brain injury and cortical spreading depression and of their contribution to overall mortality and morbidity.
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              Calcium antagonists for aneurysmal subarachnoid haemorrhage.

              Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has been incompletely elucidated, but vasospasm probably is a contributing factor. Experimental studies have suggested that calcium antagonists can prevent or reverse vasospasm and have neuroprotective properties. To determine whether calcium antagonists improve outcome in patients with aneurysmal SAH. We searched the Cochrane Stroke Group Trials Register (last searched April 2006), MEDLINE (1966 to March 2006) and EMBASE (1980 to March 2006). We handsearched two Russian journals (1990 to 2003), and contacted trialists and pharmaceutical companies in 1995 and 1996. Randomised controlled trials comparing calcium antagonists with control, or a second calcium antagonist (magnesium sulphate) versus control in addition to another calcium antagonist (nimodipine) in both the intervention and control groups. Two review authors independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. Sixteen trials, involving 3361 patients, were included in the review; three of the studies were of magnesium sulphate in addition to nimodipine. Overall, calcium antagonists reduced the risk of poor outcome: the relative risk (RR) was 0.81 (95% confidence interval (CI) 0.72 to 0.92); the corresponding number of patients needed to treat was 19 (95% CI 1 to 51). For oral nimodipine alone the RR was 0.67 (95% CI 0.55 to 0.81), for other calcium antagonists or intravenous administration of nimodipine the results were not statistically significant. Calcium antagonists reduced the occurrence of secondary ischaemia and showed a favourable trend for case fatality. For magnesium in addition to standard treatment with nimodipine, the RR was 0.75 (95% CI 0.57 to 1.00) for a poor outcome and 0.66 (95% CI 0.45 to 0.96) for clinical signs of secondary ischaemia. Calcium antagonists reduce the risk of poor outcome and secondary ischaemia after aneurysmal SAH. The results for 'poor outcome' depend largely on a single large trial of oral nimodipine; the evidence for other calcium antagonists is inconclusive. The evidence for nimodipine is not beyond all doubt, but given the potential benefits and modest risks of this treatment, oral nimodipine is currently indicated in patients with aneurysmal SAH. Intravenous administration of calcium antagonists cannot be recommended for routine practice on the basis of the present evidence. Magnesium sulphate is a promising agent but more evidence is needed before definite conclusions can be drawn.
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                Author and article information

                Journal
                Transl Neurosci
                Transl Neurosci
                tnsci
                tnsci
                Translational Neuroscience
                De Gruyter
                2081-3856
                2081-6936
                01 September 2018
                2018
                : 9
                : 99-105
                Affiliations
                [1 ]deptDepartment of Neurosurgery , University Hospital Wuerzburg , Josef-Schneider-Str. 11, 97080, Wuerzburg, Germany
                Author notes
                Article
                tnsci-2018-0016
                10.1515/tnsci-2018-0016
                6124155
                30191076
                990f810d-0920-472b-8306-eee7a116667b
                © 2018 Ekkehard Kunze et al., published by De Gruyter

                This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

                History
                : 20 October 2017
                : 20 February 2018
                Page count
                Pages: 7
                Categories
                Regular Articles

                subarachnoid hemorrhage,magnesium,neuroprotection,delayed cerebral infarction

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