Ronald Boet

Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage (IMASH) A Randomized, Double-Blinded, Placebo-Controlled, Multicenter Phase III Trial

Background and Purpose— Pilot clinical trials using magnesium sulfate in patients with acute aneurysmal subarachnoid hemorrhage have reported trends toward improvement in clinical outcomes. This Phase III study aimed to compare intravenous magnesium sulfate infusion with saline placebo among such patients. Methods— We recruited patients with aneurysmal subarachnoid hemorrhage within 48 hours of onset from 10 participating centers. The patients were randomly assigned to magnesium sulfate infusion titrated to a serum magnesium concentration twice the baseline concentration or saline placebo for 10 to 14 days. Patients and assessors were blinded to treatment allocation. The study is registered at www.strokecenter.org/trials (as Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage [IMASH]) and www.ClinicalTrials.gov (NCT00124150). Results— Of the 327 patients recruited, 169 were randomized to receive treatment with intravenous magnesium sulfate and 158 to receive saline (placebo). The proportions of patients with a favorable outcome at 6 months (Extended Glasgow Outcome Scale 5 to 8) were similar, 64% in the magnesium sulfate group and 63% in the saline group (OR, 1.0; 95% CI, 0.7 to 1.6). Secondary outcome analyses (modified Rankin Scale, Barthel Index, Short Form 36, and clinical vasospasm) also showed no significant differences between the 2 groups. Predefined subgroups included age, admission World Federation of Neurological Surgeons grade, pre-existing hypertension, intracerebral hematoma, intraventricular hemorrhage, location of aneurysm, size of aneurysm, and mode of aneurysm treatment. In none of the subgroups did the magnesium sulfate group show a better outcome at 6 months. Conclusions— The results do not support a clinical benefit of intravenous magnesium sulfate infusion over placebo infusion in patients with acute aneurysmal subarachnoid hemorrhage.

Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: a prospective randomized pilot study.

We performed a randomized, double-blind, pilot study on magnesium sulfate (MgSO4) infusion for aneurysmal subarachnoid hemorrhage (SAH). Sixty patients with SAH were randomly allocated to receive either MgSO4 80 mmol/day or saline infusion for 14 days. Patients also received intravenous nimodipine. Episodes of vasospasm were treated with hypertensive and hypervolemic therapy. Neurologic status was assessed 6 months after hemorrhage using the Barthel index and Glasgow Outcome Scale. Incidences of cardiac and pulmonary complications were also recorded. Patient characteristics, severity of SAH, and surgical treatment did not differ between groups. The incidence of symptomatic vasospasm decreased from 43% in the saline group to 23% in patients receiving MgSO4 infusion, but it did not reach statistical significance, P=0.06. For patients who had transcranial Doppler-detected vasospasm, defined as mean flow velocity >120 cm/s and a Lindegaard index >3, the duration was shorter in the magnesium group compared with controls (P<0.01). There was, however, no difference between groups in functional recovery or Glasgow Outcome Scale score. The incidence of adverse events such as brain swelling, hydrocephalus, and nosocomial infection was also similar in patients receiving MgSO4 or saline. In this small pilot study, MgSO4 infusion for aneurysmal SAH is feasible. On the basis of the preliminary data, a larger study recruiting approximately 800 patients is required to test for a possible neuroprotective effect of magnesium after SAH.

Non-surgical primary treatment of chronic subdural haematoma: Preliminary results of using dexamethasone

From a series of 112 cases (64 men and 48 women, aged 37 – 91 years) of chronic subdural haematoma (CSDH) in a 2-year period from January 1998 to December 1999, we have prospectively studied a group of 30 patients, who were managed non-operatively: 26 patients were treated with dexamethasone (Group 1) and four patients expectantly (Group 4). Nineteen patients (73%) from Group 1 were confused or had focal neurological deficits on admission. The mean maximum thickness of the CSDH was 12 mm. Only one of these cases (4%) required surgical drainage 6 weeks after steroid therapy. One patient died of an unrelated stroke (mortality = 4%). Two patients (8%) were left severely disabled. No significant complication from steroid therapy was documented. Out of the 85 surgically treated patients, 69 patients underwent surgical drainage in addition to steroid therapy (Group 2). Thirteen patients were treated with burr-hole drainage only (Group 3). The mean maximum thickness of the CSDH for these two groups were both 16 mm. Comparing with group 1, the redrainage rate of Group 2 [4% (3/69, p = 1)] and that of Group 3 [15% (2/13, p = 0.253)] were not significantly different. 50% of patients in Group 4 (2/4, p = 0.039) required delayed surgical drainage. The mortality rates of Groups 2, 3 and 4 were 3% (2/69, p = 1), 15% (2/13, p = 0.253) and 50% (2/4, p = 0.039), respectively. Our results suggest that steroid treatment in a selected group of patients is a good option, particularly in patients with co-morbidity.

Magnesium Sulfate in the Management of Patients with Fisher Grade 3 Subarachnoid Hemorrhage: A Pilot Study

OBJECTIVETo evaluate the effect of magnesium sulfate (MgSO4) on the clinical course of patients with severe aneurysmal subarachnoid hemorrhage (SAH). METHODSTen patients with Fisher Grade 3 aneurysmal SAH were evaluated. The patients were given a bolus as well as a constant infusion of intravenous MgSO4 up to 10 days postictus. Blood magnesium levels were obtained to adjust the daily requirement of MgSO4. The goal was to raise the serum level to 2.0 to 2.5 mmol/L or twice the baseline serum level. Daily transcranial Doppler (TCD) ultrasonography was performed on each patient, insonating both anterior cerebral and middle cerebral arteries. Further management followed standard protocols, including the use of nimodipine and hypervolemic therapy. TCD ultrasonographic findings, as well as clinical evidence of cerebral vasospasm, were documented. All patients had a 3-month assessment using the Glasgow Outcome Scale. RESULTSAfter administration of a 20 mmol MgSO4 bolus infusion and an average daily continuous infusion of 84.7 mmol, 8 of 10 patients achieved the predetermined serum magnesium levels. No adverse affects were noted during the infusions. Five patients exhibited evidence of vasospasm on TCD ultrasonography; vasospasm was severe in two patients (velocities, >200 cm/s). Three patients, including the two patients in whom TCD ultrasonography demonstrated severe vasospasm, exhibited clinical evidence of vasospasm. Two patients had a Glasgow Outcome Scale score of 3; the remainder had Glasgow Outcome Scale scores of 5. CONCLUSIONAdministration guidelines for the use of MgSO4 in aneurysmal SAH were established. A prospective double-blind placebo-controlled trial is required to establish the effectiveness of MgSO4 for treating vasospasm in aneurysmal SAH.

The surgical treatment of intracranial aneurysms based on computer Tomographic angiography alone – streamlining the acute mananagement of symptomatic aneurysms

Summary. Background: We aimed to prospectively assess the usefulness of computer tomographic angiography (CTA) in streamlining the management of symptomatic intracranial aneurysms in a tertiary neurosurgical unit, from admission to surgery. Methods: We performed a prospective evaluation over a 2-year period of all symptomatic intracranial aneurysms managed according to a standardized departmental protocol, to assess how CTA has impacted the decision-making process pertaining to the suitability of this investigation to proceed directly to surgery. Findings: A total of 90 patients with intracranial aneurysms were treated over the 2-year period. 23 (26%) underwent endovascular occlusion while 67 (74%) patients underwent a surgical clipping procedure. In the surgical group, 22 (33%) patients had their aneurysms clipped based on CTA alone, while 45 (67%) required additional conventional angiography prior to surgery. Thus around one quarter of all patients treated for symptomatic intracranial aneurysms in our unit had their aneurysm secured surgically based solely on CTA. Interpretation: CTA significantly influences the acute management of symptomatic intracranial aneurysms by streamlining the decision-making process during the early and acute management of these lesions.

Aneurysm recurrence after treatment of paraclinoid/ophthalmic segment aneurysms - A treatment-modality assessment

SummaryObject. The treatment of 21 paraclinoid/ophthalmic segment internal carotid artery aneurysms (PCOSAs) over a seven year period in a regional neurosurgical center was reviewed to assess the degree of obliteration and recurrence rate of these aneurysms after treatment by surgical and endovascular methods.Method and result. An assessment of the clinical notes, operation records and cerebral angiograms was made to evaluate the rate of residual and recurrent aneurysms after treatment and at follow-up. In the coiling group, the aneurysm recurrence rate was eight out of fifteen aneurysms (53%). Four recurrences were from previously totally occluded aneurysms. Out of the six surgical cases, five had follow-up angiography performed. All had stable occlusions of their aneurysms including one with subtotal occlusion. Two clipping procedures after previous coiling achieved total occlusion of aneurysm on follow-up angiography.Conclusion. Based on our case series we conclude that PCOSAs frequently recur after primary treatment. GDC coiling was associated with a higher rate of recurrent aneurysms when compared with surgical treatment. A review of the literature on the surgical and endovascular treatment of PCOSAs support this observation.

Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis

IntroductionPrevious meta-analyses of magnesium sulphate infusion in the treatment of aneurysmal subarachnoid hemorrhage (SAH) have become outdated due to recently published clinical trials. Our aim was thus to perform an up-to-date systemic review and meta-analysis of published data on the use of magnesium sulphate infusion in aneurysmal SAH patients.MethodsA systemic review and meta-analysis of the literature was carried out on published randomized controlled clinical trials that investigated the efficacy of magnesium sulphate infusion in aneurysmal SAH patients. The results were analyzed with regard to delayed cerebral ischemia (DCI), delayed cerebral infarction, and favorable neurological outcomes at three and six months. The risks of bias were assessed using the Jadad criteria, with a Jadad score >3 indicating a lower such risk. Meta-analyses are presented in terms of relative risk (RR) with 95% confidence intervals (CIs).ResultsSix eligible studies with 875 patients were reviewed. The pooled RR for DCI was 0.87 (95% CI, 0.36 to 2.09; P = 0.75). That for delayed cerebral infarction was 0.58 (95% CI, 0.35 to 0.97; P = 0.04), although this result did not persist if only randomized clinical trials with a lower risk of bias were included (RR 0.61, 95% CI, 0.31 to 1.22; P = 0.17). The pooled RR for a favorable outcome at three months was 1.14 (95% CI, 0.99 to 1.31; P = 0.07), and that for a favorable outcome at six months was 1.08 (95% CI, 0.94 to 1.24; P = 0.29).ConclusionsThe present findings do not lend support to a beneficial effect of magnesium sulphate infusion on delayed cerebral infarction. The reduction in DCI and improvement in the clinical outcomes of aneurysmal SAH patients following magnesium sulphate infusion observed in previous pilot studies are not confirmed, although a beneficial effect cannot be ruled out because of sample size limitation.

Health-Related Quality of Life After Aneurysmal Subarachnoid Hemorrhage: Profile and Clinical Factors:

BACKGROUND:Health-related quality of life has recently been suggested as a supplement to the traditional neurological outcome measures from the patients perspective according to the World Health Organization model and may capture the effects of other factors such as posttraumatic stress disorder and neuroendocrine dysfunction. OBJECTIVE:To explore the profile and clinical factors of quality of life after aneurysmal subarachnoid hemorrhage using the data we obtained from the recently completed Intravenous Magnesium Sulphate After Aneurysmal Subarachnoid Hemorrhage (IMASH) trial. METHODS:This study was registered at www.strokecenter.org/trials and www.ClinicalTrials.gov (NCT00124150). Data from a patient cohort obtained with the Short Form-36 questionnaire completed at 6 months were used for analysis. RESULTS:Patients with aneurysmal subarachnoid hemorrhage demonstrated a decrease in quality of life according to the Short Form-36 at 6 months. The physical and mental health scores correlated with the Extended Glasgow Outcome Scale and had the potential to avoid the ceiling effect. Multiple regression analyses showed that the physical component scores were related to age, World Federation of Neurological Surgeons grade, and chronic hydrocephalus and that the mental component scores were not related to the traditional prognostic factors. CONCLUSION:Subarachnoid hemorrhage caused a decrease in quality of life. Chronic hydrocephalus is related to a decrease in physical health quality of life.

Effect of ischemic preconditioning on brain tissue gases and pH during temporary cerebral artery occlusion.

Previous studies have demonstrated that a brief period of ischemia protect against subsequent severe ischemic insults to the brain, i.e. preconditioning. We evaluated the effects of ischemic preconditioning, produced by 2 min proximal temporary artery occlusion, on brain tissue gases and acidity during clipping of cerebral aneurysm. Twelve patients with aneurysmal subarachnoid hemorrhage were recruited. All patients received standard anesthetics. After craniotomy, a calibrated multiparameter catheter was inserted to measure oxygen (PtO2) tension, carbon dioxide (PtCO2) tension and pH (pHt) in tissue at risk of ischemia during temporary artery occlusion. In patients assigned to the preconditioning group, proximal artery was occluded initially for 2 min and was allowed to reperfuse for 30 min. All patients underwent cerebral artery occlusion for clipping of aneurysm. The rate of change in PtO2, PtCO2 and pHt after artery occlusion were compared between groups using unpaired t test. Baseline brain tissue gases and pHt were similar between groups. Following artery occlusion, the decline in PtO2 and pHt were significantly slower in the preconditioning group compared with the routine care group. These results suggested that ischemic preconditioning attenuates tissue hypoxia during subsequent artery occlusion. Brief occlusion of the proximal artery may be a simple maneuver for brain protection during complex cerebrovascular surgery.

Ultra-early (within 24 Hours) aneurysm treatment after subarachnoid hemorrhage

BACKGROUND The timing of definitive aneurysm treatment (coiling or clipping) in acute aneurysm subarachnoid hemorrhage was a subject of controversy. Although most vascular neurosurgeons agreed on early aneurysm treatment (within the first 72 hours), whether ultra-early aneurysm treatment (within the first 24 hours) was beneficial remained debatable. We aimed to investigate whether ultra-early aneurysm treatment is associated with better neurological outcome in all patients or only good-grade patients or only poor-grade patients. METHODS Two-hundred and seventy-six (84%) patients had hemorrhage onset time and aneurysm treatment time available for analysis. Values of P < 0.05 were taken as statistically significant, and P values between 0.05 and 0.10 were considered to be a trend. RESULTS For the 96 poor-grade (World Federation of Neurological Surgeons grading scale 4 to 5) patients, there was a significant association between Short Form-36 mental scores and ultra-early aneurysm treatment (50 ± 10 vs. 46 ± 10, P = 0.019) and a trend toward association between ultra-early surgery and favorable neurological outcome (odds ratio 2.4 [95% confidence interval 1.0 to 6.0], P = 0.062). A reduction in clinical rebleeding (12% vs. 22%, P = 0.168) was observed in patients undergoing ultra-early aneurysm treatment. CONCLUSIONS Aneurysm treatment performed within the 24-hour window may be associated with a better outcome and halve the clinical rebleeding risk in poor-grade aneurysmal subarachnoid hemorrhage patients.