Clinical study on cognitive dysfunction after spontaneous subarachnoid haemorrhage: patient profiles and relationship to cholinergic dysfunction

Wong, George Kwok Chu; Wong, R.C.P.; Mok, Vincent; Fan, Dorothy S. P.; Leung, Gilberto Ka Kit; Wong, Adrian; Chan, Agnes S.; Zhu, Cannon Xian Lun; Poon, Wai-sang

doi:10.1007/s00701-009-0425-z

Cited by 29 publications

(15 citation statements)

References 23 publications

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“…26 Abnormalities in cognitive function are common after surgery for aneurysmal SAH, even among patients with a good functional outcome, and can occur in up to 44% of survivors. [27][28][29] This academically funded study was done without any industry support using generic medications and weakness would include lack of on-site trial monitoring due to restraints in funding. We have not incorporated daily blood pressure data in the trial design.…”

Section: Discussionmentioning

confidence: 99%

Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage (IMASH)

Wong

Poon

Chan

et al. 2010

Stroke

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193

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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.

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Section: Discussionmentioning

confidence: 99%

Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage (IMASH)

Wong

Poon

Chan

et al. 2010

Stroke

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193

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“…patterns of cognitive impairments post-SAH vary [13] though most report significant impairment across domains [14][15][16] . These inconsistencies are likely due to differing samples, with fewer cognitive deficits reported when participants with unfavourable neurological outcome, greater age ( 1 70 years) and aphasia are exclud ed [13] .…”

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confidence: 99%

“…Cognitive impairments post-SAH affect memory [15][16][17][18] , executive function, language, visual perception, attention, and motor and psychomotor speed [8,14,17] . While cognitive deficits have been documented 5 years post-SAH [19] , testing time varied within studies from 1 day to 5 years post-SAH [19,20] , none are populationbased, and most exclude the very old [21] and those with severe SAH [16] .…”

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confidence: 99%

Cognitive and Functional Outcomes of 5-Year Subarachnoid Haemorrhage Survivors: Comparison to Matched Healthy Controls

2011

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Background and Purpose: While neuropsychological deficits have been the focus of research post-subarachnoid haemorrhage (SAH), population-based information on long-term neuropsychological impairment post-SAH are lacking. Neither the profile of long-term neuropsychological deficits nor its relationship to long-term functional outcomes has been established. Methods: This was a cross-sectional population-based study of long-term (5 years) neuropsychological and functional outcomes post-SAH. Participants were 27 five-year survivors of SAH previously enrolled in the Auckland Regional Community Stroke study (2002–2003). Twenty-six age-, gender- and ethnicity-matched controls were used to compare mood, functional (i.e. disability; handicap; quality of life, QoL) and neuropsychological outcomes (i.e. verbal memory, visual memory, executive functioning, language, processing speed and visuoperceptual abilities) of SAH survivors. Results: SAH survivors were more depressed and significantly more impaired in the areas of disability, handicap, and QoL than controls. SAH survivors also had significant cognitive deficits across domains when compared to controls. Depressed mood and baseline functioning were related to worse functional outcomes at 5 years post-SAH. Whilst poor cognitive functioning, particularly in the domains of visual memory and language, impacted long-term functional outcomes of SAH survivors. Conclusions: Five-year SAH survivors have many functional and cognitive deficits compared to matched controls. Language and visual memory emerged as independent factors associated with their current functioning.

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“…22,27 Abnormalities in cognitive function are common after surgery/intervention for aneurysmal SAH, even among patients with a good functional outcome, and can occur in ≤44% of survivors. 28,29 Cognitive assessments would be of interest to investigate in future neuroprotective clinical trials for aneurysmal SAH.…”

Section: Discussionmentioning

confidence: 99%

“…После операции/вмеша-тельства по поводу аневризматического САК часто развиваются нарушения когнитивной функции, даже среди пациентов с благоприятным функциональным исходом, и встречаются у ≤44% выживших пациентов [28,29]. В связи с этим в будущих клинических испыта-ниях нейропротекторов при аневризматическом САК следует проводить оценку когнитивной функции.…”

Section: ■ обсуждениеunclassified

High-Dose Simvastatin for Aneurysmal Subarachnoid Hemorrhage

Wong

Chan

Siu

et al. 2015

Stroke

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A lthough aneurysmal subarachnoid hemorrhage (SAH) accounts for only 3% to 5% of strokes, its profound consequences and unique window of intervention justify its classification as a separate entity.1 Early aneurysm occlusion, expert endovascular neurosurgery and microsurgery, and the use of oral nimodipine and neurointensive care are now standard treatment procedures. 2,3 Nevertheless, aneurysmal SAH is still associated with mortality after 1 month for half of all patients, whereas another quarter is left with disabilities. 1 After aneurysmal SAH, 18% to 56% of patients demonstrate the evidence of secondary ischemia with clinical deterioration, which is also known as delayed ischemic deficit (DID). 4,5 The time lag of 3 to 10 days is unique and offers the potential to intervene before clinical deterioration. Pathologically, the basal subarachnoid distribution of deoxyhemoglobin and early hypoxic-ischemic brain injury contribute to the diffuse distribution of complex biological processes that involve endothelial cells. 6,7 Statin improves endothelial vasomotor function; increases nitric oxide bioavailability; possesses antioxidant properties; counters thrombus formation; induces angiogenesis, endogenous cell proliferation, and neurogenesis; increases the synaptic protein synaptophysin; induces vascular stabilization and neuroblast migration; and suppresses cytokine responses during cerebral ischemia. [7][8][9][10][11][12] Experimental evidence also indicates the benefit of simvastatin in the treatment of aneurysmal SAH. 13 Three randomized placebo-controlled pilot trials have supported the use of statins (2 with 80 mg of simvastatin and 1 with 40 mg of pravastatin) for the treatment of aneurysmal SAH. [14][15][16] In the Duke University Medical Center study, clinical vasospasm was significantly reduced from 60% to 26% by simvastatin treatment (80 mg daily).14 In the Massachusetts General Hospital study, vasospasm-related ischemic infarct was reduced from 25% to 11% by simvastatin treatment (80 mg daily). 16Background and Purpose-Experimental evidence has indicated the benefits of simvastatin for the treatment of subarachnoid hemorrhage. Two randomized placebo-controlled pilot trials that used the highest clinically approved dose of simvastatin (80 mg daily) gave positive results despite the fact that a lower dose of simvastatin (40 mg daily) did not improve clinical outcomes. We hypothesized that a high dose of 80 mg of simvastatin daily for 3 weeks would reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with a lower dose (40 mg of simvastatin daily) and lead to improved clinical outcomes. Methods-The study design was a randomized controlled double-blinded clinical trial. Patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of the ictus) from 6 neurosurgical centers were recruited for 3 years. The primary outcome measure was the presence of delayed ischemic deficits, and secondary outcome measures included a modified Rankin disability score ...

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Clinical study on cognitive dysfunction after spontaneous subarachnoid haemorrhage: patient profiles and relationship to cholinergic dysfunction

Cited by 29 publications

References 23 publications

Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage (IMASH)

Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage (IMASH)

Cognitive and Functional Outcomes of 5-Year Subarachnoid Haemorrhage Survivors: Comparison to Matched Healthy Controls

High-Dose Simvastatin for Aneurysmal Subarachnoid Hemorrhage

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