Cognitive Impairment in Aneurysmal Subarachnoid Hemorrhage Patients with Delayed Cerebral Infarction: Prevalence and Pattern

Chu, Alberto Chi Ho; Wong, George Kwok Chu; Lam, S.S.; Wong, Adrian; Ngai, Karine; Poon, Wai Sang; Mok, Vincent

doi:10.1007/978-3-319-04981-6_51

Cited by 11 publications

(11 citation statements)

References 16 publications

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“…Approximately 40% will be cognitively impaired (Dombovy et al, 1998 ), which is influenced by the incidence of CV, DCI, and infarction, but unrelated to the initial location of the ruptured aneurysm (MacDonald et al, 2012 ). Cognitive domain deficits commonly affected in aSAH patients with DCI are verbal memory, language, and visuospatial memory and skills (Caeiro et al, 2011 ; Chu et al, 2015a ). DCI has been associated with poor outcomes after SAH, but even with good outcomes, persistent cognitive deficits can still manifest, limiting psychosocial functioning.…”

Section: Clinical Sahmentioning

confidence: 99%

A Comparison of Pathophysiology in Humans and Rodent Models of Subarachnoid Hemorrhage

Leclerc

Garcia

Diller

et al. 2018

Front. Mol. Neurosci.

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Non-traumatic subarachnoid hemorrhage (SAH) affects an estimated 30,000 people each year in the United States, with an overall mortality of ~30%. Most cases of SAH result from a ruptured intracranial aneurysm, require long hospital stays, and result in significant disability and high fatality. Early brain injury (EBI) and delayed cerebral vasospasm (CV) have been implicated as leading causes of morbidity and mortality in these patients, necessitating intense focus on developing preclinical animal models that replicate clinical SAH complete with delayed CV. Despite the variety of animal models currently available, translation of findings from rodent models to clinical trials has proven especially difficult. While the explanation for this lack of translation is unclear, possibilities include the lack of standardized practices and poor replication of human pathophysiology, such as delayed cerebral vasospasm and ischemia, in rodent models of SAH. In this review, we summarize the different approaches to simulating SAH in rodents, in particular elucidating the key pathophysiology of the various methods and models. Ultimately, we suggest the development of standardized model of rodent SAH that better replicates human pathophysiology for moving forward with translational research.

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Section: Clinical Sahmentioning

confidence: 99%

A Comparison of Pathophysiology in Humans and Rodent Models of Subarachnoid Hemorrhage

Leclerc

Garcia

Diller

et al. 2018

Front. Mol. Neurosci.

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“…Cognitive dysfunction is an increasingly recognized cause of disability in SAH survivors occuring in 7 to 15% of patients [ 81 , 82 ]. In view of the positive clinical results of Cerebrolysin in treating vascular dementia and Alzheimer’s disease, we hypothesized that an improvement in neurocognitive performance could be detected in SAH patients [ 83 , 84 ].…”

Section: Discussionmentioning

confidence: 99%

Randomized, placebo-controlled, double-blind, pilot trial to investigate safety and efficacy of Cerebrolysin in patients with aneurysmal subarachnoid hemorrhage

Woo

et al. 2020

BMC Neurol

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Asbtract Background There are limited neuroprotective treatment options for patients with aneurysmal subarachnoid hemorrhage (SAH). Cerebrolysin, a brain-specific proposed pleiotropic neuroprotective agent, has been suggested to improve global functional outcomes in ischemic stroke. We investigated the efficacy, safety and feasibility of administering Cerebrolysin for SAH patients. Methods This was a prospective, randomized, double-blind, placebo-controlled, single-center, parallel-group pilot study. Fifty patients received either daily Cerebrolysin (30 ml/day) or a placebo (saline) for 14 days (25 patients per study group). The primary endpoint was a favorable Extended Glasgow Outcome Scale (GOSE) of 5 to 8 (moderate disability to good recovery) at six-months. Secondary endpoints included the modified Ranking Scale (mRS), the Montreal Cognitive Assessment (MOCA) score, occurrence of adverse effects and the occurrence of delayed cerebral ischemia (DCI). Results No severe adverse effects or mortality attributable to Cerebrolysin were observed. No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 1.49; 95% confidence interval (CI): 0.43–5.17). Secondary functional outcome measures for favorable six-month recovery i.e. a mRS of 0 to 3 (OR: 3.45; 95% CI 0.79–15.01) were comparable for both groups. Similarly, there was no difference in MOCA neurocognitive performance (p-value: 0.75) and in the incidence of DCI (OR: 0.85 95% CI: 0.28–2.59). Conclusions Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. However, the neutral results of this trial suggest that it does not improve the six-month global functional performance of patients. Clinical trial registration Name of Registry: ClinicalTrials.gov Trial Registration Number: NCT01787123. Date of Registration: 8th February 2013.

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“…Cognitive dysfunction is gradually being recognized as an important source of disability in SAH survivors occuring in 7-15% of patients with DCI being a major predictor. [61,62] Coupled with the positive clinical results of Cerebrolysin in treating vascular dementia and Alzheimer's disease, we also hypothesized that an improvement in neurocognitive performance could be detected in SAH patients, but no significant difference between the study groups existed. [63,64] This may be due to the relatively short two-week course of administration that was designed to predominantly exploit Cerebrolysin's neuroprotective action.…”

Section: Discussionmentioning

confidence: 99%

Randomized, Placebo-controlled, Double-blind, Pilot Trial to Investigate Safety and Efficacy of Cerebrolysin in Patients with Aneurysmal Subarachnoid Hemorrhage

Woo

Lam

et al. 2019

Preprint

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Background There are limited treatment options for aneurysmal subarachnoid hemorrhage (SAH)-induced delayed cerebral ischemia, a major determinant of mortality and morbidity. Cerebrolysin, a brain-specific pleiotropic neuroprotective agent, has been suggested to improve functional outcomes in ischemic stroke. We investigated the efficacy, safety and feasibility of Cerebrolysin for conferring such benefits in SAH patients. Methods This was a prospective, randomized, double-blind, placebo-controlled, single-center, parallel-group pilot study. 50 patients received either daily Cerebrolysin (30ml/day) or a placebo (saline) for 14 days (25 patients per study group). The primary endpoint was a favorable Extended Glasgow Outcome Score (GOSE) of 5 to 8 (moderate disability to good recovery) at six-months. Secondary endpoints included the occurrence of adverse effects, six-month mortality, the occurrence of cerebral vasospasm, delayed cerebral ischemia and infarction. Results No severe adverse effects or mortality attributable to Cerebrolysin were observed. No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 0.53; 95% confidence interval (CI): 0.43-5.17). Secondary functional outcome measures for good six-month recovery indicated by a modified Rankin Scale of 0 to 2 (OR: 0.53; 95% CI 0.43-5.17) and a Barthel Index of 70 or more (OR: 0.52; 95% CI: 0.29-12.72) were also similar for both groups. There was a significantly lower risk of three- and six-month mortality for patients that received Cerebrolysin (OR: 0.46; 95% CI: 0.33-0.63). There were no deaths in the Cerebrolysin group, but the morality rate for the control group was 16% (4/25). The commonest cause of death was due to delayed cerebral ischemia. There were no differences in the overall incidence of delayed cerebral ischemia (p-value: 0.78), cerebral vasospasm (p-value: 0.16) and infarction (p-value: 0.77) between the two groups. Conclusions Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. Results suggest a benefit in reducing three- and six-month mortality. Due to the exploratory nature of this study and its small sample size, these findings should be confirmed in a larger-scale clinical trial.

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Cognitive Impairment in Aneurysmal Subarachnoid Hemorrhage Patients with Delayed Cerebral Infarction: Prevalence and Pattern

Abstract: In patients with aSAH, delayed cerebral infarction was associated with a specific pattern of cognitive domain deficits. The pathophysiology should be further investigated.

Cited by 11 publications

References 16 publications

A Comparison of Pathophysiology in Humans and Rodent Models of Subarachnoid Hemorrhage

A Comparison of Pathophysiology in Humans and Rodent Models of Subarachnoid Hemorrhage

Randomized, placebo-controlled, double-blind, pilot trial to investigate safety and efficacy of Cerebrolysin in patients with aneurysmal subarachnoid hemorrhage

Randomized, Placebo-controlled, Double-blind, Pilot Trial to Investigate Safety and Efficacy of Cerebrolysin in Patients with Aneurysmal Subarachnoid Hemorrhage

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