Abstract 194: Cognitive Outcome in Acute Simvastatin Treatment for Aneurysmal Subarachnoid Hemorrhage

Objectives: Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid haemorrhage (SAH). Recently, acute simvastatin treatment was not shown to be beneficial in neurological outcome using modified Rankin Scale. Cognitive function is another important dimension of outcome assessment and yet had not been investigated in statin studies for aneurysmal subarachnoid hemorrhage. We therefore explored whether acute simvastatin treatment would improve cognitive outcomes. Methods: The study recruited SAH patients with acute simvastatin treatment enrolled in a randomized controlled double-blinded clinical trial (ClinicalTrials.gov Identifier: NCT01038193). A control cohort of SAH patients without simvastatin treatment was identified with propensity score matching of age and admission grade. Primary outcome measure was Montreal Cognitive Assessment (MoCA). Secondary outcome measures were delayed ischaemic deficit (DID), delayed cerebral infarction, modified Rankin Scale (mRS), and Mini-Mental State Examination( MMSE). Results: Fifty-one SAH patients with acute simvastatin treatment and 51 SAH patients without simvastatin treatment were recruited for analysis. At 3 months, there were no differences in MoCA scores (MoCA: 21+/-6 vs. 21+/-5, p=0.772). MoCA-assessed cognitive impairment (MoCA<26) was not different (75% vs. 80%, OR 0.7, 95%CI 0.3 to 1.8, p=0.477). There were also no differences in DID, delayed cerebral infarction, favorable mRS outcome, and MMSE scores, and MMSE-assessed cognitive impairment between both groups. Conclusions: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage.

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Cognitive outcome in acute simvastatin treatment for aneurysmal subarachnoid hemorrhage: A propensity matched analysis

Journal of the Neurological Sciences ◽

10.1016/j.jns.2015.08.013 ◽

2015 ◽

Vol 358 (1-2) ◽

pp. 58-61 ◽

Cited By ~ 7

Author(s):

George K.C. Wong ◽

Adrian Wong ◽

Beny C.Y. Zee ◽

Wai S. Poon ◽

Matthew T.V. Chan ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Cognitive Outcome ◽

Simvastatin Treatment

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

Neurovascular Events After Subarachnoid Hemorrhage ◽

10.1007/978-3-319-04981-6_51 ◽

2014 ◽

pp. 303-306 ◽

Cited By ~ 4

Author(s):

Alberto Chi Ho Chu ◽

George Kwok Chu Wong ◽

Sandy Wai Lam ◽

Adrian Wong ◽

Karine Ngai ◽

...

Keyword(s):

Cognitive Impairment ◽

Subarachnoid Hemorrhage ◽

Cerebral Infarction ◽

Aneurysmal Subarachnoid Hemorrhage

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Effect of Cilostazol on Cerebral Vasospasm and Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized, Double-Blind, Placebo-Controlled Trial

Cerebrovascular Diseases ◽

10.1159/000445509 ◽

2016 ◽

Vol 42 (1-2) ◽

pp. 97-105 ◽

Cited By ~ 22

Author(s):

Naoya Matsuda ◽

Masato Naraoka ◽

Hiroki Ohkuma ◽

Norihito Shimamura ◽

Katsuhiro Ito ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Infarction ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Control Group ◽

Independent Factor ◽

Double Blind ◽

End Points ◽

Double Blind Placebo ◽

Poor Outcome

Background: Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm. Methods: Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment. Results: One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period. Conclusions: Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol.

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Vasospasm severity is associated with cerebral infarction after subarachnoid hemorrhage

10.1101/2021.04.20.21255798 ◽

2021 ◽

Author(s):

Samuel B Snider ◽

Ibrahim Migdady ◽

Sarah L LaRose ◽

Morgan E Mckeown ◽

Robert W Regenhardt ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Infarction ◽

Negative Predictive Value ◽

Predictive Value ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Time Varying ◽

Single Center ◽

Early Screening ◽

Angiographic Vasospasm

AbstractBackgroundThe presence of angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed-cerebral ischemia (DCI)-related cerebral infarction and worsened neurological outcome. Transcranial doppler (TCD) measurements of cerebral blood velocity are commonly used after aSAH to screen for vasospasm. We sought to determine whether time-varying TCD measured vasospasm severity is associated with cerebral infarction and to investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction.MethodsWe used a retrospective, single-center cohort of consecutive adult aSAH patients with angiographic vasospasm and at least one TCD study. Our primary outcome was DCI-related cerebral infarction, defined as an infarction developing at least 2 days after any surgical intervention without an alternative cause. Time-varying TCD vasospasm severity was defined ordinally (absent, mild, moderate, severe) by the most abnormal vessel on each post-admission hospital day. Cox proportional-hazards models were used to examine associations between time-varying vasospasm severity and infarction. The optimal TCD-based time/severity thresholds for predicting infarction were then identified using the Youden J statistic.ResultsOf 218 aSAH patients with angiographic vasospasm, 27 (12%) developed DCI-related infarction. As compared to those without infarction, patients with infarction had higher modified Fisher scale (mFS) scores, and an earlier onset of more-severe vasospasm. Adjusted for mFS, vasospasm severity was associated with infarction (aHR 1.9, 95% CI: 1.3-2.6). A threshold of at least mild vasospasm severity on hospital day 4 had a negative predictive value of 92% for the development of infarction, but a positive predictive value of 25%.ConclusionsIn aSAH, TCD-measured vasospasm severity is associated with DCI-related infarction. In a single-center dataset, a TCD-based threshold for predicting infarction had a high negative predictive value, supporting its role as an early screening tool to identify at-risk patients.

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Severity of cerebral vasospasm associated with development of collaterals following aneurysmal subarachnoid hemorrhage

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2017-013410 ◽

2018 ◽

Vol 10 (7) ◽

pp. 638-643

Author(s):

Fawaz Al-Mufti ◽

Jens Witsch ◽

Nathan Manning ◽

Michael Crimmins ◽

Krishna Amuluru ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Weighted Kappa ◽

Observational Cohort Study ◽

Cognitive Outcome ◽

Multivariable Model ◽

Final Infarct Size ◽

Observational Cohort

IntroductionCerebral collateral circulation has been studied extensively in ischemic stroke where it has been shown to be a predictor of reperfusion, final infarct size, and outcome. Little is known about the significance of the collaterals in the setting of aneurysmal subarachnoid hemorrhage (aSAH). We sought to evaluate the effect of cerebral vasospasm on the development of cerebral collaterals following aneurysmal subarachnoid hemorrhage and the effects of the latter on delayed cerebral ischemia (DCI).MethodsWe retrospectively evaluated 64 aSAH patients with evidence of DCI between day 5 and 7, enrolled in a prospectively maintained observational cohort study. Angiograms were evaluated by four blinded neurointerventionalists. We compared good collateral grades to poor collateral grades, additionally we compared enrolled individuals with any collaterals versus patients who had no collaterals.ResultsInter-rater reliability for collateral grades was substantial (weighted kappa 0.632). Mild vasospasm was more frequent in patients with poor collateral grades compared with patients with good collateral grades (32% vs 4% P=0.012). There was no difference between the collateral groups with regards to DCI, functional, or cognitive outcome. Patients adjudicated to have any collaterals were more likely to have severe vasospasm (62% vs 33% P=0.023) and less likely to have mild vasospasm (37% vs 9% P=0.007). In a multivariable model, vasospasm severity remained associated with collateral status, while aneurysm location was not.ConclusionsThe severity of vasospasm following aSAH was associated with the development of collaterals. There was no difference between collateral grades with regards to DCI or outcome.

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Microstructural White Matter Abnormalities and Cognitive Impairment After Aneurysmal Subarachnoid Hemorrhage

Stroke ◽

10.1161/strokeaha.118.021622 ◽

2018 ◽

Vol 49 (9) ◽

pp. 2040-2045 ◽

Cited By ~ 4

Author(s):

Yael D. Reijmer ◽

Marc S. van den Heerik ◽

Rutger Heinen ◽

Alexander Leemans ◽

Jeroen Hendrikse ◽

...

Keyword(s):

Cognitive Impairment ◽

Subarachnoid Hemorrhage ◽

White Matter ◽

Aneurysmal Subarachnoid Hemorrhage ◽

White Matter Abnormalities

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Transcranial Doppler for Early Prediction of Cognitive Impairment after Aneurysmal Subarachnoid Hemorrhage and the Associated Clinical Biomarkers

Stroke Research and Treatment ◽

10.1155/2020/8874605 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Ahmed Esmael ◽

Tamer Belal ◽

Khaled Eltoukhy

Keyword(s):

Blood Pressure ◽

Cognitive Impairment ◽

Subarachnoid Hemorrhage ◽

Cognitive Function ◽

Cerebral Artery ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Clinical Biomarkers ◽

Poor Cognitive Function ◽

Impaired Cognition

Background and Aim. Cognitive impairment after aneurysmal subarachnoid hemorrhage (aSAH) stays under investigation. This study is aimed at predicting the cognitive impairment by transcranial Doppler (TCD) and detecting the associated clinical biomarkers of impaired cognition after aSAH after 3 months from the onset. Methods. Prospective study included 40 cases with acute aSAH. Initial evaluation by Glasgow Coma Scale (GCS) and the severity of aSAH was detected by both the clinical Hunt and Hess and radiological Fisher’s grading scales. TCD was done for all patients five times within 10 days measuring the mean flow velocities (MFVs) of cerebral arteries. At the 3-month follow-up, patients were classified into two groups according to Montreal Cognitive Assessment (MoCA) scale: the first group was 31 cases (77.5%) with intact cognitive functions and the other group was 9 cases (22.5%) with impaired cognition. Results. Patients with impaired cognitive functions showed significantly lower mean GCS ( p = 0.03 ), significantly higher mean Hunt and Hess scale grades ( p = 0.04 ), significantly higher mean diabetes mellitus (DM) ( p = 0.03 ), significantly higher mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) ( p = 0.02 and p = 0.005 , respectively), and significantly higher MFVs measured within the first 10 days. The patients with cognitive impairment were accompanied by a higher incidence of hydrocephalus ( p = 0.01 ) and a higher incidence of delayed cerebral ischemia (DCI) ( p < 0.001 ). Logistic regression analysis detected that MFV ≥ 86 cm / s in the middle cerebral artery (MCA), MFV ≥ 68 cm / s in the anterior cerebral artery (ACA), and MFV ≥ 45 cm / s in the posterior cerebral artery (PCA) were significantly associated with increased risk of cognitive impairment. Conclusion. Cognitive impairment after the 3-month follow-up phase in aSAH patients was 22.5%. Acute hydrocephalus and DCI are highly associated with poor cognitive function in aSAH. Increased MFV is a strong predictor for poor cognitive function in aSAH. This trial is registered with NCT04329208.

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Frequency and clinical impact of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.2008.109.12.1052 ◽

2008 ◽

Vol 109 (6) ◽

pp. 1052-1059 ◽

Cited By ~ 104

Author(s):

J. Michael Schmidt ◽

Katja E. Wartenberg ◽

Andres Fernandez ◽

Jan Claassen ◽

Fred Rincon ◽

...

Keyword(s):

Risk Factors ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Infarction ◽

Clinical Symptoms ◽

External Ventricular Drain ◽

Delayed Cerebral Ischemia ◽

Neurological Deterioration ◽

Modified Rankin Scale ◽

Poor Grade

Object The authors sought to determine frequency, risk factors, and impact on outcome of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage (SAH). Methods The authors prospectively studied 580 patients with SAH admitted to their center between July 1996 and May 2002. Delayed cerebral ischemia (DCI) from vasospasm was defined as 1) a new focal neurological deficit or decrease in level of consciousness, 2) a new infarct revealed by follow-up CT imaging, or both, after excluding causes other than vasospasm. Outcome at 3 months was assessed using the modified Rankin Scale. Results Delayed cerebral ischemia occurred in 121 (21%) of 580 patients. Of those with DCI, 36% (44 patients) experienced neurological deterioration without a corresponding infarct, 42% (51 patients) developed an infarct in conjunction with neurological deterioration, and 21% (26 patients) had a new infarct on CT without concurrent neurological deterioration. In a multivariate analysis, risk factors for asymptomatic DCI included coma on admission, placement of an external ventricular drain, and smaller volumes of SAH (all p ≤ 0.03). Patients with asymptomatic DCI were less likely to be treated with vasopressor agents than those with symptomatic DCI (64 vs 86%, p = 0.01). After adjusting for clinical grade, age, and aneurysm size, the authors found that there was a higher frequency of death or moderate-to-severe disability at 3 months (modified Rankin Scale Score 4–6) in patients with asymptomatic DCI than in patients with symptomatic DCI (73 vs 40%, adjusted odds ratio 3.9, 95% confidence interval 1.3–12.0, p = 0.017). Conclusions Approximately 20% of episodes of DCI after SAH are characterized by cerebral infarction in the absence of clinical symptoms. Asymptomatic DCI is particularly common in comatose patients and is associated with poor outcome. Strategies directed at diagnosing and preventing asymptomatic infarction from vasospasm in patients with poor-grade SAH are needed.

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Cognitive Outcome in Childhood-Onset Epilepsy: A Five-Decade Prospective Cohort Study

Journal of the International Neuropsychological Society ◽

10.1017/s1355617716001077 ◽

2017 ◽

Vol 23 (4) ◽

pp. 332-340 ◽

Cited By ~ 7

Author(s):

Mira Karrasch ◽

Petri Tiitta ◽

Bruce Hermann ◽

Juho Joutsa ◽

Shlomo Shinnar ◽

...

Keyword(s):

Cohort Study ◽

Cognitive Impairment ◽

Population Based ◽

Cognitive Outcomes ◽

Cognitive Outcome ◽

Healthy Controls ◽

Childhood Onset ◽

Semantic Function ◽

Active Epilepsy

AbstractObjectives: Little is known about the very long-term cognitive outcome in patients with childhood-onset epilepsy. The aim of this unique prospective population-based cohort study was to examine cognitive outcomes in aging participants with childhood-onset epilepsy (mean onset age=5.3 years) five decades later (mean age at follow-up=56.5 years).Methods: The sample consisted of 48 participants with childhood-onset epilepsy and 48 age-matched healthy controls aged 48–63 years. Thirty-six epilepsy participants were in remission and 12 continued to have seizures. Cognitive function was examined with 11 neuropsychological tests measuring language and semantic function, episodic memory, and learning, visuomotor function, executive function, and working memory. Results: The risk of cognitive impairment was very high in participants with continuing seizures; odds ratio (OR)=11.7 (95% confidence interval [CI] (2.8, 49.6), p=.0008). They exhibited worse performances across measures of language and semantic function, and visuomotor function compared to participants with remitted epilepsy and healthy controls. In the participants with remitted epilepsy, the risk of cognitive impairment was somewhat elevated, but not statistically significant; OR=2.6 (95% CI [0.9, 7.5], p=.08).Conclusions: Our results showed that the distinction of continued versus discontinued seizures was critical for determining long-term cognitive outcome in childhood-onset epilepsy. Few participants in remission exhibited marked cognitive impairment compared to age-matched peers. However, a subgroup of participants with decades long active epilepsy, continuous seizure activity and anti-epileptic drug (AED) medication, showed clinically significant cognitive impairment and are thus in a more precarious position when entering older age. (JINS, 2017, 23, 332–340)

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