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Aneurysmal subarachnoid hemorrhage (aSAH) is a significant public health concern, annually affecting over 30,000 Americans and ranking among the leading causes of stroke-related life-years lost in individuals aged 65 and younger. Delayed cerebral ischemia (DCI), occurring in 20% to 40% of aSAH survivors, is a major contributor to brain injury and disability. Timely recognition of DCI is crucial for improving neurological outcomes and preventing irreversible cerebral infarction. However, current methods have substantial limitations, hindering early and reliable detection. This proposal seeks to address these challenges through determining the ability of perfusion imaging to predict DCI and correlate with neurological and neuropsychological outcomes.
Patients with a diagnosis of aSAH and no early radiologic vasospasm on admission demonstrated by DSA will receive a CT Perfusion (CTP) scan within 48 hours of aSAH symptom onset. The researchers seek to determine whether these baseline scans will identify perfusion parameters predictive of DCI. At 12-months mark post-hemorrhage, neurological and neuropsychological tests will be conducted to determine whether perfusion imaging correlates with neurological and neuropsychological outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients diagnosed with aSAH | Experimental | Patients will undergo the following study procedures:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CTP scan | Radiation | Patients with diagnosed aSAH and no evidence of early radiologic vasospasm will receive a CTP scan within 48 hours of aSAH symptom onset. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of Delayed Cerebral Ischemia (DCI) | DCI will be diagnosed using the 2010 consensus definition, including new focal neurological impairments (e.g., hemiparesis, aphasia, apraxia, hemianopia, or neglect) or a decrease of ≥2 points on the Glasgow Coma Scale lasting ≥1 hour, not immediately after aneurysm treatment and not due to other identifiable causes. | During hospitalization (within 14 days of aneurysmal subarachnoid hemorrhage (aSAH)) |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation Between Baseline Perfusion Parameters and 12-Month Neurological Outcome | Assessment of whether poor baseline perfusion profile (DCI Index Score (DIS) > 0.06) correlates with worse outcomes on neurological and neuropsychological assessments including modified Rankin Scale (mRS), 36-Item Short Form Health Survey (SF-36), and standardized cognitive test z-scores. | 12 months post-aSAH |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anna Maria Bombardieri, MD, PhD | Contact | (650) 723-6412 | abomba@stanford.edu | |
| Ksenia Kasimova, MD | Contact | 6507889458 | kasimova@stanford.edu |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34325514 | Background | Dodd WS, Laurent D, Dumont AS, Hasan DM, Jabbour PM, Starke RM, Hosaka K, Polifka AJ, Hoh BL, Chalouhi N. Pathophysiology of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review. J Am Heart Assoc. 2021 Aug 3;10(15):e021845. doi: 10.1161/JAHA.121.021845. Epub 2021 Jul 30. | |
| 24323051 | Background |
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| ID | Term |
|---|---|
| D013345 | Subarachnoid Hemorrhage |
| D002545 | Brain Ischemia |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| Neurological and neuropsychological testing | Diagnostic Test | All enrolled patients will receive neurological and neuropsychological assessment at 12 months after aSAH. |
|
| Modified Rankin Scale (mRS) | Measurement of functional disability using mRS, categorized as favorable (0-3) or unfavorable (4-6), to assess long-term disability and its association with baseline perfusion. | 12 months post-aSAH |
| Health-Related Quality of Life (HRQoL, SF-36) | HRQoL will be reported as standardized z-scores, with higher scores indicating better performance. | 12 months post-aSAH |
| Global Mental Status - Montreal Cognitive Assessment (MoCA) | Screens for mild cognitive impairment across multiple cognitive domains. Raw scores range from 0 to 30. Favorable outcome: MoCA score ≥ 26, unfavorable outcome: MoCA score < 26 (suggestive of cognitive impairment). | 12 months post-aSAH |
| Executive Functioning - Wisconsin Card Sorting Test (WCST) | Measures executive functioning, including cognitive flexibility and problem-solving. The number of categories completed and total errors will be converted to age-adjusted z-scores. Favorable outcome: z-score ≥ -1.0, unfavorable outcome: z-score < -1.0 (indicative of cognitive impairment in executive functioning). | 12 months post-aSAH |
| Processing Speed - Symbol Digit Modalities Test (SDMT) | Assesses visual scanning, tracking, and motor speed. Raw scores are adjusted for age and converted to z-scores. Favorable outcome: z-score ≥ -1.0, unfavorable outcome: z-score < -1.0 | 12 months post-aSAH |
| Language - Boston Naming Test (BNT) | Evaluates confrontational word retrieval and naming ability. Scores are standardized using age norms. Favorable outcome: z-score ≥ -1.0, unfavorable outcome: z-score < -1.0 | 12 months post-aSAH |
| Verbal Fluency - FAS Test | Tests lexical fluency by asking participants to generate words beginning with F, A, and S in a set time period. Z-scores are calculated from age-adjusted norms. Favorable outcome: z-score ≥ -1.0, unfavorable outcome: z-score < -1.0 | 12 months post-aSAH |
| Memory - Hopkins Verbal Learning Test-Revised (HVLT-R) | Assesses verbal learning and memory, including immediate recall, delayed recall, and recognition. Performance is normed and converted into z-scores. Favorable outcome: z-score ≥ -1.0, unfavorable outcome: z-score < -1.0 | 12 months post-aSAH |
| Composite Neuropsychological Test Scores | Analysis of cognitive function via composite z-scores derived from tests across executive function, memory, language, verbal fluency, processing speed, and global cognition (e.g., MoCA, HVLT-R, Boston Naming Test). Worse outcomes are defined by lower neuropsychological z-scores. | 12 months post-aSAH |
| Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014 Jan;10(1):44-58. doi: 10.1038/nrneurol.2013.246. Epub 2013 Dec 10. |
| 22879655 | Background | Rowland MJ, Hadjipavlou G, Kelly M, Westbrook J, Pattinson KT. Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm. Br J Anaesth. 2012 Sep;109(3):315-29. doi: 10.1093/bja/aes264. |
| 12766355 | Background | Baumgartner RW. Transcranial color duplex sonography in cerebrovascular disease: a systematic review. Cerebrovasc Dis. 2003;16(1):4-13. doi: 10.1159/000070108. |
| 34867722 | Background | Nguyen AM, Williamson CA, Pandey AS, Sheehan KM, Rajajee V. Screening Computed Tomography Angiography to Identify Patients at Low Risk for Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage. Front Neurol. 2021 Nov 12;12:740241. doi: 10.3389/fneur.2021.740241. eCollection 2021. |
| 24309123 | Background | Mir DI, Gupta A, Dunning A, Puchi L, Robinson CL, Epstein HA, Sanelli PC. CT perfusion for detection of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. AJNR Am J Neuroradiol. 2014 May;35(5):866-71. doi: 10.3174/ajnr.A3787. Epub 2013 Dec 5. |
| 31284055 | Background | Starnoni D, Maduri R, Hajdu SD, Pierzchala K, Giammattei L, Rocca A, Grosfilley SB, Saliou G, Messerer M, Daniel RT. Early Perfusion Computed Tomography Scan for Prediction of Vasospasm and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage. World Neurosurg. 2019 Oct;130:e743-e752. doi: 10.1016/j.wneu.2019.06.213. Epub 2019 Jul 5. |
| 26825134 | Background | Bashir A, Andresen M, Bartek J Jr, Cortsen M, Eskesen V, Wagner A. Intra-arterial nimodipine for cerebral vasospasm after subarachnoid haemorrhage: Influence on clinical course and predictors of clinical outcome. Neuroradiol J. 2016 Feb;29(1):72-81. doi: 10.1177/1971400915626429. Epub 2016 Jan 29. |
| 17636626 | Background | Dorhout Mees SM, Rinkel GJ, Feigin VL, Algra A, van den Bergh WM, Vermeulen M, van Gijn J. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2007 Jul 18;2007(3):CD000277. doi: 10.1002/14651858.CD000277.pub3. |
| 30053563 | Background | Hosmann A, Rauscher S, Wang WT, Dodier P, Bavinzski G, Knosp E, Gruber A. Intra-Arterial Papaverine-Hydrochloride and Transluminal Balloon Angioplasty for Neurointerventional Management of Delayed-Onset Post-Aneurysmal Subarachnoid Hemorrhage Vasospasm. World Neurosurg. 2018 Nov;119:e301-e312. doi: 10.1016/j.wneu.2018.07.138. Epub 2018 Jul 24. |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |