{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T01:04:03Z","timestamp":1786755843344,"version":"build-2736575974"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Bern"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neurochir"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract\n<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>There is increasing evidence that inflammation plays a role in the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH) and in the development of delayed cerebral ischemia (DCI). However, the assessment and interpretation of classically defined inflammatory parameters is difficult in aSAH patients. The objective of this study was to investigate the relationship between easily assessable findings (hyperventilation, fever, white blood cell count (WBC), and C-reactive protein (CRP)) and the occurrence of DCI and unfavorable neurological outcome at discharge in aSAH patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Retrospective analysis of prospectively collected data from a single center cohort. We evaluated the potential of clinical signs of inflammation (hyperventilation, fever) and simple inflammatory laboratory parameters CRP and WBC to predict unfavorable outcomes at discharge and DCI in a multivariate analysis. A cutoff value for CRP was calculated by Youden\u2019s <jats:italic>J<\/jats:italic> statistic. Outcome was measured using the modified Rankin score at discharge, with an unfavorable outcome defined as modified Rankin scale (mRS)\u2009&gt;\u20093.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We included 97 consecutive aSAH patients (63 females, 34 males, mean age 58\u00a0years) in the analysis. Twenty-one (22%) had major disability or died by the time of hospital discharge. Among inflammatory parameters, CRP over 100\u00a0mg\/dl on day 2 was an independent predictor for worse neurological outcome at discharge. The average C-reactive protein level in the first 14\u00a0days was higher in patients with a worse neurological outcome (96.6, SD 48.3 vs 56.3\u00a0mg\/dl, SD 28.6) in the first 14\u00a0days after aSAH. C-reactive protein on day 2 was an indicator of worse neurological outcome. No inflammatory parameter was an independent predictor of DCI. After multivariate adjustment, DCI, increased age, and more than 1\u00a0day of mechanical ventilation were significant predictors of worse neurological outcome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Early elevated CRP levels were a significant predictor of worse neurological outcome at hospital discharge and may be a useful marker of later deterioration in aSAH.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00701-022-05256-0","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T22:02:26Z","timestamp":1653602546000},"page":"1805-1814","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["C-reactive protein elevation predicts in-hospital deterioration after aneurysmal subarachnoid hemorrhage: a retrospective observational study"],"prefix":"10.1007","volume":"164","author":[{"given":"Ostini","family":"Alessandro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warschkow","family":"Rene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolf","family":"Stefan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filipovic","family":"Miodrag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seule","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bozinov","family":"Oliver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietsch","family":"Urs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"5256_CR1","doi-asserted-by":"publisher","first-page":"e519","DOI":"10.1161\/STROKEAHA.110.581975","volume":"41","author":"T Al-Khindi","year":"2010","unstructured":"Al-Khindi T, Macdonald RL, Schweizer TA (2010) Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke 41:e519-536. https:\/\/doi.org\/10.1161\/STROKEAHA.110.581975","journal-title":"Stroke"},{"key":"5256_CR2","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1186\/s13054-020-03342-2","volume":"24","author":"S Amodio","year":"2020","unstructured":"Amodio S, Bouzat P, Robba C, Taccone FS (2020) Rethinking brain injury after subarachnoid hemorrhage. Crit Care 24:612. https:\/\/doi.org\/10.1186\/s13054-020-03342-2","journal-title":"Crit Care"},{"key":"5256_CR3","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1161\/STROKEAHA.118.023902","volume":"50","author":"CE van Donkelaar","year":"2019","unstructured":"van Donkelaar CE, Bakker NA, Birks J, Veeger NJGM, Metzemaekers JDM, Molyneux AJ, Groen RJM, van Dijk JMC (2019) Prediction of outcome after aneurysmal subarachnoid hemorrhage. Stroke 50:837\u2013844. https:\/\/doi.org\/10.1161\/STROKEAHA.118.023902","journal-title":"Stroke"},{"key":"5256_CR4","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1161\/STR.0b013e3182587839","volume":"43","author":"ES Connolly Jr","year":"2012","unstructured":"Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P, American Heart Association Stroke C, Council on Cardiovascular R, Intervention, Council on Cardiovascular N, Council on Cardiovascular S, Anesthesia, Council on Clinical C (2012) Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association\/American Stroke Association. Stroke 43:1711\u20131737. https:\/\/doi.org\/10.1161\/STR.0b013e3182587839","journal-title":"Stroke"},{"key":"5256_CR5","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1007\/s12028-008-9054-2","volume":"8","author":"R Dhar","year":"2008","unstructured":"Dhar R, Diringer MN (2008) The burden of the systemic inflammatory response predicts vasospasm and outcome after subarachnoid hemorrhage. Neurocrit Care 8:404\u2013412. https:\/\/doi.org\/10.1007\/s12028-008-9054-2","journal-title":"Neurocrit Care"},{"key":"5256_CR6","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1136\/jnnp.70.4.534","volume":"70","author":"K Fassbender","year":"2001","unstructured":"Fassbender K, Hodapp B, Rossol S, Bertsch T, Schmeck J, Schutt S, Fritzinger M, Horn P, Vajkoczy P, Kreisel S, Brunner J, Schmiedek P, Hennerici M (2001) Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry 70:534\u2013537. https:\/\/doi.org\/10.1136\/jnnp.70.4.534","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"5256_CR7","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1212\/01.wnl.0000258543.45879.f5","volume":"68","author":"A Fernandez","year":"2007","unstructured":"Fernandez A, Schmidt JM, Claassen J, Pavlicova M, Huddleston D, Kreiter KT, Ostapkovich ND, Kowalski RG, Parra A, Connolly ES, Mayer SA (2007) Fever after subarachnoid hemorrhage: risk factors and impact on outcome. Neurology 68:1013\u20131019. https:\/\/doi.org\/10.1212\/01.wnl.0000258543.45879.f5","journal-title":"Neurology"},{"key":"5256_CR8","doi-asserted-by":"publisher","first-page":"E22","DOI":"10.3171\/2009.2.FOCUS08311","volume":"26","author":"KN Fountas","year":"2009","unstructured":"Fountas KN, Tasiou A, Kapsalaki EZ, Paterakis KN, Grigorian AA, Lee GP, Robinson JS Jr (2009) Serum and cerebrospinal fluid C-reactive protein levels as predictors of vasospasm in aneurysmal subarachnoid hemorrhage. Clinical article. Neurosurg Focus 26:E22. https:\/\/doi.org\/10.3171\/2009.2.FOCUS08311","journal-title":"Neurosurg Focus"},{"key":"5256_CR9","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1179\/016164109X12464612122650","volume":"32","author":"D Graetz","year":"2010","unstructured":"Graetz D, Nagel A, Schlenk F, Sakowitz O, Vajkoczy P, Sarrafzadeh A (2010) High ICP as trigger of proinflammatory IL-6 cytokine activation in aneurysmal subarachnoid hemorrhage. Neurol Res 32:728\u2013735. https:\/\/doi.org\/10.1179\/016164109X12464612122650","journal-title":"Neurol Res"},{"key":"5256_CR10","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1097\/ANA.0b013e31826047a2","volume":"24","author":"YT Jeon","year":"2012","unstructured":"Jeon YT, Lee JH, Lee H, Lee HK, Hwang JW, Lim YJ, Park HP (2012) The postoperative C-reactive protein level can be a useful prognostic factor for poor outcome and symptomatic vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol 24:317\u2013324. https:\/\/doi.org\/10.1097\/ANA.0b013e31826047a2","journal-title":"J Neurosurg Anesthesiol"},{"key":"5256_CR11","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s00701-011-1243-7","volume":"154","author":"S Juvela","year":"2012","unstructured":"Juvela S, Kuhmonen J, Siironen J (2012) C-reactive protein as predictor for poor outcome after aneurysmal subarachnoid haemorrhage. Acta Neurochir 154:397\u2013404. https:\/\/doi.org\/10.1007\/s00701-011-1243-7","journal-title":"Acta Neurochir"},{"key":"5256_CR12","doi-asserted-by":"publisher","first-page":"e1014","DOI":"10.1016\/j.wneu.2018.10.203","volume":"122","author":"PMR Lai","year":"2019","unstructured":"Lai PMR, See AP, Silva MA, Gormley WB, Frerichs KU, Aziz-Sultan MA, Du R (2019) Noninfectious fever in aneurysmal subarachnoid hemorrhage: association with cerebral vasospasm and clinical outcome. World Neurosurg 122:e1014\u2013e1019. https:\/\/doi.org\/10.1016\/j.wneu.2018.10.203","journal-title":"World Neurosurg"},{"key":"5256_CR13","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1212\/WNL.0b013e3181dd42b3","volume":"74","author":"CE Lovelock","year":"2010","unstructured":"Lovelock CE, Rinkel GJ, Rothwell PM (2010) Time trends in outcome of subarachnoid hemorrhage: population-based study and systematic review. Neurology 74:1494\u20131501. https:\/\/doi.org\/10.1212\/WNL.0b013e3181dd42b3","journal-title":"Neurology"},{"key":"5256_CR14","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1227\/NEU.0b013e31828048ce","volume":"72","author":"C Muroi","year":"2013","unstructured":"Muroi C, Hugelshofer M, Seule M, Tastan I, Fujioka M, Mishima K, Keller E (2013) Correlation among systemic inflammatory parameter, occurrence of delayed neurological deficits, and outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery 72:367\u2013375; discussion 375. https:\/\/doi.org\/10.1227\/NEU.0b013e31828048ce","journal-title":"Neurosurgery"},{"key":"5256_CR15","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1097\/01.ana.0000181693.30750.af","volume":"18","author":"RD Rothoerl","year":"2006","unstructured":"Rothoerl RD, Axmann C, Pina AL, Woertgen C, Brawanski A (2006) Possible role of the C-reactive protein and white blood cell count in the pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol 18:68\u201372. https:\/\/doi.org\/10.1097\/01.ana.0000181693.30750.af","journal-title":"J Neurosurg Anesthesiol"},{"key":"5256_CR16","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1177\/0271678X19841443","volume":"39","author":"AR Saand","year":"2019","unstructured":"Saand AR, Yu F, Chen J, Chou SH (2019) Systemic inflammation in hemorrhagic strokes - a novel neurological sign and therapeutic target? J Cereb Blood Flow Metab 39:959\u2013988. https:\/\/doi.org\/10.1177\/0271678X19841443","journal-title":"J Cereb Blood Flow Metab"},{"key":"5256_CR17","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/s12028-010-9432-4","volume":"13","author":"A Sarrafzadeh","year":"2010","unstructured":"Sarrafzadeh A, Schlenk F, Gericke C, Vajkoczy P (2010) Relevance of cerebral interleukin-6 after aneurysmal subarachnoid hemorrhage. Neurocrit Care 13:339\u2013346. https:\/\/doi.org\/10.1007\/s12028-010-9432-4","journal-title":"Neurocrit Care"},{"key":"5256_CR18","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3340\/jkns.2007.41.3.153","volume":"41","author":"SY Oh","year":"2007","unstructured":"Oh SY, Kwon JT, Hong HJ, Kim YB, Suk JS (2007) Relationship between leukocytosis and vasospasms following aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc 41:153\u2013156. https:\/\/doi.org\/10.3340\/jkns.2007.41.3.153","journal-title":"J Korean Neurosurg Soc"},{"key":"5256_CR19","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1097\/ANA.0b013e3182806465","volume":"25","author":"O Solaiman","year":"2013","unstructured":"Solaiman O, Singh JM (2013) Hypocapnia in aneurysmal subarachnoid hemorrhage: incidence and association with poor clinical outcomes. J Neurosurg Anesthesiol 25:254\u2013261. https:\/\/doi.org\/10.1097\/ANA.0b013e3182806465","journal-title":"J Neurosurg Anesthesiol"},{"key":"5256_CR20","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/0090-3019(87)90038-3","volume":"27","author":"A Spallone","year":"1987","unstructured":"Spallone A, Acqui M, Pastore FS, Guidetti B (1987) Relationship between leukocytosis and ischemic complications following aneurysmal subarachnoid hemorrhage. Surg Neurol 27:253\u2013258. https:\/\/doi.org\/10.1016\/0090-3019(87)90038-3","journal-title":"Surg Neurol"},{"key":"5256_CR21","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1186\/1471-2105-9-307","volume":"9","author":"C Strobl","year":"2008","unstructured":"Strobl C, Boulesteix AL, Kneib T, Augustin T, Zeileis A (2008) Conditional variable importance for random forests. BMC Bioinformatics 9:307. https:\/\/doi.org\/10.1186\/1471-2105-9-307","journal-title":"BMC Bioinformatics"},{"key":"5256_CR22","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1227\/NEU.0000000000000963","volume":"77","author":"CL Turner","year":"2015","unstructured":"Turner CL, Budohoski K, Smith C, Hutchinson PJ, Kirkpatrick PJ, Murray GD, collaborators S, (2015) Elevated baseline C-reactive protein as a predictor of outcome after aneurysmal subarachnoid hemorrhage: data from the Simvastatin in Aneurysmal Subarachnoid Hemorrhage (STASH) trial. Neurosurgery 77:786\u2013792; discussion 792-783. https:\/\/doi.org\/10.1227\/NEU.0000000000000963","journal-title":"Neurosurgery"},{"key":"5256_CR23","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1007\/s12028-011-9586-8","volume":"15","author":"MD Vergouwen","year":"2011","unstructured":"Vergouwen MD, Participants in the International Multi-Disciplinary Consensus Conference on the Critical Care Management of Subarachnoid H (2011) Vasospasm versus delayed cerebral ischemia as an outcome event in clinical trials and observational studies. Neurocrit Care 15:308\u2013311. https:\/\/doi.org\/10.1007\/s12028-011-9586-8","journal-title":"Neurocrit Care"},{"key":"5256_CR24","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.1161\/STROKEAHA.110.589275","volume":"41","author":"MD Vergouwen","year":"2010","unstructured":"Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB (2010) Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke 41:2391\u20132395. https:\/\/doi.org\/10.1161\/STROKEAHA.110.589275","journal-title":"Stroke"},{"key":"5256_CR25","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1097\/01.ccx.0000216571.80944.65","volume":"12","author":"KE Wartenberg","year":"2006","unstructured":"Wartenberg KE, Mayer SA (2006) Medical complications after subarachnoid hemorrhage: new strategies for prevention and management. Curr Opin Crit Care 12:78\u201384. https:\/\/doi.org\/10.1097\/01.ccx.0000216571.80944.65","journal-title":"Curr Opin Crit Care"},{"key":"5256_CR26","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1007\/s12028-015-0138-5","volume":"23","author":"CASK Williamson","year":"2015","unstructured":"Williamson CASK, Tipirneni R, Roark CD, Pandey AS, Thompson BG, Rajajee V (2015) The association between spontaneous hyperventilation, delayed cerebral ischemia, and poor neurological outcome in patients with subarachnoid hemorrhage. Neurocrit Care 23:330\u2013338. https:\/\/doi.org\/10.1007\/s12028-015-0138-5","journal-title":"Neurocrit Care"},{"key":"5256_CR27","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s40560-018-0353-1","volume":"6","author":"S Yokoyama","year":"2018","unstructured":"Yokoyama S, Hifumi T, Okazaki T, Noma T, Kawakita K, Tamiya T, Minamino T, Kuroda Y (2018) Association of abnormal carbon dioxide levels with poor neurological outcomes in aneurysmal subarachnoid hemorrhage: a retrospective observational study. J Intensive Care 6:83. https:\/\/doi.org\/10.1186\/s40560-018-0353-1","journal-title":"J Intensive Care"}],"container-title":["Acta Neurochirurgica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00701-022-05256-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00701-022-05256-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00701-022-05256-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T08:07:10Z","timestamp":1656144430000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00701-022-05256-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,26]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["5256"],"URL":"https:\/\/doi.org\/10.1007\/s00701-022-05256-0","relation":{},"ISSN":["0942-0940"],"issn-type":[{"value":"0942-0940","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,26]]},"assertion":[{"value":"1 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the local ethics review board (protocol no. EKSG 12\/016) and was performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments. All patients gave their informed consent prior to their inclusion in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}