Skip to main content

Advertisement

SpringerLink
Log in

Elevated blood glucose is associated with aggravated brain edema in acute stroke

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Background and purpose

Clinical outcome after endovascular thrombectomy in patients with acute ischemic stroke still varies significantly. Higher blood glucose levels (BGL) have been associated with worse clinical outcome, but the pathophysiological causes are not yet understood. We hypothesized that higher levels of BGL are associated with more pronounced ischemic brain edema and worse clinical outcome mediated by cerebral collateral circulation.

Methods

178 acute ischemic stroke patients who underwent mechanical thrombectomy were included. Early ischemic brain edema was determined using quantitative lesion water uptake on initial computed tomography (CT) and collateral status was assessed with an established 5-point scoring system in CT-angiography. Good clinical outcome was defined as functional independence (modified Rankin Scale [mRS] score 0–2). Multivariable logistic regression analysis was performed to predict functional independence and linear regression analyses to investigate the impact of BGL and collateral status on water uptake.

Results

The mean BGL at admission was significantly lower in patients with good outcome at 90 days (116.5 versus 138.5 mg/dl; p < 0.001) and early water uptake was lower (6.3% versus 9.6%; p < 0.001). The likelihood for good outcome declined with increasing BGL (odds ratio [OR] per 100 mg/dl BGL increase: 0.15; 95% CI 0.02–0.86; p = 0.039). Worse collaterals (1% water uptake per point, 95% CI 0.4–1.7%) and higher BGL (0.6% per 10 mg/dl BGL, 95% CI 0.3–0.8%) were significantly associated with increased water uptake.

Conclusion

Elevated admission BGL were associated with increased early brain edema and poor clinical outcome mediated by collateral status. Patients with higher BGL might be targeted by adjuvant anti-edematous treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Broocks G, Faizy TD, Flottmann F, Schon G, Langner S, Fiehler J, Kemmling A, Gellissen S (2018) Subacute infarct volume with edema correction in computed tomography is equivalent to final infarct volume after ischemic stroke: improving the comparability of infarct imaging endpoints in clinical trials. Investig Radiol 53:472–476

    Article  Google Scholar 

  2. Broocks G, Flottmann F, Ernst M, Faizy TD, Minnerup J, Siemonsen S, Fiehler J, Kemmling A (2018) Computed tomography-based imaging of voxel-wise lesion water uptake in ischemic brain: relationship between density and direct volumetry. Investig Radiol 53:207–213

    Article  Google Scholar 

  3. Broocks G, Flottmann F, Scheibel A, Aigner A, Faizy TD, Hanning U, Leischner H, Broocks SI, Fiehler J, Gellissen S, Kemmling A (2018) Quantitative lesion water uptake in acute stroke computed tomography is a predictor of malignant infarction. Stroke 49:1906–1912

    Article  Google Scholar 

  4. Broocks G, Hanning U, Flottmann F, Schoenfeld M, Faizy T, Sporns P, Baumgart M, Leischner H, Schoen G, Minnerup J, Thomalla G, Fiehler J, Kemmling A (2019) Clinical benefit of thrombectomy in stroke patients with low ASPECTS is mediated by edema reduction. Brain 142:1399–1407

    Article  Google Scholar 

  5. Broocks G, Kemmling A, Aberle J, Kniep H, Bechstein M, Flottmann F, Leischner H, Faizy TD, Nawabi J, Schon G, Sporns P, Thomalla G, Fiehler J, Hanning U (2019) Ischemic lesion water uptake in acute stroke: is blood glucose related to cause and effect? J Stroke 21:347–349

    Article  Google Scholar 

  6. Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Bailey P, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater LA, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM, Investigators E-IT (2018) Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med 378:1573–1582

    Article  CAS  Google Scholar 

  7. Dzialowski I, Klotz E, Goericke S, Doerfler A, Forsting M, von Kummer R (2007) Ischemic brain tissue water content: CT monitoring during middle cerebral artery occlusion and reperfusion in rats. Radiology 243:720–726

    Article  Google Scholar 

  8. Galego O, Jesus-Ribeiro J, Baptista M, Sargento-Freitas J, Martins AI, Silva F, Santos GC, Cunha L, Nunes C, Machado E (2018) Collateral pial circulation relates to the degree of brain edema on CT 24 hours after ischemic stroke. Neuroradiol J 31:456–463

    Article  Google Scholar 

  9. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG, Collaborators H (2016) Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 387:1723–1731

    Article  Google Scholar 

  10. Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R (1996) 'Malignant' middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol 53:309–315

    Article  CAS  Google Scholar 

  11. Hill MD, Martin RH, Mikulis D, Wong JH, Silver FL, Terbrugge KG, Milot G, Clark WM, Macdonald RL, Kelly ME, Boulton M, Fleetwood I, McDougall C, Gunnarsson T, Chow M, Lum C, Dodd R, Poublanc J, Krings T, Demchuk AM, Goyal M, Anderson R, Bishop J, Garman D, Tymianski M, Investigators Et (2012) Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol 11:942–950

    Article  CAS  Google Scholar 

  12. Kim JT, Liebeskind DS, Jahan R, Menon BK, Goyal M, Nogueira RG, Pereira VM, Gralla J, Saver JL (2018) Impact of hyperglycemia according to the collateral status on outcomes in mechanical thrombectomy. Stroke 49:2706–2714

    Article  CAS  Google Scholar 

  13. Kimberly WT, Battey TW, Pham L, Wu O, Yoo AJ, Furie KL, Singhal AB, Elm JJ, Stern BJ, Sheth KN (2014) Glyburide is associated with attenuated vasogenic edema in stroke patients. Neurocrit Care 20:193–201

    Article  CAS  Google Scholar 

  14. Kunte H, Schmidt S, Eliasziw M, del Zoppo GJ, Simard JM, Masuhr F, Weih M, Dirnagl U (2007) Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke. Stroke 38:2526–2530

    Article  CAS  Google Scholar 

  15. Liu R, Wang H, Xu B, Chen W, Turlova E, Dong N, Sun CL, Lu Y, Fu H, Shi R, Barszczyk A, Yang D, Jin T, Mannucci E, Feng ZP, Sun HS (2016) Cerebrovascular safety of sulfonylureas: the role of KATP channels in neuroprotection and the risk of stroke in patients with type 2 diabetes. Diabetes 65:2795–2809

    Article  CAS  Google Scholar 

  16. Lu GD, Ren ZQ, Zhang JX, Zu QQ, Shi HB (2018) Effects of diabetes mellitus and admission glucose in patients receiving mechanical thrombectomy: a systematic review and meta-analysis. Neurocrit Care 29:426–434

    Article  CAS  Google Scholar 

  17. Malhotra K, Ahmed N, Filippatou A, Katsanos AH, Goyal N, Tsioufis K, Manios E, Pikilidou M, Schellinger PD, Alexandrov AW, Alexandrov AV, Tsivgoulis G (2019) Association of elevated blood pressure levels with outcomes in acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis. J Stroke 21:78–90

    Article  Google Scholar 

  18. Mandava P, Martini SR, Munoz M, Dalmeida W, Sarma AK, Anderson JA, Fabian RH, Kent TA (2014) Hyperglycemia worsens outcome after rt-PA primarily in the large-vessel occlusive stroke subtype. Transl Stroke Res 5:519–525

    Article  Google Scholar 

  19. Martini SR, Kent TA (2007) Hyperglycemia in acute ischemic stroke: a vascular perspective. J Cereb Blood Flow Metab 27:435–451

    Article  CAS  Google Scholar 

  20. Mayfield J (1998) Diagnosis and classification of diabetes mellitus: new criteria. Am Fam Physician 58(1355–1362):1369–1370

    Google Scholar 

  21. Menon BK, Smith EE, Coutts SB, Welsh DG, Faber JE, Goyal M, Hill MD, Demchuk AM, Damani Z, Cho KH, Chang HW, Hong JH, Sohn SI (2013) Leptomeningeal collaterals are associated with modifiable metabolic risk factors. Ann Neurol 74:241–248

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Minnerup J, Broocks G, Kalkoffen J, Langner S, Knauth M, Psychogios MN, Wersching H, Teuber A, Heindel W, Eckert B, Wiendl H, Schramm P, Fiehler J, Kemmling A (2016) Computed tomography-based quantification of lesion water uptake identifies patients within 4.5 hours of stroke onset: A multicenter observational study. Ann Neurol 80:924–934

    Article  Google Scholar 

  23. Nawabi J, Flottmann F, Hanning U, Bechstein M, Schoen G, Kemmling A, Fiehler J, Broocks G (2018) Futile recanalization with poor clinical outcome is associated with increased edema volume after ischemic stroke. Invest Radiol 54:282–287

    Article  Google Scholar 

  24. Nikneshan D, Raptis R, Pongmoragot J, Zhou L, Johnston SC, Saposnik G, Investigators of the Registry of the Canadian Stroke N, Stroke Outcomes Research Canada Working G (2013) Predicting clinical outcomes and response to thrombolysis in acute stroke patients with diabetes. Diabetes Care 36:2041–2047

    Article  Google Scholar 

  25. Ntaios G, Egli M, Faouzi M, Michel P (2010) J-shaped association between serum glucose and functional outcome in acute ischemic stroke. Stroke 41:2366–2370

    Article  CAS  Google Scholar 

  26. Osei E, den Hertog HM, Berkhemer OA, Fransen PS, Roos YB, Beumer D, van Oostenbrugge RJ, Schonewille WJ, Boiten J, Zandbergen AA, Koudstaal PJ, Dippel DW, Investigators MCp (2016) Increased admission and fasting glucose are associated with unfavorable short-term outcome after intra-arterial treatment of ischemic stroke in the MR CLEAN pretrial cohort. J Neurol Sci 371:1–5

    Article  CAS  Google Scholar 

  27. Osei E, Fonville S, Zandbergen AAM, Koudstaal PJ, Dippel DWJ, den Hertog HM (2018) Impaired fasting glucose is associated with unfavorable outcome in ischemic stroke patients treated with intravenous alteplase. J Neurol 265:1426–1431

    Article  CAS  Google Scholar 

  28. Parkinson FE, Hatch GM (2016) Is there enhanced risk of cerebral ischemic stroke by sulfonylureas in type 2 diabetes? Diabetes 65:2479–2481

    Article  CAS  Google Scholar 

  29. Rocha M, Jovin TG (2017) Fast versus slow progressors of infarct growth in large vessel occlusion stroke: clinical and research implications. Stroke 48:2621–2627

    Article  Google Scholar 

  30. Rosso C, Corvol JC, Pires C, Crozier S, Attal Y, Jacqueminet S, Deltour S, Multlu G, Leger A, Meresse I, Payan C, Dormont D, Samson Y (2012) Intensive versus subcutaneous insulin in patients with hyperacute stroke: results from the randomized INSULINFARCT trial. Stroke 43:2343–2349

    Article  Google Scholar 

  31. Serrano-Martin X, Payares G, Mendoza-Leon A (2006) Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis. Antimicrob Agents Chemother 50:4214–4216

    Article  CAS  Google Scholar 

  32. Sheth KN, Elm JJ, Beslow LA, Sze GK, Kimberly WT (2016) Glyburide advantage in malignant edema and stroke (GAMES-RP) trial: rationale and design. Neurocrit Care 24:132–139

    Article  CAS  Google Scholar 

  33. Sheth KN, Elm JJ, Molyneaux BJ, Hinson H, Beslow LA, Sze GK, Ostwaldt AC, Del Zoppo GJ, Simard JM, Jacobson S, Kimberly WT (2016) Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 15:1160–1169

    Article  CAS  Google Scholar 

  34. Sheth KN, Kimberly WT, Elm JJ, Kent TA, Mandava P, Yoo AJ, Thomalla G, Campbell B, Donnan GA, Davis SM, Albers GW, Jacobson S, Simard JM, Stern BJ (2014) Pilot study of intravenous glyburide in patients with a large ischemic stroke. Stroke 45:281–283

    Article  CAS  Google Scholar 

  35. Sheth KN, Kimberly WT, Elm JJ, Kent TA, Yoo AJ, Thomalla G, Campbell B, Donnan GA, Davis SM, Albers GW, Jacobson S, del Zoppo G, Simard JM, Stern BJ, Mandava P (2014) Exploratory analysis of glyburide as a novel therapy for preventing brain swelling. Neurocrit Care 21:43–51

    Article  CAS  Google Scholar 

  36. Shi L, Rocha M, Leak RK, Zhao J, Bhatia TN, Mu H, Wei Z, Yu F, Weiner SL, Ma F, Jovin TG, Chen J (2018) A new era for stroke therapy: Integrating neurovascular protection with optimal reperfusion. J Cereb Blood Flow Metab. https://doi.org/10.1177/0271678X18798162

    Article  PubMed  PubMed Central  Google Scholar 

  37. Simard JM, Chen M, Tarasov KV, Bhatta S, Ivanova S, Melnitchenko L, Tsymbalyuk N, West GA, Gerzanich V (2006) Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke. Nat Med 12:433–440

    Article  CAS  Google Scholar 

  38. Somannavar S, Ganesan A, Deepa M, Datta M, Mohan V (2009) Random capillary blood glucose cut points for diabetes and pre-diabetes derived from community-based opportunistic screening in India. Diabetes Care 32:641–643

    Article  CAS  Google Scholar 

  39. Souza LC, Yoo AJ, Chaudhry ZA, Payabvash S, Kemmling A, Schaefer PW, Hirsch JA, Furie KL, Gonzalez RG, Nogueira RG, Lev MH (2012) Malignant CTA collateral profile is highly specific for large admission DWI infarct core and poor outcome in acute stroke. AJNR Am J Neuroradiol 33:1331–1336

    Article  CAS  Google Scholar 

  40. Sporns PB, Minnerup J, Warneke N, Dziewas R, Hanning U, Berkemeyer S, Zoubi T, Heindel W, Schwindt W, Niederstadt T (2017) Impact of the implementation of thrombectomy with stent retrievers on the frequency of hemicraniectomy in patients with acute ischemic stroke. Clin Neuroradiol 27:193–197

    Article  CAS  Google Scholar 

  41. Thoren M, Azevedo E, Dawson J, Egido JA, Falcou A, Ford GA, Holmin S, Mikulik R, Ollikainen J, Wahlgren N, Ahmed N (2017) Predictors for cerebral edema in acute ischemic stroke treated with intravenous thrombolysis. Stroke 48:2464–2471

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Gabriel Broocks, Helge Kniep, Matthias Bechstein, Fabian Flottmann, Hannes Leischner, Tobias D. Faizy, Jawed Nawabi, Jens Fiehler & Uta Hanning

  2. Department of Neuroradiology, Westpfalz-Klinikum, Kaiserslautern, Germany

    Andre Kemmling & Peter Sporns

  3. Faculty of Medicine Mannheim, University of Heidelberg, Heidelberg, Germany

    Andre Kemmling

  4. Department of Radiology, Charité University Medical Center, Berlin, Germany

    Jawed Nawabi

  5. Department of Endocrinology and Diabetology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Jens Aberle

  6. Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Gerhard Schön

  7. Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Götz Thomalla

Authors
  1. Gabriel Broocks
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andre Kemmling
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jens Aberle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helge Kniep
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthias Bechstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fabian Flottmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hannes Leischner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tobias D. Faizy
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jawed Nawabi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gerhard Schön
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Peter Sporns
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Götz Thomalla
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jens Fiehler
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Uta Hanning
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriel Broocks.

Ethics declarations

Conflicts of interest

Prof. Fiehler: Research support: German Ministry of Science and Education (BMBF and BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB), Medtronic, Microvention, Philips, Stryker, Consultant for: Acandis, Boehringer Ingelheim, Cerenovus, Covidien, Evasc Neurovascular, MD Clinicals, Medtronic, Medina, Microvention, Penumbra, Route92, Stryker, Transverse Medical. Prof. Thomalla: Consultant for Acandis, Bayer Healthcare, Boehringer Ingelheim, BristolMyersSquibb/Pfizer, Covidien, Glaxo Smith Kline; lead investigator of the WAKE-UP study; Principal Investigator of the THRILL study; Grants by the European Union (Grant No. 278276 und 634809) and Deutsche Forschungsgemeinschaft (SFB 936, Projekt C2). All author authors report no disclosures.

Ethical approval

Anonymized data were recorded in accordance with ethical review board approval and institutional review board waived informed consent. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Broocks, G., Kemmling, A., Aberle, J. et al. Elevated blood glucose is associated with aggravated brain edema in acute stroke. J Neurol 267, 440–448 (2020). https://doi.org/10.1007/s00415-019-09601-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-019-09601-9

Search

Navigation