Brain Volume Changes in Patients with Acute Brain Dysfunction Due to Sepsis

  • Günseli OrhunEmail author
  • Erdem Tüzün
  • Başar Bilgiç
  • Perihan Ergin Özcan
  • Serra Sencer
  • Mehmet Barburoğlu
  • Figen Esen
Original Work



Sepsis-induced brain dysfunction (SIBD) is often encountered in sepsis patients and is related to increased morbidity. No specific tests are available for SIBD, and neuroimaging findings are often normal. In this study, our aim was to analyze the diagnostic value of volumetric analysis of the brain structures and to find out its significance as a prognostic measure.


In this prospective observational study, brain magnetic resonance imaging (MRI) sections of 25 consecutively enrolled SIBD patients (17 with encephalopathy and 8 with coma) and 22 healthy controls underwent volumetric evaluation by an automated segmentation method.


Ten SIBD patients had normal MRI, and 15 patients showed brain lesions or atrophy. The most prominent volume reduction was found in cerebral and cerebellar white matter, cerebral cortex, hippocampus, and amygdala, whereas deep gray matter regions and cerebellar cortex were relatively less affected. SIBD patients with normal MRI showed significantly reduced volumes in hippocampus and cerebral white matter. Caudate nuclei, putamen, and thalamus showed lower volume values in non-survivor SIBD patients, and left putamen and right thalamus showed a more pronounced volume reduction in coma patients.


Volumetric analysis of the brain appears to be a sensitive measure of volumetric changes in SIBD. Volume reduction in specific deep gray matter regions might be an indicator of unfavorable outcome.


Sepsis Brain dysfunction Neuroimaging Volume change Volumetric analysis 



The authors thank the personnel of the Multidisciplinary Critical Care Unit at the University of Istanbul for support and are indebted to Bio. Fatma Vildan Adali for assistance.

Author Contributions

GO, ET, BB, SS, and FE contributed to conception and design of the study. GO, PEÖ, and FE contributed to acquisition, analysis, and interpretation of data from sepsis patients. BB contributed to acquisition, analysis, and interpretation of volumetric analysis of brain regions. SS and MB contributed to acquisition, analysis, and interpretation of brain magnetic resonance imaging. ET and BB performed the statistical analysis. GO, ET, BB, and FE were involved in drafting the manuscript or revising it critically for important intellectual content. All authors read and approved the final manuscript.

Source of Support

This study was funded by Scientific Research Projects Coordination Unit of Istanbul University (Grant Nos. 35165 and 2793/53037).

Conflict of interest

All authors declare that they have no conflict of interests.

Ethical Approval/Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The study was approved by the Institutional Review Board (approval number: 2013/98), and informed consent was obtained from all individual participants or their relatives included in the study.


  1. 1.
    Iacobone E, Bailly-Salin J, Polito A, et al. Sepsis-associated encephalopathy and its differential diagnosis. Crit Care Med. 2009;37(10):S331–6.CrossRefGoogle Scholar
  2. 2.
    Girard TD, Jackson JC, Pandharipande PP, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010;38(7):1513.CrossRefGoogle Scholar
  3. 3.
    Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291(14):1753–62.CrossRefGoogle Scholar
  4. 4.
    Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787–94.CrossRefGoogle Scholar
  5. 5.
    Hopkins RO, Weaver LK, Collingridge D, et al. Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2005;171(4):340–7.CrossRefGoogle Scholar
  6. 6.
    Gofton TE, Young GB. Sepsis-associated encephalopathy. Nat Rev Neurol. 2012;8(10):557–66.CrossRefGoogle Scholar
  7. 7.
    Polito A, Eischwald F, Maho AL, et al. Pattern of brain injury in the acute setting of human septic shock. Crit Care. 2013;17(5):R204.CrossRefGoogle Scholar
  8. 8.
    Bartynski WS, Boardman JF, Zeigler ZR, Shadduck RK, Lister J. Posterior reversible encephalopathy syndrome in infection, sepsis, and shock. AJNR Am J Neuroradiol. 2006;27(10):2179–90.Google Scholar
  9. 9.
    Suchyta MR, Jephson A, Hopkins RO. Neurologic changes during critical illness: brain imaging findings and neurobehavioral outcomes. Brain Imaging Behav. 2010;4(1):22–34.CrossRefGoogle Scholar
  10. 10.
    Orhun G, Tüzün E, Özcan PE, et al. Association between inflammatory markers and cognitive outcome in patients with acute brain dysfunction due to sepsis. Arch Neuropsychiatry. 2019;56(1):63.Google Scholar
  11. 11.
    Orhun G, Esen F, Ozcan PE, et al. Neuroimaging findings in sepsis-induced brain dysfunction: association with clinical and laboratory findings. Neurocrit Care. 2019;30(1):106–17.CrossRefGoogle Scholar
  12. 12.
    Semmler A, Widmann CN, Okulla T, et al. Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors. J Neurol Neurosurg Psychiatry. 2013;84(1):62–9.CrossRefGoogle Scholar
  13. 13.
    Heming N, Mazeraud A, Verdonk F, et al. Neuroanatomy of sepsis-associated encephalopathy. Crit Care. 2017;21(1):65.CrossRefGoogle Scholar
  14. 14.
    Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.CrossRefGoogle Scholar
  15. 15.
    Sutter R, Chalela JA, Leigh R, et al. Significance of parenchymal brain damage in patients with critical illness. Neurocrit Care. 2015;23(2):243–52.CrossRefGoogle Scholar
  16. 16.
    Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001;286(21):2703–10.CrossRefGoogle Scholar
  17. 17.
    Sessler CN, Gosnell MS, Grap MJ, et al. The Richmond Agitation–Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):1338–44.CrossRefGoogle Scholar
  18. 18.
    Posner JB, Plum F, Saper CB, Schiff N. Plum and Posner’s diagnosis of stupor and coma, vol. 17. Oxford: OUP USA; 2007.Google Scholar
  19. 19.
    Fischl B, Salat DH, Busa E, et al. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002;33(3):341–55.CrossRefGoogle Scholar
  20. 20.
    Gunther ML, Morandi A, Krauskopf E, et al. The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: the VISIONS cohort magnetic resonance imaging study*. Crit Care Med. 2012;40(7):2022–32.CrossRefGoogle Scholar
  21. 21.
    Finke C, Kopp UA, Pajkert A, et al. Structural hippocampal damage following anti-N-methyl-d-aspartate receptor encephalitis. Biol Psychiatry. 2016;79(9):727–34.CrossRefGoogle Scholar
  22. 22.
    Finke C, Pruss H, Heine J, et al. Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. JAMA Neurol. 2017;74(1):50–9.CrossRefGoogle Scholar
  23. 23.
    Yoneda Y, Mori E, Yamashita H, Yamadori A. MRI volumetry of medial temporal lobe structures in amnesia following herpes simplex encephalitis. Eur Neurol. 1994;34(5):243–52.CrossRefGoogle Scholar
  24. 24.
    Anderson VM, Fisniku LK, Khaleeli Z, et al. Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study. Mult Scler. 2010;16(9):1083–90.CrossRefGoogle Scholar
  25. 25.
    Semmler A, Hermann S, Mormann F, et al. Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism. J Neuroinflammation. 2008;5:38.CrossRefGoogle Scholar
  26. 26.
    Peng QY, Wang YM, Chen CX, et al. Inhibiting the CD38/cADPR pathway protected rats against sepsis associated brain injury. Brain Res. 2018;1678:56–63.CrossRefGoogle Scholar
  27. 27.
    Fu Q, Wu J, Zhou X-Y, et al. NLRP3/Caspase-1 pathway-induced pyroptosis mediated cognitive deficits in a mouse model of sepsis-associated encephalopathy. Inflammation. 2019;42:306–18.CrossRefGoogle Scholar
  28. 28.
    Zaghloul N, Addorisio ME, Silverman HA, et al. Forebrain cholinergic dysfunction and systemic and brain inflammation in murine sepsis survivors. Front Immunol. 2017;8:1673.CrossRefGoogle Scholar
  29. 29.
    Femminella GD, Ninan S, Atkinson R, et al. Does microglial activation influence hippocampal volume and neuronal function in Alzheimer’s disease and Parkinson’s Disease dementia? J Alzheimers Dis. 2016;51(4):1275–89.CrossRefGoogle Scholar
  30. 30.
    Kondo A, Sugiura C, Fujii Y, et al. Fulminant sepsis-associated encephalopathy in two children: serial neuroimaging findings and clinical course. Neuropediatrics. 2009;40(4):157–61.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2019

Authors and Affiliations

  1. 1.Department of Anesthesiology and Intensive Care, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey
  2. 2.Department of Neuroscience, Aziz Sancar Institute of Experimental MedicineIstanbul UniversityIstanbulTurkey
  3. 3.Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey
  4. 4.Department of Neuroradiology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey

Personalised recommendations