Encephalopathy in Sepsis

  • A. Polito
  • S. Siami
  • T. Sharshar
Conference paper


Encephalopathy is a frequent neurological manifestation of sepsis. The term, sepsis encephalopathy, is certainly misleading. An encephalopathy can be a direct consequence of sepsis but it can also be secondary to various associated complications of sepsis, such as liver or renal failure, drug toxicity, or metabolic disturbances. Because of the difficulty in discriminating a septic from a non-septic origin, the terms “sepsis-associated encephalopathy” or “critical illness encephalopathy” may be more appropriate. In addition, a pathophysiological definition would be questionable as a multitude of pathogenic mechanisms are involved.


Septic Shock Septic Patient Posterior Reversible Encephalopathy Syndrome Brain Dysfunction Focal Neurological Sign 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Eidelman LA, Putterman D, Putterman C, Sprung CL (1996) The spectrum of septic encephalopathy. Definitions, etiologies, and mortalities. JAMA 275:470–473PubMedCrossRefGoogle Scholar
  2. 2.
    Young GB, Bolton CF, Archibald YM, Austin TW, Wells GA (1992) The electroencephalogram in sepsis-associated encephalopathy. J Clin Neurophysiol 9:145–152PubMedGoogle Scholar
  3. 3.
    Zauner C, Gendo A, Kramer L, et al (2002) Impaired subcortical and cortical sensory evoked potential pathways in septic patients. Crit Care Med 30:1136–1139PubMedCrossRefGoogle Scholar
  4. 4.
    Nguyen DN, Spapen H, Su F, et al (2006) Elevated serum levels of S-100β protein and neuronspecific enolase are associated with brain injury in patients with severe sepsis and septic shock. Crit Care Med 34:1967–1974PubMedCrossRefGoogle Scholar
  5. 5.
    Tracey KJ (2002) The inflammatory reflex. Nature 420:853–859PubMedCrossRefGoogle Scholar
  6. 6.
    Berridge CW, Waterhouse BD (2003) The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42: 33–84PubMedCrossRefGoogle Scholar
  7. 7.
    Sharshar T, Hopkinson NS, Orlikowski D, Annane D (2005) The brain in sepsis — culprit and victim. Crit Care 9:37–44PubMedCrossRefGoogle Scholar
  8. 8.
    Roth J, Harre EM, Rummel C, Gerstberger R, Hubschle T (2004) Signaling the brain in systemic inflammation: role of sensory circumventricular organs. Front Biosci 9:290–300PubMedCrossRefGoogle Scholar
  9. 9.
    Lacroix S, Feinstein D, Rivest (1998) The bacterial endotoxin lipopolysaccharide has the ability to target the brain in upregulating its membrane CD14 receptor within specific cellular populations. Brain Pathol 8:625–640PubMedGoogle Scholar
  10. 10.
    Breder CD, Hazuka C, Ghayur T, et al (1994) Regional induction of tumor necrosis factor alpha expression in the mouse brain after systemic lipopolysaccharide administration. Proc Natl Acad Sci USA 91:11393–11397PubMedCrossRefGoogle Scholar
  11. 11.
    Galea E, Reis DJ, Feinstein DL (1994) Cloning and expression of inducible nitric oxide synthase from rat astrocytes. J Neurosci Res 37:406–414PubMedCrossRefGoogle Scholar
  12. 12.
    Heyen JR, Ye S, Finck BN, Johnson RW (2000) Interleukin(IL)-10 inhibits IL-6 production in microglia by preventing activation of NF-kappaB. Brain Res Mol Brain Res 77:138–147PubMedCrossRefGoogle Scholar
  13. 13.
    Fontana A, Kristensen F, Dubs R, Gemsa D, Weber E (1982) Production of prostaglandin E and an interleukin-1 like factor by cultured astrocytes and C6 glioma cells. J Immunol 129: 2413–2419PubMedGoogle Scholar
  14. 14.
    Caggiano AO, Kraig RP (1999) Prostaglandin E receptor subtypes in cultured rat microglia and their role in reducing lipopolysaccharide-induced interleukin-1beta production. J Neurochem 72:565–575PubMedCrossRefGoogle Scholar
  15. 15.
    Elmquist JK, Scammell TE, Saper CB (1997) Mechansims of CNS resposne to systemic immune challenge: the febrile response. Trends Neurosci 20:565–570PubMedCrossRefGoogle Scholar
  16. 16.
    Kadoi Y, Saito S, Kunimoto F, Imai T, Fujita T (1996) Impairment of the brain beta-adrenergic system during experimental endotoxemia. J Surg Res 61:496–502PubMedCrossRefGoogle Scholar
  17. 17.
    Pavlov VA, Ochani M, Gallowitsch-Puerta M, et al (2006) Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci USA 103:5219–5223PubMedCrossRefGoogle Scholar
  18. 18.
    Ebersoldt M, Sharshar T, Annane D (2007) Sepsis-associated delirium. Intensive Care Med 33:941–950PubMedCrossRefGoogle Scholar
  19. 19.
    Papadopoulos MC, Davies DC, Moss RF, Tighe D, Bennett ED (2000) Pathophysiology of septic encephalopathy: a review. Crit Care Med 28:3019–3024PubMedCrossRefGoogle Scholar
  20. 20.
    Kim WG, Mohney RP, Wilson B, Jeohn GH, Liu B, Hong JS (2000) Regional difference in susceptibility to lipopolysaccharide neurotoxicity in the rat brain: role of microglia. J Neurosci 20:6309–6316PubMedGoogle Scholar
  21. 21.
    Sharshar T, Gray F, Poron F, Raphael JC, Gajdos P, Annane D (2002) Multifocal necrotizing leukoencephalopathy in septic shock. Crit Care Med 30:2371–2375PubMedCrossRefGoogle Scholar
  22. 22.
    Barichello T, Fortunato JJ, Vitali AM, et al (2006) Oxidative variables in the rat brain after sepsis induced by cecal ligation and perforation. Crit Care Med 34:886–889PubMedCrossRefGoogle Scholar
  23. 23.
    Christians ES, Yan LJ, Benjamin IJ (2002) Heat shock factor 1 and heat shock proteins: critical partners in protection against acute cell injury. Crit Care Med 30:S43–50CrossRefGoogle Scholar
  24. 24.
    Chuang YC, Tsai JL, Chang AY, Chan JY, Liou CW, Chan SH (2002) Dysfunction of the mitochondrial respiratory chain in the rostral ventrolateral medulla during experimental endotoxemia in the rat. J Biomed Sci 9:542–548PubMedCrossRefGoogle Scholar
  25. 25.
    Chan JY, Chang AY, Wang LL, Ou CC, Chan SH (2007) Protein kinase C-dependent mitochondrial translocation of proapoptotic protein Bax on activation of inducible nitric-oxide synthase in rostral ventrolateral medulla mediates cardiovascular depression during experimental endotoxemia. Mol Pharmacol 71:1129–1139PubMedCrossRefGoogle Scholar
  26. 26.
    Messaris E, Memos N, Chatzigianni E, et al (2004) Time-dependent mitochondrial-mediated programmed neuronal cell death survival in sepsis. Crit Care Med 32:1764–1770PubMedCrossRefGoogle Scholar
  27. 27.
    Sharshar T, Gray F, Lorin de la Grandmaison G, et al (2003) Apoptosis of neurons in cardiovascular autonomie centres triggered by inducible nitric oxide synthase after death from septic shock. Lancet 362:1799–1805Google Scholar
  28. 28.
    Kadoi Y, Goto F (2004) Selective inducible nitric oxide inhibition can restore hemodynamics, but does not improve neurological dysfunction in experimentally-induced septic shock in rats. Anesth Analg 99:212–220PubMedCrossRefGoogle Scholar
  29. 29.
    Wong ML, Rettori V, al-Shekhlee A, et al (1996) Inducible nitric oxide synthase gene expression in the brain during systemic inflammation. Nat Med 2:581–584PubMedCrossRefGoogle Scholar
  30. 30.
    Clawson CC, Hartmann JF, Vernier RL (1966) Electron microscopy of the effect of gram-negative endotoxin on the blood-brain barrier. J Comp Neurol 127:183–198PubMedCrossRefGoogle Scholar
  31. 31.
    Papadopoulos MC, Lamb FJ, Moss RF, Davies DC, Tighe D, Bennett ED (1999) Faecal peritonitis causes oedema and neuronal injury in pig cerebral cortex. Clin Sci (Lond) 96:461–466CrossRefGoogle Scholar
  32. 32.
    Kafa IM, Ari I, Kurt MA (2007) The peri-microvascular edema in hippocampal CA1 area in a rat model of sepsis. Neuropathology 27:213–220PubMedCrossRefGoogle Scholar
  33. 33.
    Sharshar T, Carlier R, Bernard F, et al (2007) Brain lesions in septic shock: a magnetic resonance imaging study. Intensive Care Med 33:798–806PubMedCrossRefGoogle Scholar
  34. 34.
    Bartynski WS, Boardman JF, Zeigler ZR, Shadduck RK, Lister J (2006) Posterior reversible encephalopathy syndrome in infection, sepsis, and shock. AJNR Am J Neuroradiol 27: 2179–2190PubMedGoogle Scholar
  35. 35.
    Sharshar T, Annane D, de la Grandmaison G, Brouland JP, Hopkinson NS, Gray F (2004) The neuropathology of septic shock. Brain Pathol 14:21–33PubMedGoogle Scholar
  36. 36.
    Pedersen M, Brandt CT, Knudsen GM, et al (2007) The effect of S. pneumoniae bacteremia on cerebral blood flow autoregulation in rats. J Cereb Blood Flow Metab 13:13Google Scholar
  37. 37.
    Mori F, Nishie M, Houzen H, Yamaguchi J, Wakabayashi K (2006) Hypoglycemic encephalopathy with extensive lesions in the cerebral white matter. Neuropathology 26:147–152PubMedCrossRefGoogle Scholar
  38. 38.
    Sprung CL, Cerra FB, Freund HR, et al (1991) Amino acid alterations and encephalopathy in the sepsis syndrome. Crit Care Med 19:753–757PubMedCrossRefGoogle Scholar
  39. 39.
    Monfort P, Munoz MD, ElAyadi A, Kosenko E, Felipo V (2002) Effects of hyperammonemia and liver failure on glutamatergic neurotransmission. Metab Brain Dis 17:237–250PubMedCrossRefGoogle Scholar
  40. 40.
    Ely EW, Inouye SK, Bernard GR, et al (2001) Delirium in mechanically ventilated patients. Validity and reliability of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). JAMA 286:2703–2710PubMedCrossRefGoogle Scholar
  41. 41.
    de Jonghe B, Cook D, Griffith L, et al (2003) Adaptation to the Intensive Care Environment (ATICE): development and validation of a new sedation assessment instrument. Crit Care Med 31:2344–2354PubMedCrossRefGoogle Scholar
  42. 42.
    Ely EW, Truman B, Manzi DJ, Sigl JC, Shintani A, Bernard GR (2004) Consciousness monitoring in ventilated patients: bispectral EEG monitors arousal not delirium. Intensive Care Med 30:1537–1543PubMedCrossRefGoogle Scholar
  43. 43.
    Piazza O, Russo E, Cotena S, Esposito G, Tufano R (2007) Elevated S100B levels do not correlate with the severity of encephalopathy during sepsis. Br J Anaesth 24:24Google Scholar
  44. 44.
    Finelli PF, Uphoff DF (2004) Magnetic resonance imaging abnormalities with septic encephalopathy. J Neurol Neurosurg Psychiatry 75:1189–1191PubMedCrossRefGoogle Scholar
  45. 45.
    Li H, Forstermann U (2000) Nitric oxide in the pathogenesis of vascular disease. J Pathol 190:244–254PubMedCrossRefGoogle Scholar
  46. 46.
    Lopez A, Lorente JA, Steingrub J, et al (2004) Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med 32:21–30PubMedCrossRefGoogle Scholar
  47. 47.
    Veszelka S, Urbanyi Z, Pazmany T, et al (2003) Human serum amyloid P component attenuates the bacterial lipopolysaccharide-induced increase in blood-brain barrier permeability in mice. Neurosci Lett 352:57–60PubMedCrossRefGoogle Scholar
  48. 48.
    Esen F, Erdem T, Aktan D, et al (2005) Effect of magnesium sulfate administration on bloodbrain barrier in a rat model of intraperitoneal sepsis: a randomized controlled experimental study. Crit Care 9:R18–23PubMedCrossRefGoogle Scholar
  49. 49.
    Huang M, Liu W, Li Q, Wu CF (2002) Endogenous released ascorbic acid suppresses ethanolinduced hydroxyl radical production in rat striatum. Brain Res 944:90–96PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media Inc. 2008

Authors and Affiliations

  • A. Polito
    • 1
  • S. Siami
    • 1
  • T. Sharshar
    • 1
  1. 1.Respiratory Muscle LaboratoryHopital Raymond PoincareGarchesFrance

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