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Published in: Metabolic Brain Disease 3/2010

01-09-2010 | Original Paper

Serum proinflammatory cytokines correlate with diffusion tensor imaging derived metrics and 1H-MR spectroscopy in patients with acute liver failure

Authors: Rakesh Kumar Gupta, Santosh Kumar Yadav, Murali Rangan, Ram Kishore Singh Rathore, Michael Albert Thomas, Kashi Nath Prasad, Chandra Mohan Pandey, Vivek Anand Saraswat

Published in: Metabolic Brain Disease | Issue 3/2010

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Abstract

Hyperammonemia and inflammation are major contributing factors in the development of cerebral edema (CE) in acute liver failure (ALF). Aim of this study was to look for the relationship between proinflammatory cytokines with diffusion tensor imaging (DTI) derived metrics and 1H-MR spectroscopy (1H-MRS) derived Glutamate/Glutamine (Glx). Fourteen patients with ALF and 14 age/sex matched controls were included in this study. All subjects had undergone clinical, biochemical, MR imaging and 1H-MRS studies. Serum proinflammatory cytokines (IL-6 and TNF-α), blood ammonia level and Glx were computed for independent t-test and Pearson correlation. Serum proinflammatory cytokines, blood ammonia level and brain Glx were significantly increased in ALF patients as compared to controls. Blood ammonia level and Glx showed significant positive correlation with proinflammatory cytokines. Spectroscopy voxel derived spherical anisotropy (CS) showed positive correlation with Glx while mean diffusivity (MD) showed negative correlation. Proinflammatory cytokines showed positive correlation with CS and negative correlation with MD in various brain regions including spectroscopy voxel. Significant correlation of Glx, CS and MD with proinflammatory cytokines suggests that both DTI derived metrics and 1H-MRS measure the synergistic effect of hyperammonemia and proinflammatory cytokines and may be used as non-invasive tools for understanding the pathogenesis of CE in ALF.
Literature
go back to reference Atterbury CE, Maddrey WC, Conn HO (1978) Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy. A controlled, double-blind clinical trial. Am J Dig Dis 23:398–406CrossRefPubMed Atterbury CE, Maddrey WC, Conn HO (1978) Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy. A controlled, double-blind clinical trial. Am J Dig Dis 23:398–406CrossRefPubMed
go back to reference Basser PJ (1995) Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 8:333–344CrossRefPubMed Basser PJ (1995) Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 8:333–344CrossRefPubMed
go back to reference Blei AT (2004) Infection, inflammation and hepatic encephalopathy, synergism redefined. J Hepatol 40:327–330CrossRefPubMed Blei AT (2004) Infection, inflammation and hepatic encephalopathy, synergism redefined. J Hepatol 40:327–330CrossRefPubMed
go back to reference Brusilow SW, Traystman R (1986) Hepatic encephalopathy. N Engl J Med 20(314):786–787 Brusilow SW, Traystman R (1986) Hepatic encephalopathy. N Engl J Med 20(314):786–787
go back to reference Cauli O, Rodrigo R, Piedrafita B, Boix J, Felipo V (2007) Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology 46:514–519CrossRefPubMed Cauli O, Rodrigo R, Piedrafita B, Boix J, Felipo V (2007) Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology 46:514–519CrossRefPubMed
go back to reference Chavarria L, Oria M, Romero-Gimenez J, Alonso J, Lope-Piedrafita S, Cordoba J (2010) Diffusion tensor imaging supports the cytotoxic origin of brain edema in a rat model of acute liver failure. Gastroenterology 138:1566–1573CrossRefPubMed Chavarria L, Oria M, Romero-Gimenez J, Alonso J, Lope-Piedrafita S, Cordoba J (2010) Diffusion tensor imaging supports the cytotoxic origin of brain edema in a rat model of acute liver failure. Gastroenterology 138:1566–1573CrossRefPubMed
go back to reference Cordoba J, Gottstein J, Blei A (1996) Glutamine, myoinositol, and organic osmolytes after portacaval anastomosis in the rat: implications for ammonia-induced brain edema. Hepatology 27:919–923 Cordoba J, Gottstein J, Blei A (1996) Glutamine, myoinositol, and organic osmolytes after portacaval anastomosis in the rat: implications for ammonia-induced brain edema. Hepatology 27:919–923
go back to reference Duchini A, Govindarajan S, Santucci M, Zampi G, Hofman FM (1996) Effects of tumor necrosis factor-alpha and interleukin-6 on fluid-phase permeability and ammonia diffusion in CNS-derived endothelial cells. J Investig Med 44:474–482PubMed Duchini A, Govindarajan S, Santucci M, Zampi G, Hofman FM (1996) Effects of tumor necrosis factor-alpha and interleukin-6 on fluid-phase permeability and ammonia diffusion in CNS-derived endothelial cells. J Investig Med 44:474–482PubMed
go back to reference Hasan KM, Parker DL, Alexander AL (2001) Comparison of gradient encoding schemes for diffusion-tensor MRI. J Magn Reson Imaging 13:769–780CrossRefPubMed Hasan KM, Parker DL, Alexander AL (2001) Comparison of gradient encoding schemes for diffusion-tensor MRI. J Magn Reson Imaging 13:769–780CrossRefPubMed
go back to reference Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A (2004) Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol 41:613–620CrossRefPubMed Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A (2004) Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol 41:613–620CrossRefPubMed
go back to reference Jayakumar AR, Norenberg MD (2010) The Na-K-Cl Co-transporter in astrocyte swelling. Metab Brain Dis 25:31–38CrossRefPubMed Jayakumar AR, Norenberg MD (2010) The Na-K-Cl Co-transporter in astrocyte swelling. Metab Brain Dis 25:31–38CrossRefPubMed
go back to reference Kale RA, Gupta RK, Saraswat VA, Hasan KM, Trivedi R, Mishra AM, Ranjan P, Pandey CM, Narayana PA (2006) Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy. Hepatology 43:698–706CrossRefPubMed Kale RA, Gupta RK, Saraswat VA, Hasan KM, Trivedi R, Mishra AM, Ranjan P, Pandey CM, Narayana PA (2006) Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy. Hepatology 43:698–706CrossRefPubMed
go back to reference Martinez-Hernandez A, Bell KP, Norenberger MD (1977) Glutamine synthetase: glial localization in brain. Science 195:1356–1385CrossRefPubMed Martinez-Hernandez A, Bell KP, Norenberger MD (1977) Glutamine synthetase: glial localization in brain. Science 195:1356–1385CrossRefPubMed
go back to reference O’Beirne JP, Chouhan M, Hughes RD (2006) The role of infection and inflammation in the pathogenesis of hepatic encephalopathy and cerebral edema in acute liver failure. Nat Clin Pract Gastroenterol Hepatol 3:118–119CrossRefPubMed O’Beirne JP, Chouhan M, Hughes RD (2006) The role of infection and inflammation in the pathogenesis of hepatic encephalopathy and cerebral edema in acute liver failure. Nat Clin Pract Gastroenterol Hepatol 3:118–119CrossRefPubMed
go back to reference Odeh M, Sabo E, Srugo I, Oliven A (2005) Relationship between tumor necrosis factor-alpha and ammonia in patients with hepatic encephalopathy due to chronic liver failure. Ann Med 37:603–612CrossRefPubMed Odeh M, Sabo E, Srugo I, Oliven A (2005) Relationship between tumor necrosis factor-alpha and ammonia in patients with hepatic encephalopathy due to chronic liver failure. Ann Med 37:603–612CrossRefPubMed
go back to reference Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LC Model. NMR Biomed 14:260–264CrossRefPubMed Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LC Model. NMR Biomed 14:260–264CrossRefPubMed
go back to reference Rai V, Nath K, Saraswat VA, Purwar A, Rathore RKS, Gupta RK (2008) Measurement of cytotoxic and interstitial components of cerebral edema in acute hepatic failure by diffusion tensor imaging. J Magn Reson Imaging 28:334–341CrossRefPubMed Rai V, Nath K, Saraswat VA, Purwar A, Rathore RKS, Gupta RK (2008) Measurement of cytotoxic and interstitial components of cerebral edema in acute hepatic failure by diffusion tensor imaging. J Magn Reson Imaging 28:334–341CrossRefPubMed
go back to reference Rolando N, Wade JIM, Davalos M, Wendon J, Philpott-Howard J, Williams R (2000) The systemic inflammatory response syndrome in acute liver failure. Hepatology 32:734–739CrossRefPubMed Rolando N, Wade JIM, Davalos M, Wendon J, Philpott-Howard J, Williams R (2000) The systemic inflammatory response syndrome in acute liver failure. Hepatology 32:734–739CrossRefPubMed
go back to reference Saksena S, Rai V, Saraswat VA, Rathore RKS, Purwar A, Kumar M, Thomas MA, Gupta RK (2008) Cerebral diffusion tensor imaging and in vivo proton magnetic resonance spectroscopy in patients with fulminant hepatic failure. J Gastroenterol Hepatol 23:e111–e119CrossRefPubMed Saksena S, Rai V, Saraswat VA, Rathore RKS, Purwar A, Kumar M, Thomas MA, Gupta RK (2008) Cerebral diffusion tensor imaging and in vivo proton magnetic resonance spectroscopy in patients with fulminant hepatic failure. J Gastroenterol Hepatol 23:e111–e119CrossRefPubMed
go back to reference Shawcross DL, Wright G, Olde Damink SWM, Jalan R (2007) Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 22:125–138CrossRefPubMed Shawcross DL, Wright G, Olde Damink SWM, Jalan R (2007) Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 22:125–138CrossRefPubMed
go back to reference Tandon BN, Bernauau J, O’Grady J, Gupta SD, Krisch RE, Liaw YF, Okuda K, Acharya SK (1999) Recommendations of the International Association for the Study of the Liver Subcommittee on nomenclature of acute and subacute liver failure. J Gastroenterol Hepatol 14:403–404CrossRefPubMed Tandon BN, Bernauau J, O’Grady J, Gupta SD, Krisch RE, Liaw YF, Okuda K, Acharya SK (1999) Recommendations of the International Association for the Study of the Liver Subcommittee on nomenclature of acute and subacute liver failure. J Gastroenterol Hepatol 14:403–404CrossRefPubMed
go back to reference Vaquero J, Fontana RJ, Larson AM, Bass NM, Davern TJ, Shakil AO, Han S, Harrison ME, Stravitz TR, Munoz S, Brown R, Lee WM, Blei AT (2005) Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy. Liver Transplant 11:1581–1589CrossRef Vaquero J, Fontana RJ, Larson AM, Bass NM, Davern TJ, Shakil AO, Han S, Harrison ME, Stravitz TR, Munoz S, Brown R, Lee WM, Blei AT (2005) Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy. Liver Transplant 11:1581–1589CrossRef
go back to reference Verma A, Saraswat VA, Krishna RY, Nath K, Thomas MA, Gupta RK (2008) Role of 1H-MR spectroscopy in the differentiation of acute on chronic liver failure from acute liver failure. Liver Int 28:1095–1103CrossRefPubMed Verma A, Saraswat VA, Krishna RY, Nath K, Thomas MA, Gupta RK (2008) Role of 1H-MR spectroscopy in the differentiation of acute on chronic liver failure from acute liver failure. Liver Int 28:1095–1103CrossRefPubMed
go back to reference Ware AJ, D’Agostino AN, Combes B (1971) Cerebral edema: a major complication of massive hepatic necrosis. Gastroenterology 61:877–884PubMed Ware AJ, D’Agostino AN, Combes B (1971) Cerebral edema: a major complication of massive hepatic necrosis. Gastroenterology 61:877–884PubMed
go back to reference Westin CF, Maier SE, Mamata H, Nabavi A, Jolesz FA, Kikinis R (2002) Processing and visualization for diffusion tensor MRI. Med Image Anal 6:93–108CrossRefPubMed Westin CF, Maier SE, Mamata H, Nabavi A, Jolesz FA, Kikinis R (2002) Processing and visualization for diffusion tensor MRI. Med Image Anal 6:93–108CrossRefPubMed
go back to reference Wright G, Davies NA, Shawcross DL, Hodges SJ, Zwingmann C, Brooks HF, Mani AR, Harry D, Stadlbauer V, Zou Z, Williams R, Davies C, Moore KP, Jalan R (2007) Endotoxemia produces coma and brain swelling in bile duct ligated rats. Hepatology 45:1517–1526CrossRefPubMed Wright G, Davies NA, Shawcross DL, Hodges SJ, Zwingmann C, Brooks HF, Mani AR, Harry D, Stadlbauer V, Zou Z, Williams R, Davies C, Moore KP, Jalan R (2007) Endotoxemia produces coma and brain swelling in bile duct ligated rats. Hepatology 45:1517–1526CrossRefPubMed
Metadata
Title
Serum proinflammatory cytokines correlate with diffusion tensor imaging derived metrics and 1H-MR spectroscopy in patients with acute liver failure
Authors
Rakesh Kumar Gupta
Santosh Kumar Yadav
Murali Rangan
Ram Kishore Singh Rathore
Michael Albert Thomas
Kashi Nath Prasad
Chandra Mohan Pandey
Vivek Anand Saraswat
Publication date
01-09-2010
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 3/2010
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-010-9206-x

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