International Journal of Clinical and Experimental Medical Sciences

| Peer-Reviewed |

Brain Perfusion Scintigraphy in Evaluation of Pathogenesis of Fatigue in Patients with Primary Biliary Cholangitis (PBC) – A Pilot Study

Received: 17 July 2017    Accepted: 23 August 2017    Published: 09 September 2017
Views:       Downloads:

Share This Article

Abstract

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease characterized by a breakdown of immune tolerance to mitochondrial and nuclear antigens, causing injury to the biliary epithelial cells. Fatigue is the commonest reported symptom in PBC and has a negative impact on patients' perceived quality of life, often through social isolation. It is unrelated to the severity of liver disease and appears unresponsive to current therapies, including ursodeoxycholic acid and transplantation. Fatigue in PBC is complex, with numerous associated peripheral and central nervous system (CNS) features. Initially, cholestasis causes degenerative CNS change affecting areas of the brain regulating autonomic dysfunction and sleep, and these changes lead directly to some manifestations of fatigue and the associated cognitive impairment. The aim of the study was to examine global cerebral blood flow with brain perfusion scintigraphy SPECT in well-defined group of PBC Caucasian patients with verbally reported fatigue. Twenty consecutive PBC female patients (median age 58.9, ranges 38-80; 4 cirrhotic) with mean duration of the disease 3.3 years, were prospectively enrolled into the study. Fatigue Impact Scale (FIS) questionnaire was administered to every patients at the moment of brain examination. Brain perfusion scintigraphy SPECT was performed after intravenous injection of 760-800 MBq of technetium99m labeled exametazime (99mTc –HMPAO). Then patients were examined using double head gamma camera system, and data were analyzed with dedicated nuclear medicine software. In analyzed cohort the median FIS score was 70.5 points (ranges 21-160), which was higher than previously reported. There were no correlation between age of patients at the SPECT/FIS examination, duration of the disease, the presence of liver cirrhosis, Mayo Risk Score, and FIS domains: Cognitive, Physical and Social, as well as with brain blood flow. However, positive correlation between Cognitive dimension of FIS measure and right frontal lobe perfusion impairment assessed with SPECT technic (p<0.05) was found. The results of this study showed that right lobe perfusion impairment might impact brain function in PBC. Cognitive dimension was stage-independent symptom in analyzed cohort, and cognitive impairment might be, in turn, associated with functional brain lesion.

DOI 10.11648/j.ijcems.20170304.11
Published in International Journal of Clinical and Experimental Medical Sciences (Volume 3, Issue 4, July 2017)
Page(s) 42-46
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Brain Perfusion Scintigraphy, Primary Biliary Cholangitis (PBC), Fatigue, Cognitive Impairment

References
[1] Huet PM, Deslauriers J, Tran A, Faucher C, Charbonneau J. Impact of fatigue on the quality of life of patients with primary biliary cirrhosis. Am J Gastroenterol. 2000; 95(3):760-7. doi: 10.1111/j.1572-0241.2000.01857.x. PubMed PMID: 10710071.
[2] Poupon RE, Chretien Y, Chazouilleres O, Poupon R, Chwalow J. Quality of life in patients with primary biliary cirrhosis. Hepatology. 2004; 40(2):489-94. doi: 10.1002/hep.20276. PubMed PMID: 15368455.
[3] Stanca CM, Bach N, Krause C, Tandon N, Freni MA, Gutierrez JA, et al. Evaluation of fatigue in U.S. patients with primary biliary cirrhosis. Am J Gastroenterol. 2005; 100(5):1104-9. doi: 10.1111/j.1572-0241.2005.41315.x. PubMed PMID: 15842585.
[4] McDonald C, Newton J, Lai HM, Baker SN, Jones DE. Central nervous system dysfunction in primary biliary cirrhosis and its relationship to symptoms. J Hepatol. 2010; 53(6):1095-100. doi: 10.1016/j.jhep.2010.05.036. PubMed PMID: 20810186.
[5] Newton JL, Hudson M, Tachtatzis P, Sutcliffe K, Pairman J, Burt JA, et al. Population prevalence and symptom associations of autonomic dysfunction in primary biliary cirrhosis. Hepatology. 2007; 45(6):1496-505. doi: 10.1002/hep.21609. PubMed PMID: 17538969.
[6] Newton JL, Davidson A, Kerr S, Bhala N, Pairman J, Burt J, et al. Autonomic dysfunction in primary biliary cirrhosis correlates with fatigue severity. Eur J Gastroenterol Hepatol. 2007; 19(2):125-32. doi: 10.1097/01.meg.0000252629.96043.67. PubMed PMID: 17272997.
[7] Newton JL, Allen J, Kerr S, Jones DE. Reduced heart rate variability and baroreflex sensitivity in primary biliary cirrhosis. Liver Int. 2006; 26(2):197-202. doi: 10.1111/j.1478-3231.2005.01214.x. PubMed PMID: 16448458.
[8] Keresztes K, Istenes I, Folhoffer A, Lakatos PL, Horvath A, Csak T, et al. Autonomic and sensory nerve dysfunction in primary biliary cirrhosis. World J Gastroenterol. 2004;10(20):3039-43. PubMed PMID: 15378789; PubMed Central PMCID: PMCPMC4576268.
[9] Jones DE, Al-Rifai A, Frith J, Patanwala I, Newton JL. The independent effects of fatigue and UDCA therapy on mortality in primary biliary cirrhosis: results of a 9 year follow-up. J Hepatol. 2010; 53(5):911-7. doi: 10.1016/j.jhep.2010.05.026. PubMed PMID: 20800924.
[10] Jones DE, Bhala N, Burt J, Goldblatt J, Prince M, Newton JL. Four year follow up of fatigue in a geographically defined primary biliary cirrhosis patient cohort. Gut. 2006; 55(4):536-41. doi: 10.1136/gut.2005.080317. PubMed PMID: 16299032; PubMed Central PMCID: PMCPMC1856154.
[11] Carbone M, Bufton S, Monaco A, Griffiths L, Jones DE, Neuberger JM. The effect of liver transplantation on fatigue in patients with primary biliary cirrhosis: a prospective study. J Hepatol. 2013; 59(3):490-4. doi: 10.1016/j.jhep.2013.04.017. PubMed PMID: 23628322.
[12] Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994;18 Suppl 1: S79-83. PubMed PMID: 8148458.
[13] Prince MI, James OF, Holland NP, Jones DE. Validation of a fatigue impact score in primary biliary cirrhosis: towards a standard for clinical and trial use. J Hepatol. 2000; 32(3):368-73. PubMed PMID: 10735604.
[14] Ahboucha S, Butterworth RF, Pomier-Layrargues G, Vincent C, Hassoun Z, Baker GB. Neuroactive steroids and fatigue severity in patients with primary biliary cirrhosis and hepatitis C. Neurogastroenterol Motil. 2008; 20(6):671-9. doi: 10.1111/j.1365-2982.2007.01080.x. PubMed PMID: 18282171.
[15] Ahboucha S, Pomier-Layrargues G, Vincent C, Hassoun Z, Tamaz R, Baker G, et al. Reduced plasma dehydroepiandrosterone sulfate levels are significantly correlated with fatigue severity in patients with primary biliary cirrhosis. Neurochem Int. 2008; 52(4-5):569-74. doi: 10.1016/j.neuint.2007.06.002. PubMed PMID: 17669554.
[16] Biagini MR, Tozzi A, Milani S, Grippo A, Amantini A, Capanni M, et al. Fatigue in primary biliary cirrhosis: a possible role of comorbidities. Eur J Gastroenterol Hepatol. 2008; 20(2):122-6. doi: 10.1097/MEG.0b013e3282f1cbda. PubMed PMID: 18188032.
[17] Bjornsson E, Kalaitzakis E, Neuhauser M, Enders F, Maetzel H, Chapman RW, et al. Fatigue measurements in patients with primary biliary cirrhosis and the risk of mortality during follow-up. Liver Int. 2010; 30(2):251-8. doi: 10.1111/j.1478-3231.2009.02160.x. PubMed PMID: 19922590.
[18] Bjornsson E, Simren M, Olsson R, Chapman RW. Fatigue is not a specific symptom in patients with primary biliary cirrhosis. Eur J Gastroenterol Hepatol. 2005; 17(3):351-7. PubMed PMID: 15716661.
[19] Goldblatt J, Taylor PJ, Lipman T, Prince MI, Baragiotta A, Bassendine MF, et al. The true impact of fatigue in primary biliary cirrhosis: a population study. Gastroenterology. 2002; 122(5):1235-41. PubMed PMID: 11984509.
[20] Newton JL, Gibson GJ, Tomlinson M, Wilton K, Jones D. Fatigue in primary biliary cirrhosis is associated with excessive daytime somnolence. Hepatology. 2006; 44(1):91-8. doi: 10.1002/hep.21230. PubMed PMID: 16800007.
[21] Newton JL, Okonkwo O, Sutcliffe K, Seth A, Shin J, Jones DE. Symptoms of autonomic dysfunction in chronic fatigue syndrome. QJM. 2007; 100(8):519-26. doi: 10.1093/qjmed/hcm057. PubMed PMID: 17617647.
[22] Theal JJ, Toosi MN, Girlan L, Heslegrave RJ, Huet PM, Burak KW, et al. A randomized, controlled crossover trial of ondansetron in patients with primary biliary cirrhosis and fatigue. Hepatology. 2005; 41(6):1305-12. doi: 10.1002/hep.20698. PubMed PMID: 15915460.
[23] Wunsch E, Post M, Gutkowski K, Marlicz W, Szymanik B, Hartleb M, et al. Critical flicker frequency fails to disclose brain dysfunction in patients with primary biliary cirrhosis. Dig Liver Dis. 2010; 42(11):818-21. doi: 10.1016/j.dld.2010.03.017. PubMed PMID: 20430705.
[24] Grover VP, Southern L, Dyson JK, Kim JU, Crossey MM, Wylezinska-Arridge M, et al. Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging. Aliment Pharmacol Ther. 2016; 44(9):936-45. doi: 10.1111/apt.13797. PubMed PMID: 27604637; PubMed Central PMCID: PMCPMC5082539.
[25] Schmaling KB, Lewis DH, Fiedelak JI, Mahurin R, Buchwald DS. Single-photon emission computerized tomography and neurocognitive function in patients with chronic fatigue syndrome. Psychosom Med. 2003; 65(1):129-36. PubMed PMID: 12554824.
[26] Raszeja-Wyszomirska J, Wunsch E, Krawczyk M, Rigopoulou EI, Kostrzewa K, Norman GL, et al. Assessment of health related quality of life in polish patients with primary biliary cirrhosis. Clin Res Hepatol Gastroenterol. 2016; 40(4):471-9. doi: 10.1016/j.clinre.2015.10.006. PubMed PMID: 26621536.
[27] Newton JL, Hollingsworth KG, Taylor R, El-Sharkawy AM, Khan ZU, Pearce R, et al. Cognitive impairment in primary biliary cirrhosis: symptom impact and potential etiology. Hepatology. 2008; 48(2):541-9. doi: 10.1002/hep.22371. PubMed PMID: 18563843.
[28] Cook DB, O'Connor PJ, Lange G, Steffener J. Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls. Neuroimage. 2007; 36(1):108-22. doi: 10.1016/j.neuroimage.2007.02.033. PubMed PMID: 17408973.
[29] Lange G, Wang S, DeLuca J, Natelson BH. Neuroimaging in chronic fatigue syndrome. Am J Med. 1998; 105(3A):50S-3S. PubMed PMID: 9790482.
[30] Lange G, DeLuca J, Maldjian JA, Lee H, Tiersky LA, Natelson BH. Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome. J Neurol Sci. 1999; 171(1):3-7. PubMed PMID: 10567042.
[31] Costa DC, Tannock C, Brostoff J. Brainstem perfusion is impaired in chronic fatigue syndrome. QJM. 1995; 88(11):767-73. PubMed PMID: 8542261.
[32] Fischler B, D'Haenen H, Cluydts R, Michiels V, Demets K, Bossuyt A, et al. Comparison of 99mTc HMPAO SPECT scan between chronic fatigue syndrome, major depression and healthy controls: an exploratory study of clinical correlates of regional cerebral blood flow. Neuropsychobiology. 1996; 34(4):175-83. PubMed PMID: 9121617.
[33] Schwartz RB, Garada BM, Komaroff AL, Tice HM, Gleit M, Jolesz FA, et al. Detection of intracranial abnormalities in patients with chronic fatigue syndrome: comparison of MR imaging and SPECT. AJR Am J Roentgenol. 1994; 162(4):935-41. doi: 10.2214/ajr.162.4.8141020. PubMed PMID: 8141020.
[34] Gur RE, Gur RC. Gender differences in regional cerebral blood flow. Schizophr Bull. 1990; 16(2):247-54. PubMed PMID: 2374883.
[35] Yoshiuchi K, Farkas J, Natelson BH. Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Clin Physiol Funct Imaging. 2006; 26(2):83-6. doi: 10.1111/j.1475-097X.2006.00649.x. PubMed PMID: 16494597.
[36] Ichise M, Salit IE, Abbey SE, Chung DG, Gray B, Kirsh JC, et al. Assessment of regional cerebral perfusion by 99mTc-HMPAO SPECT in chronic fatigue syndrome. Nucl Med Commun. 1992; 13(10):767-72. PubMed PMID: 1491843.
[37] Carbone M, Mells GF, Pells G, Dawwas MF, Newton JL, Heneghan MA, et al. Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology. 2013; 144(3):560-9 e7; quiz e13-4. doi: 10.1053/j.gastro.2012.12.005. PubMed PMID: 23246637.
[38] Frith J, Fattakhova G, Jones DE, Henderson E, Wilton K, Day CP, et al. Cognitive impairment in non-cirrhotic chronic liver disease is unrelated to liver disease severity but associated with ineffective baroreflex function. Gut. 2012; 61(7):1101-3. doi: 10.1136/gutjnl-2011-301216. PubMed PMID: 22057052.
[39] Hollingsworth KG, Jones DE, Taylor R, Frith J, Blamire AM, Newton JL. Impaired cerebral autoregulation in primary biliary cirrhosis: implications for the pathogenesis of cognitive decline. Liver Int. 2010; 30(6):878-85. doi: 10.1111/j.1478-3231.2010.02259.x. PubMed PMID: 20492494.
Author Information
  • Liver and Internal Medicine Unit, Department of Liver, Transplant and General Surgery of Medical University of Warsaw, Warsaw, Poland

  • Department of Nuclear Medicine, Pomeranian Medical University, Szczecin, Poland

  • Department of Liver, Transplant and General Surgery of Medical University of Warsaw, Warsaw, Poland

  • Liver and Internal Medicine Unit, Department of Liver, Transplant and General Surgery of Medical University of Warsaw, Warsaw, Poland

Cite This Article
  • APA Style

    Joanna Raszeja-Wyszomirska, Piotr Zorga, Marcin Kotulski, Bożena Birkenfeld, Piotr Milkiewicz Milkiewicz. (2017). Brain Perfusion Scintigraphy in Evaluation of Pathogenesis of Fatigue in Patients with Primary Biliary Cholangitis (PBC) – A Pilot Study. International Journal of Clinical and Experimental Medical Sciences, 3(4), 42-46. https://doi.org/10.11648/j.ijcems.20170304.11

    Copy | Download

    ACS Style

    Joanna Raszeja-Wyszomirska; Piotr Zorga; Marcin Kotulski; Bożena Birkenfeld; Piotr Milkiewicz Milkiewicz. Brain Perfusion Scintigraphy in Evaluation of Pathogenesis of Fatigue in Patients with Primary Biliary Cholangitis (PBC) – A Pilot Study. Int. J. Clin. Exp. Med. Sci. 2017, 3(4), 42-46. doi: 10.11648/j.ijcems.20170304.11

    Copy | Download

    AMA Style

    Joanna Raszeja-Wyszomirska, Piotr Zorga, Marcin Kotulski, Bożena Birkenfeld, Piotr Milkiewicz Milkiewicz. Brain Perfusion Scintigraphy in Evaluation of Pathogenesis of Fatigue in Patients with Primary Biliary Cholangitis (PBC) – A Pilot Study. Int J Clin Exp Med Sci. 2017;3(4):42-46. doi: 10.11648/j.ijcems.20170304.11

    Copy | Download

  • @article{10.11648/j.ijcems.20170304.11,
      author = {Joanna Raszeja-Wyszomirska and Piotr Zorga and Marcin Kotulski and Bożena Birkenfeld and Piotr Milkiewicz Milkiewicz},
      title = {Brain Perfusion Scintigraphy in Evaluation of Pathogenesis of Fatigue in Patients with Primary Biliary Cholangitis (PBC) – A Pilot Study},
      journal = {International Journal of Clinical and Experimental Medical Sciences},
      volume = {3},
      number = {4},
      pages = {42-46},
      doi = {10.11648/j.ijcems.20170304.11},
      url = {https://doi.org/10.11648/j.ijcems.20170304.11},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.ijcems.20170304.11},
      abstract = {Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease characterized by a breakdown of immune tolerance to mitochondrial and nuclear antigens, causing injury to the biliary epithelial cells. Fatigue is the commonest reported symptom in PBC and has a negative impact on patients' perceived quality of life, often through social isolation. It is unrelated to the severity of liver disease and appears unresponsive to current therapies, including ursodeoxycholic acid and transplantation. Fatigue in PBC is complex, with numerous associated peripheral and central nervous system (CNS) features. Initially, cholestasis causes degenerative CNS change affecting areas of the brain regulating autonomic dysfunction and sleep, and these changes lead directly to some manifestations of fatigue and the associated cognitive impairment. The aim of the study was to examine global cerebral blood flow with brain perfusion scintigraphy SPECT in well-defined group of PBC Caucasian patients with verbally reported fatigue. Twenty consecutive PBC female patients (median age 58.9, ranges 38-80; 4 cirrhotic) with mean duration of the disease 3.3 years, were prospectively enrolled into the study. Fatigue Impact Scale (FIS) questionnaire was administered to every patients at the moment of brain examination. Brain perfusion scintigraphy SPECT was performed after intravenous injection of 760-800 MBq of technetium99m labeled exametazime (99mTc –HMPAO). Then patients were examined using double head gamma camera system, and data were analyzed with dedicated nuclear medicine software. In analyzed cohort the median FIS score was 70.5 points (ranges 21-160), which was higher than previously reported. There were no correlation between age of patients at the SPECT/FIS examination, duration of the disease, the presence of liver cirrhosis, Mayo Risk Score, and FIS domains: Cognitive, Physical and Social, as well as with brain blood flow. However, positive correlation between Cognitive dimension of FIS measure and right frontal lobe perfusion impairment assessed with SPECT technic (p<0.05) was found. The results of this study showed that right lobe perfusion impairment might impact brain function in PBC. Cognitive dimension was stage-independent symptom in analyzed cohort, and cognitive impairment might be, in turn, associated with functional brain lesion.},
     year = {2017}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Brain Perfusion Scintigraphy in Evaluation of Pathogenesis of Fatigue in Patients with Primary Biliary Cholangitis (PBC) – A Pilot Study
    AU  - Joanna Raszeja-Wyszomirska
    AU  - Piotr Zorga
    AU  - Marcin Kotulski
    AU  - Bożena Birkenfeld
    AU  - Piotr Milkiewicz Milkiewicz
    Y1  - 2017/09/09
    PY  - 2017
    N1  - https://doi.org/10.11648/j.ijcems.20170304.11
    DO  - 10.11648/j.ijcems.20170304.11
    T2  - International Journal of Clinical and Experimental Medical Sciences
    JF  - International Journal of Clinical and Experimental Medical Sciences
    JO  - International Journal of Clinical and Experimental Medical Sciences
    SP  - 42
    EP  - 46
    PB  - Science Publishing Group
    SN  - 2469-8032
    UR  - https://doi.org/10.11648/j.ijcems.20170304.11
    AB  - Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease characterized by a breakdown of immune tolerance to mitochondrial and nuclear antigens, causing injury to the biliary epithelial cells. Fatigue is the commonest reported symptom in PBC and has a negative impact on patients' perceived quality of life, often through social isolation. It is unrelated to the severity of liver disease and appears unresponsive to current therapies, including ursodeoxycholic acid and transplantation. Fatigue in PBC is complex, with numerous associated peripheral and central nervous system (CNS) features. Initially, cholestasis causes degenerative CNS change affecting areas of the brain regulating autonomic dysfunction and sleep, and these changes lead directly to some manifestations of fatigue and the associated cognitive impairment. The aim of the study was to examine global cerebral blood flow with brain perfusion scintigraphy SPECT in well-defined group of PBC Caucasian patients with verbally reported fatigue. Twenty consecutive PBC female patients (median age 58.9, ranges 38-80; 4 cirrhotic) with mean duration of the disease 3.3 years, were prospectively enrolled into the study. Fatigue Impact Scale (FIS) questionnaire was administered to every patients at the moment of brain examination. Brain perfusion scintigraphy SPECT was performed after intravenous injection of 760-800 MBq of technetium99m labeled exametazime (99mTc –HMPAO). Then patients were examined using double head gamma camera system, and data were analyzed with dedicated nuclear medicine software. In analyzed cohort the median FIS score was 70.5 points (ranges 21-160), which was higher than previously reported. There were no correlation between age of patients at the SPECT/FIS examination, duration of the disease, the presence of liver cirrhosis, Mayo Risk Score, and FIS domains: Cognitive, Physical and Social, as well as with brain blood flow. However, positive correlation between Cognitive dimension of FIS measure and right frontal lobe perfusion impairment assessed with SPECT technic (p<0.05) was found. The results of this study showed that right lobe perfusion impairment might impact brain function in PBC. Cognitive dimension was stage-independent symptom in analyzed cohort, and cognitive impairment might be, in turn, associated with functional brain lesion.
    VL  - 3
    IS  - 4
    ER  - 

    Copy | Download

  • Sections