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

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 technetium 99m labeled exametazime ( 99m Tc -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.