Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection

Kumar, Ajay; Deep, Amar; Gupta, Rakesh K.; Atam, Virendra; Mohindra, Samir

doi:10.1016/j.jceh.2017.03.011

Cited by 19 publications

(10 citation statements)

References 44 publications

(67 reference statements)

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“…The present study is also generally consistent with previous neuroimaging studies demonstrating a range of HCV associated CNS effects (Forton, Allsop et al 2001, Taylor, Letendre et al 2004, Weissenborn, Krause et al 2004, McAndrews, Farcnik et al 2005, Grover, Pavese et al 2012, Bladowska, Zimny et al 2013, Bladowska, Knysz et al 2014, Thames, Castellon et al 2015, Pflugrad, Meyer et al 2016, Kharabian Masouleh, Herzig et al 2017, Kumar, Deep et al 2017), and with the literature on neuroimmune pathways leading to HCV associated neuropsychiatric symptoms and CNS changes. Viruses can cross tight junctions due to high levels of viremia and inflammation, and HCV RNA has been detected in cerebrospinal fluid and brain parenchyma (Laskus, Radkowski et al 2002, Laskus, Radkowski et al 2005, Letendre, Paulino et al 2007, Adinolfi, Nevola et al 2015).…”

Section: Discussionsupporting

confidence: 92%

“…Specifically, our primary objective was to determine whether, relative to non-infected controls, individuals with HCV exhibit differences in brain activation during a DDT. Previous neuroimaging studies comparing untreated adults with HCV to non-infected controls have found a variety of HCV associated changes using various methods (electroencephalogram (EEG) (Weissenborn, Krause et al 2004); magnetic resonance spectroscopy (MRS) (Forton, Allsop et al 2001, Taylor, Letendre et al 2004, Weissenborn, Krause et al 2004, McAndrews, Farcnik et al 2005, Bladowska, Zimny et al 2013, Thames, Castellon et al 2015); multimodal MRI or diffusion tensor imaging (DTI) (Bladowska, Zimny et al 2013, Thames, Castellon et al 2015, Kharabian Masouleh, Herzig et al 2017, Kumar, Deep et al 2017); perfusion-weighted MRI (Bladowska, Zimny et al 2013, Bladowska, Knysz et al 2014); positron emission tomography (PET) (Grover, Pavese et al 2012, Pflugrad, Meyer et al 2016)). Collectively, findings could be interpreted to suggest that HCV causes or is associated with central nervous system (CNS) inflammation, damage, and/or neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

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Functional MRI and delay discounting in patients infected with hepatitis C

McCready

Kohno

Kolessar³

et al. 2018

J. Neurovirol.

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Background: Hepatitis C virus infected (HCV+) adults evidence increased rates of psychiatric and cognitive difficulties. This is the first study to use functional magnetic resonance imaging (fMRI) to examine brain activation in untreated HCV+ adults. Objective: To determine whether, relative to non-infected controls (CTLs), HCV+ adults exhibit differences in brain activation during a delay discounting task (DDT), a measure of one’s tendency to choose smaller immediate rewards over larger delayed rewards - one aspect of impulsivity. Methods: 20 adults with HCV and 26 CTLs completed an fMRI protocol during the DDT. Results: Mixed effects regression analyses of Hard versus Easy trials of the DDT showed that, compared with CTLs, the HCV+ group exhibited less activation in the left lateral occipital gyrus, precuneus and superior frontal gyrus. There were also significant interactive effects for Hard – Easy contrasts in the bilateral medial frontal gyrus, left insula, left precuneus, left inferior parietal lobule, and right temporal occipital gyrus; the CTL group evidenced a positive relationship between impulsivity and activation, while the HCV+ group exhibited a negative relationship. Within the HCV+ group, those with high viral load chose immediate rewards more often than those with low viral load, regardless of choice difficulty; those with low viral load chose immediate rewards more often on hard choices relative to easy choices. Conclusions: Results show that HCV+ patients exhibit greater impulsive behavior when presented with difficult choices, and impulsivity is negatively related to activation in regions important for cognitive control. Thus, interventions that decrease impulsive choice may be warranted with some HCV+ patients.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Functional MRI and delay discounting in patients infected with hepatitis C

McCready

Kohno

Kolessar³

et al. 2018

J. Neurovirol.

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“…Bladowska et al [56], however, observed a decrease in diffusivity in several white matter tracts in their study. One other study also found significantly decreased fractional anisotropy (an index of microstructural integrity) in asymptomatic HCV positive patients on sensory, inferior longitudinal fascicules and STR fibre bundles compared with uninfected healthy controls [58].…”

Section: Neuroimaging Studiesmentioning

confidence: 86%

Expert Opinion on Managing Chronic HCV in Patients with Neuropsychiatric Manifestations

et al. 2018

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Neurological manifestations of hepatitis C virus infection appear to be under-recognised in clinical practice despite the majority of HCV-infected patients experiencing symptoms such as fatigue, depression, and cognitive dysfunction. There is also growing evidence for a link between HCV infection and an increased risk of Parkinson's disease. The mechanism underpinning the association between HCV and these neuropsychiatric syndromes still requires further investigation. Here we review the pre-clinical and clinical evidence for a link between HCV and effects on the CNS leading to neuropsychiatric syndromes. Lastly, we describe how improvements in neuropsychiatric manifestations of HCV following treatment have been observed, which is subsequently reflected in an overall improvement in health-related quality of life.

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“…Reduced cortical thickness in frontal areas with [26] or without [27] occipital involvement Posterior insula and thalamic atrophy [9] Progressive amygdala and parahippocampal atrophy [9] DAA Reduced frontal cortical volumes [28] DTI Increased MD and reduced FA in global WM [15] more evident in fronto-temporal areas [29] and body of CC [9,24,30] Increased MD in external capsule [4] and fronto-occipital fasciculus [4,9,24] Decreased FA in bilateral middle cerebellar peduncles [24] and superior thalamic radiation [31] Increased FA in the basal ganglia [4] DAA Increased FA in association, commissural and projection tracts [25] Decreased MD in association and projection tract [25] fMRI Altered cortical connectivity possibly due to frontal deficit [32,33] IFN-α Reduced ventral striatum activation [22] and global network efficiency [34] MRS Decreased NAA in anterior [35][36][37] and posterior WM [4,37] Normal [18,35,[37][38][39][40][41][42] or decreased NAA in cortical GM [43] Increased Cho in frontal [35,37,38,43,44] and posterior WM…”

Section: Structural Imagingmentioning

confidence: 99%

“…In HCV-infected subjects, reduced local complexity with increased anisotropy is observed in the basal ganglia, correlating mainly with semantic fluency, and in the bilateral thalami [4]. Thalamic efferents, as the superior thalamic radiation, also show structural alterations that correlate with impairment on tests of attention and executive functions [31].…”

Section: Diffusion Tensor Imaging (Dti)mentioning

confidence: 99%

Neuroimaging Findings in Chronic Hepatitis C Virus Infection: Correlation with Neurocognitive and Neuropsychiatric Manifestations

Tagliapietra

Monaco

2020

IJMS

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Chronic hepatitis C virus (HCV) infection is commonly associated with neurocognitive dysfunction, altered neuropsychological performance and neuropsychiatric symptoms. Quantifiable neuropsychological changes in sustained attention, working memory, executive function, verbal learning and recall are the hallmark of HCV-associated neurocognitive disorder (HCV-AND). This constellation is at variance with the neuropsychological complex that is seen in minimal hepatic encephalopathy, which is typified by an array of alterations in psychomotor speed, selective attention and visuo-constructive function. Noncognitive symptoms, including sleep disturbances, depression, anxiety and fatigue, which are less easily quantifiable, are frequently encountered and can dominate the clinical picture and the clinical course of patients with chronic HCV infection. More recently, an increased vulnerability to Parkinson’s disease among HCV-infected patients has also been reported. The degree to which neurocognitive and neuropsychiatric changes are due to HCV replication within brain tissues or HCV-triggered peripheral immune activation remain to be determined. Without absolute evidence that clearly exonerates or indicts HCV, our understanding of the so-called “HCV brain syndrome”, relies primarily on clinical and neuropsychological assessments, although other comorbidities and substance abuse may impact on neurocognitive function, thus confounding an appropriate recognition. In recent years, a number of functional and structural brain imaging studies have been of help in recognizing possible biological markers of HCV-AND, thus providing a rationale for guiding and justifying antiviral therapy in selected cases. Here, we review clinical, neuroradiological, and therapeutic responses to interferon-based and interferon-free regimens in HCV-related cognitive and neuropsychiatric disorder.

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Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection

Abstract: Our result show that HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using DTT metrics.

Cited by 19 publications

References 44 publications

Functional MRI and delay discounting in patients infected with hepatitis C

Functional MRI and delay discounting in patients infected with hepatitis C

Expert Opinion on Managing Chronic HCV in Patients with Neuropsychiatric Manifestations

Neuroimaging Findings in Chronic Hepatitis C Virus Infection: Correlation with Neurocognitive and Neuropsychiatric Manifestations

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