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Ogbole G, Efidi R, Odo J, Okorie C, Makanjuola T, Adeyinka A, Sammet C, Berzins B, Onoja A, Ogunniyi A, Ragin A, Taiwo B. Brain computed tomography perfusion analysis in HIV-seropositive adults with and without neurocognitive impairment in Nigeria: outcomes and challenges of a pilot study. Pan Afr Med J 2023; 46:15. [PMID: 38035155 PMCID: PMC10683175 DOI: 10.11604/pamj.2023.46.15.36320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 09/03/2023] [Indexed: 12/02/2023] Open
Abstract
Introduction the significance of cerebrovascular disease in HIV-associated neurocognitive disorder (HAND) in a homogeneous black population has not yet been determined. This incident case-control study used CT perfusion imaging to quantify and compare regional cerebral blood flow parameters in neuro-cognitively impaired and unimpaired HIV+ participants of the Ibadan Cohort on Neuro AIDS (ICON) in Nigeria. Methods this was an incident case-control study consisting of twenty-seven HIV+ adults, classified based on Frascati criteria into neurocognitive impaired (n=18) and unimpaired (n=9) groups, who had brain computed tomographic perfusion (CTP) with a 64-slice Toshiba T scanner. The standard deviation (SD) of regional mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV) values were calculated for bilateral basal ganglia (BG), frontal, parietal, temporal, and occipital regions from CT perfusion maps. The regional mean values and variability (SD) in the CTP measures were compared in the groups using an independent student t-test. Results differentially higher variability in the bilateral CBF measures in the parietal (right; OR = 1.14, x̄ =5.61, p=0.041, CI=0.27-11.35/left; OR = 1.16, x̄=7.01, p=0.03, CI=5.6-13.47) and time to peak (TTP) measures in the basal ganglia (right; OR = 3.78, x̄=0.88, p=0.032, CI=0.081-1.67/left; OR = 2.44, x̄=1.48, p=0.020, CI=0.26-2.71) and occipital (right; OR = 2.18, x̄=1.32, p=0.018, CI=0.25-2.38/left; OR = 1.93, x̄=1.08, p=0.034, CI=0.086-2.06) regions were observed in the cognitively impaired group compared to the unimpaired group. Conclusion the study evidence suggests that alterations in cerebral perfusion implicated in HIV-associated neurocognitive disorder may be possibly demonstrated using CTP, a readily available resource in most African countries saddled with the highest burden of HIV.
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Affiliation(s)
- Godwin Ogbole
- Department of Radiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Richard Efidi
- Department of Radiology, University College Hospital (UCH), University of Ibadan, Ibadan, Nigeria
| | - Joseph Odo
- Department of Radiology, University College Hospital (UCH), University of Ibadan, Ibadan, Nigeria
| | - Chinonye Okorie
- Department of Radiology, University College Hospital (UCH), University of Ibadan, Ibadan, Nigeria
| | - Tomiwa Makanjuola
- Department of Neurology, University College Hospital (UCH), Ibadan, Nigeria
| | - Abiodun Adeyinka
- Department of Radiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Christina Sammet
- Ann & Robert H. Lurie Children's Hospital Chicago, Chicago, Illinois 60611, the United States
| | - Baiba Berzins
- Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, United States
| | - Akpa Onoja
- Department of Biostatistics, University of Ibadan, Ibadan, Nigeria
| | - Adesola Ogunniyi
- Department of Neurology, University College Hospital (UCH), Ibadan, Nigeria
| | - Ann Ragin
- Department of Radiology, Northwestern University, Evanston, Illinois, United States
| | - Babafemi Taiwo
- Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, United States
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Amirsardari Z, Rahmani F, Rezaei N. Cognitive impairments in HCV infection: From pathogenesis to neuroimaging. J Clin Exp Neuropsychol 2019; 41:987-1000. [PMID: 31405320 DOI: 10.1080/13803395.2019.1652728] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Extrahepatic manifestations of hepatitis C virus (HCV) infection, in particular cognitive impairments, can be present in the absence of clinical liver dysfunction. Executive memory, attention, and concentration are cognitive domains that are most frequently affected. Microstructural and functional changes in cortical gray matter and basal ganglia associate these neuropsychiatric changes in early HCV infection. No study has covered the relationship between imaging features of HCV-related cognitive impairment and HCV pathology. Herein we summarize evidence suggesting a direct pathology of HCV in microglia, astrocytes, and microvascular endothelial cells, and a neuroinflammatory response in HCV-related cognitive decline. Lipoproteins and their receptors mediate HCV infectivity in the central nervous system and confer susceptibility to HCV-related cognitive decline. Magnetic resonance spectroscopy has revealed changes compatible with reactive gliosis and microglial activation in basal ganglia, frontal and occipital white matter, in the absence of cirrhosis or hepatic encephalopathy. Similarly, diffusion imaging shows evidence of structural disintegrity in the axonal fibers of white matter tracts associated with temporal and frontal cortices. We also discuss the cognitive benefits and side-effects of the two most popular therapeutic protocols interferon-based therapy and interferon-free therapy using direct acting anti-virals. Evidences support a network-based pattern of disruption in functional connectivity in HCV patients and a common neuronal substrate for HCV-related and interferon-therapy-associated cognitive decline. These evidences might help identify patients who benefit from either interferon-based or interferon-free treatment regimen.
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Affiliation(s)
- Zahra Amirsardari
- Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences , Tehran , Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Farzaneh Rahmani
- Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences , Tehran , Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Nima Rezaei
- NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN) , Tehran , Iran.,Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran , Iran
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Bladowska J, Pawłowski T, Fleischer-Stępniewska K, Knysz B, Małyszczak K, Żelwetro A, Rymer W, Inglot M, Waliszewska-Prosół M, Ejma M, Podgórski P, Zimny A, Sąsiadek M. Interferon-free therapy as the cause of white matter tracts and cerebral perfusion recovery in patients with chronic hepatitis C. J Viral Hepat 2019; 26:635-643. [PMID: 30702208 DOI: 10.1111/jvh.13069] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 01/09/2019] [Indexed: 02/06/2023]
Abstract
The purpose of this study was to assess cerebral microstructural and perfusion changes in patients with chronic hepatitis C virus (HCV) infection before and after interferon-free therapy, using advanced magnetic resonance (MR) techniques. Eleven HCV-positive patients underwent diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) using a 1.5T MR unit, before and 24 weeks after completion of interferon-free therapy. DTI fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from 14 white matter tracts. PWI values of relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were assessed from 8 areas, including basal ganglia, and cortical and white matter locations. In HCV-positive patients therapy with ombitasvir, paritaprevir boosted with ritonavir and dasabuvir, with or without ribavirin, was scheduled. Cognitive tests were used to assess cognitive function. We found increased FA values after interferon-free therapy compared to values obtained before treatment in HCV patients in almost all white matter tracts. We also observed elevated rCBV values in basal ganglia after therapy. There were significant correlations between improvement in the score of cognitive tests and increased FA values in both inferior fronto-occipital fascicles and left posterior cingulum after treatment. Liver fibrosis regression in elastography, APRI and improvement in cognitive tests were observed. This is the first report of interferon-free therapy as the cause of white matter tracts recovery as well as cerebral perfusion improvement in HCV-infected patients, indicating better functioning of frontal lobes after interferon-free treatment.
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Affiliation(s)
- Joanna Bladowska
- Department of General Radiology, Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland
| | - Tomasz Pawłowski
- Division of Psychotherapy and Psychosomatic Medicine, Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland
| | - Katarzyna Fleischer-Stępniewska
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland
| | - Brygida Knysz
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland
| | - Krzysztof Małyszczak
- Division of Psychotherapy and Psychosomatic Medicine, Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland
| | | | - Weronika Rymer
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland
| | - Małgorzata Inglot
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland
| | | | - Maria Ejma
- Department of Neurology, Wroclaw Medical University, Wroclaw, Poland
| | - Przemysław Podgórski
- Department of General Radiology, Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland
| | - Anna Zimny
- Department of General Radiology, Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland
| | - Marek Sąsiadek
- Department of General Radiology, Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland
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Marciniewicz E, Podgórski P, Pawłowski T, Małyszczak K, Fleischer-Stępniewska K, Knysz B, Waliszewska-Prosół M, Żelwetro A, Rymer W, Inglot M, Ejma M, Sąsiadek M, Bladowska J. Evaluation of brain volume alterations in HCV-infected patients after interferon-free therapy: A pilot study. J Neurol Sci 2019; 399:36-43. [PMID: 30769221 DOI: 10.1016/j.jns.2019.02.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 01/31/2019] [Accepted: 02/01/2019] [Indexed: 12/20/2022]
Abstract
The study was performed to evaluate cerebral volume changes in HCV-infected subjects before and after interferon-free therapy with direct-acting antiviral agents (DAA). We aimed also to estimate the impact of successful DAA therapy on the neuropsychological state of patients. Eleven HCV genotype 1 (GT1) patients treated with ombitasvir/paritaprevir (boosted with ritonavir) and dasabuvir, with or without ribavirin underwent brain magnetic resonance (MR) before and 24 weeks after completion of therapy. All patients achieved sustained viral response. Precise automatic parcellation was made using the fully-available software FreeSurfer 6.0. Statistically significant volume deceleration six months after treatment was found in the subcallosal cingulate gyrus, transverse frontopolar gyri and sulci, anterior segment of the circular sulcus of the insula and horizontal ramus of the anterior segment of the lateral sulcus. After DAA therapy we found statistically significant improvement in the performance of all three tasks of the Rey Complex Figure Test that permits the evaluation of different functions (attention, planning, working,memory). Additionally, significant amelioration in Percentage Conceptual Level Responses in The Wisconsin Card Sorting Test (a neurocognitive test for assessing intellectual functioning) was also discovered. Successful interferon-free therapy may lead to transient cerebral atrophy, probably by reducing neuroinflammation and oedema. This is the first pilot study of the alterations in brain volume after successful interferon-free therapy in chronic HCV patients. Longitudinal follow-up study is needed to observe further effects of therapy on cerebral structures volume changes.
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Affiliation(s)
- Ewelina Marciniewicz
- Department of General Radiology, Interventional Radiology and Neuroradiology, Radiology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.
| | - Przemysław Podgórski
- Department of General Radiology, Interventional Radiology and Neuroradiology, Radiology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
| | - Tomasz Pawłowski
- Division of Psychotherapy and Psychosomatic Medicine, Department of Psychiatry, Wroclaw Medical University, L. Pasteura 10, 50-367 Wroclaw, Poland.
| | - Krzysztof Małyszczak
- Division of Psychotherapy and Psychosomatic Medicine, Department of Psychiatry, Wroclaw Medical University, L. Pasteura 10, 50-367 Wroclaw, Poland
| | - Katarzyna Fleischer-Stępniewska
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiences, Wroclaw Medical University, Koszarowa 5, 51-149 Wroclaw, Poland
| | - Brygida Knysz
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiences, Wroclaw Medical University, Koszarowa 5, 51-149 Wroclaw, Poland
| | | | - Agnieszka Żelwetro
- The Institute of Psychology, University of Wroclaw, J.W. Dawida 1, 50-527 Wroclaw, Poland
| | - Weronika Rymer
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiences, Wroclaw Medical University, Koszarowa 5, 51-149 Wroclaw, Poland.
| | - Małgorzata Inglot
- Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiences, Wroclaw Medical University, Koszarowa 5, 51-149 Wroclaw, Poland.
| | - Maria Ejma
- Department of Neurology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.
| | - Marek Sąsiadek
- Department of General Radiology, Interventional Radiology and Neuroradiology, Radiology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.
| | - Joanna Bladowska
- Department of General Radiology, Interventional Radiology and Neuroradiology, Radiology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland
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McCready H, Kohno M, Kolessar M, Dennis L, Kriz D, Luber H, Anderson R, Chang M, Sasaki A, Flora K, Vandenbark A, Mitchell SH, Loftis JM, Hoffman WF, Huckans M. Functional MRI and delay discounting in patients infected with hepatitis C. J Neurovirol 2018; 24:738-751. [PMID: 30298201 PMCID: PMC6279508 DOI: 10.1007/s13365-018-0670-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Revised: 04/23/2018] [Accepted: 08/15/2018] [Indexed: 02/06/2023]
Abstract
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. 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. Twenty adults with HCV and 26 CTLs completed an fMRI protocol during the DDT. 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. 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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Affiliation(s)
- Holly McCready
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Milky Kohno
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Michael Kolessar
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of PM&R and Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Laura Dennis
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Daniel Kriz
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Hannah Luber
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Renee Anderson
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Michael Chang
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- The Northwest Hepatitis C Resource Center, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Anna Sasaki
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- The Northwest Hepatitis C Resource Center, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Kenneth Flora
- Department of Gastroenterology, The Oregon Clinic, Portland, OR, USA
| | - Arthur Vandenbark
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Neurology, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Molecular Microbiology and Immunology, School of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Suzanne H Mitchell
- Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Oregon Institute of Occupational Health Sciences, School of Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Jennifer M Loftis
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- The Northwest Hepatitis C Resource Center, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - William F Hoffman
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
- Department of Behavioral Neuroscience, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA
- Behavioral Health & Clinical Neurosciences Division, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA
| | - Marilyn Huckans
- Research and Development, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA.
- Department of Psychiatry, School of Medicine, Oregon Health and Science University, Portland, OR, USA.
- The Northwest Hepatitis C Resource Center, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA.
- Behavioral Health & Clinical Neurosciences Division, VA Portland Health Care System, 3710 SW US Veteran's Hospital Road, Portland, OR, 97239, USA.
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6
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Pfefferbaum A, Zahr NM, Sassoon SA, Kwon D, Pohl KM, Sullivan EV. Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in Human Immunodeficiency Virus Infection: Contributions From Alcohol, Substance Use, and Hepatitis C Coinfection. BIOLOGICAL PSYCHIATRY: COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2018; 3:844-859. [PMID: 30093343 DOI: 10.1016/j.bpsc.2018.06.006] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 06/16/2018] [Accepted: 06/18/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Life expectancy of successfully treated human immunodeficiency virus (HIV)-infected individuals is approaching normal longevity. The growing HIV population ≥50 years of age is now at risk of developing HIV-associated neurocognitive disorder, acquiring coinfection with the hepatitis C virus (HCV), and engaging in hazardous drinking or drug consumption that can adversely affect trajectories of the healthy aging of brain structures. METHODS This cross-sectional/longitudinal study quantified regional brain volumes from 1101 magnetic resonance imaging scans collected over 14 years in 549 participants (25 to 75 years of age): 68 HIV-infected individuals without alcohol dependence, 60 HIV-infected individuals with alcohol dependence, 222 alcohol-dependent individuals, and 199 control subjects. We tested 1) whether localized brain regions in HIV-infected individuals exhibited accelerated aging, or alternatively, nonaccelerated premature aging deficits; and 2) the extent to which alcohol or substance dependence or HCV coinfection altered brain aging trajectories. RESULTS The HIV-infected cohort exhibited steeper declining volume trajectories than control subjects, consistently in the frontal cortex. Nonaccelerated volume deficits occurred in the temporal, parietal, insular, and cingulate regions of all three diagnostic groups. Alcohol and drug dependence comorbidities and HCV coinfection exacerbated HIV-related volume deficits. Accelerated age interactions in frontal and posterior parietal volumes endured in HIV-infected individuals free of alcohol or substance dependence and HCV infection comorbidities. Functionally, poorer HIV-associated neurocognitive disorder scores and Veterans Aging Cohort Study indices correlated with smaller regional brain volumes in the HIV-infected individuals without alcohol dependence and alcohol-dependent groups. CONCLUSIONS HIV infection itself may confer a heightened risk of accelerated brain aging, potentially exacerbated by HCV coinfection and substance dependency. Confirmation would require a prospective study with a preinfection baseline.
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Affiliation(s)
- Adolf Pfefferbaum
- Center for Health Sciences, SRI International, Menlo Park, California; Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California
| | - Natalie M Zahr
- Center for Health Sciences, SRI International, Menlo Park, California; Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California
| | | | - Dongjin Kwon
- Center for Health Sciences, SRI International, Menlo Park, California; Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California
| | - Kilian M Pohl
- Center for Health Sciences, SRI International, Menlo Park, California
| | - Edith V Sullivan
- Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
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7
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Interferon-free therapy in hepatitis C virus (HCV) monoinfected and HCV/HIV coinfected patients: effect on cognitive function, fatigue, and mental health. J Neurovirol 2018; 24:557-569. [PMID: 29785584 DOI: 10.1007/s13365-018-0647-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 03/27/2018] [Accepted: 04/26/2018] [Indexed: 12/13/2022]
Abstract
The efficacy and safety of interferon-free therapies for hepatitis C virus (HCV) infection have been reported. Considering the accumulating evidence for a direct central nervous system infection by HCV, we aim to evaluate the effect of direct acting antivirals (DAA) therapy on cognitive function in HCV patients. We conducted a longitudinal analysis of the cognitive performance of 22 patients (8 HCV+, 14 HCV+/HIV+) who completed neuropsychological testing at baseline and at week 12 after DAA therapy. In 20 patients, we analyzed specific attention parameters derived from an experimental testing based on the Theory of Visual Attention (TVA). Depression, fatigue, and mental health were assessed as patient reported outcomes. At baseline, 54.5% of the patients met the criteria for cognitive impairment and 40% showed impairment in TVA parameters. Follow-up analysis revealed significant improvements in the domains of visual memory/learning, executive functions, verbal fluency, processing speed, and motor skills but not in verbal learning and attention/working memory. We did not observe significant improvement in visual attention measured by TVA. Fatigue and mental health significantly improved at follow-up. Our findings indicate that successful DAA treatment leads to cognitive improvements in several domains measured by standard neuropsychological testing. The absence of improvement in TVA parameters and of significant improvement in the domain of attention/working memory might reflect the persistence of specific cognitive deficits after HCV eradication. In summary, DAA treatment seems to have a positive effect on some cognitive domains and leads to an improvement in mental health and fatigue in HCV-infected patients.
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8
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Oriolo G, Egmond E, Mariño Z, Cavero M, Navines R, Zamarrenho L, Solà R, Pujol J, Bargallo N, Forns X, Martin-Santos R. Systematic review with meta-analysis: neuroimaging in hepatitis C chronic infection. Aliment Pharmacol Ther 2018. [PMID: 29536563 DOI: 10.1111/apt.14594] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chronic hepatitis C is considered a systemic disease because of extra-hepatic manifestations. Neuroimaging has been employed in hepatitis C virus-infected patients to find in vivo evidence of central nervous system alterations. AIMS Systematic review and meta-analysis of neuroimaging research in chronic hepatitis C treatment naive patients, or patients previously treated without sustained viral response, to study structural and functional brain impact of hepatitis C. METHODS Using PRISMA guidelines a database search was conducted from inception up until 1 May 2017 for peer-reviewed studies on structural or functional neuroimaging assessment of chronic hepatitis C patients without cirrhosis or encephalopathy, with control group. Meta-analyses were performed when possible. RESULTS The final sample comprised 25 studies (magnetic resonance spectroscopy [N = 12], perfusion weighted imaging [N = 1], positron emission tomography [N = 3], single-photon emission computed tomography [N = 4], functional connectivity in resting state [N = 1], diffusion tensor imaging [N = 2] and structural magnetic resonance imaging [N = 2]). The whole sample was of 509 chronic hepatitis C patients, with an average age of 41.5 years old and mild liver disease. A meta-analysis of magnetic resonance spectroscopy studies showed increased levels of choline/creatine ratio (mean difference [MD] 0.12, 95% confidence interval [CI] 0.06-0.18), creatine (MD 0.85, 95% CI 0.42-1.27) and glutamate plus glutamine (MD 1.67, 95% CI 0.39-2.96) in basal ganglia and increased levels of choline/creatine ratio in centrum semiovale white matter (MD 0.13, 95% CI 0.07-0.19) in chronic hepatitis C patients compared with healthy controls. Photon emission tomography studies meta-analyses did not find significant differences in PK11195 binding potential in cortical and subcortical regions of chronic hepatitis C patients compared with controls. Correlations were observed between various neuroimaging alterations and neurocognitive impairment, fatigue and depressive symptoms in some studies. CONCLUSIONS Patients with chronic hepatitis C exhibit cerebral metabolite alterations and structural or functional neuroimaging abnormalities, which sustain the hypothesis of hepatitis C virus involvement in brain disturbances.
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Affiliation(s)
- G Oriolo
- Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain.,Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain
| | - E Egmond
- Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain.,Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.,Department of Health and Clinical Psychology, Faculty of Psychology, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Z Mariño
- Liver Unit, Hospital Clinic, IDIBAPS, Centro Investigación Biomédica en Red de Enfermedades hepáticas y digestivas, (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - M Cavero
- Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain.,Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain
| | - R Navines
- Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain.,Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain
| | - L Zamarrenho
- Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo (USP), Ribeirão Preto (SP), Brazil
| | - R Solà
- Liver Unit, Parc de Salut Mar, Universitat Autonoma de Barcelona, Barcelona, Spain
| | - J Pujol
- MRI Research Unit, Department of Radiology, Hospital del Mar, CIBERSAM, Barcelona, Spain
| | - N Bargallo
- Center of Diagnostic Image (CDIC), Hospital Clinic, Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain
| | - X Forns
- Liver Unit, Hospital Clinic, IDIBAPS, Centro Investigación Biomédica en Red de Enfermedades hepáticas y digestivas, (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - R Martin-Santos
- Department of Psychiatry and Psychology, Hospital Clinic, Institut d'Investigació Biomèdica Arthur Pi I Sunyer (IDIBAPS), Centro Investigación Biomédica en Red de Salud Mental (CIBERSAM), University of Barcelona, Barcelona, Spain.,Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain.,Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo (USP), Ribeirão Preto (SP), Brazil
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9
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Zahr NM. The Aging Brain With HIV Infection: Effects of Alcoholism or Hepatitis C Comorbidity. Front Aging Neurosci 2018; 10:56. [PMID: 29623036 PMCID: PMC5874324 DOI: 10.3389/fnagi.2018.00056] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 02/20/2018] [Indexed: 12/11/2022] Open
Abstract
As successfully treated individuals with Human Immunodeficiency Virus (HIV)-infected age, cognitive and health challenges of normal aging ensue, burdened by HIV, treatment side effects, and high prevalence comorbidities, notably, Alcohol Use Disorders (AUD) and Hepatitis C virus (HCV) infection. In 2013, people over 55 years old accounted for 26% of the estimated number of people living with HIV (~1.2 million). The aging brain is increasingly vulnerable to endogenous and exogenous insult which, coupled with HIV infection and comorbid risk factors, can lead to additive or synergistic effects on cognitive and motor function. This paper reviews the literature on neuropsychological and in vivo Magnetic Resonance Imaging (MRI) evaluation of the aging HIV brain, while also considering the effects of comorbidity for AUD and HCV.
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Affiliation(s)
- Natalie M Zahr
- Neuroscience Program, SRI International, Menlo Park, CA, United States.,Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, United States
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10
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Forton D, Weissenborn K, Bondin M, Cacoub P. Expert opinion on managing chronic HCV in patients with neuropsychiatric manifestations. Antivir Ther 2018; 23:47-55. [PMID: 30451150 DOI: 10.3851/imp3245] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2018] [Indexed: 10/27/2022]
Abstract
Neurological manifestations of HCV infection appear to be under-recognized 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 central nervous system 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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Affiliation(s)
- Daniel Forton
- Department of Gastroenterology and Hepatology, St George's Hospital London, London, UK
- St George's University of London, London, UK
| | | | | | - Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France
- INSERM, UMR_S 959, Paris, France
- CNRS, FRE3632, F-75005, Paris, France
- AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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11
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Abstract
Human immunodeficiency virus (HIV) enters the brain early after infecting humans and may remain in the central nervous system despite successful antiretroviral treatment. Many neuroimaging techniques were used to study HIV+ patients with or without opportunistic infections. These techniques assessed abnormalities in brain structures (using computed tomography, structural magnetic resonance imaging (MRI), diffusion MRI) and function (using functional MRI at rest or during a task, and perfusion MRI with or without a contrast agent). In addition, single-photon emission computed tomography with various tracers (e.g., thallium-201, Tc99-HMPAO) and positron emission tomography with various agents (e.g., [18F]-dexoyglucose, [11C]-PiB, and [11C]-TSPO tracers), were applied to study opportunistic infections or HIV-associated neurocognitive disorders. Neuroimaging provides diagnoses and biomarkers to quantitate the severity of brain injury or to monitor treatment effects, and may yield insights into the pathophysiology of HIV infection. As the majority of antiretroviral-stable HIV+ patients are living longer, age-related comorbid disorders (e.g., additional neuroinflammation, cerebrovascular disorders, or other dementias) will need to be considered. Other highly prevalent conditions, such as substance use disorders, psychiatric illnesses, and the long-term effects of combined antiretroviral therapy, all may lead to additional brain injury. Neuroimaging studies could provide knowledge regarding how these comorbid conditions impact the HIV-infected brain. Lastly, specific molecular imaging agents may be needed to assess the central nervous system viral reservoir.
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Affiliation(s)
- Linda Chang
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States; Department of Medicine and Department of Neurology, John A. Burns School of Medicine, University of Hawaii, Manoa, United States.
| | - Dinesh K Shukla
- Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, United States
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12
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Abstract
Combined antiretroviral therapy (CART) has turned HIV-infection to a treatable chronic disease during which many patients survive to middle and older age. However, they prematurely develop non-AIDS comorbidities such as cardiovascular disease, metabolic syndrome, diabetes, and HIV-associated neurocognitive disorders (HAND). Microcirculatory changes and endothelial dysfunction occur early both in HIV-infected and in aging patients, in whom they usually precede cardiovascular and neurocognitive impairments. Also, mild cognitive involvement has been reported in women during the menopausal transition. Disruption of the blood-brain barrier, as well as microvascular and cerebral blood flow changes, has been reported in HIV patients with HAND, including postmenopausal women. However, most studies addressing this issue included women aged less than 50 years. Whether HIV-infected women growing older with CART would be subsequently exposed to an increased progression of cognitive impairment overtime remains unknown.
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Affiliation(s)
- Jean-Jacques Monsuez
- AP-HP, Cardiology, Hôpital René Muret, Hôpitaux universitaires de Paris Seine Saint-Denis, Avenue du docteur Schaeffner, F-93270, Sevran, France.
| | - Catherine Belin
- AP-HP, Neurology, Hôpital Avicenne, Hôpitaux universitaires de Paris Seine Saint-Denis, Bobigny, France
| | - Olivier Bouchaud
- AP-HP, Infectious diseases, Hôpital Avicenne, Hôpitaux universitaires de Paris Seine Saint-Denis, Bobigny, France
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13
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Jiang DZ, Zhou DY, Wu WQ, Wu GY, Quan H. Value of multi-b value DWI in the assessment of early cerebral changes in asymptomatic HIV-positive adolescents. Acta Radiol 2017; 58:867-875. [PMID: 27733641 DOI: 10.1177/0284185116673123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Background Magnetic resonance imaging (MRI) and functional MRI techniques have been widely used in the diagnosis of human immunodeficiency virus (HIV) infection related diseases. Purpose To explore whether magnetic resonance diffusion-weighted imaging (DWI) can track water molecular diffusion changes in the brain of asymptomatic HIV-positive adolescents. Material and Methods Multi-b value DWI was performed in 23 adolescents, including 15 HIV-positive participants and eight HIV-negative healthy participants. Mean apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (ADCs) values, fast apparent diffusion coefficient (ADCf) values, distribution diffusion coefficient (DDC) values, and heterogeneity index (α) values were calculated within regions of interest (ROIs) in the frontal lobes, basal ganglia, and temporal lobe. Non-parametric tests were then performed. Results In the bilateral frontal lobes, the mean α values in HIV-positive participants were significantly increased compared with those in healthy participants (right side P = 0.001; left side P = 0.000). In the left frontal lobe, the mean DDC value in HIV-positive participants was significantly increased compared with that in healthy participants ( P = 0.008). In the bilateral frontal lobes, the mean ADCf values in HIV-positive participants were significantly lower than those in healthy participants (right side P = 0.011; left side P = 0.008). In the left basal ganglia, the mean α values in HIV-positive participants were significantly lower than that in healthy participants ( P = 0.013). Conclusion Multi-b value DWI could reflect the early characteristics of water molecule diffusion in HIV infections.
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Affiliation(s)
- Da-Zhen Jiang
- Key Laboratory of Artificial Micro- & Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, PR China
| | - Ding-Yi Zhou
- Key Laboratory of Artificial Micro- & Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, PR China
| | - Wei-Qing Wu
- Key Laboratory of Artificial Micro- & Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, PR China
| | - Guang-Yao Wu
- Medical Imaging department of the Zhongnan Hospital of Wuhan University, Wuhan, PR China
| | - Hong Quan
- Key Laboratory of Artificial Micro- & Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, PR China
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14
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Abstract
Combination antiretroviral treatment is associated with clear benefits in HIV-positive subjects, and is also effective in the central nervous system (CNS), meaning HIV-associated dementia is now an uncommon event. Nevertheless, a significant number of patients show symptoms of neurocognitive impairment which may negatively affect their quality of life. Although several risk factors for HIV-associated neurocognitive disorders have been identified, there is no clear recommendation for their prevention and management. In this review, the penetration of drugs into the cerebrospinal fluid/CNS is discussed as well as the viral and clinical consequences associated with higher/lower compartmental exposure. We also review the potential interventions according to the currently identified underlying mechanisms, including persistent CNS immune activation, legacy effects, low-level viral replication and escape, co-morbidities, and antiretroviral-associated direct and indirect 'neurotoxicity'. Adjunctive therapies and interventions (including neuro-rehabilitation) are then briefly discussed. The treatment of HIV infection in the CNS is a complex area of therapeutics requiring multidisciplinary interventions and further study.
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Affiliation(s)
- A Calcagno
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, c/o Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy.
| | - G Di Perri
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, c/o Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy
| | - S Bonora
- Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, c/o Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy
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15
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Yarlott L, Heald E, Forton D. Hepatitis C virus infection, and neurological and psychiatric disorders - A review. J Adv Res 2016; 8:139-148. [PMID: 28149649 PMCID: PMC5272938 DOI: 10.1016/j.jare.2016.09.005] [Citation(s) in RCA: 79] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Revised: 09/09/2016] [Accepted: 09/09/2016] [Indexed: 02/06/2023] Open
Abstract
An association between hepatitis C virus infection and neuropsychiatric symptoms has been proposed for some years. A variety of studies have been undertaken to assess the nature and severity of these symptoms, which range from fatigue and depression to defects in attention and verbal reasoning. There is evidence of mild neurocognitive impairment in some patients with HCV infection, which is not fully attributable to liver dysfunction or psychosocial factors. Further evidence of a biological cerebral effect has arisen from studies using magnetic resonance spectroscopy; metabolic abnormalities correlate with cognitive dysfunction and resemble the patterns of neuroinflammation that have been described in HIV infection. Recent research has suggested that, in common with HIV infection, HCV may cross the blood brain barrier leading to neuroinflammation. Brain microvascular endothelial cells, astrocytes and microglia may be minor replication sites for HCV. Importantly, patient reported outcomes improve following successful antiviral therapy. Further research is required to elucidate the molecular basis for HCV entry and replication in the brain, and to clarify implications and recommendations for treatment.
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Affiliation(s)
- Lydia Yarlott
- Department of Gastroenterology and Hepatology, St George's University Hospitals NHS Foundation Trust, Blackshaw Rd, London SW17 0QT, United Kingdom
| | - Eleanor Heald
- Department of Gastroenterology and Hepatology, St George's University Hospitals NHS Foundation Trust, Blackshaw Rd, London SW17 0QT, United Kingdom
| | - Daniel Forton
- Department of Gastroenterology and Hepatology, St George's University Hospitals NHS Foundation Trust, Blackshaw Rd, London SW17 0QT, United Kingdom; St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom
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16
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Hjerrild S, Renvillard SG, Leutscher P, Sørensen LH, Østergaard L, Eskildsen SF, Videbech P. Reduced cerebral cortical thickness in Non-cirrhotic patients with hepatitis C. Metab Brain Dis 2016; 31:311-9. [PMID: 26530221 DOI: 10.1007/s11011-015-9752-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 10/21/2015] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) infection is associated with fatigue, depression, and cognitive impairment even in the absence of severe liver fibrosis or cirrhosis. HCV has been hypothesised to cause neurodegenerative changes through low-grade neuroinflammation. Our aim was to examine whether cortical thickness (CTh) differs between chronic HCV patients and healthy controls, suggestive of cortical atrophy. In this case-control study 43 HCV patients without severe liver fibrosis, substance abuse, or comorbid HIV or hepatitis B virus infection, and 43 age and sex matched controls underwent MRI. Cortical thickness was measured using a surface based approach. Participants underwent semi-structured psychiatric interview and fatigue was assessed using the fatigue severity scale. HCV was associated with higher fatigue scores, and 58 % of HCV patients suffered from significant fatigue (p < 0.0001). Depression was observed in 16 % of patients. Areas of significantly reduced CTh were found in both left and right occipital cortex and in the left frontal lobe after correction for multiple comparisons (p < 0.05). No association between fatigue, former substance abuse, or psychotropic medication and CTh was found. No overall difference in cerebral white and grey matter volume was found. The findings support the hypothesis that HCV is associated with neurodegenerative changes.
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Affiliation(s)
- Simon Hjerrild
- Department for Affective Disorders, Aarhus University Hospital, Skovagervej 2, 8240, Risskov, Denmark.
- Center of Functionally Integrative Neuroscience (CFIN), Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - Signe Groth Renvillard
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
- Department for Affective Disorders, Aarhus University Hospital, Skovagervej 2, 8240, Risskov, Denmark
| | - Peter Leutscher
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
| | | | - Leif Østergaard
- Center of Functionally Integrative Neuroscience (CFIN), Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Simon Fristed Eskildsen
- Center of Functionally Integrative Neuroscience (CFIN), Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Poul Videbech
- Department for Affective Disorders, Aarhus University Hospital, Skovagervej 2, 8240, Risskov, Denmark
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17
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Jiang DZ, Zhong Y, Zhou DY, Wu WQ, Wu GY, Quan H. Application of brain multi-b-value diffusion-weighted imaging (DWI) in adolescent orphans from AIDS families. Br J Radiol 2016; 89:20150732. [PMID: 26892165 DOI: 10.1259/bjr.20150732] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVE To evaluate the application value of multi-b-value diffusion-weighted imaging (DWI) with mono-exponential model and stretched-exponential model in the diagnosis of HIV-positive patients. METHODS Multi-b-value (0, 50, 150, 200, 400, 600, 800 s mm(-2)) DWI was performed in 23 adolescent orphans from AIDS families, including 15 HIV-positive subjects and 8 HIV-negative healthy subjects. Apparent diffusion coefficient (ADC) values were fitted by mono-exponential model; distribution diffusion coefficient (DDC) values and heterogeneity index (α) values were fitted by stretched-exponential model in bilateral basal ganglia, then non-parametric tests were performed. RESULTS The signal intensity attenuation in multi-b-value DWI could be well described by both mono-exponential model and stretched-exponential model. In the left basal ganglia, mean α-values in HIV-positive subjects (α = 0.848 ± 0.068) were significantly lower than that in healthy subjects (α = 0.923 ± 0.050, p = 0.013). There was no statistical difference of α-values between HIV-positive subjects and healthy control subjects in the right basal ganglia. Apart from these, there were also no statistical differences of DDC values or ADC values between two groups in bilateral basal ganglia (all p > 0.05). In bilateral basal ganglia, DDC values were positively correlated with ADC values in HIV-positive patients (right basal ganglia: r = 0.832, p = 0.000; left basal ganglia: r = 0.770, p = 0.001) as well as in healthy cases (right basal ganglia: r = 0.927, p = 0.001; left basal ganglia: r = 0.878, p = 0.004). Receiver operating characteristic (ROC) curve analysis yielded area under the ROC curve (Az) values of 0.817 (p = 0.014 < 0.05) in the left basal ganglia. The sensitivity and specificity were 62.5% and 86.7%, respectively. CONCLUSION Through the study of asymptomatic HIV-positive subjects when b < 1000 s mm(-2), we can see stretched-exponential model DWI can provide more information than mono-exponential model DWI. ADVANCES IN KNOWLEDGE Multi-b-value DWI was performed in subjects with HIV. DWI measurements could be neuroimaging biomarkers of cerebral injury in the course of HIV infection.
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Affiliation(s)
- Da-Zhen Jiang
- 1 Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, China
| | - Yang Zhong
- 1 Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, China
| | - Ding-Yi Zhou
- 1 Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, China
| | - Wei-Qing Wu
- 1 Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, China
| | - Guang-Yao Wu
- 2 Medical Imaging Department of the Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Hong Quan
- 1 Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, China
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18
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Monaco S, Mariotto S, Ferrari S, Calabrese M, Zanusso G, Gajofatto A, Sansonno D, Dammacco F. Hepatitis C virus-associated neurocognitive and neuropsychiatric disorders: Advances in 2015. World J Gastroenterol 2015; 21:11974-11983. [PMID: 26576086 PMCID: PMC4641119 DOI: 10.3748/wjg.v21.i42.11974] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 09/11/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Since its identification in 1989, hepatitis C virus (HCV) has emerged as a worldwide health problem with roughly 185 million chronic infections, representing individuals at high risk of developing cirrhosis and liver cancer. In addition to being a frequent cause of morbidity and mortality due to liver disease, HCV has emerged as an important trigger of lymphoproliferative disorders, owing to its lymphotropism, and of a wide spectrum of extra-hepatic manifestations (HCV-EHMs) affecting different organ systems. The most frequently observed HCV-EHMs include mixed cryoglobulinemia and cryoglobulinemic vasculitis, B-cell non-Hodgkin’s lymphoma, nephropathies, thyreopathies, type 2 diabetes mellitus, cardiovascular diseases, and several neurological conditions. In addition, neuropsychiatric disorders and neurocognitive dysfunction are reported in nearly 50% of patients with chronic HCV infection, which are independent of the severity of liver disease or HCV replication rates. Fatigue, sleep disturbance, depression and reduced quality of life are commonly associated with neurocognitive alterations in patients with non-cirrhotic chronic HCV infection, regardless of the stage of liver fibrosis and the infecting genotype. These manifestations, which are the topic of this review, typically occur in the absence of structural brain damage or signal abnormalities on conventional brain magnetic resonance imaging (MRI), although metabolic and microstructural changes can be detected by in vivo proton magnetic resonance spectroscopy, perfusion-weighted and diffusion tensor MRI, and neurophysiological tests of cognitive processing. Several lines of evidence, including comparative and longitudinal neuropsychological assessments in patients achieving spontaneous or treatment-induced viral clearance, support a major pathogenic role for HCV in neuropsychiatric and neurocognitive disorders.
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19
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Su YY, Yang GF, Lu GM, Wu S, Zhang LJ. PET and MR imaging of neuroinflammation in hepatic encephalopathy. Metab Brain Dis 2015; 30:31-45. [PMID: 25514861 DOI: 10.1007/s11011-014-9633-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Accepted: 11/17/2014] [Indexed: 12/11/2022]
Abstract
Neurological or psychiatric abnormalities associated with hepatic encephalopathy (HE) range from subclinical findings to coma. HE is commonly accompanied with the accumulation of toxic substances in bloodstream. The toxicity effect of hyperammonemia on astrocyte, such as the alteration in neurotransmission, oxidative stress, astrocyte swelling, is considered as an important factor in the pathogenesis of HE. Besides, neuroinflammation has captured more attention in the process of HE, but the mechanism of neuroinflammation leading to HE remains unclear. Molecular imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) targeting activated microglia and/ or other mediators appear to be promising noninvasive approaches to assess HE. This review focuses on novel imaging and therapy strategies of neuroinflammation in HE.
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Affiliation(s)
- Yun Yan Su
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, 210002, China
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