Spinal cord hypometabolism associated with infection by human T-cell lymphotropic virus type 1(HTLV-1).

BACKGROUND: HTLV-1 infection is endemic in Brazil. About 1 to 2% of the Brazilian population is estimated to be infected, but most infected HTLV-1 individuals do not know about their own infection, which favors the continuity of sexual and vertical virus transmission. In addition, HTLV-1 associated central nervous system diseases and their pathophysiologic mechanisms are not fully understood. This study aimed to evaluate the correlation of spinal cord metabolism, viral and inflammatory profiles with features of neurological presentation in HTLV-1 infected individuals. METHODOLOGY: This is a cross-sectional study of a cohort including 48 HTLV-1 infected individuals clinically classified as asymptomatic-AG (N = 21), symptomatic-SG (N = 11) and HAM/TSP-HG (N = 16) and a nested case-control study with HTLV-1 infected individuals-HIG (N = 48) and HTLV-1 non infected controls-CG (N = 30) that had their spinal cord analysed by Positron Emission Tomography with 18F-Fluordeoxyglucose (18F-FDG PET/CT). HTLV-1 infected individuals had 18F-FDG PET/CT results analyzed with clinical and demographic data, proviral load, cytokines and chemokines in the blood and cerebrospinal fluid (CSF). PRINCIPAL FINDINGS: 18F-FDG PET/CT showed hypometabolism in the thoracic spinal cord in HTLV-1 infected individuals. The method had an accuracy of 94.4% to identify HAM/TSP. A greater involvement of the thoracic spinal cord was observed, although hypometabolism was also observed in the cervical spinal cord segment in HTLV-1 infected individuals. Individuals with HAM/TSP showed a pro-inflammatory profile in comparison to asymptomatic and symptomatic groups, with a higher level of Interferon-inducible T-cell alpha chemoattractant (ITAC/CXCL11), IL-6, IL-12p70 in the plasma; and ITAC, IL-4, IL-5, IL-8 (CXCL8) and TNF-alpha in the CSF. Using regression, thoracic spinal cord SUV (standardized uptake value) and CSF ITAC level were identified as the HAM/TSP predictors in the multivariate model. CONCLUSIONS: 18F-FDG PET/CT imaging showed spinal cord hypometabolism in most HTLV-1 infected individuals, even in the asymptomatic HTLV-1 group. Thoracic spinal cord hypometabolism and CSF-ITAC levels were identified predictors of HAM/TSP. SIGNIFICANCE: Our findings suggested that in most HTLV-1 infected individuals there was compromise of central nervous system (CNS) structures despite of the lack of clinical symptoms. To explain the found hypometabolism, the role of microcirculatory and metabolic factors in the pathogenesis of neurological diseases associated with HTLV-1 infection must be further investigated. It is paramount to evaluate the central nervous function and to compare the performance among HTLV-1 infected individuals considered asymptomatic to the uninfected controls.

Plasma and cerebrospinal fluid levels of cytokines as disease markers of neurologic manifestation in long-term HTLV-1 infected individuals.

AIM: The aim of this study is to evaluate the presence of a particular immunological profile in individuals long-term infected with HTLV-1, followed presenting different clinical courses. MATERIALS & METHODS: Forty-eight individuals were evaluated for 19 cytokines analyzed in cerebrospinal fluid and plasma of patients with HTLV-1 presenting with and without neurological symptoms. RESULTS: Proinflammatory cytokines and the chemokine ligand 11 (ITAC/CXCL11) were increased in individuals with HTLV-1 coursing with neurological symptoms. CONCLUSION: Different cytokines' expression profile in the presence of neurological symptoms may help to understand and characterize the progression for severe clinical presentations.

Brain Metabolism Changes in Patients Infected with HTLV-1.

The Human T-cell leukemia virus type-I (HTLV-1) is the causal agent of HTLV-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HAM/TSP is the result of demyelination and cell death in the spinal cord and disruption of the blood-brain barrier (BBB), mediated by a virus-induced inflammatory response. In this study, we applied Positron Emission Tomography with 18F-fluordeoxyglucose (18F-FDG PET) to evaluate brain metabolism in a group of 47 patients infected with HTLV-1, and 18 healthy controls. Patients were divided into three groups according to their neurological symptoms. A machine learning (ML) based Gaussian Processes classification algorithm (GPC) was applied to classify between patient groups and controls and also to organize the three patient groups, based on gray and white matter brain metabolism. We found that GPC was able to differentiate the HAM/TSP group from controls with 85% accuracy (p = 0.003) and the asymptomatic seropositive patients from controls with 85.7% accuracy (p = 0.001). The weight map suggests diffuse cortical hypometabolism in both patient groups when compared to controls. We also found that the GPC could separate the asymptomatic HTLV-1 patients from the HAM/TSP patients, but with a lower accuracy (72.7%, p = 0.026). The weight map suggests a diffuse pattern of lower metabolism in the asymptomatic group when compared to the HAM/TSP group. These results are compatible with distinctive patterns of glucose uptake into the brain of HTLV-1 patients, including those without neurological symptoms, which differentiate them from controls. Furthermore, our results might unveil surprising aspects of the pathophysiology of HAM/TSP and related diseases, as well as new therapeutic strategies.