Schütze Manuel, Romanelli Luiz C F, Rosa Daniela V, Carneiro-Proietti Anna B F, Nicolato Rodrigo, Romano-Silva Marco A, Brammer Michael, de Miranda Débora M
Faculdade de Medicina, Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, Universidade Federal de Minas Gerais Belo Horizonte, Brazil.
Faculdade de Medicina, Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, Universidade Federal de Minas GeraisBelo Horizonte, Brazil; Fundação HemominasBelo Horizonte, Brazil; Grupo Interdisciplinar de Pesquisas em HTLV - GIPHBelo Horizonte, Brazil.
Front Mol Neurosci. 2017 Feb 28;10:52. doi: 10.3389/fnmol.2017.00052. eCollection 2017.
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 ( = 0.003) and the asymptomatic seropositive patients from controls with 85.7% accuracy ( = 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%, = 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.
人类I型T细胞白血病病毒（HTLV-1）是HTLV相关脊髓病/热带痉挛性截瘫（HAM/TSP）的病原体。HAM/TSP是由病毒诱导的炎症反应介导的脊髓脱髓鞘、细胞死亡以及血脑屏障（BBB）破坏的结果。在本研究中，我们应用18F-氟脱氧葡萄糖正电子发射断层扫描（18F-FDG PET）来评估47例HTLV-1感染患者和18名健康对照者的脑代谢情况。根据神经症状将患者分为三组。应用基于机器学习（ML）的高斯过程分类算法（GPC）对患者组和对照组进行分类，并根据脑灰质和白质代谢情况对三个患者组进行分类。我们发现GPC能够以85%的准确率（P = 0.003）将HAM/TSP组与对照组区分开来，以85.7%的准确率（P = 0.001）将无症状血清阳性患者与对照组区分开来。权重图显示，与对照组相比，两个患者组均存在弥漫性皮质代谢减低。我们还发现GPC能够将无症状HTLV-1患者与HAM/TSP患者区分开来，但准确率较低（72.7%，P = 0.026）。权重图显示，与HAM/TSP组相比，无症状组存在弥漫性代谢减低模式。这些结果与HTLV-1患者大脑中独特的葡萄糖摄取模式相符，包括那些没有神经症状的患者，这使他们与对照组有所区别。此外，我们的结果可能揭示HAM/TSP及相关疾病病理生理学中令人惊讶的方面，以及新的治疗策略。
