Evidence of Brain Inflammation in Patients with Human T-Lymphotropic Virus Type 1–Associated Myelopathy (HAM): A Pilot, Multimodal Imaging Study Using ¹¹C-PBR28 PET, MR T1-Weighted, and Diffusion-Weighted Imaging

Abstract

HTLV-1-associated myelopathy (HAM; HTLV-1 is human T-lymphotropic virus type 1) is a chronic debilitating neuroinflammatory disease with a predilection for the thoracic cord. Tissue damage is attributed to the cellular immune response to HTLV-1-infected lymphocytes. The brains of HTLV-1-infected patients, with and without HAM but no clinical evidence of brain involvement, were examined using a specific 18-kDa translocator protein ligand, 11 C-PBR28, and T1-weighted and diffusion-weighted MRI. Methods: Five subjects with HAM and 2 HTLV-1 asymptomatic carriers were studied. All underwent clinical neurologic assessment including cognitive function and objective measures of gait, quantification of HTLV-1 proviral load in peripheral blood mononuclear cells, and human leukocyte antigenantigen D related expression on circulating CD81 lymphocytes. 11 C-PBR28 PET and MRI were performed on the same day. 11 C-PBR28 PET total volume of distribution and distribution volume ratio (DVR) were estimated using 2-tissue-compartment modeling. MRI data were processed using tools from the FMRIB Software Library to estimate mean diffusivity (MD) and gray matter (GM) fraction changes. The results were compared with data from age-matched healthy volunteers. Results: Across the whole brain, the total volume of distribution for the subjects with HAM (5.44 ± 0.84) was significantly greater than that of asymptomatic carriers (3.44 ± 0.80). The DVR of the thalamus in patients with severe and moderate HAM was higher than that in the healthy volunteers, suggesting increased translocator protein binding (z . 4.72). Subjects with more severe myelopathy and with high DR expression on CD81 lymphocytes had increased DVR and MD (near-significant correlation found for the right thalamus MD: P 5 0.06). On the T1-weighted MRI scans, the GM fraction of the brain stem was reduced in all HTLV-1-infected patients compared with controls (P , 0.001), whereas the thalamus GM fraction was decreased in patients with HAM and correlated with the disease severity. There was no correlation between neurocognitive function and these markers of central nervous system inflammation. Conclusion: This pilot study suggests that some patients with HAM have asymptomatic inflammation in the brain, which can be detected and monitored by 11 C-PBR28 PET together with structural and diffusion-weighted MRI.

Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [11C]PBR28 study

“…There is currently no universal consensus on the optimum analytical approaches for estimation of microglial activation using TSPO tracers (Bloomfield et al, 2016a; Narendran and Frankle, 2016; Turkheimer et al, 2015b). DVR as an outcome measure has been validated in animals, where inflammatory stimuli increase DVRs and microglial markers (Converse et al, 2011; Imaizumi et al, 2007) and also in other human studies using [ 11 C]PBR28 (Dimber et al, 2016; Lyoo et al, 2015) and [ 11 C]-(R)-PK11195 (Rissanen et al, 2014). V T is generally accepted to be the preferred outcome measure in the absence of a clear reference region.…”

Immunopathogenesis and Cellular Interactions in Human T-Cell Leukemia Virus Type 1 Associated Myelopathy/Tropical Spastic Paraparesis

“…Lesions are primarily located in white matter of lower thoracic cord of the patients and infiltrating cells mainly comprise T-cells (Iwasaki, 1993;Wu et al, 1993;Matsuoka et al, 1998), where viral and cellular interactions result in spinal manifestations of HAM/TSP. Evidence of neurodegeneration and metabolic changes also exists in brains of both ACs and to a greater extent in HAM/TSP patients (Dimber et al, 2016;Schütze et al, 2017). The inflammation in brain is accompanied by global cognitive impairment and executive dysfunction in HAM/TSP patients (Champs et al, 2019).…”

Lombalgia em portadores de paraparesia espástica tropical/mielopatia associada ao HTLV 1

“…Um sintoma clínico associado à Paraparesia Espástica Tropical/ Mielopatia Associada ao Vírus Linfotrópico de Células T Humanas tipo 1 (PET/MAH) é a dor lombar, sendo uma queixa recorrente e que faz parte do critério diagnóstico da Organização Mundial da Saúde (OMS) para esta doença 3,4 . A freqüência desse sintoma varia de 44% a 79% e está relacionada a um maior tempo de evolução da doença, baixo nível funcional e um alto grau de incapacidade.…”