Cognitive impairment in HTLV-1-associated myelopathy, proviral load and inflammatory markers

Abstract

Objectives: Myelopathy is a well-established long-term clinical manifestation of HTLV-1 infection. Besides motor dysfunction, cognitive impairment may be another consequence of HTLV-1 infection. Moreover, inflammatory markers may be associated with cognitive impairment in these patients. The present study compared the cognitive performance of HAM/TSP patients with healthy controls and investigated the associations between cognitive performance, proviral load and blood inflammatory markers. Methods: Eighty-three patients fulfilling diagnostic criteria for HAM/TSP were submitted to a comprehensive clinical, cognitive and functional evaluation, brain magnetic resonance imaging and determination of levels of IL-1β, IL-6, TNF-α, immunoglobulins and HTLV-1 proviral load in blood and cerebrospinal fluid. The control group was composed of 88 cognitively healthy subjects, matched for age, sex and educational level. Results: Compared to healthy subjects, HAM/TSP patients displayed significant global cognitive impairment and executive function deficits. HAM/TSP cognitive impairment was significantly associated with altered levels of IgM, IgG, IL-6 and TNF-α in blood. There was no association between HAM/TSP cognitive impairment and HTLV-1 proviral load. Conclusions: This study suggests cognitive impairment may be a long-term clinical manifestation of HTLV-1 infection, which seems to be linked to the persistent inflammatory activity that is found in the disease.

Ocular vestibular evoked myogenic potential (VEMP) reveals mesencephalic HTLV-1-associated neurological disease

“…Therefore, although image and immunological data could add information to the present work, the lack of these results does not influence the valuable information that in HTLV-1 infection classified as asymptomatic, the cervical spine can present subclinical alterations, but not the upper CNS. On the contrary, in HAM, abnormal cervical VEMP and ocular VEMP have showed alterations in the spine as well as in the upper CNS, which is in line with the findings of cognitive alterations in HAM [47].…”

Case Report: Cognitive Impairment without Clinical Spinal Disease May Be the First Sign of HTLV-1 Neurological Alteration

“…[1][2][3] Approximately 4% of infected individuals will develop HAM. 4,5 However, subclinical manifestations may precede the diagnosis of HAM and extrapolate its typical medullary symptoms, including otoneurological, [6][7][8] subcortical, and cortical 9,10 impairment.…”

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

“…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). The exact mechanisms of neurodegeneration and myelin loss in CNS are not understood, but three putative mechanisms have been proposed: (1) direct infection of CNS resident cells; (2) bystander damage to resident cells of CNS during chronic inflammation; and (3) Cross-reaction of Abs and molecular mimicry (Figure 4; Olière et al, 2011;Bangham, 2018;Nozuma and Jacobson, 2019).…”

“…It can be hypothesized that Infected lymphocytes could cross the barrier in this manner and express HTLV-1 proteins in CNS parenchyma. The presence of HTLV-1 in CNS induces inflammation and cytokine release by the resident CNS cells and migratory immune cells characterized by increased levels of TNF, IFN-γ, IL-1α, IL-β, and IL-6 in CSF and spinal cords of HAM/TSP patients (Umehara et al, 1994;Banerjee et al, 2007b;Champs et al, 2019). The ensuing recruitment of inflammatory cells from peripheral blood induces a vicious cycle of inflammation which is detrimental to CNS resident cells (Umehara et al, 1993;Furuya et al, 1999;Banerjee et al, 2007b).…”