Evolution of erectile dysfunction in individuals infected with human T-lymphotropic virus 1: a prospective cohort study.

BACKGROUND: Virtually all patients with human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) have some degree of erectile dysfunction (ED), but ED is also found in a large percentage of HTLV-1 carriers. AIM: To evaluate the evolution of ED in individuals infected with HTLV-1 who were followed for up to 15 years. METHODS: This prospective cohort study included men infected with HTLV-1 who had ED, were aged 18 to 70 years, and were followed from January 2004 to December 2019. We used the International Index of Erectile Function-5 (IIEF-5), the Expanded Disability Status Scale and Osame Motor Disability Scale, and the Overactive Bladder Symptom Score (OABSS) to define and stratify ED, neurologic disability, and bladder dysfunction, respectively. OUTCOMES: Time to development of severe ED was the main outcome. RESULTS: We studied 90 men with ED (mean ± SD age, 52.8 ± 9.78 years). At baseline, 42 were carriers, 16 had probable HAM/TSP, and 32 had definite HAM/TSP. IIEF-5 was highest among carriers and lowest in patients with definite HAM/TSP, whereas OABSS was lowest in carriers and highest in patients with definite HAM/TSP. Median (IQR) follow-up was 8.50 years (3.00-12.00). IIEF-5 fell significantly from baseline to last follow-up among carriers and patients with probable and definite HAM/TSP. There was an inverse correlation between the IIEF-5 and the OABSS at last follow-up (r = -0.62, P < .001). In survival analysis, the time to development of severe ED was significantly shorter in patients with definite HAM/TSP when compared with carriers (P = .001) and those with probable HAM/TSP (P = .014). The presence of definite HAM/TSP at baseline was independently associated with the development of severe ED, after adjustment for baseline age and proviral load (hazard ratio, 6.74; P = .008). CLINICAL IMPLICATIONS: Formal assessment of erectile function should be part of the routine clinical assessment of individuals infected with HTLV-1; worsening erectile function should alert clinicians to the possibility of neurologic deterioration. STRENGTHS AND LIMITATIONS: This is the first prospective cohort study to describe the course of ED in men infected with HTLV-1. The small sample size and absence of seronegative controls are limitations. CONCLUSION: ED is a slowly progressive clinical manifestation of HTLV-1 infection, and the degree of neurologic compromise at baseline is the main predictor of time to progression to severe ED.

Diffusion tensor imaging metrics in diagnosis of HTLV-1-associated myelopathy.

OBJECTIVE: In the diagnosis of HTLV-1-associated myelopathy (HAM), while magnetic resonance imaging (MRI) is essential to exclude other diseases, its power is limited regarding HAM diagnosis, as only 30% of affected patients present with spinal cord atrophy. Diffusion tensor imaging (DTI) may enable the detection of damage in the white matter microstructure. Here, we quantitatively assess spinal cord damage using DTI and evaluate conventional MRI parameters of the spinal cord in HTLV-1-infected individuals. METHODS: This cross-sectional study involved 33 HTLV-1 carriers, 28 patients with definite-HAM, and 11 seronegative healthy subjects (HS). Region-of-interest (ROI)-based fractional anisotropy (FA) and mean diffusivity (MD) measurements were performed in the upper thoracic and lumbar regions of the spinal cord. Thoracic index was defined as 1/ (anteroposterior diameter × transverse diameter) measured at the fifth 5th vertebral level. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cutoff FA, MD, and thoracic index values. RESULTS: Spinal cord atrophy was observed in 15 (53.6%) patients with definite-HAM. The area under the ROC curve in the thoracic spinal cord was 0.824 (95% CI, 0.716-0.932), 0.839 (95% CI: 0.736-0.942), and 0.838 (95% CI: 0.728-0.949) for FA, MD, and the thoracic index, respectively. Lower FA and higher MD values were observed in the definite-HAM group compared to HTLV-1 carriers and HS at the T5 vertebral level (p < 0.01). INTERPRETATION: Complementary to conventional MRI, DTI analysis of the spinal cord and thoracic index determination can offer additional insight that may prove useful in the diagnosis of HAM.

Neurologic, clinical, and immunologic features in a cohort of HTLV-1 carriers with high proviral loads.

A high proviral load (PVL) is recognized as a risk factor for human T cell leukemia virus-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but there is a lack of prospective studies evaluating whether or not HTLV-1 carriers with high PVL are at risk of developing HAM/TSP or other HTLV-1-related diseases. Here, we compare the incidence of clinical manifestations and the cytokine levels in 30 HTLV-1 carriers with high (> 50,000 copies/106 PBMC) and an equal number of subjects with low proviral load. Participants were followed for 3 to 16 years (median of 11 years). The PVL, IFN-γ, TNF, and IL-10 levels were quantified at entry and at the end of the follow-up. Among the self-reported symptoms in the initial evaluation, only the presence of paresthesia on the hands was more frequent in the group with high PVL (p < 0.04). The production of IFN-γ was higher in the group with high PVL group (median of 1308 versus 686 pg/ml, p < 0.011) when compared with the control group in the first assessment. There was no difference in the occurrence of urinary symptoms or erectile dysfunction, periodontal disease, Sicca syndrome, and neurologic signs between the two groups during the follow-up. The observation that none of the HTLV-1 carriers with high PVL and with exaggerated inflammatory response progressed to HAM/TSP indicates that other factors in addition to the PVL and an exaggerated immune response are involved in the pathogenesis of HAM/TSP.