RESUMEN
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.
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Personas con Discapacidad , Disfunción Eréctil , Virus Linfotrópico T Tipo 1 Humano , Trastornos Motores , Paraparesia Espástica Tropical , Masculino , Humanos , Adulto , Persona de Mediana Edad , Disfunción Eréctil/complicaciones , Estudios ProspectivosRESUMEN
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.
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Imagen de Difusión Tensora , Paraparesia Espástica Tropical , Atrofia , Benchmarking , Estudios Transversales , Imagen de Difusión Tensora/métodos , HumanosRESUMEN
BACKGROUND: While bladder dysfunction is observed in the majority of patients with human T cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM), it is also observed in patients who do not fulfill all diagnostic criteria for HAM. These patients are classified as having possible or probable HAM/TSP. However, it remains unclear whether the severity and progression of bladder dysfunction occurs similarly between these two groups. OBJECTIVE: Compare the severity and evolution of bladder dysfunction in HTLV-1-infected patients with possible and definite HAM/TSP. METHODS: The present prospective cohort study followed 90 HTLV-1 patients with possible HAM/TSP and 84 with definite HAM/TSP between April 2011 and February 2019. Bladder dysfunction was evaluated by bladder diary, overactive bladder symptoms scores (OABSS) and urodynamic studies. Bladder dysfunction progression was defined as the need for clean self-intermittent catheterization (CIC). RESULTS: At baseline, nocturia, urgency and OABSS scores were worse in definite compared to possible HAM/TSP patients. The main urodynamic finding was detrusor overactivity, present in 77.8% of the patients with definite HAM/TSP versus 58.7% of those with possible HAM/TSP (P = 0.05). Upon study conclusion, the cumulative frequency of patients requiring CIC increased in both groups, from 2 to 6 in possible HAM/TSP and from 28 to 44 in definite HAM/TSP patients. The estimated time to need for CIC was 6.7 years (95%CI 6.5-7.0) in the possible HAM/TSP group compared to 5.5 years (95%CI 4.8-6.1) in the definite HAM/TSP group. CONCLUSIONS: Although both groups showed similarities in bladder dysfunction and tended to progress to requiring CIC over time, patients with possible HAM/TSP presented less severe manifestations at baseline and progressed more slowly than those with definite HAM/TSP.
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Progresión de la Enfermedad , Infecciones por HTLV-I/complicaciones , Paraparesia Espástica Tropical/complicaciones , Enfermedades de la Vejiga Urinaria/complicaciones , Adulto , Estudios de Cohortes , Femenino , Virus Linfotrópico T Tipo 1 Humano , Humanos , Cateterismo Uretral Intermitente/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , UrodinámicaRESUMEN
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.
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Portador Sano/inmunología , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Leucocitos Mononucleares/inmunología , Provirus/inmunología , Adulto , Anciano , Portador Sano/diagnóstico , Portador Sano/virología , Disfunción Eréctil/diagnóstico , Disfunción Eréctil/genética , Disfunción Eréctil/inmunología , Disfunción Eréctil/virología , Femenino , Expresión Génica , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-I/genética , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/crecimiento & desarrollo , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-10/genética , Interleucina-10/inmunología , Leucocitos Mononucleares/virología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Nocturia/diagnóstico , Nocturia/genética , Nocturia/inmunología , Nocturia/virología , Provirus/crecimiento & desarrollo , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/genética , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/virología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Carga Viral/inmunologíaRESUMEN
INTRODUCTION: Erectile dysfunction (ED) is associated with neurological damage due to human T-lymphotropic virus 1 (HTLV-1) infection, but hormonal and psychogenic factors also cause ED. AIM: To evaluate the association of psychogenic and hormonal factors with ED in men infected with HTLV-1. METHODS: In this cross-sectional study, we compared total testosterone, follicle stimulating hormone, luteinizing hormone, prolactin, anxiety symptoms, depressive symptoms, and neurologic manifestations in HTLV-1-infected men with or without ED. The International Index of Erectile Function was used to determine the degree of ED. Participants were grouped according to Osame's Motor Disability Scale and the Expanded Disability Status Scale: HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP), probable HAM/TSP, or HTLV-1 carrier. Chi-square and Fisher's exact tests were used to compare the groups, and regression analyses were used to show predictors of ED. MAIN OUTCOME MEASURE: Sexual hormonal levels, psychogenic factors, and neurologic disabilities were found to be associated with ED. RESULTS: ED was associated with age older than 60 years (P < .001), degree of neurologic involvement (P < .001), depression (P = .009), and anxiety (P = .008). In the multivariate analyses, only age and degree of neurological injury remained as risk factors for ED. CLINICAL IMPLICATIONS: Neurological manifestations are a stronger predictor of ED than hormonal and psychogenic factors in HTLV-1-infected men. STRENGTHS & LIMITATIONS: The statistical power of the study was limited due to the low number of participants, but neurologic manifestations were clearly associated with ED. There was no strong association between hormonal and psychogenic factors and ED. CONCLUSION: Hormonal and psychogenic factors did not show a strong association with ED in individuals with HTLV-1, but neurological manifestations were strongly associated with ED in these individuals. de Oliveira CJV, Neto, JAC, Andrade RCP, et al. Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV-1. J Sex Med 2019; 16:1763-1768.
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Disfunción Eréctil/epidemiología , Infecciones por HTLV-I/complicaciones , Conducta Sexual , Adulto , Estudios Transversales , Depresión/epidemiología , Personas con Discapacidad , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Trastornos Motores/epidemiología , Paraparesia Espástica Tropical/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Erectile dysfunction (ED) occurs in more than 50% of patients with human T-cell lymphotropic virus type 1 (HTLV-1) infection. In the general population, atherosclerosis is the main risk factor related to ED. AIM: To compare the contribution of neurologic disorders from HTLV-1 with that of atherosclerosis as risk factors for ED in men with HTLV-1. METHODS: In this cross-sectional study, men 18 to 70 years old with HTLV-1 were classified into one of two groups according to the presence or absence of ED. They were compared for obesity, waist circumference, dyslipidemia, metabolic syndrome, diabetes mellitus, high blood pressure, and neurologic manifestations. Comparisons between proportions were performed using the χ2 or Fisher exact test. Logistic regression analysis was performed to identify predictors of ED. Subjects with HTLV-1 were classified into three groups based on Osame's Disability Motor Scale and the Expanded Disability Status Scale: (i) HTLV-1 carriers; (ii) probable HTLV-1-associated myelopathy or tropical spastic paraparesis; and (iii) definitive HTLV-1-associated myelopathy or tropical spastic paraparesis. The International Index of Erectile Function was used to determine the degree of ED. RESULTS: In univariate logistic regression, age older 60 years (P = .003), diabetes mellitus (P = .042), and neurologic disease (P < .001) were associated with ED. In the multivariate model, the odds of ED was highest in patients with neurologic disease (odds ratio = 22.1, 95% CI = 5.3-92.3), followed by high blood pressure (odds ratio = 6.3, 95% CI = 1.4-30.5) and age older than 60 years (odds ratio = 4.6, 95% CI = 1.3-17.3). CLINICAL IMPLICATIONS: In men infected with HTLV-1, neurologic dysfunction is a stronger predictor of ED than risk factors for atherosclerosis. STRENGTHS AND LIMITATIONS: The small number of patients limited the power of the statistical analysis, but clearly neurologic manifestations had a greater association with ED than risk factors for atherosclerosis, and there was no association between metabolic syndrome and severity of ED. CONCLUSION: Neurologic impairment is the major cause of ED in individuals infected with HTLV-1 and risk factors for atherosclerosis did not have a strong relation with ED in this population. de Oliveira CJV, Neto JAC, Andrade RCP, et al. Risk Factors for Erectile Dysfunction in Men With HTLV-1. J Sex Med 2017;14:1195-1200.
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Disfunción Eréctil/virología , Infecciones por HTLV-I/complicaciones , Virus Linfotrópico T Tipo 1 Humano , Adulto , Anciano , Estudios Transversales , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Obesidad/complicaciones , Oportunidad Relativa , Factores de Riesgo , Circunferencia de la Cintura , Adulto JovenRESUMEN
Urinary symptoms occur in 19% of human T-cell lymphotropic virus type 1 (HTLV-1)-infected patients who do not fulfill criteria for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and in almost 100% of HAM/TSP patients. Few studies have evaluated therapies for overactive bladder (OAB) caused by HTLV-1 infection. This case report describes the effect of onabotulinum toxin A on the urinary manifestations of three patients with HAM/TSP and OAB symptoms. The patients were intravesically administered 200 units of Botox®. Their incontinence episodes improved, and their OAB symptoms scores (OABSS) reduced significantly. These data indicate that Botox® should be a treatment option for OAB associated with HTLV-1 infection.
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Inhibidores de la Liberación de Acetilcolina/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Paraparesia Espástica Tropical/complicaciones , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/virología , Adulto JovenRESUMEN
Urinary symptoms occur in 19% of human T-cell lymphotropic virus type 1 (HTLV-1)-infected patients who do not fulfill criteria for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and in almost 100% of HAM/TSP patients. Few studies have evaluated therapies for overactive bladder (OAB) caused by HTLV-1 infection. This case report describes the effect of onabotulinum toxin A on the urinary manifestations of three patients with HAM/TSP and OAB symptoms. The patients were intravesically administered 200 units of Botox®. Their incontinence episodes improved, and their OAB symptoms scores (OABSS) reduced significantly. These data indicate that Botox® should be a treatment option for OAB associated with HTLV-1 infection.