Hypothesis / aims of study
The Human T Cell Lymphotropic Virus Type 1 (HTLV-1) is the causal agent of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infects 10 - 20 million people around the world. Urinary manifestation mainly of overactive bladder are documented in all patients with HAM/TSP and is the main complain of patients with probable HAM/TSP. It is well known that damage of the neurological system may cause urinary symptoms. However, few studies have characterized the type of urologic dysfunction in HTLV-1 infected subjects , the clinical course of the urological disease and the relationship between these symptoms with inflammatory cytokines and proviral load. Inflammatory cytokines are more expressed in HAM/TSP group and in patients infected by HTLV-1 presenting erectile dysfunction compared with HTLV-1 carriers and in patients with overactive bladder, its not clear if inflammatory cytokines and proviral load represent predictors of vesical or neurological disease dysfunction(1,2). The aim of this study is to analyze the clinical evolution of vesical dysfunction associated with HTLV-1 infection and it’s relationship with inflammatory cytokines and proviral load. We also aim to investigate if vesical dysfunction represent a predictor of neurological disease progression.
Study design, materials and methods
A total of 175 HTLV-1 infected subjects with urinary dysfunction were followed up in a prospective cohort study since April 2011 till November 2018, in an outpatient facility. The diagnosis of HTLV-1 infection was made by ELISA and confirmed with Western Blot. The patients were stratified in two groups: probable HAM/TSP and definite HAM/TSP. They were evaluated by the overactive bladder symptoms score (OABSS), bladder diary, laboratorial tests every 6 months, by echography annually and by at least two urodynamic studies over the cohort. All patients had anticholinergic drugs prescribed. The progression of the disease was defined by a composite model composed by the following criteria: need for additional non-conservative treatment (physiotherapy, onabotulinum toxin), loss of vesical complacency (<20cmH2O/mL), increase in more than 30% in OABSS, persistence of OABSS > 10 one year to another, presence of ureterohydronephrosis and the need for self-intermittent catheterization or permanent catheter (Foley) to promote bladder emptying. Survival analysis was performed to estimate time to anticholinergic and non conservative treatment (physiotherapy or surgery), time to CIC and to disease progression. Binary logistic regression was performed to investigate if OABSS could be a predictor of neurologic disease progression, characterized by 01 point increase in Osame´s Motor Disability Scale (OMDS).
This cohort study included 175 HTLV-1 infected patients with urinary complaints were analyzed. Of these patients, 85 patients initially had definite HAM/TSP. The mean of the age of the patients was 51.4 + 11.9 years in probable HAM/TSP group and 51.2 + 12.9 years in definite HAM/TSP group (P>0,05). Gender, scholarship, marital status and length of follow up were not statistically different between the two groups. The main urodynamic finding was detrusor hyperactivity (63.9% in probable HAM/TSP group versus 74.1% in definite HAM/TSP group, P>0.05). After a mean follow-up of 5 years, there was a significant reduction in urgency episodes and an increase in daytime voiding, while nocturia episodes and OABSS did not vary statistically significant. The frequency of clean self-intermittent catheterization to promote bladder emptying remained stable (5%) in probable HAM/TSP group, but increased from 34% to 49% over the cohort period in the definite HAM/TSP group. Regarding progression of urinary dysfunction, 40.7% of the patients in both groups had the urologic disease progressed as defined by the composite model. In a regression model, proviral load and inflammatory cytokines were not associated with urologic disease progression. During the cohort, we observed that 12/90 (13,3%) patients in probable HAM/TSP group increased in 01 point in the OMDS. In binary logistic regression, OABSS in 3 periods of cohort could not predict the progression of neurological status (P>0.05). In survival analyses, the median time to anticholinergic treatment was 4.0 years (IQ = 2 – 8.5 years) in probable HAM/TSP group versus 2.0 years (IQ = 1.0 – 6.5). The median time to physiotherapy or any surgery was 3.0 years (IQ = 1.5 – 3.5) and 3.0 (IQ = 2.0 – 6.0), to require CIC was 4.5 (IQ = 4.0 – 6.75) and 4.0 years (IQ = 2.0 – 6.0), and to disease progression was 3.0 years (IQ = 2.0 – 4.25) and 3.0 (IQ = 2.0 – 4.0), respectively in probable HAM/TSP and definite HAM/TSP group.
Interpretation of results
The majority of the patients presenting vesical dysfunction did not developed neurological disease over the cohort period. In addition, inflammatory cytokines and pro viral load was not considered predictors of vesical dysfunctions. These findings may reflect that vesical dysfunction may represent an isolated form of the HTLV-1 infection syndrome, clarifying that the infection mays develop 3 pathways: asymptomatic, vesical dysfunction (storage or voiding symptoms), previously considered probable HAM/TSP, and definite HAM/TSP.