Néviton Castro

Urinary and sexual manifestations of patients infected by HTLV-I

HTLV-I is considered to be a virus of low morbidity, since the principal diseases associated with this viral infection, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL), are observed in less than 5% of infected individuals. Urinary symptoms are frequent in patients with myelopathy and consist principally of nocturia, frequency, urgency, and urinary incontinence; however, the importance of these dysfunctions and their correlation with myelopathy is still to be fully clarified. This review gives particular emphasis to the high frequency of urinary and sexual complaints not only in patients with myelopathy but also in individuals considered to be HTLV-I carriers. Detrusor overactivity and bladder-sphincter dyssynergia are the most common urodynamic findings. The fact that urinary complaints and urodynamic parameters reported in individuals considered to be carriers are similar to those detected in patients with myelopathy supports the hypothesis that urinary disorders may represent an oligosymptomatic form of HAM/TSP. Erectile dysfunction is frequently observed in HTLV-I-infected patients with or without myelopathy. Urinary tract infections are also highly prevalent in these patients. Despite the lack of an effective treatment for myelopathy, the use of anticholinergic drugs and phosphodiesterase type 5 (PDE5) inhibitors may improve urinary complaints and erectile dysfunction in these patients.

Urodynamic features of the voiding dysfunction in HTLV-1 infected individuals

OBJECTIVE To describe urodynamic abnormalities in HTLV-1 infected individuals presenting urinary symptoms and verify if these findings and quality of life (QOL) evaluation correlate with overall neurological impairment. MATERIALS AND METHODS From January/2001 to May/2004, 324 HTLV-1 seropositive subjects were evaluated to determine the occurrence of urinary symptoms. Urodynamic testing was performed in those who complained of frequency, urgency, or incontinence. They went through a complete clinical, neurological, and urological examination to investigate symptoms and signs of myelopathy. Neurological disability was assessed by Expanded Disability Status Scale (EDSS). RESULTS From the 324 patients evaluated, 78 underwent the urodynamic testing. Fifty-seven individuals were females (73.1%) and age ranged from 23 to 76 years (mean=48.7 years; SD +/- 11.6). Urodynamic testing was abnormal in 63 patients (80.8%). The major abnormality was detrusor overactivity (DO), observed in 33 individuals (33/63; 52.4%), followed by detrusor-external sphincter dyssynergia (DESD), diagnosed in 15 subjects (15/63; 25.4%). HAM/TSP patients had significantly more DESD than the HTLV-I carriers (p=0.005; OR=5.5; CI: 1.6 to 19.4). QOL was severely compromised in HAM/TSP patients. CONCLUSIONS Prominent urodynamic abnormalities were identified in individuals genuinely considered as HTLV-I carriers, suggesting an early compromise of the urinary tract; whereas HAM/TSP patients presented urodynamic findings, which posed a potential risk to the upper urinary tract (dyssynergia). Urodynamic evaluation should be performed in all HTLV-I-infected individuals with voiding complaints.

Neurological Manifestations in Human T-Cell Lymphotropic Virus Type 1 (HTLV-1)–Infected Individuals Without HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis: A Longitudinal Cohort Study

BACKGROUND Human T-cell lymphotropic virus type 1 (HTLV-1) is the agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), observed in up to 5% of infected individuals. Despite low prevalence, many HTLV-1-infected patients who do not fulfill criteria for HAM/TSP present with neurological complaints related to sensory, motor, urinary, or autonomic manifestations. The aim of this study was to determine the incidence of neurologic manifestations and risk factors associated with these outcomes. METHODS The incidence of HAM/TSP and new signs and neurologic symptoms were computed in a group of patients enrolled in a cohort study. RESULTS Of 414 subjects, 76 had definite HAM/TSP, 87 had possible or probable HAM/TSP, and 251 subjects had no neurologic manifestation and were selected for analysis. Definite HAM/TSP developed in 5 (1.47%) patients. Follow-up of at least 3 years was achieved in 51% of patients. The incidence rate was computed in 1000 person-years (206 for hand numbness, 187 for feet numbness, 130 for nocturia, and 127 for urgency). Average incidence rate in neurological exam was 76 for leg hyperreflexia, 53 for leg weakness, and 37 for Babinski sign. In the applied Expanded Disability Status Scale, the incidence rate of worsening 1 point was 134 per 1000 person-years. Kaplan-Meier curves stratified by sex and proviral load showed that females and patients with proviral load >50,000 copies/10(6) peripheral blood mononuclear cells had a higher risk of progression. CONCLUSIONS Development of neurological symptoms or signs occurred in up to 30% of asymptomatic subjects during 8 years of follow-up.

The cause of urinary symptoms among Human T Lymphotropic Virus Type I (HLTV-I) infected patients: a cross sectional study.

BackgroundHTLV-I infected patients often complain of urinary symptomatology. Epidemiological studies have suggested that these individuals have a higher prevalence and incidence of urinary tract infection (UTI) than seronegative controls. However, the diagnosis of UTI in these studies relied only on patient information and did not require confirmation by urine culture. The purpose of this study was to investigate the role of urinary tract infection (UTI) as the cause of urinary symptoms in HTLV-I infected patients.MethodsIn this cross sectional study we interviewed, and cultured urine from, 157 HTLV-I seropositive individuals followed regularly at a specialized clinic. All patients were evaluated by a neurologist and classified according to the Expanded Disability Status Scale (EDSS). Urodynamic studies were performed at the discretion of the treating physician.ResultsSixty-four patients complained of at least one active urinary symptom but UTI was confirmed by a positive urine culture in only 12 of these patients (19%); the majority of symptomatic patients (81%) had negative urine cultures. To investigate the mechanism behind the urinary complaints in symptomatic individuals with negative urine cultures, we reviewed the results of urodynamic studies performed in 21 of these patients. Most of them (90.5%) had abnormal findings. The predominant abnormalities were detrusor sphincter hyperreflexia and dyssynergia, findings consistent with HTLV-I-induced neurogenic bladder. On a multivariate logistic regression, an abnormal EDSS score was the strongest predictor of urinary symptomatology (OR 9.87, 95% CI 3.465 to 28.116, P < 0.0001).ConclusionUrinary symptomatology suggestive of UTI is highly prevalent among HTLV-I seropositive individuals but true UTI is responsible for the minority of cases. We posit that the main cause of urinary symptoms in this population is neurogenic bladder. Our data imply that HLTV-I infected patients with urinary symptomatology should not be empirically treated for UTI but rather undergo urine culture; if a UTI is excluded, further investigation with urodynamic studies should be considered.

Association of cytokines, neurological disability, and disease duration in HAM/TSP patients

OBJECTIVE To identify clinical and immunological markers associated with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). METHOD 237 HTLV-I infected individuals were clinically assessed. They were classified according to the Expanded Disability Status Scale (EDSS) and Osames Motor Disability Score (OMDS). Cytokine levels were determined in HTLV-I seropositive individuals. RESULTS 37 patients had HAM/TSP. There was a correlation between the degrees of disability assessed by both scales. There was also a correlation between the duration of HAM/TSP and the severity of disability assessed by either EDSS or OMDS. Higher levels of IFN-gamma were detected in unstimulated peripheral blood mononuclear cells (PBMC) from HAM/TSP patients as compared with HTLV-I carriers. CONCLUSION This study shows the validity of the neurological scales to classify the degree of neurological disability in HTLV-I carriers and suggests a progressive behavior of HAM/TSP. This study also shows that IFN-gamma in PBMC supernatants are markers of HAM/TSP.

Neurological symptoms and signs in HTLV-1 patients with overactive bladder syndrome

OBJECTIVE To compare neurological symptoms and signs in HTLV-1 asymptomatic carriers and HTLV-1 patients with overactive bladder (OB) syndrome. METHODS We studied 102 HTLV-1 positive individuals without HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis) divided into two groups according to the presence or absence of OB syndrome. Clinical interview, neurological exam and proviral load was performed in all patients. RESULTS AND CONCLUSIONS Individuals with OB were more commonly female (84.3 vs. 60.8% of asymptomatics, p=0.01). The prevalence of neurological complaints was higher in OB group, especially hand or foot numbness and arm or leg weakness. There was no difference between the groups in neurological strength and reflexes. Weakness complaint remained strongly associated with OB in multivariate logistic regression analysis adjusting for sex and age [adjusted odds ratio and 95%CI 3.59 (1.45-8.88) in arms and 6.68 (2.63-16.93) in legs]. Proviral load was also different between the two groups with higher level on OB individuals.

The clinical spectrum of HTLV-1 infection

The Human T lymphotropic virus type 1 (HTLV-1) infection is neglected mainly due to the concept that it is associated with a low morbidity. However, a few reports have shown that a large percentage of HTLV-1 infected subjects have signs and symptoms of a variety of diseases. Nevertheless the relationship between the cause and effect needs to be proven. The HTLV-1 associated myelopathy (HAM/TSP) and adult T-cell leukemia (ATL), the main disease associated to HTLV-1, are characterized by high proviral load and lymphocyte activation. Moreover the exaggerated inflammatory response and proviral load are markers of diseases associated with HTLV-1. In this study we compare the frequency of sicca syndrome, chronic periodontal disease (CPD), HTLV-1 associated over reactive bladder (HTLV-1 OAB), artropathy and erectile dysfunction (ED) in HTLV-1infected subjects who did not have definitive HAM/TSP with that observed in seronegative controls. The proviral load was measured by real time PCR and production of interferon–γ and TNF in supernatants of lymphocyte culture by ELISA. Of the 180 individuals participants of the study, 106 (50.8%) were female, 56 (31.1%) had sicca syndrome, 37 (20.5%) had CPD, 32 (17.7%) had HTLV-1 OAB, 29 (16.6%) had HTLV-1 associated arthropathy. Moreover of the 74 males 31 (41.8%) had ED. All these manifestations were higher (P<0.001) in HTLV-1 infected subjects than in controls. Proviral load in sicca syndrome, CPD, HTLV-1 OAB and ED patients were higher (P < 0.05) than in 78 (43,3%) HTLV-1 carriers. Patients with OAB, CPD and sicca syndrome had higher TNF and IFN-γ than HTLV1 carriers. The majority of the patients with diseases associated to HTLV1 had at least two of the above diseases. Overall 56,7% of HTLV-1 infected subjects without definitive HAM/TSP or ATL had diseases associated with HTLV1 infection indicating that HTLV-1 is associated with high morbidity.

Helminthic infection and the risk of neurologic disease progression in HTLV-1

BACKGROUND Infection with the human T-cell lymphotropic virus, type 1 (HTLV-1) has been associated with an increased Th1 response. Interestingly, a higher prevalence of helminthic coinfection has been observed among infected individuals, and subsequent modulation of the immune response typically associated with helminths may influence clinical outcomes among HTLV-1 coinfected individuals. OBJECTIVE This study was conducted to elucidate the association between helminthic coinfection and the development of clinically characterized neurologic disease that occurs in HTLV-1 infection. STUDY DESIGN In a cohort analysis, incidence of HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was recorded. Incidence of clinical outcomes and disease-free survival of several neurologic outcomes associated with HTLV-1 were estimated using the Kaplan-Meier method with log-rank tests. The relationships between helminthic infection and risk of HTLV-1 neurologic outcomes were assessed by Cox proportional hazard modeling. RESULTS Seventy-four coinfected and 79 non-coinfected patients were followed, with 92 helminthic infections observed in the coinfected group. One patient per group developed HAM/TSP and the risk of progression to neurologic disease outcomes did not differ among those with and without helminthic coinfection (p>0.45). A significant difference was noted in the prevalence of neurologic disease outcomes among all patients at the conclusion of the study (p<0.01). CONCLUSIONS These data suggest that treated helminthic infection does not affect risk of development of neurologic disease in HTLV-1 infection, and reinforce that treatment of helminths does not adversely affect patients with HTLV-1. Importantly, among all patients, an overall progression of neurologic disease was observed.

Clinical manifestations in HTLV-1 infected individuals without HAM/TSP: Results of an 8 years cohort

HTLV-1 is an endemic virus in the northeast of Brazil and is related to HAM/TSP in up to 5% of infected individuals. Despite this low prevalence it is known that a higher number of carriers presents with clinical and neurological symptoms that can be sensory, motor, urinary, inflammatory or autonomic.

Neurological manifestations in HTLV-1 patients with overactive bladder syndrome. A precursor of HAM/TSP?

At least 20 million people are infected with HTLV-I virus in the world, and 3 to 5 % develop the classical neurological or hematological manifestations of myelopathy (HAM/TSP) or T-cell leukemia (ATLL). HTLV-I-infected patients with overactive bladder syndrome may represent 37%. We studied 102 HTLV-1 positive individuals without HAM/TSP divided into two groups according to the presence or absence of overactive bladder (OB) syndrome. Individuals with OB were more commonly female (84.3% vs. 60.8% of asymptomatics, P = 0.01), but the mean age in the two groups was similar (46.4 ± 1.9 vs. 42.3 ± 1.7 years, respectively; P = 0.11). The prevalence of neurological complaints was higher in OB group, especially hand or foot numbness and arm or leg weakness. There was no difference between the groups in neurological strength and reflexes. Weakness remained strongly associated with OB in multivariate logistic regression analysis adjusting for sex and age (adjusted odds ratio and 95% CI 3.59(1.45-8.88) in arms and 6.68(2.63-16.93) in legs). In summary, we have characterized a subgroup of HTLV-1 infected patients based on urinary complaints who have more frequent neurological symptoms compared to those without OB. Longitudinal studies are needed to determine if HTLV-1 associated OB is a precursor of HAM/TSP.