André Muniz

BACKGROUND: A small fraction of Human T cell Leukemia Virus type-1 (HTLV-I) infected subjects develop a severe form of myelopathy. It has been established that patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) show an exaggerated immune response when compared with the immunological response observed in HTLV-I asymptomatic carriers. In this study the immunological responses in HAM/TSP patients and in HTLV-I asymptomatic carriers were compared using several immunological assays to identify immunological markers associated with progression from infection to disease. METHODS: Immunoproliferation assays, cytokine levels of unstimulated cultures, and flow cytometry analysis were used to evaluate the studied groups. Nonparametric tests (Mann-Whitney U test and Wilcoxon matched-pairs signed ranks) were used to compare the difference between the groups. RESULTS: Although both groups showed great variability, HAM/TSP patients had higher spontaneous lymphoproliferation as well as higher IFN-gamma levels in unstimulated supernatants when compared with asymptomatic carriers. Flow cytometry studies demonstrated a high frequency of inflammatory cytokine (IFN-gamma and TNF-alpha) producing lymphocytes in HAM/TSP as compared to the asymptomatic group. This difference was accounted for mainly by an increase in CD8 cell production of these cytokines. Moreover, the HAM/TSP patients also expressed an increased frequency of CD28-/CD8+ T cells. Since forty percent of the asymptomatic carriers had spontaneous lymphoproliferation and IFN-gamma production similar to HAM/TSP patients, IFN-gamma levels were measured eight months after the first evaluation in some of these patients to observe if this was a transient or a persistent situation. No significant difference was observed between the means of IFN-gamma levels in the first and second evaluation. CONCLUSIONS: The finding that a large proportion of HTLV-I carriers present similar immunological responses to those observed in HAM/TSP, strongly argues for further studies to evaluate these parameters as markers of HAM/TSP progression.

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.

Human T-lymphotropic virus type I (HTLV-I) causes HTLV-I-associated myelopathy/tropical spastic paraparesis and adult T cell leukemia in a small percentage of infected individuals. HTLV-I infection is increasingly associated with clinical manifestations. To determine the prevalence of clinical manifestations in HTLV-I infected individuals, we conducted a cross-sectional study of 115 HTLV-I-infected blood donors without myelopathy and 115 age- and sex-matched seronegative controls. Subjects answered a standardized questionnaire and underwent physical examination. Compared with controls, HTLV-I-infected subjects were more likely to report arm or leg weakness (OR = 3.8, 95% CI: 1.4-10.2; OR = 4.0, 95% CI: 1.6-9.8, respectively), hand or foot numbness (OR = 2.1, 95% CI: 1.1-3.9; OR = 4.8, 95% CI: 2.0-11.7, respectively), arthralgia (OR = 3.3, 95% CI: 1.7-6.4), nocturia (OR = 2.7, 95% CI: 1.04-6.8), erectile dysfunction (OR = 4.0, 95% CI: 1.6-9.8), and to have gingivitis (OR = 3.8, 95% CI: 1.8-7.9), periodontitis (OR = 10.0, 95% CI: 2.3-42.8), and dry oral mucosa (OR = 7.5, 95% CI: 1.7-32.8). HTLV-I infection is associated with a variety of clinical manifestations, which may occur in patients who have not developed myelopathy.

Objectives To describe the frequency of urologic manifestations in human T-cell lymphotropic virus type I (HTLV-I) seropositive individuals from Salvador and other cities in Bahia, Brazil, with or without clinical HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Methods A total of 218 HTLV-I seropositive subjects referred from blood banks or neurologic clinics were admitted to the HTLV-I multidisciplinary outpatient clinic from January 2001 to April 2004. They were assessed using a standardized questionnaire to determine urinary complaints and quality of life. Neurologic impairment was established using the Expanded Disability Status Scale (EDSS). HAM/TSP was considered as an EDSS score of 2 or greater. Results Nocturia (35.8%) was the most frequent finding, followed by incontinence (29.8%), urgency (25.2%), frequency (22.0%), and dysuria (15.6%). Differences were found between individuals with an EDSS score of 0 and those with an EDSS score greater than 0 but less than 2 regarding frequency, nocturia, urgency, urinary loss of any degree, and quality of life. Dysuria and great or total urinary loss were more frequent among those with severe HAM/TSP (EDSS score greater than 6). Conclusions Even HTLV-I subjects considered not to have HAM/TSP may have prominent urinary findings already present. Urologic manifestations, including nocturia and urinary loss, might be early manifestations of neurologic disease in those with HTLV-I. To describe the frequency of urologic manifestations in human T-cell lymphotropic virus type I (HTLV-I) seropositive individuals from Salvador and other cities in Bahia, Brazil, with or without clinical HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A total of 218 HTLV-I seropositive subjects referred from blood banks or neurologic clinics were admitted to the HTLV-I multidisciplinary outpatient clinic from January 2001 to April 2004. They were assessed using a standardized questionnaire to determine urinary complaints and quality of life. Neurologic impairment was established using the Expanded Disability Status Scale (EDSS). HAM/TSP was considered as an EDSS score of 2 or greater. Nocturia (35.8%) was the most frequent finding, followed by incontinence (29.8%), urgency (25.2%), frequency (22.0%), and dysuria (15.6%). Differences were found between individuals with an EDSS score of 0 and those with an EDSS score greater than 0 but less than 2 regarding frequency, nocturia, urgency, urinary loss of any degree, and quality of life. Dysuria and great or total urinary loss were more frequent among those with severe HAM/TSP (EDSS score greater than 6). Even HTLV-I subjects considered not to have HAM/TSP may have prominent urinary findings already present. Urologic manifestations, including nocturia and urinary loss, might be early manifestations of neurologic disease in those with HTLV-I.

The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS.