Long-term MS secondary progression: Derivation and validation of a clinical risk score.

OBJECTIVE: The risk of progression of multiple sclerosis (MS) related to the association of prognostic factors present at disease onset has rarely been explored. We aimed to construct a clinical risk score for MS long-term progression that could be easily applied in clinical practice. PATIENTS AND METHODS: Among 432 patients with MS, 288 patients were selected as a derivation sample for identification of the knowledge prognostic factors more associated with long-term progression. One point was given to each risk factor identified as statistically significant by the adjusted model, and the sum of the points gave the overall risk score. Subsequently the score was applied to the remaining 144 patients to confirm if those with higher scores had reached MS secondary progression. RESULTS: The prognostic factors identified as independently associated with long-term progression were: no specific MS treatment before EDSS 3, age of onset older than 30 years, pyramidal and cerebellar impairment as the first manifestation of disease, time interval between the first and second relapses less than 2 years, and African ancestry. There was no significant difference between expected and observed number of patients in progression (44 vs. 31, p = 0.966), indicating that the score was able to predict the progression in the validation sample. There was no significant difference between patients with low risk (≤ 2 points) (p = 0.98) and high risk (≥ 3 points) (p = 0.48) in the derivation versus validation samples. In the derivation sample, the patients with three or more points had a 2.8-fold increased risk of progression [hazard ratio (HR): 2.8; 95 % confidence interval (CI): 1.2-6.3; p = 0.014). CONCLUSION: The score proposed was capable of predicting long-term MS progression.

Multiple sclerosis in Brazil: A systematic review.

BACKGROUND: The natural history of multiple sclerosis (MS) in Brazil has been available in different regions of country. There is no nationwide population-based studies that express general data in Brazil. OBJECTIVE: To review and synthesize available data about MS in Brazil. MATERIAL AND METHODS: Systematic review was performed through a search of medical literature databases to identify Brazilian studies published during 1990-2012. DATA SOURCES: PubMed, SciELO, and Lilacs. KEYWORDS: "Brazil" or "Brazilian" combined with the following terms: "multiple sclerosis", "clinical profile", "demographic profile", "natural history", "clinical course", "pediatric", or "familial form". RESULTS: In total of 45 pediatric and 1922 adult patients, the median age at onset was 10 years in pediatric patients and 32 years in adult patients. Women were more affected. Motor-control complaints and relapsing-remitting phenotype at onset were the most common. Predictors to disability and progression were number of relapses during the first year of disease, older age, male gender and African ancestry. CONCLUSIONS: The profile of the MS in Brazilian seems to correspond to that observed in high-MS-prevalence areas. African ancestry is a risk factor to disability and progression early. In Brazil, factors that limit MS incidence do not interfere with the clinical pattern and outcomes.

Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase.

T helper type 17 (Th17) cytokines have been implicated in the pathogenesis of neuromyelitis optica (NMO). As humanized anti-interleukin (IL)-6R (tocilizumab) immunoglobulin (Ig)G has been used as disease-modifying therapy for NMO, the objective of our study was to investigate the role of endogenous IL-6 on NMO-derived CD4(+) T cell behaviour. High production of IL-6, IL-17 and IL-21 by CD4(+) T-cells was detected in NMO patients. Further, IL-21 and IL-6 levels were related directly to the level of neurological disabilities. The addition of anti-IL-6R IgG not only reduced directly the production of these cytokines, but also almost abolished the ability of activated autologous monocytes in enhancing IL-6, IL-17 and IL-21 release by CD4(+) T cells. In contrast, the production of IL-10 was amplified in those cell cultures. Further, anti-IL-6R monoclonal antibodies (mAb) also potentiated the ability of glucocorticoid in reducing Th17 cytokines. Finally, the in-vivo and in-vitro IL-6 levels were significantly higher among those patients who experienced clinical relapse during 2-year follow-up. In summary, our results suggest a deleterious role of IL-6 in NMO by favouring, at least in part, the expansion of corticoid-resistant Th17 cells.

[Neuropsychology of primary progressive multiple sclerosis]. / Neuropsicología de la esclerosis múltiple primaria progresiva.

INTRODUCTION: Cognitive impairment is a symptom of multiple sclerosis (MS); however, in the primary progressive form of the disease (PPMS), data on the prevalence and type of cognitive impairment are controversial. AIM: To evaluate the frequency of cognitive impairment, according to the diagnostic criteria defined by Thompson, in Brazilian patients with PPMS attending a referral center for the treatment of MS in Rio de Janeiro, Brazil. SUBJECTS AND METHODS: A battery of neuropsychological tests was used to evaluate the following cognitive functions: screening for dementia, attention/concentration, speed of information processing, verbal fluency, memory and abstract/conceptual thought. The Beck scale was used to evaluate mood disorders. Twenty-six patients with PPMS and 26 controls paired for gender, age and education level were evaluated. Statistical analysis was based on the study performed by Rao. RESULTS: The frequency of cognitive impairment in the PPMS patients in the present study was 50%. The cognitive functions most affected were: recent memory (60%), verbal fluency (40%) and speed of information processing (40%). Depression was more common in the PPMS patients compared to the control group; however, no association was found between cognitive impairment and depression. CONCLUSION: These results confirm the presence of cognitive impairment in PPMS and emphasize the need for further studies with larger sample sizes.

Differentiation of HAM/TSP from patients with multiple sclerosis infected with HTLV-I.

OBJECTIVE: To better differentiate patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) from patients with multiple sclerosis (MS) who are HTLV-I seropositive, we compared the HTLV-I antibodies and HTLV-I proviral DNA loads in CSF and peripheral blood mononuclear cells (PBMC). METHODS: Intrathecal synthesis of HTLV-I antibodies and HTLV-I proviral DNA loads in CSF and PBMC were measured and compared in 39 Brazilian patients: 17 HAM/TSP and 22 HTLV-I-seropositive non-HAM/TSP (7 with other neurologic diseases, 11 asymptomatic carriers, and 4 HTLV-I-seropositive patients with an MS-like phenotype). In addition, we followed immunologic and virologic markers in comparison to the clinical course (by Kurtzke Expanded Disability Status Scale) of seven patients (five with HAM/TSP and two with an MS-like phenotype) for a mean period of 16 (SD +/- 5) months. RESULTS: The proviral load in CSF and PBMC was higher in HAM/TSP than in non-HAM/TSP patients, except in the two HTLV-I-seropositive patients with an MS-like phenotype that also fulfilled the criteria for HAM/TSP. Higher HTLV-I proviral DNA load in CSF was associated with the higher proviral DNA load in PBMC and lower intrathecal synthesis of HTLV-I antibodies. These laboratory findings remained stable during follow-up. CONCLUSION: The high proviral load in peripheral blood mononuclear cells or in CSF or both may be a good marker of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and can differentiate patients with HAM/TSP from patients with multiple sclerosis infected with HTLV-I.

Clinical course of progressive multiple sclerosis in Brazilian patients.

OBJECTIVE: To describe the clinical course and outcome of multiple sclerosis with progressive onset in Brazilian patients. A total of 238 medical records were reviewed, 26 cases (10.9%) fulfilled Thompson criteria (2000), and 5.80% classified as primary progressive and 5.04% relapsing progressive according to Lublin and Reingold. STUDY POPULATION: 19 Caucasians and 7 non-Caucasians; male:female ratio 1.2:1, mean age at onset was 34 +/- 7.9 years. RESULTS: Non-Caucasian patients had earlier onset of disease. The most common manifestations at onset were pyramidal and cerebellar (89% and 34.6%). After 11.3 +/- 6.35 years of disease more than 50% of the patients had involvement of most of their functional systems. No statistically significant differences were observed between the subgroups. CONCLUSION: The clinical course and outcome of progressive multiple sclerosis in Brazil, a tropical country with low prevalence, were very similar to those in the multiple sclerosis high prevalence areas.