A group of neurologists and clinical neurochemists representing twelve countries worked towards a consensus on laboratory techniques to improve the quality of analysis and interpretation of cerebrospinal fluid (CSF) proteins. Consensus was approached via a virtual Lotus Notes-based TeamRoom. This new approach respecting multicultural differences, common views, and minority opinions, is available in http://www.teamspace.net/ CSF, presenting the implicit, complementary version of this explicit, printed consensus. Three key recommendations were made: CSF and (appropriately diluted) serum samples should be analyzed together in one analytical run, i.e., with reference to the same calibration curve. Results are evaluated as CSF/serum quotients, taking into account the non-linear, hyperbolic relation between immunoglobulin (Ig)- and albumin-quotients rather than using the linear IgG index or IgG synthesis rate. Controls should include materials with values within the reference ranges (IgM: 0.5-1.5 mg/l; IgA: 1-3 mg/l; IgG: 10-30 mg/l and albumin: 100-300 mg/l). The physiological, methodological and clinical significance of CSF/serum quotients is reviewed. We confirmed the previous consensus on oligoclonal IgG, in particular the usefulness of the five typical interpretation patterns. The group compared current external and internal quality assurance schemes and encouraged all members to maintain national or local traditions. Values for acceptable imprecision in the CSF quality assurance are proposed.

To study the epidemiology of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Brazil, we conducted a nationwide survey between March 1994 and April 1995. Five centers from three regions of the country participated, enrolling 163 patients. Most patients came from the northeastern and southeastern regions (93.2%). Most enrollees were white women, 42.9% and 64.4%, respectively. The most common risk factors for infection included a history of venereal diseases (30.6%) and blood transfusion (21.6%). The median age at the beginning of the disease was 42 years. The main neurologic findings were spastic paraparesis, widespread brisk tendon jerks, bilateral Babinski's sign, and bladder dysfunction. Some interregional differences reached statistical significance. The ratio of females over males increased from south to north. In addition, in both southern and southeastern regions, whites prevailed, whereas in the northeast, mulattos predominated. This follows the normal distribution of the population in these regions. A significantly higher rate of venereal diseases was found in the southeast compared with the other regions studied. A history of intravenous drug use was more frequent among patients as the sample moves south. Finally, a fluctuating course of the disease was proportionally more frequent in the southern region.

Human T cell lymphotropic virus type II (HTLV-II) is a deltaretrovirus endemic in Indian populations living in Central and South America, among Pygmies tribes from Central Africa, and epidemic among injecting drug users (IDUs) in the United States, Europe, Southeast Asia, and South America. To date only the HTLV-IIa subtype has been demonstrated among Brazilians (Amazon basin Indians, blood donors, and IDUs). We analyzed HTLV-II isolates from 12 individuals living in the urban area of Porto Alegre, Southern Brazil, identified as seropositive for HTLVI/II in a blood donation. The HTLV-II long terminal repeat (LTR) region was sequenced and compared with nucleotide sequences of isolates HTLV-IIa (Mo), HTLV-IIb (NRA) prototypes. Phylogenetic analysis of the LTR region demonstrated that seven new isolates clustered together with American Indians HTLV-IIb isolates, and five new HTLV-IIa isolates clustered within the HTLV-IIa Brazilian subgroup, named the HTLV-IIc subtype. Both HTLV-IIa and IIb seem to be endemic in the urban area of Porto Alegre, South of Brazil, and could have reached this region via the Amazon basin and the Pacific Coast ancient human migratory pathways. To our knowledge this is the first study demonstrating the presence of HTLV-IIb among the urban population in Brazil.

, os demais Membros da Equipe Técnica do Programa Nacional de DST e Aids do Ministério da Saúde# RESUMO -O Ministério da Saúde (Programa DST e Aids) reuniu especialistas para elaborar um guia inform a t i v o de manejo do paciente com HTLV. Dentre os diferentes tópicos, foram contemplados os aspectos neuro l ó g i c o s associados à infecção pelo HTLV. Um caso suspeito de doença neurológica associada ao HTLV deve incluir alteração de força e reflexos, parestesias distais e disfunção autonômica. A investigação do caso suspeito deve ser baseada na síndrome exibida pelo paciente. Para o paciente com síndrome medular, deve-se solicitar ressonância magnética da medula ou mielografia, assim como, estudo do líquor. Para o paciente com síndro m e neuropática ou miopática, deve-se solicitar eletroneuromiografia e dosagem de CPK, e para aquele com síndrome autonômica, pesquisa de hipotensão postural, ultrassonografia das vias urinárias e estudo urodinâmico. O tratamento pode ser sintomático (espasticidade, bexiga neurogênica, constipação intestinal e dor neuropática) e específico a ser feito em centros especializados.PALAVRAS-CHAVE: Ministério da Saúde, HTLV, neurologia, investigação clínica, tratamento. Guide of clinical management of HTLV patient: neurological aspectsABSTRACT -The Brazilian Ministry of Health (STD and Aids Program) invited specialists to make up an informative guide to deal with HTLV patients. Among the different topics, the neurological aspects associated to HTLV were contemplated. A suspected case should include changes in force and reflexes, distal pare s t h e s i a e and autonomic dysfunction. The investigation of such case should be based on the syndrome shown by the patient. For patients with spinal cord syndrome, magnetic resonance imaging or myelography as well as spinal fluid studies should be carried out. For patients with neuropathic or myopathic syndrome, electroneuromyography and CPK dosing should be done, and for those with autonomic syndrome, a search for postural hypotension, ultrasonography of urinary tract and urodynamic studies should be requested. The treatment may be symptomatic (spasticity, neurogenic bladder, intestinal constipation and neuro p a t h i c pain) and specific to be carried out in specialized centers.KEY WORDS: Ministry of Health, HTLV, neurology, clinical investigation, treatment.Ao longo de 2002 e 2003, o Ministério da Saúde, através do Programa Nacional de DST e Aids (PN-DST/Aids) reuniu, por várias vezes, em Brasília, um g rupo de pesquisadores brasileiros de HTLV, inclusive neurologistas, com o objetivo fundamental de elaborar um guia informativo para os diferentes p rofissionais de saúde sobre o retrovírus HTLV e suas implicações clínicas, epidemiológicas e de saúde pú-blica. O conteúdo desse guia contempla os seguintes aspectos: histórico dos re t ro v í rus I e II, descrição do HTLV, situação taxonômica do HTLV, epidemiologia, mecanismos de transmissão, patogenia, d o e nças e síndromes associadas à infecção pelo HTLV, a b o rdagem clínica do paciente infecta...

Human T-cell lymphotropic virus type II (HTLV-II) is found in many New World Indian groups on the American continent. In Brazil, HTLV-II has been found among urban residents and Indians in the Amazon region, in the North. Guaraní Indians in the South of Brazil were studied for HTLV-I/II infection. Among 52 individuals, three (5.76%) showed positive anti-HTLV-II antibodies (enzyme-linked immunosorbent assay and Western blot). This preliminary report is the first seroepidemiological study showing HTLV-II infection among Indians in the South of Brazil.

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Lymphocytes of human T-lymphotropic virus type-I (HTLV-I) infected patients were previously found tolerant to mitogenic stimuli as well as glucocorticoid treatment. These data suggest that common signaling events are impaired during this infection. The underlying mechanisms of these phenomena may include changes in cellular composition, cytokine milieu and the differential activation of mitogen-activated protein kinases (MAPKs). We investigated the role of (i) p38 and ERK MAPKs, (ii) lymphocyte subpopulations, (iii) and cytokines implicated in antigen or glucocorticoid-induced immunomodulation. Twenty-one asymptomatic carriers (AC), 19 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 21 healthy subjects took part in this study. Lymphocytes were isolated and cultured in vitro to assess lymphocyte proliferation and sensitivity to dexamethasone. The expression of phospho-MAPKs, lymphocyte subsets and cytokines were assessed by flow cytometry. Patients with HAM/TSP had a higher p38/ERK ratio (p<0.05) associated with a reduced response to mitogens (phytohaemagglutinin or PMA+ionomycin) (p<0.001) and higher sensitivity to dexamethasone (p<0.05). HAM/TSP patients presented increased frequency of activated T cells and CD8(+)CD28(-) regulatory T cells, being negatively related to the mitogenic response. These data suggest that multiple underlying mechanisms could be involved with HTLV-related changes in cellular response to mitogens and glucocorticoids.

These data suggest that the poor clinical response to steroids may be associated with spontaneous cell proliferation during HTLV infection.