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Background: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection. HAM/TSP neurological disease is a consequence of an inflammatory reaction, and adaptive immune responses, through the secretion of anti-inflammatory and pro-inflammatory cytokines, play an important role in the outcome of infection and disease progression. Studies addressing the association between cytokines functional single nucleotide polymorphisms and HAM/TSP development are scarce., Methods: The genetic polymorphisms of cytokine genes were evaluated in HAM/TSP patients (n = 68) and in asymptomatic HTLV-1 positive carriers (n = 83) from Rio de Janeiro, Brazil, in a case-control study. HTLV-1 infected patients were genotyped for SNPs in five cytokine genes: TNFA-308G/A, IL6-174G/C, IFNG + 874 T/A, TGFB at the codons + 10 T/C and + 25G/C, IL10-592C/A and -819C/T, and -1082A/G and proviral load (PVL) was quantified. Associations between genotypes, haplotypes, clinical outcome and pro viral load were evaluated., Results: Lack of association between the cytokine polymorphisms and disease outcome was observed. The genotypes TNFA-308GG, IL6-174GG/GC, IL10-592AA and -819CC and TGFb1 high producers phenotypes were correlated with higher PVL in HAM/TSP patients versus asymptomatic carriers., Conclusions: We did not observe association between cytokine polymorphisms and risk for HAM/TSP development in Brazilian HTLV-1 infected individuals, regardless of differences in PVL between HAM/TSP versus asymptomatic carriers in specific cytokine polymorphisms.

Objective: To investigate the feasibility and effectiveness of a home-based exercise program in TSP/HAM individuals., Methods: Twenty-three TSP/HAM individuals divided in two groups according to Timed Up and Go (TUG) score (<20s vs ≥20s) performed a 20-week home-based exercise program. The primary outcomes were exercise adherence, maximum voluntary isometric contraction of lower limbs (MVIC), Barthel Index and SF-36. Secondary outcomes were adverse effects and barriers to exercise practice., Results: MVIC and the social functioning domain in SF-36 improved significantly in TUG <20s group. The individuals in the TUG ≥20s group improved significantly their physical functioning domain in SF-36. The total adherence to the 20-week home-based exercise program was 90%. There were mild to moderate adverse events related to exercise program. There were no adverse events related to MVIC test., Conclusions: The home-based exercise program was feasible and effective in improving disability and quality of life in individuals with TSP/HAM.

Prion diseases are neurodegenerative illnesses due to the accumulation of small infectious pathogens containing protein but apparently lacking nucleic acid, which have long incubation periods and progress inexorably once clinical symptoms appear. Prions are uniquely resistant to a number of normal decontaminating procedures. The prionopathies [Kuru, Creutzfeldt-Jakob disease (CJD) and its variants, Gerstmann-Sträussler-Scheinker (GSS) syndrome and fatal familial insomnia (FFI)] result from accumulation of abnormal isoforms of the prion protein in the brains of normal animals on both neuronal and non-neuronal cells. The accumulation of this protein or fragments of it in neurons leads to apoptosis and cell death. There is a strong link between mutations in the gene encoding the normal prion protein in humans (PRNP) - located on the short arm of chromosome 20 - and forms of prion disease with a familial predisposition (familial CJD, GSS, FFI). Clinically a prionopathy should be suspected in any case of a fast progressing dementia with ataxia, myoclonus, or in individuals with pathological insomnia associated with dysautonomia. Magnetic resonance imaging, identification of the 14-3-3 protein in the cerebrospinal fluid, tonsil biopsy and genetic studies have been used for in vivo diagnosis circumventing the need of brain biopsy. Histopathology, however, remains the only conclusive method to reach a confident diagnosis. Unfortunately, despite numerous treatment efforts, prionopathies remain short-lasting and fatal diseases.

Study Design: Cross-sectional study., Objectives: To determine the prevalence of falls in human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and possible factors associated to their occurrence., Setting: Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz (FIOCRUZ) - Brazil., Methods: Thirty-six HAM/TSP patients able to walk at least 20 m were assessed by a questionnaire. Data regarding gender, age, duration of disease (DD), HTLV-I proviral load (HPL), frequency of physical activity (FCA), use of walking aids, functional ambulation level, the number of falls and associated injuries in the last year were reviewed. Multiple correspondence analysis was used to group characteristics of this sample according to the fall occurrence., Results: The prevalence of falls was 63.9% and we observed injuries in 47.8% of the cases. Four groups were identified in the descriptive analysis. One group was formed by faller individuals, men <60 years, independent ambulation, FCA≥3 times per week and HPL <6.6 copies per 100 cells (group B). The other one comprised non-faller patients, women ≥60 years, restricted ambulation, DD ≥7 years, use of orthosis, FCA 0-1 time per week and HPL ≥6.6 copies per 100 cells (group D). The others two groups comprised individuals that did not use orthosis (group A) and those that FCA was two times per week and DD <7 years (group C)., Conclusion: Falls occur in roughly two-thirds of ambulatory HAM/TSP patients and are associated with significant morbidity. Further studies with a larger number of patients are necessarily to identify risk factors in order to elaborate specific programs to prevent falls in this population.

Background: Routine diagnosis of Human T Lymphotropic virus (HTLV) infection is primarily serologically based; however the proportion of unresolved and indeterminate Western blot results range from 0.02% to 50% in endemic areas., Objectives: To validate a sensitive in-house quantitative multiplex real-time assay (mqRT-PCR), capable of detecting and quantifying HTLV-1 and HTLV-2, and use it to differentiate unresolved serological profiles, and monitor infection in HTLV-1 infected patients., Study Design: The mqRT-PCR was designed as a single-tube assay. Quantitative results were reported as copy number of HTLV provirus per 10(6) cells and the numbers of cells were calculated based on the quantitative result for albumin, of which there are 2 copies/cell. Assay standards were amplified from HTLV-1 infected MT-2 cells and HTLV-2 transfected CEM cells. Blood samples were obtained from HTLV seropositive former blood donors., Results: The mqRT-PCR assay was efficient (98.8-101.2%), reproducible (coefficient of variance<5%) and sensitive to 1 copy for HTLV-1, HTLV-2 and Albumin. The assay resolved the infection profile in 16/17 patients, with undetermined subtype, all of which were reassigned as HTLV-1 infections. In addition, the average PVL detected in patients suffering from HTLV-1 associated HAM/TSP (n=23, 13,450 copies/10(6) cells) was significantly higher than those detected in asymptomatic carriers (n=21, 6665 copies/10(6) cells)., Conclusions: We propose a new testing algorithm for the laboratory diagnosis of HTLV infection, which includes HTLV specific mqRT-PCR for resolving HTLV serological results. Furthermore, quantitation of PVL load by real-time PCR may be useful in assessing the link between infection and disease, and in monitoring patients undergoing therapy., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Study Design: Cross-sectional., Objectives: To describe characteristics of low-back pain in human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and to identify its neuropathic and/or non-neuropathic pain components., Setting: A reference center for the care of patients with HAM/TSP in Rio de Janeiro, Brazil., Methods: A total of 90 patients with HAM/TSP referred by tertiary care centers were consecutively assessed. The patients were submitted to a clinical protocol that included Visual Analogue Scale (VAS), Timed Up and Go Test, Bodily Pain Domain of the Short Form 36 Health Status Questionnaire, Douleur Neuropathique 4 Questions (Neuropathic Pain 4 Questions) (DN4) and McGill Pain Questionnaire., Results: The prevalence of low-back pain in the studied sample was 75.5%; pain interferes with physical functioning and worsens with movement and physical effort. It can be relieved by analgesics and rest. Average pain intensity was 51.2 mm on VAS and 1.72 on DN4. The most frequent words used to describe low-back pain were throbbing, burning, jumping and aching. Surprisingly, 32.4% patients pointed the lower extremities as the most painful and used different descriptors. The most common drugs used were analgesics, nonsteroidal anti-inflammatory drugs and tricyclic antidepressants., Conclusions: Low-back pain in HAM/TSP patients has mainly nociceptive characteristics. Conversely, descriptors for lower extremities pain suggest a neuropathic origin.

Background: Hypertrophic cardiomyopathy (HC) is the most frequent cardiac hereditary disease, caused by mutations in sarcomere protein coding genes. Although more than 430 mutations have been identified in several continents and countries, there have been no reports of mutations in Brazil., Objective: To carry out a genetic study to identify genetic mutations that cause HC in a group of patients in Espirito Santo, Brazil., Methods: Using the SSCP technique, 12 exons from the three main genes involved in HC were studied: exons 15, 20, 21, 22 and 23 of the beta-myosin heavy chain gene (MYH7), exons 7, 16, 18, 22 and 24 of the myosin binding protein C gene (MYBPC3) and exons 8 and 9 of troponin T gene (TNNT2)., Results: 16 alterations were found, including two mutations, one of them possibly pathogenic in the MYBPC3 gene (p. Glu441Lys) and another pathogenic one, previously described in the TNNT2 gene (p.Arg92Trp), 8 rare sequence variations and 6 sequence variations with allelic frequency higher than 1% (polymorphisms)., Conclusion: These data allow the conclusion that the genotyping of patients is feasible in our country. It is possible that the isolated p.Glu441Lys variant identified in exon 16 of the MYBPC3 gene is pathogenic, promoting a milder phenotype than that found when in association with other mutations. The p.Arg92Trp variant in the exon 9 of TNNT2 gene does not promote such a homogeneous phenotype as previously described and it can lead to severe hypertrophy.

Human T lymphotropic virus type 2 (HTLV-2) is characterized by a clinically asymptomatic persistent infection in the vast majority of infected individuals. In this study, we have characterized for the first time ex vivo specific CTL responses against the HTLV-2 Tax protein. We could detect CTL responses only against a single HLA-A*0201-restricted Tax2 epitope, comprising residues 11-19 (LLYGYPVYV), among three alleles screened. Virus-specific CTLs could be detected in most evaluated subjects, with frequencies as high as 24% of circulating CD8(+) T cells. The frequency of specific CTLs had a statistically significant positive correlation with proviral load levels. The majority of virus-specific CD8(+) T cells exhibited an effector memory/terminally differentiated phenotype, expressed high levels of cytotoxicity mediators, including perforin and granzyme B, and lysed in vitro target cells pulsed with Tax2((11-19)) synthetic peptide in a dose-dependent manner. Our findings suggest that a strong, effective CTL response may control HTLV-2 viral burden and that this may be a significant factor in maintaining persistent infection and in the prevention of disease in infected individuals.

HTLV-1 is a retrovirus associated with a myriad of clinical conditions, especially hematological and neurological ones. Regarding nervous system diseases, it is of utmost importance to select those cases in which HTLV-1 infection could really be associated. This is particularly true for patients from endemic areas and for HIV-infected patients and drug users, since that these groups are at a higher risk for HTLV infection. This caution in selecting neurological patients for HTLV diagnostic tests is justified by the fact that in some circumstances the seropositivity may merely represent an epiphenomenon. In this paper we enroll some neurological conditions that have been associated with HTLV-1/2 infection in the literature and discuss the real need for HTLV-1/2 diagnostic tests in each one. Because HIV/HTLV-co-infected patients seem to be at an increased risk for neurological diseases development, a special consideration about this matter is also made.

Background: In hypertrophic cardiomyopathy (HCM), interstitial myocardial fibrosis is an important histological modification that has been associated with sudden death and evolution toward myocardial dilation., Objective: To prospectively evaluate the prognostic value of the collagen volume fraction in HCM., Methods: An endomyocardial biopsy of the right ventricle was successfully performed in 21 symptomatic patients with HCM. The myocardial collagen volume fraction (CVF) was determined by histology. The CVF was also determined in fragments of nine normal hearts from subjects deceased from non-cardiac causes. The patients were divided into above-median CVF and below-median CVF groups, and their clinical and echocardiographic characteristics and survival curves were compared., Results: Among the patients, the CVF ranged from 1.86% to 29.9%, median 6.19%; in normal hearts, from 0.13% to 1.46%, median 0.61% (p <0.0001 between HCM and control). There were no significant correlations between CVF and baseline echocardiographic measures. Patients with CVF < or =6.19% and CVF> 6.19% were compared and no baseline differences were observed. However, after an average follow-up period of 110 months, four deaths occurred (two sudden, two due to heart failure) in the group with increased CVF, whereas the patients of the group with lower CVF were all alive at the end of the period (p = 0.02)., Conclusion: For the first time, myocardial fibrosis was prospectively associated with a worse prognosis in patients with HCM. Efforts should be directed to the quantification of myocardial fibrosis in HCM, on the premise that its association with the prognosis can aid in the stratification of risk for defibrillator implantation, and in the prescription of drugs that potentially promote myocardial repair.

Although human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is usually described as a chronic disabling disease, a rapid course over months or even weeks has been reported in some patients. The authors describe the clinical features of HAM/TSP in a Brazilian cohort and evaluate the prevalence of patients with a subacute progression of the disease. This was defined as the requirement of a wheelchair during the first 2 years after the onset of symptoms. Patients with this subacute course and patients with the chronic clinical course were compared in terms of their HTLV-I proviral loads (PLs) using real-time polymerase chain reaction (PCR). Seven out of 88 patients (7.9%) had a subacute progression. All patients were women and 5/7 acquired HTLV-I through sexual contact. There was no significant difference in the real-time PLs between the group with subacute evolution (mean 8.5 copies/100 cells, range 6.03 to 12.09) and those patients with a typical course of disease (mean 11.34 copies/100 cells, range 0.4 to 67.72) (P = .68), suggesting that factors other than the number of infected cells are implicated in the development of such an aggressive course of disease. Early recognition of this subgroup is important because immunosuppressive treatment might be beneficial if instituted promptly.

The human T cell lymphotropic/leukaemia virus type I (HTLV-I) causes HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The multidrug resistance associated protein 1 (ABCC1) plays multiple functions in physiopathologic responses. The expression and activity of ABCC1 was studied in T lymphocytes from uninfected and HTLV-I-infected individuals (both asymptomatic and symptomatic/HAM/TSP). ABCC1 expression and activity was reduced to nearly half in T lymphocytes from infected patients compared to control lymphocytes. Only 51.6% of CD4(+) cells from HAM/TSP patients expressed ABCC1 whereas this was seen in 60.3% from asymptomatic individuals, compared to an expression of around 86% in controls. Our results suggest that ABCC1 is negatively regulated in HTVL-I infection, supplying a novel target to investigate the pathogenesis of HTLV-I.

Study Design: Cross-sectional., Objectives: The aim of this survey is to describe the disability profile in a group of tropical spastic paraparesis/HTLV-I-associated myelopathy patients, identifying the requirements for community ambulation., Setting: Tertiary care unit, Rio de Janeiro, Brazil., Methods: Seventy-two patients were assessed (49 female and 23 male), referred by tertiary care centers, when a clinical protocol was applied., Results: The sample had an average age of 40 years and an average of 137 months of duration of the disease. The most prevalent aspects of disability found were in gait and sphincter control areas. A total of 72% of the patients were community ambulators and 17% were restricted to wheel chair. Age, strength and low-back pain interfere in activities of daily living (P<0.05). A positive correlation was found between community ambulation and the knee extensors (r=0.80) and ankle plantar flexors (r=0.74). Strength, age, low-back pain, duration of disease, asymmetric onset of the symptoms and spasticity interfered in the ability to walk (P<0.05). A rehabilitation program was proposed focusing on modifiable factors that affect disability level., Conclusion: It was possible to describe the profile of disability in this group of patients, identifying the requirements to the community ambulation.

After the first description of TSP/HAM in 1985 and the elaboration of WHO's diagnostic criteria in 1988, the experience of the professionals in this field has increased so that a critical reappraisal of these diagnostic guidelines was considered timely. Brazilian neurologists and observers from other countries met recently to discuss and propose a modified model for diagnosing TSP/HAM with levels of ascertainment as definite, probable, and possible, according to myelopathic symptoms, serological findings, and/or detection of HTLV-I DNA and exclusion of other disorders.

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 paresthesiae 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 neuropathic pain) and specific to be carried out in specialized centers.

Study Design: Survey., Objective: To determine the disability profile of a group of patients with human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), using the Functional Independence Measure (FIM) to identify the most affected functional areas., Setting: Reference center for HTLV Rio de Janeiro, Brazil., Methods: A total of 72 patients (49 female and 23 male), consecutively referred by tertiary care centers, were assessed using the FIM., Results: The average FIM score was 108 (+/-12 SD) ranging from 58 to 122. The lowest items scores were obtained in locomotion and bladder management. When divided into two groups (above, and below or equal to the average score), there were significant differences (P<0.05) in age at time of assessment, in the degree of muscular power and in low back pain. There were no significant differences in terms of age of onset and duration of the disease., Conclusions: The most affected areas in FIM motor items were locomotion (walk and stairs) and bladder management. Age, strength in lower limbs and low back pain interfere with functional activities in patients with HAM/TSP. The duration of the disease is not a significant factor for patient disabilities. The goals of rehabilitation in HAM/TSP patients should target the modifiable factors, such as pain, strength and the neurogenic bladder.

Tropical spastic paraparesis/ HTLV-I-associated myelopathy (TSP/HAM) is the classical neurological manifestation of HTLV-I. Only a few studies have described isolated peripheral neuropathy (PN) among HTLV-I infected individuals. 335 infected individuals without TSP/HAM were evaluated for the presence of PN and 45 of them showed evidences of peripheral nervous system involvement. Of these 21 patients had isolated PN, defined by clinical and/or electrophysiological criteria. Sural nerve biopsies revealed inflammatory infiltrates in 2, axonal degeneration in 2 and segmental demyelination in 1. Therefore, peripheral neuropathy can be found as an isolated manifestation of HTLV-I infection. We conclude that HTLV-I infection should be investigated in patients with PN of unknown origin.

Foreign accent syndrome (FAS), a rare disorder characterized by the emergence of a new accent perceived as foreign by listeners, is usually reported with left brain damage. We here report the case of a 28-year-old native Brazilian who appeared, to the examiner, to show a North American accent during recovery from Broca's aphasia. The lesion was due to a frontal hematoma. Without referring specifically to speech, we asked 10 independent observers to comment on a videotape of the patient's interview. Seven reported that the patient had a foreign accent, while 3 simply noted a 'strange' accent. The observers did not agree on the origin of the accent, 5 identifying it as Spanish, 1 as German, and 1 as south Brazilian. These findings suggest that FAS is not due to the acquisition of a specific foreign accent, but to impairment of the suprasegmental linguistic abilities (tone, accent, pauses, rhythm, and vocal stress) that make it possible to distinguish native language., (2004 S. Karger AG, Basel.)

Pathologicalprion protein (PrP(Sc)) is the hallmark of prion diseases affecting primarily the central nervous system. Using immunohistochemistry, paraffin-embedded tissue blot, and Western blot, we demonstrated abundant PrP(Sc) in the muscle of a patient with sporadic Creutzfeldt-Jakob disease and inclusion body myositis. Extraneural PrP(C)-PrP(Sc) conversion in Creutzfeldt-Jakob disease appears to become prominent when PrP(C) is abundantly available as substrate, as in inclusion body myositis muscle.

The human T-cell lymphotropic virus type 1 (HTLV-I) causes a neurological disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of infected individuals. Although other neurological outcomes have been described their prevalence is presently unknown. To evaluate the frequency and characteristics of neurological involvement in a population of HTLV-I-infected blood donors we investigated 196 HTLV-I positive and 196 negative blood donors from a blood center of Rio de Janeiro, Brazil. Individuals with abnormalities at the neurological examination were examined by three neurologists, and when pertinent, additional neurological investigations were performed. Descriptive analysis, Student's t-test and chi2 test were employed for statistical analysis. Neurological abnormalities were found in 71 (36.2%) of the HTLV-I positive blood donors and in only 29 (14.8%) of the HTLV-I negative donors (OR = 2.54, 95% CI = 1.67-3.59, p = 0.000002). Cases of myelopathy, motor neuron disease and myopathy were only found in the HTLV-I positive group. In addition, peripheral neuropathy (PN) was significantly more frequent in the positive group (p = 0.015). In summary, our data suggest that HTLV-I-infected individuals exhibit a wide variety of neurological manifestations apart from the classical picture of HAM/TSP.

Background: Human T cell lymphotropic virus type 1 (HTLV-I) can cause tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) and adult T cell leukaemia/lymphoma. More recently other diseases such as isolated peripheral polyneuropathy, myopathy, artropathy, and uveitis have been associated with this retrovirus. Only a few uncontrolled studies, without necessary exclusion criteria, have described mild cognitive deficits among TSP/HAM patients. To further clarify this the authors evaluated, through neuropsychological testing patients with TSP/HAM and asymptomatic infected carriers, comparing both groups with healthy controls., Objectives: To verify the presence of cognitive deficits among TSP/HAM patients and asymptomatic HTLV-1 infected carriers. In addition, the authors aimed to investigate if these deficits correlated with the degree of motor impairment in TSP/HAM patients., Methods: From a cohort of 501 HTLV-1 infected people the authors selected, according to predefined inclusion and exclusion criteria, 40 asymptomatic HTLV-1 carriers and 37 TSP/HAM patients. Neuropsychological testing was blindly performed in both groups and their scores were compared with those obtained from controls., Results: Both the HTLV-1 carrier group and the group of patients with TSP/HAM exhibited a lower performance in neuropsychological tests when compared with controls. Asymptomatic infected carriers and TSP/HAM patients did not differ in their cognitive results. Also, there was no relation between the degree of motor disability and cognitive deficits in the TSP/HAM group. Psychomotor slowing and deficits in the some domains characterised the neuropsychological impairment in HTLV-1 infection: verbal and visual memory, attention and visuomotor abilities., Conclusions: TSP/HAM as well as asymptomatic infection can be associated with mild cognitive deficits. This finding, if confirmed by further studies, will permit the inclusion of cognitive impairment among the neurological manifestations of HTLV-1.

Dermatological findings for patients with human T lymphotropic virus type 1(HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) were investigated and were compared with dermatological findings for a control group. Only xerosis, cutaneous candidiasis, and palmar erythema were significantly associated with HAM/TSP. Histopathological patterns of cutaneous lymphoma were seen in 25% of 32 patients who underwent biopsy, and, thus, the cutaneous alterations in HAM/TSP can be classified into nonspecific lesions, infectious lesions, immune-inflammatory-mediated lesions, and premalignant or malignant lesions.

The frequency and importance of dysautonomia in human T-cell lymphotrophic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) have not been fully investigated. We describe the characteristics of dysautonomia in such patients in a case-control study. Our results indicate that autonomic disturbances are more frequent in HAM/TSP than has been previously suggested, with a predominance of sympathetic nervous system dysfunction. In some of these patients, the symptoms may be severe enough to warrant specific treatment.

We present the case of a 15-year-old patient infected with HTLV-1 who developed a cutaneous T-cell lymphoma, confirmed by histopathological and immunohistochemical examination, as well as clinically and hematologically confirmed leukemia. The patient died 3 months after initial presentation of the disease. The rarity of the disease in this age group justifies the present report.

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.

Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA) is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%), 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6% in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30% of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.

Brazilian patients with HTLV-1 myelopathy present a significant spontaneous lymphocyte proliferation (SLP), and an increased response to IL-2 exogenous stimulation, in both peripheral blood lymphocytes and in whole blood proliferative assays, when compared to the control group. High antibody titers against HTLV-I antigens were also observed in comparison to healthy seropositive individuals. IL-6 was detected in cerebrospinal fluid (CSF) of 50% of the patients (10 out of 20) and TNF-alpha in four out of nineteen individuals. No correlation was found between the presence of levels of cytokines IL-6 and TNF-alpha and duration or severity of disease. The addition of cyclosporin A (CsA) significantly inhibited SLP suggesting that this therapeutic agent should be studied in HTLV-1 myelopathy. Brazilian patients with HTLV-I myelopathy present the same immunological abnormalities described in other endemic regions. The whole blood assay reflects the same results of separated blood cells and, due to its rapid execution may be used as an assay to follow clinical trials.

An account of the authors' experience in strength measurement using a hand-held dynamometer in 16 patients with Duchenne muscular dystrophy (DMD) is given. A rapid decrease of knee extension strength was observed, between 6 and 8 years of age, analysing among patients of different ages. At the same time loss of the ability to walk has occurred. An unexplainable increase in strength was observed in two patients examined in a six month interval. A short review of the literature is given and the conclusion of the importance on the wider use of the instrument.

HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is apparently a disease with a chronic evolution without spontaneous remissions. The real profile of its natural history and of the progression of the neurological disability, however, awaits confirmation. We devised the present study to evaluate the progression profile of the neurological disability of HAM/TSP in a series of 43 patients who have never received any kind of previous immune therapy. Patients were divided into different groups according to the duration of their disease. Age, gender and the Kurtzke's disability status scale (DSS) at the time of the first examination were compared. There were no statistically significant differences among groups with different disease duration. The present study suggests that the evolution of the neurological disability in HAM/TSP occurs mainly during the first year of the disease and becomes relatively stable after that. Therefore we speculate that the variable therapeutic success rates observed in many series of the literature could be due to the timing in the beginning of the pharmacological immunosuppression. Probably the therapeutic window in HAM/TSP lies within the first year of the disease. Thus it might be of utmost importance that future therapeutical trials take into consideration the duration of the disease since this factor can play an important role in the results of the trial.

Human T-cell lymphotropic virus type I (HTLV-I) can be associated with either adult T-cell leukemia or HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic progressive immune-mediated myelopathy. Skin manifestations such as xerosis and erythema may be associated with HAM/TSP. Infective dermatitis due to Staphylococcus aureus or beta-hemolytic Streptococcus has recently been described as a marker for HTLV-I infection and as a probable risk factor for the development of adult T-cell leukemia and lymphoma in Jamaican children. We report a case of folliculitis decalvans, a rare chronic follicular inflammatory process of bacterial origin that is extremely resistant to treatment, in a patient with HAM/TSP. This case suggests the possibility that the disturbance of the immune system that was observed in patients with HAM/TSP can play a role in the persistence of this severe skin lesion. In addition, the findings of our case cast doubt on the hypothesis that the cause of infective dermatitis in persons infected with HTLV-I is immunosuppression due to congenital or perinatal infection of the immature immune system.

Some Brazilian regions are considered to be endemic for human T-cell leukemia/lymphoma virus type I (HTLV-I) infection. Several studies have shown a high prevalence of HTLV-I infection among different groups such as blood donors, hemophiliacs and patients suffering from hematological and neurological diseases. Cases of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) have already been described in Brazil. We report the isolation of an HTLV-I strain from cultured lymphocytes of a TSP/HAM patient. An IL-2-dependent HTLV-I-infected T-cell line (ROB) expressing viral antigens was established and reverse transcriptase activity could be detected in the culture supernatant. Ultrastructural analysis showed immature and mature HTLV retrovirus particles. Finally, HTLV-I provirus type I was demonstrated by the polymerase chain reaction. This is the first isolation completely carried out in Latin America. The molecular analysis of viral strains, now in progress, should clarify the molecular epidemiology of HTLV-I in Brazil.

A patient with carpal tunnel syndrome (CTS) and trophic ulcers is described. Despite the healing of the ulcers after surgery for CTS, the severe sensory deficit and the electrophysiological tests have not shown any significant improvement. We think these findings argue against the hypothesis of the sensory deficit being responsible for the trophic ulcers. We favor a major role for the sympathetic disturbances as the main cause for those lesions.

HTLV-I (Human T-lymphotropic virus type I) associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immunomediated myelopathy induced by the HTLV-I. Some patients, specially those from Japan, seem to have a good response to steroid treatment. However, this has not been found in other regions of the world. High dose intravenous methylprednisolone has been used with success in patients with relapses of multiple sclerosis (MS), another autoimmune disease of the central nervous system. To test the effectiveness of methylprednisolone in patients with HAM/TSP, we devised an open trial in 23 patients. We found a very limited benefit of this form of treatment in these patients. Only one patient, who had the shortest disease duration (five months) in the whole group, showed a sustained benefit. We speculate that those patients with a shorter history, with presumably less demyelination and more inflammatory lesions, would show a better response to immunosuppressive treatments.

Calf enlargement following sciatica is a rare condition. It is reported the case of a 28-year-old woman who complained of repeated episodes of lower back pain radiating into the left buttock and foot. One year after the beginning of her symptoms, she noticed enlargement of her left calf. X-ray studies disclosed L5-S1 disk degeneration. EMG showed muscle denervation with normal motor conduction velocity. Open biopsies of the gastrocnemius muscles were performed. The left gastrocnemius muscle showed hypertrophic type 2 fibers in comparison with the right gastrocnemius. Electron microscopy showed mildly increased number of mitochondria in these fibers. A satisfactory explanation for denervation hypertrophy has yet to be provided.