Tropical Spastic Paraparesis Research Articles

The Impact of motor disability on daily life activities and in Tropical Spastic Paraparesis (HAM/TSP)

The Impact of motor disability on daily life activities and in Tropical Spastic Paraparesis (HAM/TSP)

Comparison of walking measures in patients with HTLV-1 Associated Myelopathy

Walking, a fundamental, complex, multifunctional task, is demanding of multiple body systems, interactively affecting walking capacity. Due to their restricted walking ability, activity and participation levels in patients with HTLV-1-Associated Myelopathy (pwHAM) are compromised. Primarily, the applicability of walking endurance using the 6 minute walk (6MW) and gait speed using the timed 10m walk (10mTW), in pwHAM, were explored. Distance covered, change over one year and the influence of pain were documented. Retrospectively, case notes were abstracted for gait (6MW; 10mTW) and pain, for all pwHAM, walking a minimum of 10m, at least 11 months apart. 26 pwHAM, (8-; 18-) met the assessment criteria. Mean age 58.5 years and disease duration was 10.46years ±6.02years. Observed distance walked (55m at T1 and 71m at T2) was shorter (p<0.01) than expected for age, gender and height (610m). Using a patient's 10mTW velocity to predict the 6MW distance overestimates the actual distance walked in 6 minutes (p=.00 ;p=.00). Initially the 10mTW velocity, accounted for 35% of the variance of the 6MWdistance (F=.59; p=.00), improving to 63% (F=.00; p=.00). Patients’ 10mTW velocities versus healthy age matched controls differed at baseline (p=0.00)and follow-up (p=0.00). Using a walking aid strongly correlated with the 10mTW at both time points (rs=.78 p= .00; rs=.85 p= .00). Change in pain was not significant over time. 23%(baseline)- 42%(followup) of our pwHAM, completed the 6MW. Acting as their own controls, the distance covered for the 6MW is much shorter compared to predicted values. The 10mTW velocity underestimated the degree of disability, usefully predicted functional domains and highlighted functional decline. The 6MW, independent of the 10mTW velocity, provides a functional measure of endurance. Walking capacity in pwHAM can be measured using the 10mTW for gait speed and the 6MW for endurance. These appear to represent different indicators of walking efficacy in pwHAM.

Nutritional status and behavioral factors of individuals with HTLV-1 and tropical spastic paraparesis (HAM / TSP)

Most of the HTLV-1 carriers remain asymptomatic through life, and genetic and immunological factors may be responsible for the appearance of associated diseases. Objective: To describe the nutritional status and some behavioral factors of individuals with HTLV-1 patients with tropical spastic paraparesis (HAM / TSP).

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.

In vivo immunogenicity of Tax (11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine.

Viral oncoprotein Tax plays key roles in transformation of human T cell leukemia virus (HTLV-1)-infected T cells leading to adult T cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate immunotherapeutic potential of this epitope in HLA-A2 transgenic mice in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR hybrid mouse strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly hybrid mouse strain could be used for investigating DC involvement in human class-I-restricted immune responses.

Maternal intranasal immunization with HTLV-1 Env induces Env specific antibody responses in breast milk

Human T cell lymphotropic virus type-1 (HTLV-1) is the etiologic agent of Adult T cell Leukemia and Lymphoma (ATLL) and the neurological disorder HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus prevalent worldwide with foci of high prevalence. However, effective vaccines or drugs against HTLV-1 infection are not available. Because of the severity of the diseases and the absence of a satisfactory treatment, there is indeed an urgent need for an efficient vaccine against HTLV-1 in endemic regions. HTLV-1 is associated with persistent and lifelong infections and a low incidence of lymphomas within its hosts, and can be spread through the contact with bodily fluids containing infected cells, most often from mother to offspring through breast milk. These previous observations suggest that HTLV-1 has common features in infection and protective immune mechanisms with Bovine Leukemia virus (BLV). Imm une protection of newborns by vaccination is difficult to achieve since there is not enough time to mount an immune response before exposure to the virus. Interestingly, previous study revealed that antibodies from the maternal colostrum protect from BLV infection. On the basis of the above reports, we have designed a vaccination strategy mediating transfer of neutralizing antibodies from the mother to the offspring during pregnancy and / or lactation. In the present study, we investigated the effectiveness of intranasal vaccine using HTLV-1 Env protein as an antigen in combination with a synthetic double-stranded RNA analog for the induction of specific antibody in serum and breast milk in mother mice. Full-length Env protein was synthesized using the wheat germ cell-free protein production system. Intranasal administration for mother mice with the Env protein and the synthetic double-stranded RNA adjuvant, polyriboinosinic-polyribocytidylic acid [poly(I:C)] generated significant Env-specific systemic and mucosal immune responses as evidenced by the prominent induction of serum and milk antibodies. Our results provide the first evidence that intranasal co-administration of HTLV-1 Env protein with the poly(I:C) adjuvant augments the viral-specific immunity against HTLV-1.

Retrospective clinic and urodynamic study in the Neurogenic Bladder Dysfunction caused by Human T Cell Lymphotrophic Virus Type 1 Associated Myelopathy / Tropical spastic paraparesis (HAM/TSP)

HTLV-I –associated tropical spastic paraparesis (TSP) and HTLV-I associated myelopathy (HAM) is an endemic disease in Carribean Island. Bladder-sphincter dysfunctions are almost present. Functional disablement is major. Few studies are devoted to urinary disablement, responsible for urologic complications, that gives one of the elements of the severity prognosis of the disease. The objectives of the study are first to describe clinic and urodynamic characteristics of voiding disorders in Martiniquan population, secondly evaluate if there is a relationship between motor and urinary handicap, and thirdly evaluate prognosis factors of urologic complications.

Patterns of spinal cord atrophy in HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP)

Spinal cord inflammation and atrophy contribute to debilitating symptoms in HAM/TSP. We have developed a robust and fast algorithm to determine average cross-sectional area in cervical (c-spine) and thoracic (t-spine) spinal cords by tracing contours perpendicular to the edge in T1-weighted MRI images. The cross-sectional areas in the c- and t-spines were determined in 25 HAM/TSP, 10 asymptomatic carriers (AC) and 10 healthy volunteer (HV) subjects. To date, we have followed 8 of the HAM/TSP patients longitudinally over a two-year period. When compared to the HV data, the HAM/TSP spinal cord profiles fell into four general categories: atrophic entire spine (48%), atrophic t-spine (32%), atrophic c-spine (8%), and normal (12%). The majority of ACs had similar spinal cord profiles to those in the HV group, however, 3 ACs showed a pattern similar to HAM/TSP. As a group, both HAM/TSP c- and t-spines were significantly lower than those of HV (p<0.01). In the 8 patients with follow-up scans, spinal cord size showed an overall decreasing trend over time. In a rapidly progressing patient with the shortest disease duration, we could estimate spinal cord atrophy at a rate of 11% a year in the thoracic cord. In addition, change in proviral load negatively correlated with change in both c- and t-spine cross-sectional area (p<0.05) for patients with shorter disease duration and increasing proviral loads (i.e. an increase in proviral load was associated with a more atrophic cord). These results suggest that the pattern of spinal cord tissue damage is specific to the underlying inflammatory disease, a finding that has direct implications for the use of average cross-sectional spinal cord area as a surrogate end point for clinical trials.

Incidence of tropical spastic parapesis/ HTLV-1 associated myelopathy/ (TSP/HAM) in patients followed in a Reference center in Salvador, Brasil

It is estimated that currently 5 to 10 million people are infected with HTLV-1 worldwide. In Brazil, Salvador is the city with the highest prevalence of HTLV-1 (2% in women and 1.2% in men). Tropical spastic paraparesis/ HTLV associated myelopathy (TSP/HAM) is an insidious and disabling chronic neurological disease. The incidence of TSP/HAM varies in different geographical regions with low rate in Japan and Caribbean islands and higher in Minas Gerais, Brazil. The incidence of TSP/HAM among patients attending the CHTLV in Salvador/BA, from 22 to 2013 was estimated. The outcome of interest was the evolution from asymptomatic status for TSP/HAM diagnosis, which was based on the Belem criteria. The follow-up for individuals that remained asymptomatic was the time between the year of the last medical consultation and the year of the HTLV-1 serological diagnosis and for those that developed TSP/HAM the time between the year of diagnosis of TSP/HAM and the year of HTLV-1 serological diagnosis. The exclusion criteria were a diagnosis of TSP/HAM at the first medical consultation, records with incomplete data and TSP/HAM possible diagnosis. From a sample of 243 patients, 91 were included. Two patients developed TSP/HAM definite and four had TSP/HAM probable diagnosis. The incidence density of TSP/HAM definite was 6.9 and 13 per 1,0 HTLV-1 infected individuals per year, respectively. The cumulative incidence to TSP/HAM definite was 2.29% while to TSP/HAM probable was 4.39%. The incidence rate found herein was higher than that observed in previous studies in Japan and Caribbean, however, similar to that reported in Brazil. More accurate cohort studies should be conducted to measure the actual risk of developing this disease.

Consequences of the association between HTLV-1 and tuberculosis

HTLV-1 modifies the immune response and clinical presentation of bacterial, fungal and helminthic infections. There are also evidences that helminthic infections may modify disease expression related to HTLV-1, increasing the occurrence of Adult T cell leukemia (ATL) and decreasing the development of HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). Recently it has been shown that HTLV-1 increases susceptibility for tuberculosis (TB) but the consequences of this co-infection in the clinical course of TB and HTLV-1 infection is not so clear. The aim of this study was to evaluate if TB influences neurologic disease in HTLV-1 infected subjects and to evaluate sequels of TB in HTLV-1 infected individuals. This is a nested case control study with the participation of 32 patients with previous diagnosis of TB and positivity sorology for HTLV-1 and 32 controls with HTLV-1 without TB paired by age, gender and time of admission in the clinic. Of the 32 patients with TB 29 had pulmonary TB, one had pleural TB, one laryngeal TB and the other lymphonode TB. Only 2 (6,2%) developed a second episode of TB. Among those who have been treated for TB 8 (25%) patients complained of dyspnea, 3 without evidence of pulmonary disease, 3 cases had chronic obstructive pulmonary disease (COPD) and two cases had bronchial overactivity. Regarding HTLV-1 associated disease probable HAM/TSP was diagnosed in 4 (12,5%) of the TB patients and in 6 (18,7%) of the patients who only have HTLV-1 infection (P > 0.05). Definitive HAM/TSP was diagnosed in 10 (31,2%) of the co-infected patients with HTLV-1 and TB and in 4 (12,5%) in the group who only had HTLV-1 (P < 0.05). While HTLV-1 appears to not influence the severity of Micobacterium tuberculosis infection TB was highly associated with HAM/TSP.

Assessment of functional capacity and flexibility of patients infected with HTLV-1

HTLV-1 infects 5 to 10 million people worldwide. Tropical spastic paraparesis / HTLV associated myelopathy (TSP/HAM) is a neurological disease, that impairs functional capacity, daily life activities and quality of life of infected individual. Objective: To evaluate the functional capacity and flexibility of patients infected with HTLV-1. Methods: Sample was comprised of 65 HTLV-1-infected individuals (41 asymptomatic, 24 TSP/HAM definite) followed at the referral center for HTLV of Bahiana School of Medicine and Public Health in Salvador, Brazil. Twenty-six uninfected individuals were enrolled as controls. Inclusion criteria were age from 18 to 65 years, HTLV-1 serology (ELISA and Western Blot) positive (HTLV-group) and negative (uninfected individuals) and for HTLV-1 infected individuals clinical status defined according to the Belem criteria for the HAM/TSP diagnosis. Patients with stroke or trauma history, those coinfected with HIV, HBV, HCV or syphilis were excluded. The functional capacity of all individuals was assessed using the Group of Latin American development for Maturity (GDLAM) protocol: i) 10 Meter Walking Test, ii) time to get up from a chair, iii) time to get up from the prone position and iv) time to get up from a chair and walk around the house. Test performances were expressed in seconds, and used to calculate the GDLAM index. The flexibility was assessed using the sit and reach test, measured in centimeters. Results: The GDLAM index was significantly lower in the uninfected controls (20.80±3.75 seconds) compared to both asymptomatic (26.45±5.99 seconds) and TSP/HAM patients (51.37±14.99 seconds) (p=0, 1). Moreover, the flexibility of uninfected controls (29.16 ± 7.52cm) was significantly higher compared to asymptomatic HTLV-1-infected individuals (23.36 ± 7.97cm) and HAM/TSP patients (14.45 ± 7.52cm) (p=0, 1). Conclusions: HTLV-1-infeted individuals have an impairment of their functional capacity and flexibility when compared to uninfected individuals, especially patients with TSP/HAM. Interestingly, HTLV-1 asymptomatic individuals also had a decrease of both functional capacity and flexibility, prior to clinically detectable signs of myelopathy.

Suppression of HTLV-1 transcription by SIRT1 deacetylase

Infection with HTLV-1 causes adult T-cell leukemia and tropical spastic paraparesis in different subsets of infected people. Treatments for HTLV-1-associated diseases are unspecific and unsatisfactory. Prophylactic measures have not been developed. Although HTLV-1 pathogenesis involves multiple stages and factors, high proviral load has been singled out as a major risk factor which predicts disease. HTLV-1 encodes Tax transactivator that potently activates transcription from viral long terminal repeats (LTR) and cellular promoters harbouring cAMP-responsive or KB element. Blocking Tax activity in infected cells should provide prophylactic and therapeutic benefits. In this study, we characterize the negative regulatory role of SIRT1 deacetylase in Tax-induced activation of HTLV-1 LTR. SIRT1 is a sirtuin with anti-cancer and anti-aging activity. Whereas over expression of SIRT1 abolished the activity of Tax to activate the LTR, compromising SIRT1 by RNA interference augmented Tax activation of the LTR. Resveratrol is a natural inhibitor of SIRT1 widely sold as a nutritional supplement and extensively tested for beneficial effects in various diseases. A SIRT1-dependent inhibition of the transcriptional activity of Tax was observed in cells treated with resveratrol. Consistently, treatment of HTLV-1-transformed T cells with resveratrol led to the activation of SIRT1 and the suppression of HTLV-1 proviral transcription. On the contrary, specific inhibition of SIRT1 by Sirtinol or Ex527 promoted HTLV-1 mRNA expression. The amount of HTLV-1 virion collected from culture supernatant was decreased in MT2 cells treated with resveratrol. Tax was found to interact with SIRT1 in HTLV-1-transformed T cells. Administration of resveratrol blocked the interaction of Tax with CREB and suppressed the recruitment of CREB and CRTC1 to the LTR. Taken together, our findings document the suppression of Tax activation of HTLV-1 transcription by SIRT1 and reveal potential benefits of small-molecule activators of SIRT1 such as resveratrol in the prevention and intervention of HTLV-1-associated diseases. Supported by SKY-MRF (2011), HK-RGC (HKU7674/12M, HKU7686/13M and HKU1/CRF/11G) and HK-HMRF (13121052) grants.

Development of HTLV-1 associated myelopathy/tropical spastic paraparesis in a patient with simian T-lymphotropic virus type 1-like infection.

Virus transmission from various wild and domestic animals contributes to increased risk of emerging infectious diseases in human populations. HTLV-1 is a human retrovirus associated with acute T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which originated from zoonotic transmission from various African and Asian nonhuman primates (NHPs). Similar to HTLV-1, the simian counterpart, STLV-1, causes chronic infection and leukemia and lymphoma in naturally infected monkeys. However, other clinical syndromes typically seen in human such as a chronic progressive myelopathy have not been observed in NHPs. Little is also known about the development of any neurologic and inflammatory diseases in human populations infected with STLV-1-like viruses following NHP exposure. We identified and analyzed the complete genome of a primate T lymphotropic virus type 1 (PTLV-1) isolated from a patient with typical HAM/TSP who resides in the United States but was born in Liberia. Using a novel droplet digital PCR for the detection of the HTLV-1 tax gene, the proviral load in PBMC was 14.01%; however there was a distinct difference in fluorescence amplitude compared to all other H!M/TSP patient's, suggesting viral heterogeneity. A complete PTLV-1 proviral genome was amplified from DNA extracted from the PBMCs of the HAM/TSP patient using PCR to generate nine overlapping subgenomic fragments. Phylogenetic analysis of PTLV-1 env and LTR regions showed the virus was highly related with PTLV-1 from sooty mangabey monkeys and humans exposed from NHPs in West Africa. These results suggest the patient is likely infected with STLV-1, suggesting for the first time that viral transmission from monkey to human may be associated with a chronic progressive neurologic disease.

Patient satisfaction survey for HAM-net registrants

Patient registries can foster communication between doctors and patients who have rare diseases. In order to succeed in the long term, the managers of the registry must work to raise the satisfaction of the registrants. We conducted a satisfaction survey for the HTLV-1 associated myelopathy (HAM) patient registry known as “HAM-net.” Based on the data we collected, we made several alterations, mainly to the newsletter and website. This year we repeated the survey to determine if our alterations were beneficial or not by assessing changes in satisfaction levels. We surveyed 368 patients registered to HAM-net, inquiring about their general impression of HAM-net, the requisite telephone interviews, the newsletter, and the website. The response rate was 74.7%, and 198 registrants responded to the satisfaction survey both times. The number of individuals satisfied with HAM-net in general improved from 63.6% to 77.3% of registrants. More specifically, satisfaction with the newsletter rose dramatically but no significant change was observed for the website. Therefore we concluded that focusing on the newsletter is currently the best way to improve patient satisfaction. For example, we deduced that it is beneficial to increase the volume and quality of the articles. On the other hand, we could not demonstrate that frequently updating the website was beneficial to the patients. We inferred that the website must be improved to be more appealing and useful to the patients. In this study, we showed that properly investigating patient satisfaction using a detailed questionnaire can produce the data necessary to improve patient satisfaction levels. The best way to preserve a good relationship with the registered patients in the long term is to prioritize understanding the patients’ needs and continuously work to improve their satisfaction.

Temporal Trends in HAM/TSP incidence in Martinique over 25 years (1986-2010): dramatic decrease since 2000

Background Human T-Lymphotropic virus 1 (HTLV-1) has been discovered in 1980 and linked to tropical spastic paraparesis (HAM/TSP) in 1985 in Martinique. There is no data on HAM/TSP incidence trends. We report, in the present work, the temporal trends incidence of HAM/TSP in Martinique based on patients diagnosed in our unique Neurology Department in HAM/TSP diagnosis and management over 25 years. Methods: A registry has been set up since 1986 and HAM/TSP characteristics were collected carefully. All patients, living in Martinique, with a definite HAM/TSP onset between 1986 and 2010 were included in the present hospital-based study. The 25-year study time was stratified in five-year and ten-year periods. Crude incidence rates with 95% confidence interval (95%CI) were calculated using Poisson distribution for each period. The denominator was based on data provided by French National Institute for Statistical and Economic Studies (http://www.insee.fr) Results: Overall, 153 patients were identified (mean age at onset, 53+/13.1 years; female: male ratio, 4:1). HAM/TSP incidence rates per 100,000 per 5 years (95%CI) in 1986-1990, 1991-1995, 1996-2000, 2001-2005 and 2006-2010 periods were 10 (6.8-7.3), 12.6 (9-16.1), 11.5 (8.1-14.9), 4.4 (2.56.4) and 2 (1.4-3.5). Between the two decades (1991-2000 and 2001-2010), ten-year HAM/TSP incidence rate decreased by 75% [19.1 (14.8-23.6) versus 4.9 (2.7-7.1)]. Age at onset did not differ between the different periods. Conclusion: There has been a significant decrease (75%) in HAM/TSP incidence in Martinique in the last decade. Prevention policies might have been effective in reducing HTLV-1 seroprevalence in our population. However, environmental factors such as parasite burden decrease could also account for HAM/TSP incidence dramatic fall.

Paraparesia espástica tropical autóctona en la Comunidad de Madrid. Experiencia en el cribado del virus linfotrópico de células T humanas tipo I

We have recently documented a case of tropical spastic paraparesis by HTLV-I in a Spanish patient. HTLV-I infection is rare in Europe, and hardly ever is accompanied by symptoms, but if it does it could trigger a major health issue. This case is presented here, as well as a discussion on the situations in which HTLV-I detection is justified. An analysis was made of the HTLV diagnostic requests at our centre during 2014-2015 (n=123). The diagnostic algorithm was: 1) Enzyme immunoassay, 2) Reverse hybridization, and 3) Proviral DNA detection by PCR. The results showed several situations of HTLV screening, emphasising those related to paraparesis (22%). Seven cases of HTLV-I infection were found: five in patients from endemic regions, one in an HIV-infected patient, and the case of TSP mentioned above. HTLV-I surveillance in non-endemic regions is a challenging issue, as the cost-benefit ratio is not well-established. This case report emphasises the importance of including HTLV within the differential diagnosis of insidious spastic paraparesis.

Human T-Lymphotropic Virus Type I-Associated Myelopathy

Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) is a chronic progressive myelopathy that is characterized by spastic paraparesis with bladder dysfunction that is derived from bilateral pyramidal tract involvement and neurogenic bladder, respectively. The primary neuropathological feature of HAM is chronic inflammation in the spinal cord, mainly the lower thoracic cord, which is characterized by perivascular cuffing and parenchymal infiltration of mononuclear cells. Although it is still unclear why only a very small proportion of HTLV-I carriers develop HAM, the key player in the pathogenesis of HAM is the increase of activated HTLV-I-infected cells in the peripheral blood. The exact cellular and molecular events underlying the induction of chronic inflammation in the spinal cord by HTLV-I are still unclear. However, a long-standing bystander mechanism, such as the destruction of surrounding nervous tissue by the interaction between HTLV-I-infected CD4+ T cells and HTLV-I-specific cytotoxic T cells in the spinal cord, with the cooperation of the positive feedback loop of inflammation that is derived from the migrated HTLV-I-infected cells is probably critical in the immunopathogenesis of HAM. In this review, recent advances in several fields toward the elucidation of the pathomechanisms concomitant with the establishment of new therapeutic strategies in HAM will be discussed along with an overview of the clinical features.

Common γ-chain blocking peptide reduces in vitro immune activation markers in HTLV-1 associated myelopathy/ tropical spastic paraparesis. (P6.299)

Common γ-chain blocking peptide reduces in vitro immune activation markers in HTLV-1 associated myelopathy/ tropical spastic paraparesis. (P6.299)

Pilot study of Raltegravir, an Integrase inhibitor, in Human T-cell lymphotrophic virus-1 (HTLV-1) associated myelopathy, tropical spastic paraparesis (HAM/TSP). (P6.300)

Pilot study of Raltegravir, an Integrase inhibitor, in Human T-cell lymphotrophic virus-1 (HTLV-1) associated myelopathy, tropical spastic paraparesis (HAM/TSP). (P6.300)

Prevalence of Optical Coherence Tomography (OCT) Abnormalities in a Cohort of HLTV-1 Associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP) Patients (P4.071)

Prevalence of Optical Coherence Tomography (OCT) Abnormalities in a Cohort of HLTV-1 Associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP) Patients (P4.071)