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Viruses Dec 2017Going back to their discovery in the early 1980s, both the Human T-cell Leukemia virus type-1 (HTLV-1) and the Human Immunodeficiency Virus type-1 (HIV-1) greatly... (Review)
Review
Going back to their discovery in the early 1980s, both the Human T-cell Leukemia virus type-1 (HTLV-1) and the Human Immunodeficiency Virus type-1 (HIV-1) greatly fascinated the virology scene, not only because they were the first human retroviruses discovered, but also because they were associated with fatal diseases in the human population. In almost four decades of scientific research, both viruses have had different fates, HTLV-1 being often upstaged by HIV-1. However, although being very close in terms of genome organization, cellular tropism, and viral replication, HIV-1 and HTLV-1 are not completely commutable in terms of treatment, especially because of the opposite fate of the cells they infect: death versus immortalization, respectively. Nowadays, the antiretroviral therapies developed to treat HIV-1 infected individuals and to limit HIV-1 spread among the human population have a poor or no effect on HTLV-1 infected individuals, and thus, do not prevent the development of HTLV-1-associated diseases, which still lack highly efficient treatments. The present review mainly focuses on the course of HTLV-1 infection, from the initial infection of the host to diseases development and associated treatments, but also investigates HIV-1/HTLV-1 co-infection events and their impact on diseases development.
Topics: CD4-Positive T-Lymphocytes; Coinfection; Drug Discovery; HIV Infections; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Paraparesis, Tropical Spastic; Virus Replication
PubMed: 29267225
DOI: 10.3390/v10010001 -
Neurology India 2023
Topics: Humans; Angiolipoma; Paraparesis; Spine; Spinal Neoplasms; Magnetic Resonance Imaging
PubMed: 37929504
DOI: 10.4103/0028-3886.388084 -
Annals of Clinical and Translational... Feb 2023HTLV-1 infection causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), resulting in loss of motor function. In this Phase 2 trial, we assessed the...
OBJECTIVE
HTLV-1 infection causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), resulting in loss of motor function. In this Phase 2 trial, we assessed the efficacy and safety of l-arginine in patients with HAM/TSP.
METHODS
This open-label, single-arm, Phase 2 study enrolled patients diagnosed with HAM/TSP. Patients received l-arginine at a dose of 20 g orally for 1 week and were followed-up for 3 weeks. The primary endpoint was change in walking speed in the 10-m walk test (10MWT). The main secondary endpoints were change in Timed Up and Go Test (TUGT) time, improvement in inflammatory markers in cerebrospinal fluid (CSF), safety, and tolerability.
RESULTS
The study enrolled 20 patients (13 [65%] female) with a mean age of 67.8 years (95% CI 62.3 to 73.3). Although the primary endpoint, the changes in 10MWT time between baseline (Day 0) and Day 7, did not reach statistical significance (mean percent change in time -3.5%, 95% CI -10.8% to 3.7%; P = 0.32), a significant improvement was detected between baseline and Day 14 (-9.4%, 95% CI -16.6% to -2.2%; P = 0.01). Significant improvements were also observed in selected secondary endpoints, including in TUGT time (-9.1%, 95% CI -15.5% to -2.7%; P < 0.01), and in neopterin concentration in CSF (-2.1 pmol/mL, 95% CI -3.8 to -0.5; P = 0.01). Adverse events were infrequent, mild, and resolved rapidly.
INTERPRETATION
l-arginine therapy improved motor function and decreased CSF inflammatory markers. l-arginine thus represents a promising therapeutic option for patients with HAM/TSP.
TRIAL REGISTRATION NUMBER
UMIN000023854.
Topics: Humans; Female; Aged; Male; Human T-lymphotropic virus 1; Postural Balance; Time and Motion Studies; Paraparesis, Tropical Spastic; HTLV-I Infections
PubMed: 36547017
DOI: 10.1002/acn3.51715 -
Journal of Neurovirology Oct 2020Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).... (Review)
Review
Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is an inflammatory disease of the spinal cord and clinically characterized by progressive spastic paraparesis, urinary incontinence, and mild sensory disturbance. The interaction between the host immune response and HTLV-1-infected cells regulates the development of HAM/TSP. HTLV-1 preferentially infects CD4 T cells and is maintained by proliferation of the infected T cells. HTLV-1-infected cells rarely express viral antigens in vivo; however, they easily express the antigens after short-term culture. Therefore, such virus-expressing cells may lead to activation and expansion of antigen-specific T cell responses. Infected T cells with HTLV-1 and HTLV-1-specific CD8 cytotoxic T lymphocytes invade the central nervous system and produce various proinflammatory cytokines and chemokines, leading to neuronal damage and degeneration. Therefore, cellular immune responses to HTLV-1 have been considered to play important roles in disease development of HAM/TSP. Recent studies have clarified the viral strategy for persistence in the host through genetic and epigenetic changes by HTLV-1 and host immune responses including T cell function and differentiation. Newly developed animal models could provide the opportunity to uncover the precise pathogenesis and development of clinically effective treatment. Several molecular target drugs are undergoing clinical trials with promising efficacy. In this review, we summarize recent advances in the immunopathogenesis of HAM/TSP and discuss the perspectives of the research on this disease.
Topics: Animals; CD4-Positive T-Lymphocytes; Cell Proliferation; Cytokines; Disease Models, Animal; Host-Pathogen Interactions; Human T-lymphotropic virus 1; Humans; Immunity, Cellular; Immunologic Factors; Leukemia-Lymphoma, Adult T-Cell; Lymphocyte Activation; Neurons; Neuroprotective Agents; Paraparesis, Tropical Spastic; Spinal Cord; T-Lymphocytes, Cytotoxic; Urinary Incontinence
PubMed: 32705480
DOI: 10.1007/s13365-020-00881-w -
Neurogenetics Apr 2024Hereditary spastic paraparesis (HSP) is a group of central nervous system diseases primarily affecting the spinal upper motor neurons, with different inheritance... (Review)
Review
Hereditary spastic paraparesis (HSP) is a group of central nervous system diseases primarily affecting the spinal upper motor neurons, with different inheritance patterns and phenotypes. SPG46 is a rare, early-onset and autosomal recessive HSP, linked to biallelic GBA2 mutations. About thirty families have been described worldwide, with different phenotypes like complicated HSP, recessive cerebellar ataxia or Marinesco-Sjögren Syndrome. Herein, we report five SPG46 patients harbouring five novel GBA2 mutations, the largest series described in Italy so far. Probands were enrolled in five different centres and underwent neurological examination, clinical cognitive assessment, column imaging for scoliosis assessment, ophthalmologic examination, brain imaging, GBA2 activity in peripheral blood cells and genetic testing. Their phenotype was consistent with HSP, with notable features like upper gaze palsy and movement disorders. We review demographic, genetic, biochemical and clinical information from all documented cases in the existing literature, focusing on the global distribution of cases, the features of the syndrome, its variable presentation, new potential identifying features and the significance of measuring GBA2 enzyme activity.
Topics: Adult; Female; Humans; Male; Middle Aged; Glucosylceramidase; Italy; Mutation; Pedigree; Phenotype; Spastic Paraplegia, Hereditary
PubMed: 38334933
DOI: 10.1007/s10048-024-00749-9 -
Journal of Cancer Research and... 2022Osteochondromas are usually osseous outgrowths arising from the metaphyseal region of cortical bone. Moreover, osteochondroma can also arise from flat bones and the...
Osteochondromas are usually osseous outgrowths arising from the metaphyseal region of cortical bone. Moreover, osteochondroma can also arise from flat bones and the spine. However, their origin in the ribs is extremely rare and always near the costochondral junction. We present a 26-year-old male who presented with chief complaints of difficulty in walking for 2 weeks subsequently diagnosed with osteochondroma based on the presence of a cartilage cap on Magnetic resonance imaging.
Topics: Male; Humans; Adult; Bone Neoplasms; Osteochondroma; Ribs; Paraparesis; Magnetic Resonance Imaging
PubMed: 36412449
DOI: 10.4103/jcrt.JCRT_400_20 -
Cureus Jun 2022Sarcoidosis is a chronic granulomatous disorder mostly known to affect the respiratory system. However, about 5-10% of cases develop neurological complications, either...
Sarcoidosis is a chronic granulomatous disorder mostly known to affect the respiratory system. However, about 5-10% of cases develop neurological complications, either de novo or in patients with known sarcoidosis. The most common complications as cited by current literature include cranial nerve palsies, meningitis, and myelopathy. A unilateral thalamic lesion is an extremely rare presentation of disease. As the neurological manifestations of sarcoidosis are uncommon and variable, it poses a diagnostic challenge. We present a challenging case with worsening paraparesis and a step-by-step approach to how it was diagnosed as neurosarcoidosis. We aimed to create awareness about this uncommon manifestation to avoid misdiagnosis and promote early recognition of neurosarcoidosis.
PubMed: 35720784
DOI: 10.7759/cureus.25958 -
PloS One 2018Peak oxygen uptake (VO2peak) in Paralympic sitting sports athletes represents their maximal ability to deliver energy aerobically in an upper-body mode, with values... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peak oxygen uptake (VO2peak) in Paralympic sitting sports athletes represents their maximal ability to deliver energy aerobically in an upper-body mode, with values being influenced by sex, disability-related physiological limitations, sport-specific demands, training status and how they are tested.
OBJECTIVES
To identify VO2peak values in Paralympic sitting sports, examine between-sports differences and within-sports variations in VO2peak and determine the influence of sex, age, body-mass, disability and test-mode on VO2peak.
DESIGN
Systematic literature review and meta-analysis.
DATA SOURCES
PubMed, CINAHL, SPORTDiscusTM and EMBASE were systematically searched in October 2016 using relevant medical subject headings, keywords and a Boolean.
ELIGIBILITY CRITERIA
Studies that assessed VO2peak values in sitting sports athletes with a disability in a laboratory setting were included.
DATA SYNTHESIS
Data was extracted and pooled in the different sports disciplines, weighted by the Dersimonian and Laird random effects approach. Quality of the included studies was assessed with a modified version of the Downs and Black checklist by two independent reviewers. Meta-regression and pooled-data multiple regression analyses were performed to assess the influence of sex, age, body-mass, disability, test mode and study quality on VO2peak.
RESULTS
Of 6542 retrieved articles, 57 studies reporting VO2peak values in 14 different sitting sports were included in this review. VO2peak values from 771 athletes were used in the data analysis, of which 30% participated in wheelchair basketball, 27% in wheelchair racing, 15% in wheelchair rugby and the remaining 28% in the 11 other disciplines. Fifty-six percent of the athletes had a spinal cord injury and 87% were men. Sports-discipline-averaged VO2peak values ranged from 2.9 L∙min-1 and 45.6 mL∙kg-1∙min-1 in Nordic sit skiing to 1.4 L∙min-1 and 17.3 mL∙kg-1∙min-1 in shooting and 1.3 L∙min-1 and 18.9 mL∙kg-1∙min-1 in wheelchair rugby. Large within-sports variation was found in sports with few included studies and corresponding low sample sizes. The meta-regression and pooled-data multiple regression analyses showed that being a man, having an amputation, not being tetraplegic, testing in a wheelchair ergometer and treadmill mode, were found to be favorable for high absolute and body-mass normalized VO2peak values. Furthermore, high body mass was favourable for high absolute VO2peak values and low body mass for high body-mass normalized VO2peak values.
CONCLUSION
The highest VO2peak values were found in Nordic sit skiing, an endurance sport with continuously high physical efforts, and the lowest values in shooting, a sport with low levels of displacement, and in wheelchair rugby where mainly athletes with tetraplegia compete. However, VO2peak values need to be interpreted carefully in sports-disciplines with few included studies and large within-sports variation. Future studies should include detailed information on training status, sex, age, test mode, as well as the type and extent of disability in order to more precisely evaluate the effect of these factors on VO2peak.
Topics: Athletes; Disabled Persons; Humans; Oxygen Consumption; Paraparesis; Sports; Wheelchairs
PubMed: 29474386
DOI: 10.1371/journal.pone.0192903 -
Annals of Clinical and Translational... Oct 2021Human T-cell lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive myelopathy. A high proviral load (PVL)... (Clinical Trial)
Clinical Trial
OBJECTIVE
Human T-cell lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive myelopathy. A high proviral load (PVL) is one of the main risk factors for HAM/TSP. Recently, it was shown that raltegravir could inhibit cell-free and cell-to-cell transmission of HTLV-1 in vitro. Given the substantial clinical experience in human immunodeficiency virus infection and its excellent safety profile, this agent may be an attractive therapeutic option for HAM/TSP patients.
METHODS
Sixteen subjects with HAM/TSP received raltegravir 400 mg orally twice daily in an initial 6-month treatment phase, followed by a 9-month post-treatment phase. HTLV-1 PVLs were assessed using droplet digital PCR from the PBMCs every 3 months, and from the CSF at baseline, month 6, and month 15. We also evaluated the ability of raltegravir to regulate abnormal immune responses in HAM/TSP patients.
RESULTS
While a downward trend was observed in PBMC and/or CSF PVLs of some patients, raltegravir overall did not have any impact on the PVL in this HAM/TSP patient cohort. Clinically, all patients' neurological scores and objective measurements remained relatively stable, with some expected variability. Immunologic studies showed alterations in the immune profiles of a subset of patients including decreased CD4 CD25 T cells and spontaneous lymphoproliferation.
INTERPRETATION
Raltegravir was generally well tolerated in this HAM/TSP patient cohort. A subset of patients exhibited a mild decrease in PVL as well as variations in their immune profiles after taking raltegravir. These findings suggest that raltegravir may be a therapeutic option in select HAM/TSP patients.
CLINICAL TRIAL REGISTRATION NUMBER
NCT01867320.
Topics: Adult; Aged; Female; Humans; Integrase Inhibitors; Male; Middle Aged; Paraparesis, Tropical Spastic; Pilot Projects; Raltegravir Potassium; Treatment Outcome
PubMed: 34562313
DOI: 10.1002/acn3.51437 -
BMC Musculoskeletal Disorders Feb 2021To explore the therapeutic effect of early surgical intervention for active thoracic spinal tuberculosis (TB) patients with paraparesis and paraplegia.
BACKGROUND
To explore the therapeutic effect of early surgical intervention for active thoracic spinal tuberculosis (TB) patients with paraparesis and paraplegia.
METHODS
Data on 118 active thoracic spinal TB patients with paraparesis and paraplegia who had undergone surgery at an early stage (within three weeks of paraparesis and paraplegia) from January 2008 to December 2014 were retrospectively analyzed. The operation duration, blood loss, perioperative complication rate, VAS score, ASIA grade and NASCIS score of neurological status rating, Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), kyphotic Cobb's angle, and duration of bone graft fusion were analyzed to evaluate the therapeutic effects of surgery.
RESULTS
The mean operating time was 194.2 minutes, and the mean blood loss was 871.2 ml. The perioperative complication rate was 5.9 %. The mean preoperative VAS score was 5.3, which significantly decreased to 3.2 after the operation and continued decreasing to 1.1 at follow up (P<0.05). All cases achieved an increase of at least one ASIA grade after operation. The rate of full neurological recovery for paraplegia (ASIA grade A and B) was 18.0 % and was significantly lower than the rate (100 %) for paraparesis (ASIA grade C and D) (P<0.05). On the NASCIS scale, the difference in the neurological improvement rate between paraplegia (22.2 % ± 14.1 % in sensation and 52.2 % ± 25.8 % in movement) and paraparesis (26.7 % ± 7.5 % in sensation and 59.4 % ± 7.3 % in movement) was remarkable (P<0.05). Mean preoperative ESR and CRP were 73.1 mm /h and 82.4 mg/L, respectively, which showed a significant increase after operation (P>0.05), then gradually decreased to 11.5 ± 1.8 mm/h and 2.6 ± 0.82 mg/L, respectively, at final follow up (P<0.05). The mean preoperative kyphotic Cobb's angle was 21.9º, which significantly decreased to 6.5º after operation (P<0.05) while kyphotic correction was not lost during follow up (P>0.05). The mean duration of bone graft fusion was 8.6 ± 1.3 months.
CONCLUSIONS
Early surgical intervention may be beneficial for active thoracic spinal TB patients with paraparesis and paraplegia, with surgical intervention being more beneficial for recovery from paraparesis than paraplegia.
Topics: Debridement; Humans; Lumbar Vertebrae; Paraparesis; Paraplegia; Retrospective Studies; Spinal Fusion; Thoracic Vertebrae; Treatment Outcome; Tuberculosis, Spinal
PubMed: 33612112
DOI: 10.1186/s12891-021-04078-y