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Cureus Aug 2021Subacute-onset muscle weakness can result from channelopathies, inflammatory myopathies, thyroid dysfunction, hypoparathyroidism, vitamin D deficiency, and...
Subacute-onset muscle weakness can result from channelopathies, inflammatory myopathies, thyroid dysfunction, hypoparathyroidism, vitamin D deficiency, and dyselectrolytemias like hypokalemia, hypocalcemia, and hypomagnesemia. We report a curious and extremely rare case of a 29-year-old woman with hyperemesis gravidarum presenting with disabling muscle weakness involving her lower limbs and trunk, and concurrent features of tetany. Following voluminous vomiting over the last two months, she presented with history of weakness of her lower limbs of 14 days duration, resulting in difficulty in her getting out of bed or walking unassisted. On examination, she was hypotensive (80/60 mmHg) and tachycardic (110 bpm), with flaccid weakness of her lower limbs (proximal weakness more than distal weakness - power of 1/5 at the hips bilaterally, and 3/5 at the knees and ankles bilaterally) and diminished deep tendon reflexes. She also had positive Trousseau's sign and Chvostek's sign. Interestingly, she also had thinned-out bluish sclerae, a high-arched palate, short stature, and bilateral conductive hearing loss. Laboratory evaluation revealed anemia, hyponatremia, hypokalemia, hypomagnesemia, hypochloremia, hypophosphatemia, and low vitamin D levels. Electrocardiogram showed prolonged QT interval. Her thyroid function test and parathyroid levels were normal. With parenteral replenishment of the electrolytes and vitamin D, her power improved and she was discharged on oral supplements. Thus, this case report demonstrates the importance of aggressive, early, and adequate management of hyperemesis gravidarum to prevent dyselectrolytemia-associated paraparesis.
PubMed: 34522495
DOI: 10.7759/cureus.17014 -
Frontiers in Immunology 2022Human T lymphotropic virus 1 (HTLV-1) is a human retrovirus identified as the causative agent in adult T-cell leukemia/lymphoma (ATL) and chronic-progressive... (Review)
Review
Human T lymphotropic virus 1 (HTLV-1) is a human retrovirus identified as the causative agent in adult T-cell leukemia/lymphoma (ATL) and chronic-progressive neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 is estimated to infect between 5-20 million people worldwide, although most infected individuals remain asymptomatic. HTLV-1 infected persons carry an estimated lifetime risk of approximately 5% of developing ATL, and between 0.25% and 1.8% of developing HAM/TSP. Most HTLV-1 infection is detected in CD4 T cells which causes the aggressive malignancy in ATL. In HAM/TSP, the increase of HTLV-1 provirus induces immune dysregulation to alter inflammatory milieu, such as expansion of HTLV-1-specific CD8 T cells, in the central nervous system of the infected subjects, which have been suggested to underlie the pathogenesis of HAM/TSP. Factors contributing to the conversion from asymptomatic carrier to disease state remain poorly understood. As such, the identification and tracking of HTLV-1-specific T cell biomarkers that may be used to monitor the progression from primary infection to immune dysfunction and disease are of great interest. T cell receptor (TCR) repertoires have been extensively investigated as a mechanism of monitoring adaptive T cell immune response to viruses and tumors. Breakthrough technologies such as single-cell RNA sequencing have increased the specificity with which T cell clones may be characterized and continue to improve our understanding of TCR signatures in viral infection, cancer, and associated treatments. In HTLV-1-associated disease, sequencing of TCR repertoires has been used to reveal repertoire patterns, diversity, and clonal expansions of HTLV-1-specific T cells capable of immune evasion and dysregulation in ATL as well as in HAM/TSP. Conserved sequence analysis has further been used to identify CDR3 motif sequences and exploit disease- or patient-specificity and commonality in HTLV-1-associated disease. In this article we review current research on TCR repertoires and HTLV-1-specific clonotypes in HTLV-1-associated diseases ATL and HAM/TSP and discuss the implications of TCR clonal expansions on HTLV-1-associated disease course and treatments.
Topics: Adult; Biomarkers; CD8-Positive T-Lymphocytes; Human T-lymphotropic virus 1; Humans; Paraparesis, Tropical Spastic; Receptors, Antigen, T-Cell
PubMed: 36189294
DOI: 10.3389/fimmu.2022.984274 -
Viruses Dec 2018Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of a neural chronic inflammation, called HTLV-1-associated myelopathy/tropical spastic paraparesis... (Review)
Review
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of a neural chronic inflammation, called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and of a malignant lymphoproliferation, called the adult T-cell leukemia/lymphoma (ATLL). The mechanisms through which the HTLV-1 induces these diseases are still unclear, but they might rely on immune alterations. HAM/TSP is associated with an impaired production of pro-inflammatory cytokines and chemokines, such as IFN-γ, TNF-α, CXCL9, or CXCL10. ATLL is associated with high levels of IL-10 and TGF-β. These immunosuppressive cytokines could promote a protumoral micro-environment. Moreover, HTLV-1 infection impairs the IFN-I production and signaling, and favors the IL-2, IL-4, and IL-6 expression. This contributes both to immune escape and to infected cells proliferation. Here, we review the landscape of cytokine dysregulations induced by HTLV-1 infection and the role of these cytokines in the HTLV-1-associated diseases progression.
Topics: Animals; Chemokine CXCL9; Chemokines; Cytokines; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Interferon-gamma; Interleukin-10; Leukemia-Lymphoma, Adult T-Cell; Mice; Paraparesis, Tropical Spastic; Signal Transduction; Tumor Necrosis Factor-alpha
PubMed: 30563084
DOI: 10.3390/v10120691 -
American Journal of Human Genetics Apr 2023The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for...
The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development and developmental regression after the first year of life, followed by progressive spasticity that led to gait alterations, paraparesis, and oromotor dysfunction. Most individuals had cerebral, cerebellar, or basal ganglia volume loss by brain MRI. In the available cells from affected individuals, SNAPC4 abundance was decreased compared to unaffected controls, suggesting that the bi-allelic variants affect SNAPC4 accumulation. The depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing. Analysis of available fibroblasts from affected individuals showed decreased snRNA expression and global dysregulation of alternative splicing compared to unaffected cells. Altogether, these data suggest that these bi-allelic SNAPC4 variants result in loss of function and underlie the neuroregression and progressive spasticity in these affected individuals.
Topics: Paraparesis, Spastic; Humans; Alternative Splicing; DNA-Binding Proteins; Transcription Factors; HeLa Cells; Protein Isoforms; RNA-Seq; Male; Female; Pedigree; Alleles; Infant; Child, Preschool; Child; Adolescent; Protein Structure, Secondary; RNA, Small Nuclear
PubMed: 36965478
DOI: 10.1016/j.ajhg.2023.03.001 -
Clinical Microbiology Reviews Apr 2022Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult... (Review)
Review
Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The burden of HTLV-1 infection appears to be geographically concentrated, with high prevalence in discrete regions and populations. While most high-income countries have introduced HTLV-1 screening of blood donations, few other public health measures have been implemented to prevent infection or its consequences. Recent advocacy from concerned researchers, clinicians, and community members has emphasized the potential for improved prevention and management of HTLV-1 infection. Despite all that has been learned in the 4 decades following the discovery of HTLV-1, gaps in knowledge across clinical and public health aspects persist, impeding optimal control and prevention, as well as the development of policies and guidelines. Awareness of HTLV-1 among health care providers, communities, and affected individuals remains limited, even in countries of endemicity. This review provides a comprehensive overview on HTLV-1 epidemiology and on clinical and public health and highlights key areas for further research and collaboration to advance the health of people with and at risk of HTLV-1 infection.
Topics: Adult; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Paraparesis, Tropical Spastic; Public Health
PubMed: 35195446
DOI: 10.1128/cmr.00078-21 -
Frontiers in Immunology 2022Previous studies have demonstrated the development of pulmonary impairment in individuals infected with human T-lymphotropic virus type 1 (HTLV-1). Complications, such... (Review)
Review
Previous studies have demonstrated the development of pulmonary impairment in individuals infected with human T-lymphotropic virus type 1 (HTLV-1). Complications, such as alveolitis and bronchiectasis, were found in individuals who developed tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP-HAM) due to chronic inflammation. These patients exhibited increased levels of lymphocytes (CD4+ and CD25+), cytokines (IL-2, IL-12, and IFN-γ), inflammatory chemokines (MIP-1α and IP-10), and cell adhesion molecules (ICAM-1) in the bronchoalveolar lavage fluid, with the result of chronic inflammation and lung injury. The main lesions observed at Chest high-resolution computed tomography were centrilobular nodules, parenchymal bands, lung cysts, bronchiectasis, ground-glass opacity, mosaic attenuation, and pleural thickening. It can lead to progressive changes in pulmonary function with the development of restrictive and obstructive diseases. Recent studies suggest a causal relationship between HTLV-1 and pulmonary diseases, with intensification of lesions and progressive decrease in pulmonary function. This summary updates a previous publication and addresses the general lack of knowledge regarding the relationship between TSP-HAM and pulmonary disease, providing direction for future work and the management of these individuals.
Topics: Bronchiectasis; Human T-lymphotropic virus 1; Humans; Inflammation; Lung Diseases; Lung Injury; Paraparesis, Tropical Spastic
PubMed: 35844492
DOI: 10.3389/fimmu.2022.914498 -
Viruses Jul 2022Human T cell leukemia virus type 1 (HTLV-1), the etiological agent of adult T cell leukemia/lymphoma (ATLL) and of HTLV-1-associated myelopathy/tropical spastic... (Review)
Review
Human T cell leukemia virus type 1 (HTLV-1), the etiological agent of adult T cell leukemia/lymphoma (ATLL) and of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), was identified a few years before Human Immunodeficiency Virus (HIV). However, forty years later, our comprehension of HTLV-1 immune detection and the host immune responses to HTLV-1 is far more limited than for HIV. In addition to innate and adaptive immune responses that rely on specialized cells of the immune system, host cells may also express a range of antiviral factors that inhibit viral replication at different stages of the cycle, in a cell-autonomous manner. Multiple antiviral factors allowing such an intrinsic immunity have been primarily and extensively described in the context HIV infection. Here, we provide an overview of whether known HIV restriction factors might act on HTLV-1 replication. Interestingly, many of them do not exert any antiviral activity against HTLV-1, and we discuss viral replication cycle specificities that could account for these differences. Finally, we highlight future research directions that could help to identify antiviral factors specific to HTLV-1.
Topics: Adult; Antiviral Agents; HIV Infections; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Paraparesis, Tropical Spastic
PubMed: 35893677
DOI: 10.3390/v14081611 -
Viruses Sep 2022Dendritic cells (DCs) function as a link between innate and adaptive immune responses. Retroviruses HIV-1 and HTLV-1 modulate DCs to their advantage and utilize them to... (Review)
Review
Dendritic cells (DCs) function as a link between innate and adaptive immune responses. Retroviruses HIV-1 and HTLV-1 modulate DCs to their advantage and utilize them to propagate infection. Coinfection of HTLV-1 and HIV-1 has implications for cancer malignancies. Both viruses initially infect DCs and propagate the infection to CD4 T cells through cell-to-cell transmission using mechanisms including the formation of virologic synapses, viral biofilms, and conduits. These retroviruses are both neurotrophic with neurovirulence determinants. The neuropathogenesis of HIV-1 and HTLV-1 results in neurodegenerative diseases such as HIV-associated neurocognitive disorders (HAND) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Infected DCs are known to traffic to the brain (CNS) and periphery (PNS, lymphatics) to induce neurodegeneration in HAND and HAM/TSP patients. Elevated levels of neuroinflammation have been correlated with cognitive decline and impairment of motor control performance. Current vaccinations and therapeutics for HIV-1 and HTLV-1 are assessed and can be applied to patients with HIV-1-associated cancers and adult T cell leukemia/lymphoma (ATL). These diseases caused by co-infections can result in both neurodegeneration and cancer. There are associations with cancer malignancies and HIV-1 and HTLV-1 as well as other human oncogenic viruses (EBV, HBV, HCV, HDV, and HPV). This review contains current knowledge on DC sensing of HIV-1 and HTLV-1 including DC-SIGN, Tat, Tax, and current viral therapies. An overview of DC interaction with oncogenic viruses including EBV, Hepatitis viruses, and HPV is also provided. Vaccines and therapeutics targeting host-pathogen interactions can provide a solution to co-infections, neurodegeneration, and cancer.
Topics: Adult; Coinfection; Dendritic Cells; HIV Infections; HIV Seropositivity; HIV-1; HTLV-I Infections; Host-Pathogen Interactions; Human T-lymphotropic virus 1; Humans; Neoplasms; Oncogenic Viruses; Papillomavirus Infections; Paraparesis, Tropical Spastic
PubMed: 36146843
DOI: 10.3390/v14092037 -
Virulence Dec 2023Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which...
Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients ( = 10), asymptomatic HTLV-1-infected carriers (ASP, = 8), and a second group of healthy controls ( = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.
Topics: Humans; Prognosis; Paraparesis, Tropical Spastic; Human T-lymphotropic virus 1; MicroRNAs; Biomarkers
PubMed: 37394816
DOI: 10.1080/21505594.2023.2230015 -
Surgical Neurology International 2020True intramedullary epidermoid cysts (IECs) not associated with congenital anomalies or previous spinal procedures are extremely rare. In a review of the literature... (Review)
Review
BACKGROUND
True intramedullary epidermoid cysts (IECs) not associated with congenital anomalies or previous spinal procedures are extremely rare. In a review of the literature since 1992, only 29 such cases have been reported. Here, we add three new cases in this category.
CASE DESCRIPTION
Three adults presented with spastic paraparesis attributed to thoracic IECs. Gross total microsurgical removal was achieved in two cases, while one case was a partial resection due to capsular adherence to the cord. In all three cases, patients sustained complete recoveries of neurological function and remained symptom free for an average of 5 years follow-up.
CONCLUSION
IECs are rare lesions; here, the three located in the thoracic spine, contributed to slow, progressive spastic paraparesis with/without incontinence, and resolved following total (2 patients) and partial (1 patient) resection.
PubMed: 32123605
DOI: 10.25259/SNI_540_2019