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BMC Infectious Diseases Jun 2024Human T-cell lymphotropic virus type 1 (HTLV-1), also denominated Human T-cell leukemia virus-1, induces immune activation and secretion of proinflammatory cytokines,...
BACKGROUND
Human T-cell lymphotropic virus type 1 (HTLV-1), also denominated Human T-cell leukemia virus-1, induces immune activation and secretion of proinflammatory cytokines, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Regulatory T lymphocytes (Tregs) may control of inflammation through the production of regulatory cytokines, including IL10 and TGF-β. In this study we determined the frequencies of CD4 + and CD8 + Tregs in a HAM/TSP population, compared to asymptomatic carriers and uninfected individuals, as well as investigated the profiles of regulatory and inflammatory cytokines.
METHODS
Asymptomatic HTLV-1 carriers and HAM/TSP patients were matched by sex and age. The frequencies of IL10- and/or TGF-β-producing Tregs were quantified by flow cytometry. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify HTLV-1 proviral load and the mRNA expression of cytokines and cellular receptors in peripheral blood mononuclear cells.
RESULTS
Total frequencies of CD4 + Tregs, as well as the IL10-producing CD4 + and CD8 + Treg subsets, were statistically higher in patients with HAM/TSP compared to asymptomatic HTLV-1-infected individuals. In addition, a positive correlation was found between the frequency of CD4 + IL10 + Tregs and proviral load in the HAM/TSP patients evaluated. A positive correlation was also observed between gene expression of proinflammatory versus regulatory cytokines only in HAM / TSP group.
CONCLUSIONS
A higher frequencies of IL10-producing Tregs were identified in patients with HAM/TSP. Imbalanced production of IL10 in relation to TGF-β may contribute to the increased inflammatory response characteristically seen in HAM/TSP patients.
Topics: Humans; T-Lymphocytes, Regulatory; Male; Female; Paraparesis, Tropical Spastic; Interleukin-10; Middle Aged; Human T-lymphotropic virus 1; Transforming Growth Factor beta; Adult; Viral Load; Aged; HTLV-I Infections; Carrier State
PubMed: 38943078
DOI: 10.1186/s12879-024-09494-8 -
Boletin Medico Del Hospital Infantil de... 2024Transverse myelitis (TM) is a demyelinating inflammatory disease that presents with motor, sensory, and autonomic dysfunction, which may be acute or subacute....
BACKGROUND
Transverse myelitis (TM) is a demyelinating inflammatory disease that presents with motor, sensory, and autonomic dysfunction, which may be acute or subacute. COVID-19-associated TM has been described in a scarce number of patients.
CLINICAL CASE
A 15-year-old previously healthy male patient with respiratory disease before his neurological deterioration presented to the emergency room after developing a complete medullary syndrome located at the cervical-dorsal level, with ascending and symmetric paraparesis that rapidly progressed to paraplegia, with sensory dysfunction from the T3 level, sphincter dysfunction and sudden ventilatory deterioration that required mechanical ventilation. Magnetic resonance imaging was compatible with acute TM. Inflammatory and non-inflammatory etiologies were discarded. In addition, a positive severe acute respiratory syndrome coronavirus 2 test was obtained. Treatment included steroid pulses and plasmapheresis, with an insidious evolution.
CONCLUSION
COVID-19 is an infrequent cause of TM and should be suspected when other etiologies have been ruled out.
Topics: Humans; Myelitis, Transverse; COVID-19; Male; Adolescent; Magnetic Resonance Imaging; Plasmapheresis; Respiration, Artificial; Paraplegia; Paraparesis
PubMed: 38941642
DOI: 10.24875/BMHIM.23000179 -
Medicina (Kaunas, Lithuania) May 2024: The aim of this study is to present our experience in the surgical treatment of calcified thoracic herniated disc disease via a transthoracic approach in the lateral...
Surgical Treatment of Calcified Thoracic Herniated Disc Disease via the Transthoracic Approach with the Use of Intraoperative Computed Tomography (iCT) and Microscope-Based Augmented Reality (AR).
: The aim of this study is to present our experience in the surgical treatment of calcified thoracic herniated disc disease via a transthoracic approach in the lateral position with the use of intraoperative computed tomography (iCT) and augmented reality (AR). All patients who underwent surgery for calcified thoracic herniated disc via a transthoracic transpleural approach at our Department using iCT and microscope-based AR were included in the study. : Six consecutive patients (five female, median age 53.2 ± 6.4 years) with calcified herniated thoracic discs (two patients Th 10-11 level, two patients Th 7-8, one patient Th 9-10, one patient Th 11-12) were included in this case series. Indication for surgery included evidence of a calcified thoracic disc on magnet resonance imaging (MRI) and CT with spinal canal stenosis of >50% of diameter, intractable pain, and neurological deficits, as well as MRI-signs of myelopathy. Five patients had paraparesis and ataxia, and one patient had no deficit. All surgeries were performed in the lateral position via a transthoracic transpleural approach (Five from left side). CT for automatic registration was performed following the placement of the reference array, with a high registration accuracy. Microscope-based AR was used, with segmented structures of interest such as vertebral bodies, disc space, herniated disc, and dural sac. Mean operative time was 277.5 ± 156 min. The use of AR improved orientation in the operative field for identification, and tailored the resection of the herniated disc and the identification of the course of dural sac. A control-iCT scan confirmed the complete resection in five patients and incomplete resection of the herniated disc in one patient. In one patient, complications occurred, such as postoperative hematoma, and wound healing deficit occurred. Mean follow-up was 22.9 ± 16.5 months. Five patients improved following surgery, and one patient who had no deficits remained unchanged. : Optimal surgical therapy in patients with calcified thoracic disc disease with compression of dural sac and myelopathy was resectioned via a transthoracic transpleural approach. The use of iCT-based registration and microscope-based AR significantly improved orientation in the operative field and facilitated safe resection of these lesions.
Topics: Humans; Female; Middle Aged; Intervertebral Disc Displacement; Male; Tomography, X-Ray Computed; Thoracic Vertebrae; Augmented Reality; Calcinosis; Adult; Microscopy; Treatment Outcome; Magnetic Resonance Imaging; Intervertebral Disc Degeneration
PubMed: 38929504
DOI: 10.3390/medicina60060887 -
Nature Communications Jun 2024Human T-cell leukemia virus type 1 (HTLV-1) infection is linked to the development of adult T-cell leukemia/lymphoma (ATLL) and the neuroinflammatory disease,...
Human T-cell leukemia virus type 1 (HTLV-1) infection is linked to the development of adult T-cell leukemia/lymphoma (ATLL) and the neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax oncoprotein regulates viral gene expression and persistently activates NF-κB to maintain the viability of HTLV-1-infected T cells. Here, we utilize a kinome-wide shRNA screen to identify the tyrosine kinase KDR as an essential survival factor of HTLV-1-transformed cells. Inhibition of KDR specifically induces apoptosis of Tax expressing HTLV-1-transformed cell lines and CD4 + T cells from HAM/TSP patients. Furthermore, inhibition of KDR triggers the autophagic degradation of Tax resulting in impaired NF-κB activation and diminished viral transmission in co-culture assays. Tax induces the expression of KDR, forms a complex with KDR, and is phosphorylated by KDR. These findings suggest that Tax stability is dependent on KDR activity which could be exploited as a strategy to target Tax in HTLV-1-associated diseases.
Topics: Humans; Gene Products, tax; Human T-lymphotropic virus 1; Vascular Endothelial Growth Factor Receptor-2; NF-kappa B; Paraparesis, Tropical Spastic; Cell Survival; Apoptosis; HTLV-I Infections; CD4-Positive T-Lymphocytes; T-Lymphocytes; Leukemia-Lymphoma, Adult T-Cell; Phosphorylation; HEK293 Cells
PubMed: 38918393
DOI: 10.1038/s41467-024-49737-5 -
Cureus Jun 2024Recreational use of nitrous oxide (NO), commonly known as , has increased in the last few years, bringing an increase in the number of reported cases of toxicity due to...
Recreational use of nitrous oxide (NO), commonly known as , has increased in the last few years, bringing an increase in the number of reported cases of toxicity due to this gas. Subacute combined degeneration (SCD) of the spinal cord is the most frequently reported neurological disorder due to the use of NO, as well as polyneuropathy and even psychiatric symptoms. All of these disorders are consequences of a functional deficit of vitamin B. We are reporting the cases of two patients with a history of NO abusive use presenting to the emergency department with progressive symptoms of paresthesia, ascending symmetric paraparesis, and gait ataxia, emulating the clinical characteristics of Guillain-Barré Syndrome (GBS). In both cases, magnetic resonance imaging (MRI) showed findings compatible with transverse myelitis of the cervical spinal cord, and electrodiagnosis studies reported the presence of polyneuropathy with a mixed mechanism. All these findings together pointed to the presence of myeloneuropathy due to a vitamin B deficit induced by the prolonged use of NO. Symptoms improved gradually with vitamin B supplementation and abstinence from NO. It is important to acknowledge the clinical characteristics of complications due to neurotoxicity induced by NO. Such complications are potentially reversible if they are treated appropriately and quickly. Considering the increase in N2O abuse, it should be considered a probable cause when treating patients with myelopathy and/or neuropathy of an unusual etiology.
PubMed: 38915835
DOI: 10.7759/cureus.63003 -
Gait & Posture Jun 2024Ankle Foot Orthoses (AFOs) are frequently prescribed to manage gait impairments in children with physical disability, and it is important that AFOs are prescribed and...
BACKGROUND
Ankle Foot Orthoses (AFOs) are frequently prescribed to manage gait impairments in children with physical disability, and it is important that AFOs are prescribed and fitted appropriately to maximize potential benefits. AFO tuning, manipulation of the AFO footwear combination (AFO-FC) by means of video vector analysis, is routinely used to optimize AFO use. However, the incidence or types of changes that are implemented after this type of orthotic review are unknown.
RESEARCH QUESTION
To investigate the impact of a multi-disciplinary video vector clinic on AFO provision in children with physical disability.
METHODS
All children who attended a video vector clinic over a period of 10-years from the establishment of the clinic were included in the study. Outcomes of the clinic were grouped into 5 categories: (1) No change to AFO-FC; (2) Altered/tuned AFO-FC; (3) Discontinued AFO-FC; (4) Recast AFO; (5) Change in prescription. Data were summarised narratively.
RESULTS
141 independently ambulant children were included. The diagnoses were bilateral cerebral palsy (39 %, n=55), unilateral cerebral palsy (38 %, n=54), spina bifida (9 %, n=13), hereditary spastic paraparesis (2 %, n=3) and other (11 %, n=16). No changes were made in 52 % of cases (n=74), tuning in 22 % of cases (n=31), the AFO was recast in 13 % of cases (n=19) and discontinued in 10 % of cases (n=14). A prescription change was recommended in 3 % of cases (n=4).
SIGNIFICANCE
Our findings suggest that the video vector clinic is a time efficient and effective means of assessing gait function in children with AFOs. Without assessment at the clinic, most of the children assessed would likely have been referred for a full and more time consuming 3-dimensional gait analysis. Video vector analysis at the initial AFO fitting may improve alignment and possibly reduce non-compliance at an earlier stage.
PubMed: 38905852
DOI: 10.1016/j.gaitpost.2024.06.016 -
Blood Jun 2024Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common but potentially severe adverse event associated with chimeric antigen receptor T-cell (CART)...
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common but potentially severe adverse event associated with chimeric antigen receptor T-cell (CART) therapy characterized by the development of acute neurologic symptoms following CART infusion. ICANS encompasses a wide clinical spectrum typified by mild to severe encephalopathy, seizures and/or cerebral edema. As more patients have been treated with CART new ICANS phenomenology has emerged. We present the clinical course of five children who developed acute onset of quadriparesis or paraparesis associated with abnormal brain and/or spine neuroimaging after infusion of CD19 or CD22-directed CART, adverse events not previously reported in children. Orthogonal data from autopsy studies, cerebrospinal fluid (CSF) flow cytometry and CSF proteomics/cytokine profiling demonstrated chronic white matter destruction, but a notable lack of inflammatory pathologic changes and cell populations. Instead, children with quadriparesis or paraparesis post-CART therapy had lower levels of pro-inflammatory cytokines such as interferon gamma (IFN), CCL17, CCL23, and CXCL10 than those who did not develop quadriparesis or paraparesis. Taken together, these findings imply a non-inflammatory source of this newly described ICANS phenomenon in children. The pathophysiology of some neurologic symptoms following CART may therefore have a more complex etiology than exclusive T-cell activation and excessive cytokine production.
PubMed: 38905637
DOI: 10.1182/blood.2024023933 -
AIDS Reviews Jun 2024The human T-cell leukemia virus type 1 (HTLV-1) was first described in 1980. It is spread in highly endemic regions in the world, such as the Southwestern part of Japan,...
The human T-cell leukemia virus type 1 (HTLV-1) was first described in 1980. It is spread in highly endemic regions in the world, such as the Southwestern part of Japan, sub-Saharan Africa and South America, Caribbean, Middle East, and Australo-Melanesia regions. HTLV-1 causes adult T cell leukemia and is associated with many inflammatory conditions, most notably HTLV-1-associated myelopathy/tropic spastic paraparesis. HTLV-2, first isolated in 1982, was recognized as a common infection in intravenous drug users, but a clear association with disease remains elusive. The first estimate of HTLV-1-positive individuals worldwide, in 1993, was around 10-20 millions. Due to the lack of global population-based prevalence studies, this is considered an underestimate at the moment. Furthermore, HTLV-1 prevalence in Europe is impacted by changing migration flows. Particularly, no data on HTLV-1 prevalence in the general population in Italy are available. Here, we report a systematic literature review of studies conducted in Italy on HTLV-1/2 from 1980 to 2023. Based on the criteria we adopted a total of 426 publications were found (64 reviews, 99 epidemiological, and 263 translational studies). The contents of some representative publications are summarized and discussed. Moreover, an approximate estimation of about 26,000 HTLV-1 positive foreigners living in Italy was obtained from updated data of foreigners from each single country officially registered as resident in Italy and from data on HTLV-1 prevalence among the general population in the corresponding countries.
PubMed: 38885479
DOI: 10.24875/AIDSRev.24000007 -
BMJ Neurology Open 2024Recently, there have been a few reports of atypical post-coronavirus disease 2019 (COVID-19) myelopathy manifesting tract-specific lesions similar to those due to...
INTRODUCTION
Recently, there have been a few reports of atypical post-coronavirus disease 2019 (COVID-19) myelopathy manifesting tract-specific lesions similar to those due to vitamin B deficiency. However, the precise characteristics of imaging or clinical course remain not well understood.
METHODS
A retrospective analysis of the clinical and imaging characteristics of four patients who were referred to our hospital with a unique post-COVID-19 myelopathy was performed.
RESULTS
Four-to-six weeks following COVID-19 infection in the summer of 2023, four middle-aged men developed paraparesis, hypo/dysesthesia and bladder/bowel disturbance, suggesting myelopathy. Although spinal MRI showed no abnormalities in the early stages, tract-specific longitudinal lesions along the dorsal and lateral columns became apparent as the symptoms progressed. Owing to the lack of MRI findings at the early stage, all cases were challenging to diagnose. However, the patients remained partially responsive to aggressive immunosuppressive therapies, even in the advanced stage.
DISCUSSION
We termed these tract-specific longitudinal lesions in the presented case series 'Grasshopper sign' because brain coronal and spine axial MRI findings looked like a grasshopper's antennae and face. Early identification of the characteristic MRI abnormality could allow for early intervention using intensive immunosuppressive therapy, which could improve patient outcomes.
PubMed: 38884066
DOI: 10.1136/bmjno-2024-000730 -
ENeurologicalSci Jun 2024Hereditary spastic paraplegia (HSP) is a group of genetically heterogenous neurodegenerative disorders characterized by progressive spasticity and weakness of lower...
Hereditary spastic paraplegia (HSP) is a group of genetically heterogenous neurodegenerative disorders characterized by progressive spasticity and weakness of lower limbs. We report a novel splicing variant (c.1617-2A>C) of the gene in a heterozygous carrier from an Italian family with autosomal dominant HSP. The case study describes a pure form of spastic paraparesis with the cardinal clinical features of SPG4. The novel variant affects a canonical splice site and is likely to disrupt RNA splicing. We conclude that the c.1617-2A>C substitution is a null variant, which could be classified as pathogenic; its penetrance should be further investigated.
PubMed: 38883204
DOI: 10.1016/j.ensci.2024.100506