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Journal of Neurovirology Apr 2024Human T-lymphotropic virus type 1 (HTLV-1) is classically associated with the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although the...
Human T-lymphotropic virus type 1 (HTLV-1) is classically associated with the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although the mechanisms of this neurological disorder remain unclear. In addition, some patients who develop "minor" neurological signs that do not meet diagnostic criteria for HAM/TSP are classified as asymptomatic carriers. This study aims to demonstrate the neurological symptoms of Brazilian patients living with HTLV-1 classified as not-HAM.TSP. This observational study evaluated patients treated in an HTLV reference center in Bahia, Brazil, between February 2022 and July 2023. The data were obtained through the analysis of medical records and neurological consultation. Those individuals classified as HAM/ TSP were excluded from this study. 74 patients were submitted to a careful neurological evaluation: 23 HAM/TSP, 22 were classified with intermediate syndrome (IS), and 29 were oligosymptomatic. Self-reported symptoms were significantly more common in the IS group, including urinary symptoms such as nocturia, urgency, incontinence, dysuria, weakness, paresthesia, lumbar pain, xerostomia, and xerophthalmia. Physical examination findings consistent with reduced vibratory and tactile sensitivity were more common in the IS group (p = 0.017 and p = 0.013). Alterations in the V and VIII cranial nerves were present in both groups. HTLV-1 can lead to the development of important neurological signs and symptoms in apparently asymptomatic individuals. This data highlights the need for more research into the neurological aspects of HTLV-1 infection and emphasizes the importance of early diagnosis, treatment, and support for individuals living with this virus.
PubMed: 38653958
DOI: 10.1007/s13365-024-01197-9 -
Journal of Vascular Surgery Mar 2024Spinal cord ischemia (SCI) with paraplegia or paraparesis is a devastating complication of complex aortic repair (CAR). Treatment includes cerebrospinal fluid drainage,...
OBJECTIVE
Spinal cord ischemia (SCI) with paraplegia or paraparesis is a devastating complication of complex aortic repair (CAR). Treatment includes cerebrospinal fluid drainage, maintenance of hemoglobin concentration (>10 g/L), and elevating mean arterial blood pressure. Animal and human case series have reported improvements in SCI outcomes with hyperbaric oxygen therapy (HBOT). We reviewed our center's experience with HBOT as a rescue treatment for spinal cord ischemia post-CAR in addition to standard treatment.
METHODS
A retrospective review of the University Health Network's Hyperbaric Medicine Unit treatment database identified HBOT sessions for patients with SCI post-CAR between January 2013 and June 2021. Mean estimates of overall motor function scores were determined for postoperative, pre-HBOT, post-HBOT (within 4 hours of the final HBOT session), and at the final assessment (last available in-hospital evaluation) using a linear mixed model. A subgroup analysis compared the mean estimates of overall motor function scores between improvement and non-improvement groups at given timepoints. Improvement of motor function was defined as either a ≥2 point increase in overall muscle function score in patients with paraparesis or an upward change in motor deficit categorization (para/monoplegia, paraparesis, and no deficit). Subgroup analysis was performed by stratifying by improvement or non-improvement of motor function from pre-HBOT to final evaluation.
RESULTS
Thirty patients were treated for SCI. Pre-HBOT, the motor deficit categorization was 10 paraplegia, three monoplegia, 16 paraparesis, and one unable to assess. At the final assessment, 14 patients demonstrated variable degrees of motor function improvement; eight patients demonstrated full motor function recovery. Seven of the 10 patients with paraplegia remained paraplegic despite HBOT. The estimated mean of overall muscle function score for pre-HBOT was 16.6 ± 2.9 (95% confidence interval [CI], 10.9-22.3) and for final assessment was 23.4 ± 2.9 (95% CI, 17.7-29.1). The estimated mean difference between pre-HBOT and final assessment overall muscle function score was 6.7 ± 3.1 (95% CI, 0.6-16.1). The estimated mean difference of the overall muscle function score between pre-HBOT and final assessment for the improved group was 16.6 ± 3.5 (95% CI, 7.5-25.7) vs -4.9 ± 4.2 (95% CI, -16.0 to 6.2) for the non-improved group.
CONCLUSIONS
HBOT, in addition to standard treatment, may potentially improve recovery in spinal cord function following SCI post-CAR. However, the potential benefits of HBOT are not equally distributed among subgroups.
Topics: Humans; Aortic Aneurysm, Thoracic; Hemiplegia; Hyperbaric Oxygenation; Paraparesis; Paraplegia; Spinal Cord; Spinal Cord Ischemia; Treatment Outcome
PubMed: 37925040
DOI: 10.1016/j.jvs.2023.10.055 -
Journal of Virology Feb 2024Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus responsible for adult T-cell leukemia/lymphoma, a severe and fatal CD4+ T-cell malignancy. Additionally,...
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus responsible for adult T-cell leukemia/lymphoma, a severe and fatal CD4+ T-cell malignancy. Additionally, HTLV-1 can lead to a chronic progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis. Unfortunately, the prognosis for HTLV-1-related diseases is generally poor, and effective treatment options are limited. In this study, we designed and synthesized a codon optimized HTLV-1 envelope (Env) mRNA encapsulated in a lipid nanoparticle (LNP) and evaluated its efficacy as a vaccine candidate in an established rabbit model of HTLV-1 infection and persistence. Immunization regimens included a prime/boost protocol using Env mRNA-LNP or control green fluorescent protein (GFP) mRNA-LNP. After immunization, rabbits were challenged by intravenous injection with irradiated HTLV-1 producing cells. Three rabbits were partially protected and three rabbits were completely protected against HTLV-1 challenge. These rabbits were then rechallenged 15 weeks later, and two rabbits maintained sterilizing immunity. In Env mRNA-LNP immunized rabbits, proviral load and viral gene expression were significantly lower. After viral challenge in the Env mRNA-LNP vaccinated rabbits, an increase in both CD4+/IFN-γ+ and CD8+/IFN-γ+ T-cells was detected when stimulating with overlapping Env peptides. Env mRNA-LNP elicited a detectable anti-Env antibody response after prime/boost vaccination in all animals and significantly higher levels of neutralizing antibody activity. Neutralizing antibody activity was correlated with a reduction in proviral load. These findings hold promise for the development of preventive strategies and therapeutic interventions against HTLV-1 infection and its associated diseases.IMPORTANCEmRNA vaccine technology has proven to be a viable approach for effectively triggering immune responses that protect against or limit viral infections and disease. In our study, we synthesized a codon optimized human T-cell leukemia virus type 1 (HTLV-1) envelope (Env) mRNA that can be delivered in a lipid nanoparticle (LNP) vaccine approach. The HTLV-1 Env mRNA-LNP produced protective immune responses against viral challenge in a preclinical rabbit model. HTLV-1 is primarily transmitted through direct cell-to-cell contact, and the protection offered by mRNA vaccines in our rabbit model could have significant implications for optimizing the development of other viral vaccine candidates. This is particularly important in addressing the challenge of enhancing protection against infections that rely on cell-to-cell transmission.
Topics: Animals; Humans; Rabbits; Antibodies, Neutralizing; Antibody Formation; Codon; Human T-lymphotropic virus 1; Leukemia, T-Cell; mRNA Vaccines; Neurodegenerative Diseases; RNA, Messenger; Viral Vaccines
PubMed: 38193692
DOI: 10.1128/jvi.01623-23 -
International Journal of Surgery Case... Oct 2023Solitary spinal plasmacytoma (SSP) is an uncommon neoplasm originating from bone marrow plasma cells. Although infrequent in the thoracic region, it has the potential to...
INTRODUCTION AND IMPORTANCE
Solitary spinal plasmacytoma (SSP) is an uncommon neoplasm originating from bone marrow plasma cells. Although infrequent in the thoracic region, it has the potential to induce substantial damage. In this study, we present the case of a patient with thoracic spine SSP treated through surgical intervention.
CASE PRESENTATION
We report the case of a 38-year-old female who presented with progressive mid-back pain, numbness, weakness in both lower limbs and gait disturbance. Imaging showed an osteolytic lesion with vertebral collapse of T11. MRI was strongly suggestive of solitary plasmocytoma. Hematologic tests were normal. Surgery was carried out. At the first stage, a posterior approach with laminectomy and fixation were performed. Biopsy of tumor cells confirmed the diagnosis of SSP. At the second stage, a trans-thoracic approach was performed, the tumor was resected in a single block and anterior interbody fusion was done. After the surgery the patient fully recovered from the paraparesis and at two years follow up no recurrence of tumor cells was detected.
CLINICAL DISCUSSION
Spinal malignant bone tumors are rare, with solitary plasmacytoma being the most common. Diagnosis of SSP is based on bone biopsy findings. MRI and CT scans assess tumor extent and spinal stability. Prognosis relates to the likelihood of progressing into multiple myeloma. Though radiotherapy is common, surgery offers local control, especially for instability and neurological issues.
CONCLUSION
SSP in the thoracic spine is a rare condition that requires a multidisciplinary approach and a prompt treatment.
PubMed: 37738828
DOI: 10.1016/j.ijscr.2023.108799 -
Spinal Cord Series and Cases Jul 2023Rosai-Dorfman Disease (RDD) is a rare benign histiocytic disease that infrequently affects the spine. We report two cases of spinal RDD and review the relevant... (Review)
Review
INTRODUCTION
Rosai-Dorfman Disease (RDD) is a rare benign histiocytic disease that infrequently affects the spine. We report two cases of spinal RDD and review the relevant literature. This report addresses the various diagnostic dilemmas related to the evaluation of Spinal RDD and its treatment.
CASE PRESENTATION
Case 1: A 32-year-old male presented with low back pain and left anterior thigh for last 8 months. On examination, there was sensory diminution on inner aspects of the thigh with an absent left knee jerk. CT/MRI scans revealed an extradural lesion at L2/3 with neural compression. PET scan showed several hypermetabolic lesions in ribs, humerus, femur, and vertebrae. He underwent en bloc excision of the extradural mass with L2-3 pedicle screw-rod fixation and was later managed with chemotherapy. Case 2: A 42-year-old male presented with spastic paraparesis with urinary incontinence for the last 4 weeks. On examination, he had a neurological level of T6. MRI scan revealed a lesion in posterior elements of T6-7 compressing the spinal cord. He underwent T6-7 laminectomy with decompression. In both cases, the diagnosis was confirmed by histopathology and further managed by Hemato-oncologist. They both did well at 1-year follow-up with improvement in neurology.
DISCUSSION
Spinal RDD to date remains a large diagnostic dilemma with no pathognomonic clinical or radiological features; mimicking many osteolytic lesions in the spine. The diagnosis is purely histopathological and immunological. The lesion's complete surgical excision is the mainstay of treatment with a better prognosis and decreased chances of recurrences.
Topics: Male; Humans; Adult; Histiocytosis, Sinus; Spine; Spinal Cord; Laminectomy; Femur
PubMed: 37516782
DOI: 10.1038/s41394-023-00600-7 -
Journal of Endovascular Therapy : An... Dec 2023Spinal cord injury (SCI) is a devastating complication of thoracoabdominal aortic (TAA) repair. The use of prophylactic cerebrospinal fluid drainage (CSFD) as part of a...
Spinal Cord Protection During Thoracic and Thoracoabdominal Endovascular Aortic Repair: 5-Year Results of a Preventive Protocol Including Prophylactic Cerebrospinal Fluid Drainage in High-Risk Patients.
PURPOSE
Spinal cord injury (SCI) is a devastating complication of thoracoabdominal aortic (TAA) repair. The use of prophylactic cerebrospinal fluid drainage (CSFD) as part of a protective protocol during endovascular repair is controversial. This article reports the results of the prophylactic use of CSFD as part of the of a prevention protocol implemented in 2016.
METHODS
Retrospective review of spinal cord outcomes (SCI rate and CSFD-related complications) in patients treated endovascularly for TAA disease at a single institution from 2016 (implementation of an institutional SCI risk reduction protocol) to 2021. Patients were classified as high risk (≥2 factors), intermediate risk (1 factor), or low risk (0 factor). Only high-risk patients without contraindications underwent a prophylactic CSFD placement.
RESULTS
One hundred eighty-one patients were analyzed (124 males; 69.6 years): 130 (69%) aneurysms (n=24 thoracic, n=28 Crawford 1-2-3, and n=78 Crawford 4/pararenal), 35 (19.9%) chronic aneurysmal dissections, and 16 (8.8%) acute complicated type B dissections. Interventions were staged in 31 (17.2%) cases, and consisted of 74 (41%) Thoracic EndoVascular Aneurysm Repair (TEVAR) and 107 (59%) Fenestrated Branched EndoVascular Aneurysm Repair (F-BEVAR). Sixty-nine (38.1%) patients were identified as being at high risk of SCI and CSFD was used prophylactically in 64 of them (4 failures and 1 contraindication). Spinal cord injury occurred in 8 cases (4 paraparesis, 4 paraplegias including 2 permanent), of which 3 had a prophylactic CSFD and 5 underwent rescue drainage. In addition, 4 patients developed SCI related to prophylactic CSFD (intradural hematoma), resulting in 1 paraparesis and 3 paraplegias. Other CSFD-related complications were mild (6) or moderate (2), for a total of 12 complications (17%). Factors associated with major drain complications were: curative anticoagulation 36 hours after drain removal (n=1), multiple punctures (n=1), platelet count <100 000 at drain removal (n=1), and bipolar disorder (n=2). Overall, 4 patients had permanent paraplegia and 1 had sphincter dysfunction at the last follow-up. Mean follow-up was 17 months. Mortality was 4.4% at 30 days and 13.3% at 18 months, including 3 (1.6%) aortic-related deaths.
CONCLUSIONS
With the protocol we used to protect the spinal cord, we report results comparable with the SCI literature and highlight the risks associated with prophylactic CSFD use, which requires a better understanding of contraindications.
PubMed: 38084383
DOI: 10.1177/15266028231215972 -
Frontiers in Microbiology 2023Infection with human T cell lymphotropic virus type 1 (HTLV-1) is endemic in Brazil and is linked with pro-inflammatory conditions including HTLV-1-associated...
INTRODUCTION
Infection with human T cell lymphotropic virus type 1 (HTLV-1) is endemic in Brazil and is linked with pro-inflammatory conditions including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neuroinflammatory incapacitating disease that culminates in loss of motor functions. The mechanisms underlying the onset and progression of HAM/TSP are incompletely understood. Previous studies have demonstrated that inflammation and infectious agents can affect the expression of cellular prion protein (PrP) in immune cells.
METHODS
Here, we investigated whether HTLV-1 infection affected PrP content in cell lines and primary CD4cells using flow cytometry and western blot assays.
RESULTS
We found that HTLV-1 infection decreased the expression levels of PrP and HTLV-1 encoded p12, an endoplasmic reticulum resident protein also known to affect post-transcriptionally cellular proteins such as MHC-class I and the IL-2 receptor. In addition, we observed a reduced percentage of CD4 T cells from infected individuals expressing PrP, which was reflected by IFN type II but not IL-17 expression.
DISCUSSION
These results suggested that PrP downregulation, linked to both HTLV-1 p12 and IFN-γ expression in CD4 cells, may play a role in the neuropathogenesis of HTLV-1 infection.
PubMed: 37637115
DOI: 10.3389/fmicb.2023.1175679 -
Molecular Neurobiology Mar 2024Human T cell leukemia virus type 1 (HTLV-1) is the first human oncogenic retrovirus to be discovered and causes two major diseases: a progressive neuro-inflammatory... (Review)
Review
Human T cell leukemia virus type 1 (HTLV-1) is the first human oncogenic retrovirus to be discovered and causes two major diseases: a progressive neuro-inflammatory disease, termed HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), and an aggressive malignancy of T lymphocytes known as adult T cell leukemia (ATL). Innate and acquired immune responses play pivotal roles in controlling the status of HTLV-1-infected cells and such, the outcome of HTLV-1 infection. Natural killer cells (NKCs) are the effector cells of the innate immune system and are involved in controlling viral infections and several types of cancers. The ability of NKCs to trigger cytotoxicity to provide surveillance against viruses and cancer depends on the balance between the inhibitory and activating signals. In this review, we will discuss NKC function and the alterations in the frequency of these cells in HTLV-1 infection.
PubMed: 38436833
DOI: 10.1007/s12035-024-03999-8 -
Child's Nervous System : ChNS :... Apr 2024Extradural malignant rhabdoid tumors of the spine are highly malignant and invasive tumors (WHO grade IV) with poor prognosis, most frequently occurring in young... (Review)
Review
BACKGROUND
Extradural malignant rhabdoid tumors of the spine are highly malignant and invasive tumors (WHO grade IV) with poor prognosis, most frequently occurring in young children before 2 years of age. Pain and motor deficit are the most common presenting signs.
CASE DESCRIPTION
We report a case of a 2-year-old girl presenting with axial ataxia and paraparesis related to an extradural malignant rhabdoid tumor causing posterior thoracic spinal cord compression (D3-D6). She underwent two near-total removal of the tumor, adjuvant chemotherapy according to the Eu-Rhab protocol and proton beam therapy. She then developed multiple cranial nerve paresis (meningeal carcinomatosis) after 4 cycles of chemotherapy and died at 4.32 months of follow-up.
DISCUSSION AND CONCLUSION
The role of the PET scan was essential to guide us to remove a residue, while two concomitant spinal MRIs were considered negative. We reviewed the 16 cases reported in the literature. Multiple surgeries and radiotherapy seem to be correlated with longer survival. No child younger than 2 years old had a documented survival higher than 4.32 months.
Topics: Female; Humans; Child, Preschool; Rhabdoid Tumor; Thoracic Vertebrae; Magnetic Resonance Imaging; Spinal Cord Compression
PubMed: 37995013
DOI: 10.1007/s00381-023-06224-4 -
World Neurosurgery Apr 2024Our study presents a single-center experience of resection of intradural spinal tumors either with or without using intraoperative computed tomography-based registration...
BACKGROUND
Our study presents a single-center experience of resection of intradural spinal tumors either with or without using intraoperative computed tomography-based registration and microscope-based augmented reality (AR). Microscope-based AR was recently described for improved orientation in the operative field in spine surgery, using superimposed images of segmented structures of interest in a two-dimensional or three-dimensional mode.
METHODS
All patients who underwent surgery for resection of intradural spinal tumors at our department were retrospectively included in the study. Clinical outcomes in terms of postoperative neurologic deficits and complications were evaluated, as well as neuroradiologic outcomes for tumor remnants and recurrence.
RESULTS
112 patients (57 female, 55 male; median age 55.8 ± 17.8 years) who underwent 120 surgeries for resection of intradural spinal tumors with the use of intraoperative neuromonitoring were included in the study, with a median follow-up of 39 ± 34.4 months. Nine patients died during the follow-up for reasons unrelated to surgery. The most common tumors were meningioma (n = 41), schwannoma (n = 37), myopapillary ependymomas (n = 12), ependymomas (n = 10), and others (20). Tumors were in the thoracic spine (n = 46), lumbar spine (n = 39), cervical spine (n = 32), lumbosacral spine (n = 1), thoracic and lumbar spine (n = 1), and 1 tumor in the cervical, thoracic, and lumbar spine. Four biopsies were performed, 10 partial resections, 13 subtotal resections, and 93 gross total resections. Laminectomy was the common approach. In 79 cases, patients experienced neurologic deficits before surgery, with ataxia and paraparesis as the most common ones. After surgery, 67 patients were unchanged, 49 improved and 4 worsened. Operative time, extent of resection, clinical outcome, and complication rate did not differ between the AR and non-AR groups. However, the use of AR improved orientation in the operative field by identification of important neurovascular structures.
CONCLUSIONS
High rates of gross total resection with favorable neurologic outcomes in most patients as well as low recurrence rates with comparable complication rates were noted in our single-center experience. AR improved intraoperative orientation and increased surgeons' comfort by enabling early identification of important anatomic structures; however, clinical and radiologic outcomes did not differ, when AR was not used.
PubMed: 38642835
DOI: 10.1016/j.wneu.2024.04.071