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British Journal of Neurosurgery Dec 2023Intradural spinal lipomas are very rare and constitute less than 1% of all spinal tumors. Such tumors are usually associated with spinal dysraphism and occur mostly in...
INTRODUCTION
Intradural spinal lipomas are very rare and constitute less than 1% of all spinal tumors. Such tumors are usually associated with spinal dysraphism and occur mostly in the lumbosacral or cervical region. Intradural spinal lipomas tends to be intramedullary or subpial. Meningeal melanocytoma is further rarer cases that comprise less than 0.1% of cases. These usually occur in the fifth or fifth decade and chances of malignant transformation are high.
CASE REPORT
Here, we report an extremely rare case (first to the best of our knowledge) of a 9 years female child who presented to us with rapid progressing paraparesis. She was operated and found to have an intradural purely extramedullary spinal lipoma without spinal dysraphism. Moreover, she had melanin pigment deposits all over her meninges which is further rare. On presentation, the patient was bedridden but after surgery, the patient improved and could walk without support.
CONCLUSIONS
To the best of our knowledge, this is the first case of spinal cord lipoma in dorsal location along with melanin pigments in the meninges. We discuss the pathogenesis, presentation and management of intradural extramedullary spinal lipomas.
Topics: Humans; Child; Female; Magnetic Resonance Imaging; Melanins; Spinal Cord Neoplasms; Spinal Dysraphism; Lipoma
PubMed: 34148439
DOI: 10.1080/02688697.2021.1937518 -
Medical Oncology (Northwood, London,... Oct 2023Human T-cell lymphotropic virus type 1 (HTLV-1) is the first identified human retrovirus responsible for two significant diseases: HTLV-1-associated myelopathy/tropical...
Human T-cell lymphotropic virus type 1 (HTLV-1) is the first identified human retrovirus responsible for two significant diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although the majority of infected individuals remain asymptomatic carriers, a small percentage may develop ATLL or HAM/TSP. In tumorigenesis, a crucial process is angiogenesis, which involves the formation of new blood vessels. However, the precise mechanism of HTLV-1 associated angiogenesis remains unclear. This study aims to investigate the gene regulation involved in the angiogenesis signaling pathway associated with HTLV-1 infection. The research enrolled 20 male participants, including asymptomatic carriers and healthy individuals. Blood samples were collected and screened using ELISA for HTLV-1 confirmation, and PCR was performed for both Tax and HBZ for validation. RNA extraction and cDNA synthesis were carried out, followed by RT-qPCR analysis targeting cellular genes involved in angiogenesis. Our findings indicate that gene expression related to angiogenesis was elevated in HTLV-1 ACs patients. However, the differences in gene expression of the analyzed genes, including HSP27, Paxillin, PDK1, PTEN, RAF1, SOS1, and VEGFR2 between ACs and healthy individuals were not statistically significant. This suggests that although angiogenesis-related genes may show increased expression in HTLV-1 infection, they might not be robust indicators of ATLL progression in asymptomatic carriers. The results of our study demonstrate that angiogenesis gene expression is altered in ACs of HTLV-1, indicating potential involvement of angiogenesis in the early stages before ATLL development. While we observed elevated angiogenesis gene expression in ACs, the lack of statistical significance between ACs and healthy individuals suggests that these gene markers may not be sufficient on their own to predict the development of ATLL in asymptomatic carriers.
Topics: Adult; Humans; Male; Human T-lymphotropic virus 1; Leukemia-Lymphoma, Adult T-Cell; Signal Transduction; Carcinogenesis; Cell Transformation, Neoplastic
PubMed: 37792095
DOI: 10.1007/s12032-023-02177-5 -
Indian Journal of Pathology &... Jun 2024HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL) are both severe diseases caused by Human T-lymphotropic...
BACKGROUND
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL) are both severe diseases caused by Human T-lymphotropic virus type 1 (HTLV-1) infection, while about 95% of infected cases remain asymptomatic. Genes that play a role in ATLL development are assumed to be dissimilar from the ones that are crucial factors for HAM/TSP occurrence.
OBJECTIVE
The expression of six genes including BRCA1, CHUCK, ESR1, NFKBIA, PIK3R1, and PPARG were assessed in two groups of HAM/TSP and ATLL patients. Materials and Methods: cDNA was synthesized from purified RNA, and RT-qPCR was conducted to assess the expression of the genes in two groups. Any possible correlation among the genes' expression was also calculated. Results: BRCA1 and CHUCK expressions were higher in HAM/TSP patients in comparison with ATLL patients. However, ESR1, NFKBIA, PIK3R1, and PPARG are more expressed in ATLL cases than HAM/TSP. A significant positive correlation was observed between BRCA1 and NFKBIA in HAM/TSP group. In addition, a significant negative correlation between PIK3R1 and PPARG in HAM/TSP and between ESR1 and NFKBIA in the ATLL group was obtained.
CONCLUSION
HAM/TSP or ATLL stem from a disturbance in the expression of diverse genes and these dissimilarities should be discovered to reach a better understanding of disease treatment as well as screening and assessing the asymptomatic carriers' condition for developing severe disease.
PubMed: 38847220
DOI: 10.4103/ijpm.ijpm_1007_22 -
International Journal of Gynaecology... Jan 2024Pregnancy, a nutritionally demanding situation in terms of macro- and micronutrient supply owing to heightened maternal, placental, and fetal needs, significantly...
OBJECTIVE
Pregnancy, a nutritionally demanding situation in terms of macro- and micronutrient supply owing to heightened maternal, placental, and fetal needs, significantly affects thiamine reserves. Thiamine deficiency during pregnancy and the postpartum period, presenting with varied manifestations and outcomes, is a relatively common condition in our population. The study aimed to understand the various manifestations and outcomes of acute thiamine deficiency in pregnant and postpartum women, emphasizing the significance of early recognition and thiamine therapy to prevent serious complications during pregnancy and after childbirth.
METHODS
This prospective study conducted in a tertiary care center in North India enrolled consecutive pregnant and postpartum women presenting with clinical features consistent with thiamine deficiency disorders, such as thiamine deficiency-related neuropathy, high-output heart failure, heart failure with reduced ejection fraction, Wernicke's encephalopathy, gastric beriberi, and thiamine-responsive acute pulmonary hypertension. In addition to capturing medical history including drug intake, dietary consumption, and comorbidities, women underwent brief relevant clinical examinations and laboratory assessments, including whole-blood thiamine levels. Response to intravenous thiamine supplementation was also monitored.
RESULTS
Data of 31 women (12 pregnant, 19 postpartum) with a diagnosis of acute thiamine deficiency and a mean age of 28.88 ± 2.69 years were analyzed. The mean thiamine level was 1.28 ± 0.44 μg/dL with mean blood lactate of 3.46 ± 3.33. The most common presentation was gastric beriberi (n = 10), followed by paraparesis (n = 6), high-output heart failure (n = 6), acute pulmonary hypertension, heart failure with reduced ejection fraction (n = 3 each), and an acute confusional state (n = 2). All patients responded to thiamine challenge.
CONCLUSION
In the context of borderline thiamine status, particularly in our population with endemic thiamine deficiency and heightened demand for thiamine during pregnancy and the peripartum period, the deficiency can have varied and serious manifestations of dry and wet beriberi. Early recognition of the clinical features and thiamine therapy can be life-saving. There is a need for validated clinical criteria owing to the non-availability of thiamine testing in resource-limited settings.
Topics: Female; Humans; Pregnancy; Adult; Beriberi; Hypertension, Pulmonary; Prospective Studies; Placenta; Thiamine Deficiency; Thiamine; Heart Failure; Parturition
PubMed: 37458305
DOI: 10.1002/ijgo.14989 -
Cancers May 2024Intramedullary melanocytomas are exceedingly rare, with only twenty-four cases reported up to now. They present as local invasive tumors despite their benign biological... (Review)
Review
BACKGROUND
Intramedullary melanocytomas are exceedingly rare, with only twenty-four cases reported up to now. They present as local invasive tumors despite their benign biological behavior. Attempting a complete safe resection often results in severe post-operative neurological deficits, as in our case presented here.
METHODS
A systematic review was conducted across the PubMed and Scopus databases including studies published till February 2024.
RESULTS
A total of 19 studies were included, encompassing 24 cases. A similar distribution between sexes was noted (M:F 13:11), with ages ranging from 19 to 79 years. The thoracic segment was most affected, and intermediate-grade melanocytoma (19 cases) was the most common histotype. Radiographically, intramedullary melanocytomas usually appear as hyperintense hemorrhagic lesions peripheral to the central canal with focal nodular enhancement. Intraoperatively, they are black-reddish to tan and are tenaciously adherent lesions. In the sampled studies, IONM employment was uncommon, and post-operative new-onset neurological deficits were described in 16 cases. Adjuvant RT was used in four cases and its value is debatable. Recurrence is common (10 cases), and adjuvant therapies (RT or repeated surgery) seem to play a palliative role.
CASE PRESENTATION
A 68-year-old woman presented with a three-year history of worsening spastic paraparesis and loss of independence in daily activities (McCormick grade 4). An MRI revealed an intramedullary tumor from Th5 to Th7, characterized by T1-weighted hyperintensity and signs of recent intralesional hemorrhage. Multimodal neuromonitoring, comprising the D-Wave, guided the resection of a black-tan-colored tumor with hyper-vascularization and strong adherence to the white matter. During final dissection of the lesion to obtain gross total resection (GTR), a steep decline in MEPs and D-Wave signals was recorded. Post-operatively, the patient had severe hypoesthesia with Th9 level and segmental motor deficits, with some improvement during neurorehabilitation. Histopathology revealed an intermediate-grade melanocytoma (CNS WHO 2021 classification). A four-month follow-up documented the absence of relapse.
CONCLUSIONS
This literature review highlights that intramedullary T1 hyperintense hemorrhagic thoracic lesions in an adult patient should raise the suspicion of intramedullary melanocytoma. They present as locally aggressive tumors, due to local invasiveness, which often lead to post-operative neurological deficits, and frequent relapses, which overwhelm therapeutic strategies leading to palliative care after several years.
PubMed: 38791946
DOI: 10.3390/cancers16101867 -
Reports of Biochemistry & Molecular... Oct 2023The significance of HTLV-1 proviral load as a prognostic biomarker in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) has been a subject of...
BACKGROUND
The significance of HTLV-1 proviral load as a prognostic biomarker in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) has been a subject of controversy. This study aims to assess the impact of HTLV-1 proviral load (PVL) on the clinical outcome in patients with HAM/TSP.
METHODS
An absolute quantitative HTLV-1 PVL RT-qPCR, TaqMan method was developed with 100% sensitivity and specificity. Then, from 2005-2018, the HTLV-1 PVL of 90 eligible newly diagnosed HAM/TSP patients were assessed for demographic, clinical symptoms and their associations with HTLV-1-PVL.
RESULTS
The quality control of the designed RT-qPCR showed a sensitivity and specificity of 100%. Spasticity in lower limbs in 58.9% and urinary symptoms in 17.8% of HAM/TSPs were observed. Using this designed RT-qPCR, the HTLV-1-PVL strongly affected spasticity and sphincter disturbance (p=0.05). The multivariate logistic test showed that only the beginning of lower limb weakness along with tremor was associated with PVL (OR: 2.78. 95% CI (0.99-1.02) and p=0.05). Urinary incontinence was prevalent among these patients; however, no association was identified with the HTLV-1 proviral load (PVL).
CONCLUSIONS
The absolute RT-qPCR developed for measuring HTLV-1 proviral load (PVL) demonstrated reliable results. Despite a high prevalence of urinary incontinence in these patients, no association was observed with the PVL. Consequently, it appears that HTLV-1 proviral load is specifically associated with developing spasticity in HAM/TSP.
PubMed: 38618262
DOI: 10.61186/rbmb.12.3.393 -
Frontiers in Medicine 2023Human T-lymphotropic virus 1 (HTLV-1) infected individuals remain as asymptomatic carriers (ACs) or can develop the chronic neurological disorder HTLV-1-associated...
Differential modulation of IL-4, IL-10, IL-17, and IFN-γ production mediated by IgG from Human T-lymphotropic virus-1 (HTLV-1) infected patients on healthy peripheral T (CD4+, CD8+, and γδ) and B cells.
Human T-lymphotropic virus 1 (HTLV-1) infected individuals remain as asymptomatic carriers (ACs) or can develop the chronic neurological disorder HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or the adult T-cell leukemia/lymphoma (ATLL), and the immunological mechanisms involved in this pathologies need to be elucidated. Recently, it has been demonstrated that induced or naturally developed IgG repertoires obtained from different groups of donors, grouped by immune status, can modulate human T and B cell functions. Here we aimed to evaluate if the IgG obtained from HTLV-1-infected ACs, HAM/TSP, and ATLL patients can differentially modulate the production of cytokines by human T and B cells. With this purpose, we cultured PBMCs with IgG purified from ACs, HAM/TSP, or ATLL donors and evaluated the frequency and intracellular cytokine production by flow cytometry. Our results indicate that IgG from HAM/TSP patients could induce an augment of IL-17-producing CD4+ T cells, reduce the frequency of IL-4-producing CD4+ T cells, increase IFN-γ-producing CD8+ T cells, and reduce IL-4-producing CD8+ T cells. IgG from ATLL could reduce the frequency of IL-4-producing CD4+ T cells, similarly to IgG from HAM/TSP /TSP, and could reduce the frequency of IFN-γ-producing γδT cells without influence on IL-17- and IL4-producing γδT and could reduce the frequency of IL-10- producing B cells. Finally, IgG from both HAM/TSP and ATLL patients could reduce the frequency of IFN-γ producing B cells. In conclusion, these results suggest that these preparations are active, partly overlapping in their effects, and able to elicit distinct effects on target populations.
PubMed: 37711742
DOI: 10.3389/fmed.2023.1239706 -
Genes Jul 2023Spinocerebellar disorders are a vast group of rare neurogenetic conditions, generally characterized by overlapping clinical symptoms including progressive cerebellar...
Spinocerebellar disorders are a vast group of rare neurogenetic conditions, generally characterized by overlapping clinical symptoms including progressive cerebellar ataxia, spastic paraparesis, cognitive deficiencies, skeletal/muscular and ocular abnormalities. The objective of the present study is to identify the underlying genetic causes of the rare spinocerebellar disorders in the Pakistani population. Herein, nine consanguineous families presenting different spinocerebellar phenotypes have been investigated using whole exome sequencing. Sanger sequencing was performed for segregation analysis in all the available individuals of each family. The molecular analysis of these families identified six novel pathogenic/likely pathogenic variants; : c.1093del, : c.1201C>T, : c.2156A>T, : c.2171-3T>G, : c.3145T>A, and : c.334_335dup, and three already reported pathogenic variants; : c.159_176del, : c.689T>G, and : c.5308_5311del. The clinical features of all patients in each family are concurrent with the already reported cases. Hence, the current study expands the mutation spectrum of rare spinocerebellar disorders and implies the usefulness of next-generation sequencing in combination with clinical investigation for better diagnosis of these overlapping phenotypes.
Topics: Humans; Pakistan; Pedigree; Mutation; Cerebellar Ataxia; DNA Helicases; RNA Helicases; Multifunctional Enzymes
PubMed: 37510308
DOI: 10.3390/genes14071404 -
NeuroRehabilitation 2024Multiple sclerosis (MS) is the most common neurologic disease in young adults. Spasticity is one of its most disabling symptoms, with botulinum toxin A type A (BoNT-A)... (Clinical Trial)
Clinical Trial
BACKGROUND
Multiple sclerosis (MS) is the most common neurologic disease in young adults. Spasticity is one of its most disabling symptoms, with botulinum toxin A type A (BoNT-A) being one of the treatments of choice for this symptom.
OBJECTIVE
We assessed the response to abobotulinumtoxinA in improving walking ability and fatigue in patients with spastic paraparesis caused by MS.
METHODS
We performed a real-world, multicenter, prospective, open-label low-intervention trial in 84 patients with MS and spastic paraparesis of the lower limbs infiltrated with abobotulinumtoxinA (LINITOX study). The response of spasticity, walking ability and fatigue is analyzed in 4 cycles of ultrasound-guided injection in the lower limbs.
RESULTS
The patients improved their walking ability by an average of 11.34% meters measured with 6-Minute Walk Test (6MWT), and decreased the percentage of fatigue by 6.86% (4.66 percentage points less), in the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) 4 weeks after abobotulinumtoxinA injection, both values are statistically significant. This improvement seems to persist over time, throughout the cycles.
CONCLUSION
We found improved walking ability and less fatigue in patients with MS-related spastic paresis of the lower limbs after injection of abobotulinumtoxinA.
Topics: Humans; Botulinum Toxins, Type A; Female; Male; Multiple Sclerosis; Adult; Neuromuscular Agents; Paraparesis, Spastic; Middle Aged; Prospective Studies; Fatigue; Gait; Treatment Outcome
PubMed: 38875050
DOI: 10.3233/NRE-240038 -
Immunobiology Nov 2023Human T-lymphotropic virus 1 (HTLV-1) affects 5-10 million individuals worldwide. Most of those infected with this virus remain asymptomatic; however, 0.25%-4% of...
Human T-lymphotropic virus 1 (HTLV-1) affects 5-10 million individuals worldwide. Most of those infected with this virus remain asymptomatic; however, 0.25%-4% of individuals develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while 2%-4% develop adult T-cell leukemia/lymphoma (ATLL). Understanding the immune response inherent in this infection is extremely important. The role of T helper type 1 (Th1) and Th2 cells in HTLV-1 infection is well known; however, exploring the different subtypes of immune responses is also necessary. The role of Th9 cells in HTLV-1 infection and the mechanisms involved in their interference in the pathophysiological process of HAM/TSP is poorly understood. This study aimed to evaluate the expression profiles of PU.1, interferon regulatory factor 4 (IRF-4), and cytokine interleukin-9 (IL-9) during the induction of peripheral immune response and their role in the HTLV-1-infected patients' neurological symptoms. This analytical cross-sectional study was carried out at the Laboratory of Clinical and Epidemiology of Endemic Diseases and the Laboratory of Immunopathology, both from the Tropical Medicine Center at the Federal University of Pará. Assessment of neurological parameters was performed (gait, Expanded Kurtzke Disability State Scale (EDSS) score, upper and lower limb reflexes, Hoffman's sign, Babinski reflex, and clonus reflex). For Th9 cell analysis, peripheral blood samples were collected from HTLV-1-infected patients; then, the lymphomononuclear cells were separated followed by the isolation of messenger ribonucleic acid (mRNA). Complementary deoxyribonucleic acid (cDNA) synthesis each sample was carried out. The gene expression levels of PU.1, IRF-4, and IL-9 as well as those of constitutive genes (glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and β-actin) were quantified by real-time polymerase chain reaction (qPCR). This study included 81 HTLV-1-infected patients, of whom 47 were asymptomatic, 13 were mono/oligosymptomatic (MOS), and 21 developed HAM/TSP. IL-9 was the least expressed gene among the three studied groups. The MOS group showed the lowest expression levels of PU.1, IRF-4, and IL-9. HAM/TSP patients showed lower IL-9 protein quantification. Negative correlations were found between IL and 9 and EDSS in MOS patients and between PU.1, EDSS, IRF-4, and EDSS in the HAM/TSP group. An association was found between IL and 9 and Babinski reflex in the HAM/TSP group, suggesting that this gene was more highly expressed in patients who did not have this pathological sign. Th9 cells may interfere with the neurological progression of HAM/TSP and act as a protective factor.
Topics: Adult; Humans; Human T-lymphotropic virus 1; Interleukin-9; Cross-Sectional Studies; Paraparesis, Tropical Spastic; HTLV-I Infections
PubMed: 37657359
DOI: 10.1016/j.imbio.2023.152740