RESUMO
Human T-lymphotropic virus type-1 (HTLV-1) was the first discovered human oncogenic retrovirus, the etiological agent of two serious diseases have been identified as adult T-cell leukaemia/lymphoma malignancy and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a debilitating chronic neuro-myelopathy. Despite more than 40 years of molecular, histopathological and immunological studies on HTLV-1-associated diseases, the virulence and pathogenicity of this virus are yet to be clarified. The reason why the majority of HTLV-1-infected individuals (â¼95%) remain asymptomatic carriers is still unclear. The deterioration of the immune system towards oncogenicity and autoimmunity makes HTLV-1 a natural probe for the study of malignancy and neuro-inflammatory diseases. Additionally, its slow worldwide spreading has prompted public health authorities and researchers, as urged by the WHO, to focus on eradicating HTLV-1. In contrast, neither an effective therapy nor a protective vaccine has been introduced. This comprehensive review focused on the most relevant studies of the neuro-inflammatory propensity of HTLV-1-induced HAM/TSP. Such an emphasis on the virus-host interactions in the HAM/TSP pathogenesis will be critically discussed epigenetically. The findings may shed light on future research venues in designing and developing proper HTLV-1 therapeutics.
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Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Paraparesia Espástica Tropical/virologia , Paraparesia Espástica Tropical/imunologia , Infecções por HTLV-I/virologia , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/complicações , Interações Hospedeiro-Patógeno/imunologia , Animais , Interações entre Hospedeiro e Microrganismos/imunologiaRESUMO
Volitional movement requires descending input from the motor cortex and sensory feedback through the spinal cord. We previously developed a paired brain and spinal electrical stimulation approach in rats that relies on convergence of the descending motor and spinal sensory stimuli in the cervical cord. This approach strengthened sensorimotor circuits and improved volitional movement through associative plasticity. In humans, it is not known whether posterior epidural spinal cord stimulation targeted at the sensorimotor interface or anterior epidural spinal cord stimulation targeted within the motor system is effective at facilitating brain evoked responses. In 59 individuals undergoing elective cervical spine decompression surgery, the motor cortex was stimulated with scalp electrodes and the spinal cord was stimulated with epidural electrodes, with muscle responses being recorded in arm and leg muscles. Spinal electrodes were placed either posteriorly or anteriorly, and the interval between cortex and spinal cord stimulation was varied. Pairing stimulation between the motor cortex and spinal sensory (posterior) but not spinal motor (anterior) stimulation produced motor evoked potentials that were over five times larger than brain stimulation alone. This strong augmentation occurred only when descending motor and spinal afferent stimuli were timed to converge in the spinal cord. Paired stimulation also increased the selectivity of muscle responses relative to unpaired brain or spinal cord stimulation. Finally, clinical signs suggest that facilitation was observed in both injured and uninjured segments of the spinal cord. The large effect size of this paired stimulation makes it a promising candidate for therapeutic neuromodulation. KEY POINTS: Pairs of stimuli designed to alter nervous system function typically target the motor system, or one targets the sensory system and the other targets the motor system for convergence in cortex. In humans undergoing clinically indicated surgery, we tested paired brain and spinal cord stimulation that we developed in rats aiming to target sensorimotor convergence in the cervical cord. Arm and hand muscle responses to paired sensorimotor stimulation were more than five times larger than brain or spinal cord stimulation alone when applied to the posterior but not anterior spinal cord. Arm and hand muscle responses to paired stimulation were more selective for targeted muscles than the brain- or spinal-only conditions, especially at latencies that produced the strongest effects of paired stimulation. Measures of clinical evidence of compression were only weakly related to the paired stimulation effect, suggesting that it could be applied as therapy in people affected by disorders of the central nervous system.
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Potencial Evocado Motor , Córtex Motor , Músculo Esquelético , Medula Espinal , Córtex Motor/fisiologia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Medula Espinal/fisiologia , Adulto , Músculo Esquelético/fisiologia , Músculo Esquelético/inervação , Estimulação da Medula Espinal/métodos , Idoso , Estimulação Elétrica/métodosRESUMO
Canine degenerative myelopathy (DM), a fatal neurodegenerative disease in dogs, shares clinical and genetic features with amyotrophic lateral sclerosis, a human motor neuron disease. Mutations in the SOD1 gene encoding Cu/Zn superoxide dismutase (SOD1) cause canine DM and a subset of inherited human amyotrophic lateral sclerosis. The most frequent DM causative mutation is homozygous E40K mutation, which induces the aggregation of canine SOD1 but not of human SOD1. However, the mechanism through which canine E40K mutation induces species-specific aggregation of SOD1 remains unknown. By screening human/canine chimeric SOD1s, we identified that the humanized mutation of the 117th residue (M117L), encoded by exon 4, significantly reduced aggregation propensity of canine SOD1E40K. Conversely, introducing a mutation of leucine 117 to methionine, a residue homologous to canine, promoted E40K-dependent aggregation in human SOD1. M117L mutation improved protein stability and reduced cytotoxicity of canine SOD1E40K. Furthermore, crystal structural analysis of canine SOD1 proteins revealed that M117L increased the packing within the hydrophobic core of the ß-barrel structure, contributing to the increased protein stability. Our findings indicate that the structural vulnerability derived intrinsically from Met 117 in the hydrophobic core of the ß-barrel structure induces E40K-dependent species-specific aggregation in canine SOD1.
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Doenças do Cão , Mutação , Doenças Neurodegenerativas , Superóxido Dismutase-1 , Animais , Cães , Humanos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/veterinária , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Doenças do Cão/genética , Doenças do Cão/metabolismo , Especificidade da EspécieRESUMO
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.
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BACKGROUND: Human T-lymphotropic virus (HTLV-1) is a neglected virus with worldwide distribution of over 10 million people and is the cause of two main associated diseases Adult T cell Leukemia-Lymphoma (ATLL), and HTLV-1-associated Myelopathy/Tropical Spastic paraparesis (HAM/TSP). The IL-17 cytokine family plays a crucial role in the host immunity against HTLV-1 and the development of associated disease. A systematic review was conducted to analyze all research reporting on the levels or expression of the IL-17 HTLV-1 infection and associated diseases. METHODS: The literature search was conducted in electronic databases including PubMed/Medline and Web of Sciences until January 31st, 2024, followed by the PRISMA guidelines. RESULTS: Our search revealed 20 eligible articles to be included in our study. The total number of cases studied was 1420, of which 386 were carriers without any symptoms, and were 176 ATLL and 237 HAM/TSP. The IL-17 cytokine family production or mRNA expression was higher in HAM/TSP patients but showed a trend toward reduction in the case of ATLL. CONCLUSIONS: Our results showed that while The IL-17 cytokine family plays a significant role in the immunopathogenesis of disease and clinical status of patients with inflammatory disorders such as HAM/TSP, IL-17 production is diminished and the RORC/IL-17 signaling pathway is downregulated during ATLL. Our data suggest that boosting the RORC/IL-17 signaling pathway in ATLL and using anti-IL-17 agents in HAM/TSP and other HTLV-related inflammatory conditions might benefit patients and improve their outcomes.
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BACKGROUND: Diffusion magnetic resonsance imaging (dMRI) can potentially predict the postoperative outcome of cervical spondylotic myelopathy (CSM). PURPOSE: To explore preoperative dMRI parameters to predict the postoperative outcome of CSM through multifactor correlation analysis. STUDY TYPE: Prospective. POPULATION: Post-surgery CSM patients; 102 total, 73 male (52.42 ± 10.60 years old) and 29 female (52.0 ± 11.45 years old). FIELD STRENGTH/SEQUENCE: 3.0 T/Turbo spin echo T1/T2-weighted, T2*-weighted multiecho gradient echo and dMRI. ASSESSMENT: Spinal cord function was evaluated using modified Japanese Orthopedic Association (mJOA) scoring at different time points: preoperative and 3, 6, and 12 months postoperative. Single-factor correlation and t test analyses were conducted based on fractional anisotropy (FA), mean diffusivity, intracellular volume fraction, isotropic volume fraction, orientation division index, increased signal intensity, compression ratio, age, sex, symptom duration and operation method, and multicollinearity was calculated. The linear quantile mixed model (LQMM) and the linear mixed-effects regression model (LMER) were used for multifactor correlation analysis using the combinations of the above variables. STATISTICAL TESTS: Distance correlation, Pearson's correlation, multiscale graph correlation and t tests were used for the single-factor correlation analyses. The variance inflation factor (VIF) was used to calculate multicollinearity. LQMM and LMER were used for multifactor correlation analyses. P < 0.05 was considered statistically significant. RESULTS: The single-factor correlation between all variables and the postoperative mJOA score was weak (all r < 0.3). The linear relationship was stronger than the nonlinear relationship, and there was no significant multicollinearity (VIF = 1.10-1.94). FA values in the LQMM and LMER models had a significant positive correlation with the mJOA score (r = 5.27-6.04), which was stronger than the other variables. DATA CONCLUSION: The FA value based on dMRI significantly positively correlated with CSM patient postoperative outcomes, helping to predict the surgical outcome and formulate a treatment plan before surgery. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.
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Doenças da Medula Espinal , Espondilose , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Imagem de Tensor de Difusão/métodos , Espondilose/diagnóstico por imagem , Espondilose/cirurgia , Espondilose/patologia , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/cirurgia , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the feasibility and effectiveness of applying intraoperative ultrasound (IOUS) to evaluate spinal canal expansion in patients undergoing French-door cervical laminoplasty (FDCL). MATERIALS AND METHODS: Twenty-five patients who underwent FDCL for multilevel degenerative cervical myelopathy were prospectively recruited. Formulae describing the relationship between laminoplasty opening angle (LOA) and laminoplasty opening size, the increase in sagittal canal diameter and the spinal canal area were deduced with trigonometric functions. The LOA was measured with IOUS imaging during surgery, and other spinal canal parameters were assessed. Actual spinal canal enlargement was verified on postoperative CT images. Linear correlation analysis and BlandâAltman analysis were used to evaluate correlation and agreement between the intraoperative and postoperative measurements. RESULTS: The LOA at C5 measured with IOUS was 27.54 ± 3.12°, and it was 27.23 ± 3.02° on postoperative CT imaging. Linear correlation analysis revealed a significant correlation between IOUS and postoperative CT measurements (r = 0.88; p < 0.01). Bland-Altman plots showed good agreement between these two methods, with a mean difference of 0.30°. For other spinal canal expansion parameter measurements, correlation analysis showed a moderate to a high degree of correlation (p < 0.01), and Bland-Altman analysis indicated good agreement. CONCLUSION: In conclusion, during the French-door cervical laminoplasty procedure, application of IOUS can accurately evaluate spinal canal expansion. This innovative method may be helpful in improving surgical accuracy by enabling the operator to measure and determine canal enlargement during surgery, leading to ideal clinical outcomes and fewer postoperative complications. CLINICAL RELEVANCE STATEMENT: The use of intraoperative ultrasonography to assess spinal canal expansion following French-door cervical laminoplasty may improve outcomes for patients undergoing this procedure by providing more accurate measurements of spinal canal expansion. KEY POINTS: ⢠Spinal canal expansion after French-door cervical laminoplasty substantially influences operative prognosis; insufficient or excessive lamina opening may result in unexpected outcomes. ⢠Prediction of spinal canal expansion during surgery was previously impracticable, but based on this study, intraoperative ultrasonography offers an innovative approach and strongly agrees with postoperative CT measurement. ⢠Since this is the first research to offer real-time canal expansion guidance for cervical laminoplasty, it may improve the accuracy of the operation and produce ideal clinical outcomes with fewer postoperative complications.
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Laminoplastia , Doenças da Medula Espinal , Humanos , Laminoplastia/efeitos adversos , Laminoplastia/métodos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Canal Medular/diagnóstico por imagem , Canal Medular/cirurgia , Ultrassonografia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/complicações , Estudos RetrospectivosRESUMO
OBJECTIVES: To evaluate the ability of intraoperative CEUS to predict neurological recovery in patients with degenerative cervical myelopathy (DCM). METHODS: Twenty-six patients with DCM who underwent laminoplasty and intraoperative ultrasound (IOUS) were included in this prospective study. The modified Japanese Orthopaedic Association (mJOA) scores and MRI were assessed before surgery and 12 months postoperatively. The anteroposterior diameter (APD), maximum spinal cord compression (MSCC), and area of signal changes in the cord at the compressed and normal levels were measured and compared using MRI and IOUS. Conventional blood flow and CEUS indices (time to peak, ascending slope, peak intensity (PI), and area under the curve (AUC)) at different levels during IOUS were calculated and analysed. Correlations between all indicators and the neurological recovery rate were evaluated. RESULTS: All patients underwent IOUS and intraoperative CEUS, and the total recovery rate was 50.7 ± 33.3%. APD and MSCC improved significantly (p < 0.01). The recovery rate of the hyperechoic lesion group was significantly worse than that of the isoechoic group (p = 0.016). 22 patients were analysed by contrast analysis software. PI was higher in the compressed zone than in the normal zone (24.58 ± 3.19 versus 22.43 ± 2.39, p = 0.019). ΔPI compress-normal and ΔAUC compress-normal of the hyperechoic lesion group were significantly higher than those of the isoechoic group (median 2.19 versus 0.55, p = 0.017; 135.7 versus 21.54, p = 0.014, respectively), and both indices were moderately negatively correlated with the recovery rate (r = - 0.463, p = 0.030; r = - 0.466, p = 0.029). CONCLUSIONS: Signal changes and microvascular perfusion evaluated using CEUS during surgery are valuable predictors of cervical myelopathy prognosis. CLINICAL RELEVANCE STATEMENT: In the spinal cord compression area of degenerative cervical myelopathy, especially in the hyperechoic lesions, intraoperative CEUS showed more significant contrast agent perfusion than in the normal area, and the degree was negatively correlated with the neurological prognosis. KEY POINTS: ⢠Recovery rates in patients with hyperechoic findings were lower than those of patients without lesions detected during intraoperative ultrasound. ⢠The peak intensity of CEUS was higher in compressed zones than in the normal parts of the spinal cord. ⢠Quantitative CEUS comparisons of the peak intensity and area under the curve at the compressed and normal levels of the spinal cord revealed differences that were inversely correlated to the recovery rate.
Assuntos
Medula Cervical , Compressão da Medula Espinal , Doenças da Medula Espinal , Humanos , Compressão da Medula Espinal/patologia , Estudos Prospectivos , Medula Cervical/diagnóstico por imagem , Medula Cervical/cirurgia , Medula Cervical/patologia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Vértebras Cervicais/patologia , Medula Espinal/patologia , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/patologia , Imageamento por Ressonância Magnética , Resultado do TratamentoRESUMO
We report the case of a Syrian female refugee with late diagnosis of glutaric aciduria type 1 characterised by massive axial hypotonia and quadriplegia who only started adequate diet upon arrival in Switzerland at the age of 4 years, after a strenuous migration journey. Soon after arrival, she died from an unexpected severe upper cervical myelopathy, heralded by acute respiratory distress after a viral infection. This was likely due to repeated strains on her hypotonic neck and precipitated by an orthotopic os odontoideum who led to atlanto-axial subluxation. This case reminds us not to omit handling patients with insufficient postural control and hypotonia with great care to avoid progressive cervical myelopathy.
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Erros Inatos do Metabolismo dos Aminoácidos , Encefalopatias Metabólicas , Glutaril-CoA Desidrogenase , Processo Odontoide , Doenças da Medula Espinal , Pré-Escolar , Feminino , Humanos , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Glutaril-CoA Desidrogenase/deficiência , Hipotonia MuscularRESUMO
BACKGROUND: The factors underlying the topography of nitrous oxide (N2O)-induced neurological complications are unknown. METHODS: We included all consecutive patients admitted to the university hospital of Marseille for N2O-induced neurological complications in a prospective observational study. Patients underwent neurological examination, spinal cord magnetic resonance imaging, and nerve conduction studies within the first 4 weeks after admission. RESULTS: In total, 61 patients were included: 45% with myeloneuropathy, 34% with isolated myelopathy, and 21% with isolated neuropathy. On multivariable analysis, the odds of myelopathy were associated with the amount of weekly N2O consumption (~600 g cylinder per week, odds ratio [OR] = 1.11, 95% confidence interval [CI] = 1.001-1.24). The extent of the myelopathy (number of vertebral segments) was correlated with the number of ~600-g cylinders consumed weekly (ρ = 0.40, p < 0.005). The odds of neuropathy were associated with the duration of consumption (per month; OR = 1.29, 95% CI = 1.05-1.58). Mean lower-limb motor nerve amplitude was correlated with the duration of consumption (in months; ρ = -0.34, p < 0.05). CONCLUSIONS: The odds of myelopathy increased with the amount of N2O consumption, and the odds of neuropathy increased with the duration of N2O exposure, which suggests distinct pathophysiological mechanisms underlying these two neurological complications.
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Óxido Nitroso , Doenças da Medula Espinal , Humanos , Óxido Nitroso/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Doenças da Medula Espinal/induzido quimicamente , Doenças da Medula Espinal/diagnóstico por imagem , Estudos Prospectivos , Imageamento por Ressonância Magnética , Condução Nervosa/efeitos dos fármacos , Condução Nervosa/fisiologia , Adulto , Doenças do Sistema Nervoso Periférico/induzido quimicamenteRESUMO
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-ß. 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-ß-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-ß may contribute to the increased inflammatory response characteristically seen in HAM/TSP patients.
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Vírus Linfotrópico T Tipo 1 Humano , Interleucina-10 , Paraparesia Espástica Tropical , Linfócitos T Reguladores , Fator de Crescimento Transformador beta , Humanos , Linfócitos T Reguladores/imunologia , Masculino , Feminino , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/virologia , Interleucina-10/imunologia , Interleucina-10/genética , Pessoa de Meia-Idade , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Fator de Crescimento Transformador beta/metabolismo , Adulto , Carga Viral , Idoso , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/virologia , Portador Sadio/imunologia , Portador Sadio/virologiaRESUMO
PURPOSE: Degenerative cervical myelopathy (DCM) is a common cause of spinal cord dysfunction. In this study, we explored the potential of magnetization transfer ratio (MTR) for evaluating the structural integrity of spinal cord tracts in patients with clinically significant DCM. METHODS: Fifty-three patients with DCM and 41 patients with cervical radiculopathy were evaluated using high-resolution cervical spinal cord magnetic resonance imaging (MRI), which included the magnetization transfer technique. MRI data were analyzed with the Spinal Cord Toolbox (v5.5); MTR values in each spinal tract were calculated and compared between groups after correction for patient age and sex. Correlations between MTR values and patients' clinical disability rate were also evaluated. RESULTS: A statistically significant reduction in the average MTR of the spinal cord white matter, as well as the MTR of the ventral columns and lateral funiculi, was revealed in the DCM group (adjusted p < 0.01 for all comparisons). Furthermore, reductions in MTR values in the fasciculus cuneatus, spinocerebellar, rubrospinal, and reticulospinal tracts were found in patients with DCM (adjusted p < 0.01 for all comparisons). Positive correlations between the JOA score and the MTR within the ventral columns of the spinal cord (R = 0.38, adjusted p < 0.05) and the ventral spinocerebellar tract (R = 0.41, adjusted p < 0.05) were revealed. CONCLUSION: The findings of our study indicate that demyelination in patients with DCM primarily affects the spinal tracts of the extrapyramidal system, and the extent of these changes is related to the severity of the condition.
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Medula Cervical , Compressão da Medula Espinal , Doenças da Medula Espinal , Substância Branca , Humanos , Doenças da Medula Espinal/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Imageamento por Ressonância Magnética/métodos , Medula Cervical/diagnóstico por imagem , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologiaRESUMO
We report a unique case of cervical anterior spinal artery (ASA) infarction in a 49-year-old male with hypercholesterolemia and sleep apnea. The patient experienced sudden cervical pain, quadriparesis, areflexia, and urinary incontinence after swallowing a large food bolus. Imaging revealed an infarction at the C3-C5 levels and an anomalous right vertebral artery (VA) originating from the thoracic aorta, tightly enclosed between the aorta and a vertebral column with an anterior osteophyte. This aberrant VA was the primary vascular supply to the ASA, with no contribution from the left VA or supreme intercostal arteries. We propose that transient injury to the right VA, induced by compression between the aortic arch, the food bolus, and the osteophyte, led to temporary hypoperfusion of the ASA, causing a watershed ischemic injury in the mid cervical cord's anterior gray matter. The article also provides an in-depth discussion of the developmental and clinical characteristics associated with this rare vascular anomaly.
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Osteófito , Malformações Vasculares , Masculino , Humanos , Pessoa de Meia-Idade , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/anormalidades , Pescoço , Vértebras Cervicais/diagnóstico por imagem , Infarto/diagnóstico por imagem , Infarto/etiologiaRESUMO
PURPOSE: We sought to use the fractional amplitude of low-frequency fluctuation (fALFF) method to investigate the changes in spontaneous brain activity in CSM patients and their relationships with clinical features. METHODS: We recruited 20 patients with CSM, and 20 healthy controls (HCs) matched for age, sex, and education status. The fALFF method was used to evaluate the altered spontaneous brain activities. The Pearson correlation analysis of fALFF and the clinical features were carried out. RESULTS: Compared with HC, CSM group showed increased fALFF values in the left middle frontal gyrus, inferior parietal lobule, and right angular gyrus. Decreased fALFF values were found in the right lingual gyrus, cuneus (P < 0.05). Pearson correlation analysis shows that the fALFF values of all CSM were positively correlated with JOA score in the right angular gyrus (r = 0.518, P < 0.05). CONCLUSION: CSM patients have abnormal fALFF distribution in multiple brain regions and might be an appealing alternative approach for further exploration of the pathological and neuropsychological states in CSM.
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Encéfalo , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/patologia , Mapeamento Encefálico/métodos , Lobo Occipital , Lobo FrontalRESUMO
The human T cell leukemia virus type 1 (HTLV-1) is a pathogenic retrovirus that persists as a provirus in the genome of infected cells and can lead to adult T cell leukemia (ATL). Worldwide, more than 10 million people are infected and approximately 5% of these individuals will develop ATL, a highly aggressive cancer that is currently incurable. In the last years, genome editing tools have emerged as promising antiviral agents. In this proof-of-concept study, we use substrate-linked directed evolution (SLiDE) to engineer Cre-derived site-specific recombinases to excise the HTLV-1 proviral genome from infected cells. We identified a conserved loxP-like sequence (loxHTLV) present in the long terminal repeats of the majority of virus isolates. After 181 cycles of SLiDE, we isolated a designer-recombinase (designated RecHTLV), which efficiently recombines the loxHTLV sequence in bacteria and human cells with high specificity. Expression of RecHTLV in human Jurkat T cells resulted in antiviral activity when challenged with an HTLV-1 infection. Moreover, expression of RecHTLV in chronically infected SP cells led to the excision of HTLV-1 proviral DNA. Our data suggest that recombinase-mediated excision of the HTLV-1 provirus represents a promising approach to reduce proviral load in HTLV-1-infected individuals, potentially preventing the development of HTLV-1-associated diseases.
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Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Adulto , Humanos , Vírus Linfotrópico T Tipo 1 Humano/genética , Paraparesia Espástica Tropical/tratamento farmacológico , Paraparesia Espástica Tropical/genética , Provírus/genética , AntiviraisRESUMO
The objective is to investigate the presentation, complications, management, and outcomes of copper deficiency-induced neurological pathologies due to Wilson disease (WD) overtreatment. We examined the case of a WD patient who developed a low thoracic dorsal myelopathy due to chronic hypocupremia from excessive zinc therapy. A comprehensive literature review was conducted to identify similar cases. Ten additional cases of neurological pathology resulting from copper deficiency in the context of WD over-treatment were identified, all occurring during therapy with zinc salts. Myelopathy and peripheral neuropathy were the most common complications, while two additional groups reported leukoencephalopathy. Early cytopenia was often associated with copper deficiency-related neurological pathology appearing early in the context of copper deficiency. WD patients undergoing treatment, especially with zinc salts, should be closely monitored to prevent over-treatment and the consequent copper deficiency. Regular complete blood counts could provide early detection of copper deficiency, avoiding irreversible neurological damage. Swift recognition of new neurological signs not consistent with WD and timely discontinuation of the decoppering therapy are critical for improving outcomes. The optimal management, including the potential benefit of copper supplementation in patients with WD and subsequent therapy adjustments, remains unclear and necessitates further investigation. Despite the general poor functional neurological outcomes, there were some exceptions that warrant further exploration.
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Degeneração Hepatolenticular , Doenças da Medula Espinal , Humanos , Cobre , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/diagnóstico , Seguimentos , Sais/uso terapêutico , Zinco/uso terapêutico , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/etiologiaRESUMO
We reported four patients with coronavirus disease 2019 (COVID-19)-associated myelopathies, highlighting the delayed and atypical spinal cord magnetic resonance imaging (MRI) features and the literature review. All four patients were males, aged 37 to 72 years old. The latencies from COVID-19 to the onset of myelitis were 5, 15, 30, and 80 days. The initial symptoms were numbness and weakness of lower limbs in three cases, and back pain with weakness of lower limbs in one case. The peak symptoms included paraplegia, sphincter dysfunction, sensory disturbance level, and spastic gait. The EDSS scores were 7.5, 9.0, 9.0, and 7.5, respectively. Magnetic resonance imaging (MRI) showed delayed atypical spinal cord lesions at onset, i.e., two cases without lesions, one with linear spinal meningeal enhancement, and one with punctate lesions on T2-weighted imaging (T2WI). During the follow-up period, punctate, linear, and cloudy lesions in the lateral and posterior funiculus were seen on T2WI in the peak stage. The prominent features of spinal cord lesions were linear spinal meningeal enhancement, the mismatch of deteriorated clinical symptoms, and inapparent MRI findings. All four patients were left with an obvious disability, with two patients completely bedridden and two who could stand with support. This report highlights the recognition of COVID-19-associated myelopathy even months after initial infection, especially in patients with delayed and atypical spinal cord findings on MRI.
Assuntos
COVID-19 , Mielite , Doenças da Medula Espinal , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/complicações , COVID-19/patologia , Imageamento por Ressonância Magnética/métodos , Mielite/diagnóstico por imagem , Mielite/etiologia , Mielite/patologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/diagnóstico por imagemRESUMO
PURPOSE: To present the clinical features and treatment strategy of degenerative atlantoaxial subluxation (DAAS). METHODS: Patients with DAAS treated in our institution from 2003 to 2020 were retrospectively reviewed. We utilized the Japanese Orthopedic Association (JOA) scale to evaluate the neurologic status and distance of Ranawat et al. (DOR) to measure vertical migration. RESULTS: We recruited 40 patients with > 2 years of follow-up and an average age of 62.3 ± 7.7 years. All the patients had myelopathy; only one patient had moderate trauma before exacerbation of symptoms, and the duration of symptoms was 34 ± 36 months. The most frequent radiological features were vertical migration of C1 (100%), sclerosis (100%), and narrowing of the atlantoaxial lateral mass articulations (100%). Two patients underwent transoral release combined with posterior reduction and fusion, and 38 patients underwent posterior reduction and fusion with C1 lateral mass screws-C2 pedicle screws and plate systems only. Forty cases (100%) achieved a solid atlantoaxial fusion, and 38 cases (95%) achieved anatomic atlantoaxial reduction. The JOA score increased from 9.3 ± 2.6 to 14.8 ± 2.1 (P < 0.01). DOR increased from 14.5 ± 2.5 to 17.8 ± 2.2 mm at the final follow-up (P < 0.01). Loosening of the locking caps was detected in one case, bony fusion was achieved, and harvest-site pain was reported in five patients. CONCLUSION: DAAS differs from other types of AAS and presents with anterior subluxation combined with vertical subluxation arising from degenerative changes in the atlantoaxial joints. We recommend anatomic reduction as an optimal strategy for DAAS.
Assuntos
Articulação Atlantoaxial , Doenças da Medula Óssea , Luxações Articulares , Lesões do Pescoço , Parafusos Pediculares , Doenças da Medula Espinal , Fusão Vertebral , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Luxações Articulares/complicações , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Placas Ósseas , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/cirurgia , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
PURPOSE: Laminoplasty (LP) combined with C3 laminectomy (LN) can effectively achieve spinal cord decompression while maintaining the integrity of the posterior ligament-muscle complex, thereby minimizing cervical muscle damage. However, its necessity and safety remain controversial. This study aimed to compare the safety and efficacy of LP and LP combined with C3 LN in the treatment of patients with multilevel degenerative cervical spondylotic myelopathy (DCM). METHODS: A systematic review and meta-analysis of the literature was performed. A search of PubMed, Web of Science, Embase, and the Cochrane Library databases was conducted from inception through December 2023 and updated in February 2024. Search terms included laminoplasty, laminectomy, C3 and degenerative cervical spondylosis. The literature search yielded 14 studies that met our inclusion criteria. Outcomes included radiographic results, neck pain, neurologic function, surgical parameters, and postoperative complications. We also assessed methodologic quality, publication bias, and quality of evidence. RESULTS: Fourteen studies were identified, including 590 patients who underwent LP combined with C3 LN (modified group, MG) compared to 669 patients who underwent LP (traditional group, TG). The results of the study indicated a statistically significant improvement in cervical range of motion (WMD = 3.62, 95% CI: 0.39 to 6.85) and cervical sagittal angle (WMD = 2.07, 95% CI: 0.40 to 3.74) in the MG compared to the TG at the last follow-up (very low-level evidence). The TG had a higher number of patients with complications, especially C2-3 bone fusion. There was no significant difference found in improvement of neck pain, JOA, NDI, cSVA, T1 slope at latest follow-up. CONCLUSION: LP combined with C3 LN is an effective and necessary surgical method for multilevel DCM patients to maintain cervical sagittal balance. However, due to the low quality of evidence in existing studies, more and higher quality research on the technology is needed in the future.
RESUMO
PURPOSE: This study investigates the association between handgrip strength, walking pace, and the incidence of degenerative cervical myelopathy (DCM) using the UK Biobank dataset. METHODS: We analyzed data from 364,716 UK Biobank participants without prior neurological conditions. Handgrip strength was measured with a dynamometer, and walking pace was self-reported. Cox proportional hazards models assessed hazard ratios (HRs) and 95% confidence intervals (CIs) for DCM development. RESULTS: The cohort, with an average age of 56.2 years (SD, 8.1) and 47.4% male, was followed for a median of 12.6 years. During this period, 3,993 participants (1.1%) developed DCM. A significant inverse correlation was found between handgrip strength and DCM incidence (P for trend < 0.001), with decreasing HRs for DCM across quartiles of increasing grip strength: HRs were 0.70 (95% CI: 0.64-0.76), 0.62 (95% CI: 0.57-0.68), and 0.59 (95% CI: 0.54-0.66) for the second, third, and fourth quartiles, respectively. Participants with average or brisk walking paces had a lower DCM risk (HR, 0.55; 95% CI: 0.50-0.61 and HR, 0.48; 95% CI: 0.43-0.54) compared to slow walkers. The greatest risk reduction was in those with both higher handgrip strength and faster pace (HR, 0.39; 95% CI: 0.34-0.44). CONCLUSIONS: Handgrip strength and walking pace are inversely associated with DCM incidence, suggesting their potential as cost-effective screening tools for identifying individuals at risk for DCM.