RESUMO
BACKGROUND AND OBJECTIVES: To evaluate the usefulness of CSF and plasma neurofilament light (Nf-L) as a biomarker for human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM). METHODS: Nf-L, CXCL10, and neopterin were measured by ELISA in 83 CSF samples obtained from 49 individuals living with HTLV-1/2. Plasma Nf-L was also measured by single molecule array. Results were correlated with duration of disease, age, mobility, CSF cell counts, CSF protein, and HTLV-1 proviral load. RESULTS: Nf-L was detected in all CSF samples (median [range] = 575 [791.8-2,349] pg/mL) and positively correlated with markers of inflammation (CXCL10 (r = 0.733), neopterin (r = 0.499), cell count (r = 0.403), and protein levels (r = 0.693) in CSF; p < 0.0015). There was an inverse correlation between Nf-L and duration of disease (r = -0.584, p < 0.0001). Wheelchair-dependent patients had high concentrations of markers of inflammation and neuronal damage. Concentrations of CXCL10, neopterin, and Nf-L remained elevated in follow-up samples (mean follow-up 5.2 years). Nf-L in plasma correlated with concentration of Nf-L, neopterin, CXCL10, and protein in CSF. CONCLUSIONS: Nf-L in plasma and CSF has potential to be used as a biomarker of disease activity in HAM. Neuronal damage seems to be more intense early in disease but persists long term. Wheelchair-dependent patients have ongoing neuroinflammation.
Assuntos
Infecções por HTLV-I/diagnóstico , Proteínas de Neurofilamentos/sangue , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Doenças Neuroinflamatórias/sangue , Doenças Neuroinflamatórias/líquido cefalorraquidiano , Doenças da Medula Espinal/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Quimiocina CXCL10/sangue , Quimiocina CXCL10/líquido cefalorraquidiano , Feminino , Seguimentos , Infecções por HTLV-I/sangue , Infecções por HTLV-I/líquido cefalorraquidiano , Humanos , Masculino , Pessoa de Meia-Idade , Neopterina/sangue , Neopterina/líquido cefalorraquidiano , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/fisiopatologia , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/líquido cefalorraquidianoRESUMO
Human T-cell leukemia virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare inflammatory disease causing unremitting and progressive neurological disorders, such as spastic paraparesis, neurogenic bladder, and sensory disturbance of the lower extremities. Although there is no cure, immune-modulating agents such as corticosteroids are most widely used to slow disease progression. Biomarkers for the clinical assessment of HAM/TSP should be identified because the prediction of functional prognosis and the assessment of treatment efficacy are challenging due to the slowly progressive nature of the disease. The lack of surrogate biomarkers also hampers clinical trials of new drugs. This review summarizes biomarker candidates for the clinical assessment of patients with HAM/TSP. Most of the reported biomarker candidates are associated with viral components or inflammatory mediators because immune dysregulation provoked by HTLV-1 infection is thought to cause chronic inflammation and damage the spinal cord of patients with HAM/TSP. Although information on the diagnostic accuracy of most of the reported biomarkers is insufficient, several molecules, including inflammatory mediators such as CXCL10 and neopterin in the cerebrospinal fluid, have been suggested as potential biomarkers of functional prognosis and treatment response. Several clinical trials for HAM/TSP are currently underway, and we expect that these studies will provide not only evidence pertaining to treatment, but also novel findings regarding the utility of biomarkers in this disease. The establishment of clinical biomarkers will improve patient care and promote the development of therapies for HAM/TSP.
Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Doenças da Medula Espinal , Biomarcadores/sangue , Ensaios Clínicos como Assunto , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Humanos , Mediadores da Inflamação/sangue , Laboratórios , Paraparesia Espástica Tropical/sangue , Paraparesia Espástica Tropical/virologia , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/virologiaRESUMO
STUDY DESIGN: Peripheral blood samples were obtained from 25 patients with cervical spondylotic myelopathy (CSM) and 13 healthy volunteers. OBJECTIVES: Our aim was to investigate the significance of neurodegenerative biomarkers in patients with CSM and correlate their expression with CSM severity. SUMMARY OF BACKGROUND DATA: CSM is a common disorder involving chronic progressive compression of the cervical spinal resulting in progressive neurological impairment that ranges from mild tingling in the upper limbs to complete quadriplegia. However, the immunological background related to the neurodegenerative damage and its significance in CSM is still unclear. METHODS: Protein expression profiles of 14 neurodegenerative biomarkers were measured by multiplex Luminex bead assay and further analyzed by group comparison statistics, correlation studies, and receiver-operating characteristic analysis. RESULTS: Eleven of 14 biomarkers were significantly elevated in CSM patients as compared with healthy subjects (P<0.05). Specifically, the clinical severity of CSM on the scales of Nurick and modified Japanese Orthopedics Association scale (mJOA) was inversely related to neural cell adhesion molecule (NCAM) levels (r=-0.529, P=0.007; r=-0.519, P=0.001, respectively). CONCLUSIONS: Serum level of neural cell adhesion molecule may serve as a diagnostic biomarker correlating with the severity of CSM.
Assuntos
Biomarcadores/sangue , Antígeno CD56/sangue , Vértebras Cervicais/fisiopatologia , Doenças da Medula Espinal/sangue , Espondilose/sangue , Adulto , Idoso , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/sangue , Curva ROC , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic spinal cord injury worldwide. Surgical decompression is recommended as the preferred treatment strategy for DCM as it halts disease progression and improves neurologic symptoms. We previously demonstrated that neuroinflammation, including monocytes, plays a critical role in the pathobiology of DCM and in ischemic-reperfusion injury (IRI) following surgical decompression. Monocytes are able to enter the spinal cord and brain tissues due to damage to the blood spinal cord and blood brain barrier following injury. Studies have demonstrated that stroke patients and individuals undergoing hip replacement surgery have increased systemic levels of monocytes. Additionally, changes in the signalling responses of monocytes are associated with post-surgical recovery or with ischemic neural tissue damage. Herein, we investigated the role of systemic monocytes as a predictive biomarker for clinical recovery following decompressive surgery for DCM. FINDINGS: There was a 2-fold increase in the number of monocytes in DCM patients at 24â¯h following decompression as compared to baseline levels, which was associated with a significant improvement in the modified Japanese Orthopedic Association scale (mJOA) at 6-months after surgery (pâ¯<â¯.0001). In a mouse model of DCM, depleting acute monocytes reduced the non-classical (Ly6Clow) subset from circulation (pâ¯<â¯.05) and resulted in a 1.8-fold increase in CD11b expression in the spinal cord at 5â¯weeks following decompression. Acute monocyte depletion was accompanied by a modest decline in long-term overground locomotion, as evidenced by significantly reduced hindlimb swing speed. CONCLUSIONS: This work demonstrated that decompressive surgery leads to an acute increase in peripheral monocytes in human DCM patients, which is modestly associated with clinical recovery. We anticipate that this work could contribute to the implementation of routine measurements of blood monocyte subsets, their activation state, and production of cytokines following decompressive surgery. This information could help to select perioperative anti-inflammatory treatments that can enhance the beneficial effects of decompressive surgery and reduce the incidence of post-operative complications, while avoiding a reduction in systemic monocytes.
Assuntos
Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/tendências , Monócitos/metabolismo , Recuperação de Função Fisiológica/fisiologia , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Descompressão Cirúrgica/efeitos adversos , Feminino , Humanos , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Distribuição Aleatória , Estudos RetrospectivosAssuntos
Cobre/deficiência , Derivação Gástrica/efeitos adversos , Doenças da Medula Espinal/diagnóstico por imagem , Oligoelementos/deficiência , Cobre/sangue , Cobre/uso terapêutico , Deficiências Nutricionais/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/terapia , Oligoelementos/sangue , Oligoelementos/uso terapêuticoAssuntos
Alumínio/toxicidade , Síndromes Neurotóxicas , Doenças Profissionais , Doenças da Medula Espinal , Adulto , Alumínio/sangue , Humanos , Masculino , Síndromes Neurotóxicas/sangue , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Doenças Profissionais/sangue , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/diagnóstico , Doenças Profissionais/fisiopatologia , Exposição Ocupacional , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/induzido quimicamente , Doenças da Medula Espinal/diagnóstico , Doenças da Medula Espinal/fisiopatologiaAssuntos
Doenças da Medula Espinal/diagnóstico por imagem , Xantomatose Cerebrotendinosa/diagnóstico por imagem , Adulto , Núcleos Cerebelares/diagnóstico por imagem , Pilares do Cérebro/diagnóstico por imagem , Ácido Quenodesoxicólico/uso terapêutico , Colestanotriol 26-Mono-Oxigenase/genética , Colestanol/sangue , Feminino , Humanos , Cápsula Interna/diagnóstico por imagem , Transtornos de Início Tardio , Imageamento por Ressonância Magnética , Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/tratamento farmacológico , Doenças da Medula Espinal/genética , Xantomatose Cerebrotendinosa/sangue , Xantomatose Cerebrotendinosa/tratamento farmacológico , Xantomatose Cerebrotendinosa/genéticaRESUMO
A 21-year-old university student studying abroad in the USA presented to the emergency department with double vision, lower extremity weakness with difficulty ambulating and other neuropsychiatric symptoms. MRI of the brain and spinal cord were normal. Vitamin B12 was 78 pg/mL (58 pmol/L, reference 211-911 pg/mL). The patient had been using nitrous oxide capsules used for whipped cream recharging, which she obtained from other students, a few times daily for a month for the purpose of anxiety relief. The patient was not a vegan or vegetarian. The patient was treated with intramuscular vitamin B12 repletion with partial resolution of neurologic symptoms and discharged on vitamin B12 supplementation.
Assuntos
Óxido Nitroso/efeitos adversos , Transtornos Psicóticos/etiologia , Doenças da Medula Espinal/induzido quimicamente , Transtornos Relacionados ao Uso de Substâncias/complicações , Deficiência de Vitamina B 12/induzido quimicamente , Vitamina B 12/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Diplopia/induzido quimicamente , Aconselhamento Diretivo , Feminino , Humanos , Óxido Nitroso/administração & dosagem , Transtornos Psicóticos/psicologia , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Resultado do Tratamento , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/complicações , Adulto JovemRESUMO
BACKGROUND: Patients undergoing elective spinal fusion have an alarming rate of vitamin D deficiency, but its impact on bone fusion and patient outcomes is unclear. We investigated the association of perioperative vitamin D levels, fusion rates, and patient-reported outcome in patients undergoing spinal fusion for cervical spondylotic myelopathy. METHODS: In this one-year, prospective, single-center observational study, serum 25-OH vitamin D levels were measured perioperatively in adult patients. Serum vitamin D levels <30 ng/mL were considered abnormal. The primary outcome measures were postoperative patient-reported outcomes (Neck Disability Index, Visual Analog Scale, EuroQol EQ-5D-3L, EQ-VAS). Secondary outcome measures were the presence of and time to solid bony fusion, controlling for Body Mass Index (BMI), age, and number of motion segments. RESULTS: Forty-one of 58 patients (71%) had laboratory-confirmed abnormal vitamin D levels. Patients with low vitamin D were younger (P<0.05) and had a higher BMI (P<0.05) than patients with adequate vitamin D, but the groups were otherwise similar. There were no differences in mean time to fusion between the two groups, but patients with low vitamin D reported more postoperative disability (P<0.05). Multivariate model analysis demonstrated an independent, significant association between normal vitamin D and lower postoperative neck disability index (P=0.05) and EQ-5D-3L (P=0.03). CONCLUSIONS: Vitamin D deficiency (<30 ng/mL) is highly prevalent in patients undergoing elective spinal fusion for cervical myelopathy. Low vitamin D levels were associated with worse patient-reported outcomes and were an independent predictor of greater disability, which suggests vitamin D supplementation may offer some benefit in these patients.
Assuntos
Hidroxicolecalciferóis/sangue , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/cirurgia , Fusão Vertebral/métodos , Espondilose/sangue , Espondilose/cirurgia , Deficiência de Vitamina D/sangue , Adulto , Idoso , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/fisiopatologiaRESUMO
Because there are limited clinical reports on the impact of human T-lymphotropic virus type 1 (HTLV-1) on organ transplantation, its effects on the development of adult T-cell leukemia-lymphoma (ATL), post-transplantation lymphoproliferative disorder (PTLD) and HTLV-1-associated myelopathy (HAM) or atypical HAM after organ transplantation remain unclear.We retrospectively analyzed the impact of HTLV-1 in 54 allogeneic hematopoietic stem cell transplantation (allo-HSCT) cases and 31 renal transplantation cases between January 2006 and December 2016.Among the 54 allo-HSCT cases, nine recipients with ATL tested positive for HTLV-1, and one was found to be an HTLV-1 carrier. All donors tested negative for HTLV-1. Only one HTLV-1 carrier did not present with ATL or HAM development after allo-HSCT. Among nine ATL cases after allo-HSCT, four eventually relapsed due to proliferation of recipient-derived ATL cells. However, in one ATL case, atypical HAM developed rapidly at 5 months after allo-HSCT.Among the 31 renal transplantation cases, all donors tested negative for HTLV-1, and only recipients tested positive. Only one HTLV-1 carrier recipient did not present with ATL or HAM development after renal transplantation. However, one HTLV-1-negative recipient developed PTLD in the brain 10 years after renal transplantation.In clinical practice, careful follow-up of HTLV-1 infected recipients after organ transplantation is important because atypical HAM can develop in ATL patients after allo-HSCT. Furthermore, to clarify the risk of ATL or HAM development in HTLV-1 infected recipients, we prospectively followed up our cohort.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Vírus Linfotrópico T Tipo 1 Humano , Transplante de Rim , Leucemia-Linfoma de Células T do Adulto , Doenças da Medula Espinal , Adulto , Aloenxertos , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/sangue , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/epidemiologia , Doenças da Medula Espinal/patologia , Doenças da Medula Espinal/terapiaRESUMO
OBJECTIVE: To describe clinical and radiologic features associated with myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) in a large French nationwide adult cohort, to assess baseline prognostic features of MOG-Ab-associated diseases after a first acute demyelinating syndrome, and to evaluate the clinical value of MOG-Ab longitudinal analysis. METHODS: Clinical data were obtained from 197 MOG-Ab-positive patients ≥18 years of age. Complete imaging data were available in 108, and 54 serum samples were eligible for longitudinal evaluation. For survival analysis comparison, 169 aquaporin-4 antibody (AQP4-Ab)-positive patients from the NOMADMUS database were included. RESULTS: Median age at onset was 36.46 (range 18.0-76.8) years, and patients were predominantly white (92.9%) with male:female ratio, 1.1. Clinical phenotype at onset included optic neuritis or myelitis in 90.86%, isolated brainstem or encephalopathy syndromes in 6.6%, and a combination of syndromes in 2.5%. Distinctive brain MRI findings in MOG-Ab-positive patients were thalamic and pontine lesions. Cortical and leptomeningeal lesions were found in 16.3% and 6.1%, respectively. The probability of reaching a first relapse after 2 and 5 years was 44.8% and 61.8%, respectively. MOG-Ab-positive patients were at lower risk at presentation of further clinical relapse (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.26-0.79) compared to AQP4-Ab-positive individuals. MOG-Ab-positive individuals had a lower risk of reaching Disability Status Scale score of 3.0 (HR 0.46, 95% CI 0.22-0.94) and visual acuity of 20/100 (HR 0.23, 95% CI 0.07-0.72). Finally, MOG-Ab titers were higher at relapse than in remission (p = 0.009). CONCLUSION: In adults, MOG-Ab-associated disease extends beyond clinical and radiologic abnormalities in the optic nerve and spinal cord. Despite the relapsing course, the overall visual and motor outcome is better compared with AQP4-Ab-positive patients.
Assuntos
Encefalopatias/diagnóstico , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico , Glicoproteína Mielina-Oligodendrócito/imunologia , Doenças da Medula Espinal/diagnóstico , Adolescente , Adulto , Idoso , Aquaporina 4/sangue , Autoanticorpos , Encefalopatias/sangue , Encefalopatias/imunologia , Encefalopatias/patologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/sangue , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/sangue , Prognóstico , Estudos Retrospectivos , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/imunologia , Doenças da Medula Espinal/patologia , Adulto JovemAssuntos
Cobre/deficiência , Doenças da Medula Espinal/sangue , Idoso de 80 Anos ou mais , Vértebras Cervicais/diagnóstico por imagem , Cobre/sangue , Diagnóstico Diferencial , Feminino , Humanos , Doenças da Medula Espinal/diagnóstico por imagem , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/diagnóstico por imagem , Deficiência de Vitamina B 12/tratamento farmacológicoRESUMO
High cervical myelopathy is a common entity and often encountered in clinical practice. Various pathologies can present with this symptomatology. Detailed history and a meticulous neurological examination can help us differentiate and rule out some of the close differentials. Non tuberculous ANCA positive pachymeningitis is a rare entity and a diagnosis of exclusion or following histopathological confirmation. Here we describe a case of high cervical myelopathy, the presentation, imaging and the various differentials considered and how we arrived at the diagnosis.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos , Vértebras Cervicais/diagnóstico por imagem , Descompressão Cirúrgica/métodos , Meningite/diagnóstico por imagem , Doenças da Medula Espinal/diagnóstico por imagem , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Vértebras Cervicais/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Meningite/sangue , Meningite/cirurgia , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/cirurgiaRESUMO
BACKGROUND: No definitive, antemortem diagnostic test for canine degenerative myelopathy (DM) is available. Phosphorylated neurofilament heavy (pNF-H) is a promising biomarker for nervous system diseases. HYPOTHESIS/OBJECTIVE: Cerebrospinal fluid (CSF) and serum pNF-H is a detectable biological marker for diagnosis of canine DM. ANIMALS: Fifty-three DM-affected, 27 neurologically normal, 7 asymptomatic at-risk, and 12 DM mimic dogs. METHODS: Archived CSF and serum pNF-H concentrations were determined by a commercially available ELISA. A receiver-operating characteristic (ROC) curve was generated with CSF values. RESULTS: Compared with old control dogs, median CSF pNF-H concentration was increased in all stages of DM; old dogs 5.1 ng/mL (interquartile range [IQR] 1.4-9.3) versus DM stage 1 23.9 ng/mL (IQR 20.8-29.6; P < .05) versus DM stage 2 36.8 ng/mL (IQR 22.9-51.2; P < .0001) versus DM stage 3 25.2 ng/mL (IQR 20.2-61.8; P < .001) versus DM stage 4 38.0 ng/mL (IQR 11.6-59.9; P < .01). Degenerative myelopathy stage 1 dogs had increased median CSF pNF-H concentrations compared with asymptomatic, at-risk dogs (3.4 ng/mL [IQR 1.5-10.9; P < .01]) and DM mimics (6.6 ng/mL [IQR 3.0-12.3; P < .01]). CSF pNF-H concentration >20.25 ng/mL was 80.4% sensitive (confidence interval [CI] 66.09-90.64%) and 93.6% specific (CI 78.58-99.21%) for DM. Area under the ROC curve was 0.9467 (CI 0.92-0.9974). No differences in serum pNF-H concentration were found between control and DM-affected dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: pNF-H concentration in CSF is a sensitive biomarker for diagnosis of DM. Although there was high specificity for DM in this cohort, further study should focus on a larger cohort of DM mimics, particularly other central and peripheral axonopathies.
Assuntos
Doenças do Cão/líquido cefalorraquidiano , Doenças Neurodegenerativas/veterinária , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Doenças da Medula Espinal/veterinária , Animais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Doenças do Cão/sangue , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/líquido cefalorraquidiano , Fosforilação , Curva ROC , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/líquido cefalorraquidianoAssuntos
Abscesso/diagnóstico por imagem , Doenças da Medula Espinal/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Abscesso/sangue , Abscesso/líquido cefalorraquidiano , Abscesso/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Humanos , Masculino , Medula Espinal/efeitos dos fármacos , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/líquido cefalorraquidiano , Doenças da Medula Espinal/tratamento farmacológico , Vértebras TorácicasRESUMO
BACKGROUND: The purpose of this study was to prove the hypothesis that C-reactive protein (CRP) and nerve growth factor (NGF) may be potential biomarkers for lower urinary tract disorders and may be able to distinguish between micturition dysfunctions of different origin in dogs with spinal cord diseases. NGF- and CRP- concentrations were measured in serum and urine samples using specific ELISA-Kits. Results in urine were standardized by urine-creatinine levels. RESULTS: CRP in serum was detectable in 32/76 and in urine samples in 40/76 patients. NGF could be measured in all serum and in 70/76 urine samples. Urinary CRP concentrations were significantly higher in dogs with micturition dysfunction (p = 0.0009) and in dogs with different neurological diseases (p = 0.0020) compared to the control group. However, comparing dogs with spinal cord disorders with and without associated micturition dysfunction no significant difference could be detected for NGF and CRP values in urine or serum samples. Additionally, levels did not decrease significantly, when measured at the time when the dogs regained the ability to urinate properly (urinary NGF p = 0.7962; urinary CRP p = 0.078). Urine samples with bacteria and/or leukocytes had no significant increase in urinary NGF (p = 0.1112) or CRP (p = 0.0534) concentrations, but higher CRP-levels in urine from dogs with cystitis were found compared to dogs without signs of cystitis. CONCLUSIONS: From these data we conclude that neither CRP nor NGF in urine or serum can be considered as reliable biomarkers for micturition disorders in dogs with spinal cord disorders in a clinical setting, but their production might be part of the pathogenesis of such disorders. Significantly higher levels of CRP could be found in the urine of dogs with micturition dysfunctions compared to control dogs. This phenomenon could potentially be explained by unspecific extrahepatic CRP production by smooth muscle cells in the dilated bladder.
Assuntos
Proteína C-Reativa/metabolismo , Proteína C-Reativa/urina , Doenças do Cão/sangue , Doenças do Cão/urina , Fator de Crescimento Neural/sangue , Fator de Crescimento Neural/urina , Doenças do Sistema Nervoso/veterinária , Animais , Biomarcadores/sangue , Biomarcadores/urina , Cistite/sangue , Cistite/microbiologia , Cistite/urina , Cistite/veterinária , Cães , Feminino , Masculino , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/urina , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/urina , Doenças da Medula Espinal/veterinária , MicçãoRESUMO
Transverse myelitis (TM) is associated with neuromyelitis optica (NMO) and multiple sclerosis (MS). Early recognition of useful parameters may be helpful to distinguish their difference. This retrospective study analyzed thyroid parameters from 243 serum samples (relapse = 128; remission = 115) of 178 patients with demyelinating diseases (NMO, n = 25; TM, n = 48; MS, n = 105). The relationship between thyroid and clinical parameters was analyzed. Patients with NMO and TM had a higher frequency of abnormal thyroid-stimulating hormone (TSH), anti-thyroglobulin antibodies (TG-Ab), and antithyroid peroxidase antibody (TPO-Ab) than MS patients (p<0.05). The level of TSH and TG-Ab returned to normal levels after administration of high-dose intravenous methylprednisolone (p<0.05). In 96 patients (NMO, n = 19; TM, n = 25; MS, n = 52) without treatment, serum levels of TSH, TG-Ab and TPO-Ab were significantly different between patients with and without myelitis (p<0.01). Patients positive for aquaporin-4 (AQP4) antibodies showed higher abnormalities of TSH (p = 0.001), TG-Ab (p = 0.004) and TPO-Ab (p<0.0001) levels than AQP4 antibodies negative patients. Logistic regression analyses revealed independent relationships between TSH (odds ratio [OR] â= 33.994; p<0.0001), TG-Ab (OR = 7.703; p = 0.017) and myelitis occurrence in 96 patients at the active stage. In 52 MS patients experiencing their first attack, MS patients with myelitis were associated with TSH abnormalities (OR = 42.778; p<0.0001). This study showed increased abnormalities of thyroid parameters in patients with NMO and TM than in MS patients. MS patients with myelitis also had greater TSH abnormality than in MS patients without myelitis. Abnormal TSH and TG-Ab were independently associated with myelitis occurrence in central nervous system demyelinating disorders.
Assuntos
Autoanticorpos/sangue , Doenças Desmielinizantes/sangue , Doenças Desmielinizantes/patologia , Medula Espinal/patologia , Tireotropina/sangue , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Doenças Desmielinizantes/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/epidemiologia , Mielite Transversa/sangue , Mielite Transversa/epidemiologia , Neuromielite Óptica/sangue , Neuromielite Óptica/epidemiologia , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/epidemiologia , Adulto JovemRESUMO
AIMS: Severe copper deficiency leads in humans to a treatable multisystem disease characterized by anaemia and degeneration of spinal cord and nerves, but its mechanisms have not been investigated. We tested whether copper deficit leads to alterations in fundamental copper-dependent proteins and in iron metabolism in blood and muscles of patients affected by copper deficiency myeloneuropathy, and if these metabolic abnormalities are associated with compensatory mechanisms for copper maintenance. METHODS: We evaluated the expression of critical copper enzymes, of iron-related proteins, and copper chaperones and transporters in blood and muscles from five copper-deficient patients presenting with subacute sensory ataxia, muscle paralysis, liver steatosis and variable anaemia. Severe copper deficiency was caused by chronic zinc intoxication in all of the patients, with an additional history of gastrectomy in two cases. RESULTS: The antioxidant enzyme SOD1 and subunit 2 of cytochrome c oxidase were significantly decreased in blood cells and in muscles of copper-deficient patients compared with controls. In muscle, the iron storage protein ferritin was dramatically reduced despite normal serum ferritin, and the expression of the haem-proteins cytochrome c and myoglobin was impaired. Muscle expression of the copper transporter CTR1 and of the copper chaperone CCS, was strikingly increased, while antioxidant protein 1 was diminished. CONCLUSIONS: copper-dependent enzymes with critical functions in antioxidant defences, in mitochondrial energy production, and in iron metabolism are affected in blood and muscles of patients with profound copper deficiency leading to myeloneuropathy. Homeostatic mechanisms are strongly activated to increase intracellular copper retention.