RESUMO
OBJECTIVE: To assess whether a high-salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability. METHODS: BENEFIT was a randomized clinical trial comparing early versus delayed interferon beta-1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13-16) spot urine samples throughout the 5-year follow-up. We estimated 24-hour urine sodium excretion level at each time point using the Tanaka equations, and assessed whether sodium levels estimated from the cumulative average of the repeated measures were associated with clinical (conversion to MS, Expanded Disability Status Scale [EDSS]) and magnetic resonance imaging (MRI) outcomes. RESULTS: Average 24-hour urine sodium levels were not associated with conversion to clinically definite MS over the 5-year follow-up (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.67-1.24 per 1g increase in estimated daily sodium intake), nor were they associated with clinical or MRI outcomes (new active lesions after 6 months: HR = 1.05, 95% CI = 0.97-1.13; relative change in T2 lesion volume: -0.11, 95% CI = -0.25 to 0.04; change in EDSS: -0.01, 95% CI = -0.09 to 0.08; relapse rate: HR = 0.78, 95% CI = 0.56-1.07). Results were similar in categorical analyses using quintiles. INTERPRETATION: Our results, based on multiple assessments of urine sodium excretion over 5 years and standardized clinical and MRI follow-up, suggest that salt intake does not influence MS disease course or activity. Ann Neurol 2017;82:20-29.
Assuntos
Doenças Desmielinizantes/diagnóstico , Esclerose Múltipla/diagnóstico , Sódio na Dieta/efeitos adversos , Adulto , Encéfalo/patologia , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/urina , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Interferon beta-1b/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Sódio na Dieta/urina , Adulto JovemRESUMO
Methylmalonic aciduria and homocystinuria, cblC type, is the most common inborn error of vitamin B(12) (cobalamin) metabolism. The recent cloning of the disease gene, MMACHC, has permitted genotype-phenotype correlation. In a 1-year-old girl, compound heterozygous c.271dupA and c.616C>T mutations in MMACHC were identified as causing an early onset methylmalonic aciduria and homocystinuria, cblC type, which was complicated by sensorimotor peripheral demyelinating neuropathy.
Assuntos
Doenças Desmielinizantes/urina , Homocistinúria/urina , Ácido Metilmalônico/urina , Doenças do Sistema Nervoso Periférico/urina , Doenças Desmielinizantes/complicações , Feminino , Estudos de Associação Genética , Homocistinúria/complicações , Humanos , Lactente , Condução Nervosa/fisiologia , Doenças do Sistema Nervoso Periférico/complicaçõesRESUMO
OBJECTIVE: To investigate body fluids of patients with undiagnosed leukodystrophies using in vitro (1)H-NMR spectroscopy (H-NMRS). METHODS: We conducted a cross-sectional study using high-resolution in vitro H-NMRS on CSF and urine samples. RESULTS: We found a significant increase of free sialic acid in CSF or urine in 6 of 41 patients presenting with hypomyelination of unknown etiology. Molecular genetic testing revealed pathogenic mutations in the SLC17A5 gene in all 6 patients. H-NMRS revealed an increase of N-acetylaspartylglutamate in the CSF of all patients with SLC17A5 mutation (range 13-114 micromol/L, reference <12 micromol/L). CONCLUSION: In patients with undiagnosed leukodystrophies, increased free sialic acid in CSF or urine is a marker for free sialic acid storage disorder and facilitates the identification of the underlying genetic defect. Because increase of N-acetylaspartylglutamate in CSF has been observed in other hypomyelinating disorders, it can be viewed as a marker of a subgroup of hypomyelinating disorders.
Assuntos
Doenças Desmielinizantes/líquido cefalorraquidiano , Dipeptídeos/líquido cefalorraquidiano , Transportadores de Ânions Orgânicos/genética , Doença do Armazenamento de Ácido Siálico/líquido cefalorraquidiano , Doença do Armazenamento de Ácido Siálico/diagnóstico , Simportadores/genética , Criança , Pré-Escolar , Estudos Transversais , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/urina , Feminino , Testes Genéticos , Genótipo , Humanos , Lactente , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Mutação , Ácido N-Acetilneuramínico/líquido cefalorraquidiano , Ácido N-Acetilneuramínico/urina , Doença do Armazenamento de Ácido Siálico/complicações , Doença do Armazenamento de Ácido Siálico/genética , Doença do Armazenamento de Ácido Siálico/urina , Adulto JovemRESUMO
Nitric oxide (NO) has been implicated in the immunopathogenesis of MS as a potential mediator of neuronal loss. To investigate the role of.NO in the development of progressive disease we measured the NO metabolites (nitrate and nitrite) and neopterin, in the urine of 129 patients with demyelinating disease (DD): 23 with clinically isolated syndromes compatible with demyelination and in 46 relapsing remitting (RR) and 60 patients with progressive MS. Eighty-nine of these 129 patients underwent Gd-enhanced MRI. In addition 58 normal control subjects (NC), 19 AIDS and 35 rheumatoid arthritis (RA) patients were studied. Patients with DD, AIDS and RA had significantly elevated urinary nitrate plus nitrite (nit : creat. urine) and neopterin (neopt : creat.urine) to creatinine ratios compared to NC subjects. (Median[25th - 75th%] nit : creat.urine: NC=1183[962 - 1365] vs DD=1245[875 - 2403], AIDS=1686[1231 - 2531], and RA=1950[1214 - 2726] mumol/mol, P<0.001 and median[25th - 75th%] neopt : creat.urine: NC=99[76 - 151] vs DD=163[119 - 266], AIDS=972[653 - 1456], and RA=389[257 - 623] mu mol/mol, P<0.001). Patients with early DD and RR MS had significantly elevated nit : creat.urine compared to patients with progressive MS (nit : creat. urine: 1612[1020 - 2733] vs 1159[790 - 1641] mu mol/mol, P=0.006). The nit : creat.urine and neopt : creat.urine did not correlate with clinical relapse or MRI activity. Excretion of.NO metabolites is increased in patients with early or relapsing-remitting disease.NO appears to be a double-edged sword, mediating tissue damage and modulating complex immunological functions which may be protective in MS.
Assuntos
Esclerose Múltipla/urina , Nitratos/urina , Nitritos/urina , Síndrome da Imunodeficiência Adquirida/patologia , Síndrome da Imunodeficiência Adquirida/urina , Adulto , Idoso , Artrite Reumatoide/urina , Contagem de Linfócito CD4 , Creatinina/urina , Doenças Desmielinizantes/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla Crônica Progressiva/urina , Esclerose Múltipla Recidivante-Remitente/urina , Neopterina/urina , Valores de ReferênciaRESUMO
The question of what happens to cholesterol in the adult central nervous system during its slow turnover has been addressed using rats with brain and spinal cord labeled with [4-14C]cholesterol upon intracerebral injection of labeled cholesterol into rats at 10-12 days of age. At six months after injection, 14C was found only in the brain and spinal cord and was slowly released via the rat's urine. When labeled rats were given demyelinating agents (triethyl tin chloride, hexachlorophene, sodium cyanide) and when experimental allergic encephalomyelitis was induced, a measurable increase in urinary 14C label above control levels was found. It was concluded that there is a direct relationship between the experimental demyelination induced and the increased release of cholesterol metabolites into urine. The study suggests that a clinical method could be developed to determine the rate of central nervous system demyelination by measuring the amount of urinary cholesterol metabolites.
Assuntos
Doenças do Sistema Nervoso Central/urina , Colesterol/urina , Doenças Desmielinizantes/urina , Animais , Radioisótopos de Carbono , Doenças do Sistema Nervoso Central/induzido quimicamente , Colesterol/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/urina , Hexaclorofeno/toxicidade , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Cianeto de Sódio/toxicidade , Inanição/urina , Compostos de Trietilestanho/toxicidadeRESUMO
3 male and 2 female infants with Canavan disease proven in some by brain biopsy, whose symptoms appeared within the first 4 months of life, are presented. Urinary organic acids were analyzed by gas chromatography/mass spectrometry. All excreted large amounts of N-acetylaspartic acid, probably secondary to decreased activity of its hydrolase. The pathogenetic mechanism is not well understood. Analysis of urinary organic acids can replace brain biopsy in the diagnosis of this condition, and the diagnosis can now be made prenatally.
Assuntos
Ácidos/urina , Doenças Desmielinizantes/urina , Lipidoses/urina , Ácido Aspártico/análogos & derivados , Ácido Aspártico/urina , Feminino , Humanos , Lactente , MasculinoRESUMO
Over the past decade, significant improvements in immunochemical and electrophoretic techniques have enabled collection of heretofore unavailable data on proteins in biological fluids, greatly increasing our understanding of protein physiology in the various body compartments and providing the foundation for clinical use of protein analysis in body fluids. The most striking advance has been in the diagnosis of demyelinating disease through the use of serum/cerebrospinal fluid protein ratios and the morphological evaluation of immunoglobulin banding patterns. These laboratory tests are now considered obligatory for any patient in whom demyelinating disease is suspected as the cause of neurological dysfunction. Cerebrospinal fluid protein data can also be helpful in quantitating the permeability of the blood/cerebrospinal fluid barrier in many inflammatory or infectious central nervous system disorders. Assays of individual proteins in urine can help distinguish between different types of proteinuria, and can give quantitative data on the selectivity of the glomerulus and the reabsorbing capacity of the tubules. The protein content of saliva, synovial fluid, and milk has also been well characterized, and is clinically applicable to a wide range of disorders.