RESUMEN
Long-term treatment of multiple sclerosis with natalizumab (NTZ) carries the risk of a devastating complication in the form of an encephalopathy caused by a reactivation of a latent John Cunningham virus infection (progressive multifocal leucoencephalopathy, PML). Early diagnosis is associated with considerably better prognosis. Quantitative EEG as an objective, rater-independent technique provides high sensitivity (88%) and specificity (82%) for the diagnosis of NTZ-PML. Combination of diagnostic modalities addressing static morphological (brain MRI) as well as functional (EEG) pathologic changes may improve risk management programmes.
Asunto(s)
Electroencefalografía/métodos , Factores Inmunológicos/efectos adversos , Virus JC/efectos de los fármacos , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/efectos adversos , Adulto , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Virus JC/crecimiento & desarrollo , Virus JC/patogenicidad , Leucoencefalopatía Multifocal Progresiva/inducido químicamente , Leucoencefalopatía Multifocal Progresiva/patología , Leucoencefalopatía Multifocal Progresiva/virología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/patología , Natalizumab/administración & dosificación , Pronóstico , Estudios Retrospectivos , Activación Viral/efectos de los fármacosRESUMEN
Seven subunits of the mitochondrial contact site and cristae junction (CJ) organizing system (MICOS) in humans have been recently described in function and structure. QIL1 (also named MIC13) is a small complex that is crucial for the maintenance and assembling of MICOS. A novel mutation of an essential splice site in the C19orf70 gene encoding QIL1 induces severe mitochondrial encephalopathy, hepatopathy and lactate acidosis consistent with psychomotor retardation. In addition, bilateral kidney stones were observed. Disassembly of MICOS complex subunits displays lack of MIC10-MIC26-MIC27-QIL1 subcomplex, resulting in aberrant cristae structure and a loss of cristae junctions and contact sites. In liver and muscle tissue, the activity of the respiratory chain complexes (OXPHOS) was severely impaired. Defects in MICOS complex do not only affect mitochondrial architecture, but also mitochondrial fusion, metabolic signalling, lipid trafficking and cellular electric homeostasis.
Asunto(s)
Genes Letales , Hepatopatías/genética , Proteínas de la Membrana/genética , Mitocondrias/metabolismo , Encefalomiopatías Mitocondriales/genética , Proteínas Mitocondriales/genética , Mutación , Desempeño Psicomotor , Acidosis Láctica/complicaciones , Encéfalo/diagnóstico por imagen , Transporte de Electrón , Resultado Fatal , Femenino , Humanos , Lactante , Recién Nacido , Cálculos Renales/complicaciones , Hígado/metabolismo , Hepatopatías/complicaciones , Hepatopatías/fisiopatología , Imagen por Resonancia Magnética , Encefalomiopatías Mitocondriales/complicaciones , Encefalomiopatías Mitocondriales/diagnóstico por imagen , Encefalomiopatías Mitocondriales/fisiopatología , Músculos/metabolismo , Sistemas de Lectura Abierta , Fosforilación Oxidativa , Sitios de Empalme de ARNRESUMEN
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. An intrathecal IgM synthesis is associated with a more rapid progression of MS and the intrathecal immune response to measles -, rubella -and varicella zoster virus (MRZR) which, if present, increases the likelihood of a diagnosis of MS in adults. OBJECTIVE: To evaluate the frequency of an intrathecal IgM synthesis and MRZR in children with MS. MethodsChildren with MS and a data set including clinical and treatment history, MRI at onset, in addition to a CSF analysis, and determination of antibody index (AI) of measles, rubella, and zoster antibodies, were eligible. The presence of an intrathecal IgM synthesis and/or a positive MRZ reaction were compared to biomarkers of a more progressive disease course. RESULTS: In 75 children with MS, OCBs were present in 93.3 %). 49,2 % experienced their first relapse within 6 months. 50.7 % had a total lesion load of more than 10 lesions in the first brain MRI. Spinal lesions were identified in 64 %. 23.5 % had a positive MRZR and 40.3 % an intrathecal IgM synthesis. No significant associations were detected between the presence of an intrathecal IgM synthesis and MRZR and parameters including the relapse rate in the first two years. CONCLUSION: An intrathecal IgM synthesis and a positive MRZR are found in a subset of MS children but are not associated with markers associated with a poor prognosis.
Asunto(s)
Inmunoglobulina M , Imagen por Resonancia Magnética , Esclerosis Múltiple , Humanos , Masculino , Inmunoglobulina M/líquido cefalorraquídeo , Niño , Femenino , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/líquido cefalorraquídeo , Adolescente , Herpesvirus Humano 3/inmunología , Anticuerpos Antivirales/líquido cefalorraquídeo , Anticuerpos Antivirales/sangre , Preescolar , Virus del Sarampión/inmunología , Virus de la Rubéola/inmunología , Progresión de la Enfermedad , Encéfalo/diagnóstico por imagen , Biomarcadores/líquido cefalorraquídeoRESUMEN
Metaplastic breast carcinoma, a rare entity, accounts for only about 0.02% of all breast carcinomas. It involves the transformation of mammary neoplasms into osteoid and chondroid substances. Because of the relatively small patient population and the limited number of controlled studies, there is confusion regarding its classification and staging. Its histogenesis is unknown. The authors describe a 65-year-old woman with findings consistent with metaplastic breast carcinoma. Theories as to etiology and prognosis as well as treatment are discussed.