ABSTRACT
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.
Subject(s)
Immunoglobulin M , Magnetic Resonance Imaging , Multiple Sclerosis , Humans , Male , Immunoglobulin M/cerebrospinal fluid , Child , Female , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/immunology , Multiple Sclerosis/cerebrospinal fluid , Adolescent , Herpesvirus 3, Human/immunology , Antibodies, Viral/cerebrospinal fluid , Antibodies, Viral/blood , Child, Preschool , Measles virus/immunology , Rubella virus/immunology , Disease Progression , Brain/diagnostic imaging , Biomarkers/cerebrospinal fluidABSTRACT
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.
Subject(s)
Electroencephalography/methods , Immunologic Factors/adverse effects , JC Virus/drug effects , Leukoencephalopathy, Progressive Multifocal/diagnosis , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Natalizumab/adverse effects , Adult , Female , Humans , Immunologic Factors/administration & dosage , JC Virus/growth & development , JC Virus/pathogenicity , Leukoencephalopathy, Progressive Multifocal/chemically induced , Leukoencephalopathy, Progressive Multifocal/pathology , Leukoencephalopathy, Progressive Multifocal/virology , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Multiple Sclerosis, Relapsing-Remitting/pathology , Natalizumab/administration & dosage , Prognosis , Retrospective Studies , Virus Activation/drug effectsABSTRACT
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.
Subject(s)
Genes, Lethal , Liver Diseases/genetics , Membrane Proteins/genetics , Mitochondria/metabolism , Mitochondrial Encephalomyopathies/genetics , Mitochondrial Proteins/genetics , Mutation , Psychomotor Performance , Acidosis, Lactic/complications , Brain/diagnostic imaging , Electron Transport , Fatal Outcome , Female , Humans , Infant , Infant, Newborn , Kidney Calculi/complications , Liver/metabolism , Liver Diseases/complications , Liver Diseases/physiopathology , Magnetic Resonance Imaging , Mitochondrial Encephalomyopathies/complications , Mitochondrial Encephalomyopathies/diagnostic imaging , Mitochondrial Encephalomyopathies/physiopathology , Muscles/metabolism , Open Reading Frames , Oxidative Phosphorylation , RNA Splice SitesABSTRACT
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.