RESUMEN
INTRODUCTION: Muscle-specific tyrosine kinase (MuSK) autoantibody related myasthenia gravis is characterized by bulbar and respiratory manifestations, a poor response to anticholinergics, and a generally good response to plasma exchange and rituximab. It is not known if MuSK-antibody (Ab) levels could be used to predict the clinical course Methods: Three patients for whom frequent long-term monitoring of MuSK-Ab levels and the Myasthenia Gravis Composite (MGC) scores were performed are described. RESULTS: A close relationship existed between the MuSK-Ab concentrations and the MGC score. Furthermore, a rise in Ab concentration preceded a more serious clinical relapse in all patients Conclusions: These findings suggest that MuSK-Ab concentrations may be a useful biomarker for the long-term monitoring of MuSK myasthenia gravis, particularly while in clinical remission. This may allow preemptive escalation of therapy to prevent clinical relapse, and conversely permitting greater weaning of unnecessary immunosuppression. Muscle Nerve, 2019.
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Miastenia Gravis/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Proteínas Tirosina Quinasas Receptoras/inmunología , Receptores Colinérgicos/inmunología , Rituximab/uso terapéutico , Anciano de 80 o más Años , Autoanticuerpos/sangre , Biomarcadores/sangre , Femenino , Humanos , Terapia de Inmunosupresión , Masculino , Persona de Mediana Edad , Intercambio Plasmático/métodosRESUMEN
Distal hereditary motor neuropathies comprise a clinically and genetically heterogeneous group of disorders. We recently mapped an X-linked form of this condition to chromosome Xq13.1-q21 in two large unrelated families. The region of genetic linkage included ATP7A, which encodes a copper-transporting P-type ATPase mutated in patients with Menkes disease, a severe infantile-onset neurodegenerative condition. We identified two unique ATP7A missense mutations (p.P1386S and p.T994I) in males with distal motor neuropathy in two families. These molecular alterations impact highly conserved amino acids in the carboxyl half of ATP7A and do not directly involve the copper transporter's known critical functional domains. Studies of p.P1386S revealed normal ATP7A mRNA and protein levels, a defect in ATP7A trafficking, and partial rescue of a S. cerevisiae copper transport knockout. Although ATP7A mutations are typically associated with severe Menkes disease or its milder allelic variant, occipital horn syndrome, we demonstrate here that certain missense mutations at this locus can cause a syndrome restricted to progressive distal motor neuropathy without overt signs of systemic copper deficiency. This previously unrecognized genotype-phenotype correlation suggests an important role of the ATP7A copper transporter in motor-neuron maintenance and function.
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Adenosina Trifosfatasas/genética , Proteínas de Transporte de Catión/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedad de la Neurona Motora/genética , Mutación Missense , Adenosina Trifosfatasas/química , Adenosina Trifosfatasas/metabolismo , Adolescente , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Proteínas de Transporte de Catión/química , Proteínas de Transporte de Catión/metabolismo , Células Cultivadas , Preescolar , Cobre/metabolismo , ATPasas Transportadoras de Cobre , Cartilla de ADN/genética , Femenino , Estudios de Asociación Genética , Prueba de Complementación Genética , Enfermedades Genéticas Ligadas al Cromosoma X/metabolismo , Humanos , Inmunohistoquímica , Masculino , Síndrome del Pelo Ensortijado/genética , Síndrome del Pelo Ensortijado/metabolismo , Persona de Mediana Edad , Modelos Moleculares , Datos de Secuencia Molecular , Enfermedad de la Neurona Motora/metabolismo , Linaje , ARN Mensajero/genética , ARN Mensajero/metabolismo , Homología de Secuencia de Aminoácido , Síndrome , Adulto JovenAsunto(s)
Enfermedad de Gaucher/genética , Glucosilceramidasa/genética , Mutación/genética , Enfermedad de Parkinson/genética , Adulto , Anciano , Arginina/genética , Salud de la Familia , Femenino , Enfermedad de Gaucher/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Triptófano/genéticaRESUMEN
The purpose of this study was to conduct a systematic review and meta-analysis of the published literature to evaluate the diagnostic accuracy of fluorine-18 2-fluoro-2-deoxy-D-glucose (F-FDG) PET or PET/computed tomography (CT) in the pretherapeutic staging of patients with small-cell lung cancer (SCLC). The authors conducted a systematic MEDLINE search of published articles. Two reviewers independently assessed the methodological quality of each study. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and summary receiver operating characteristic curves in the detection of extensive disease (ED) in patients with SCLC. Twelve studies with a total of 369 patients met the inclusion criteria. The pooled estimates of sensitivity, specificity, LR+, and LR- of F-FDG PET or PET/CT for the detection of ED in SCLC were 97.5% [95% confidence interval (CI), 94.2-99.2%], 98.2% (95% CI, 94.9-99.6%), 19.86 (95% CI, 9.79-40.30), and 0.06 (95% CI, 0.03-0.10), respectively. Whole-body F-FDG PET or PET/CT is a valuable imaging tool for the pretherapeutic assessment of ED in patients with SCLC.