RESUMEN
BACKGROUND: Primary hereditary microcephaly (MCPH) comprises a large group of autosomal recessive disorders mainly affecting cortical development and resulting in a congenital impairment of brain growth. Despite the identification of >25 causal genes so far, it remains a challenge to distinguish between different MCPH forms at the clinical level. METHODS: 7 patients with newly identified mutations in CDK5RAP2 (MCPH3) were investigated by performing prospective, extensive and systematic clinical, MRI, psychomotor, neurosensory and cognitive examinations under similar conditions. RESULTS: All patients displayed neurosensory defects in addition to microcephaly. Small cochlea with incomplete partition type II was found in all cases and was associated with progressive deafness in 4 of them. Furthermore, the CDK5RAP2 protein was specifically identified in the developing cochlea from human fetal tissues. Microphthalmia was also present in all patients along with retinal pigmentation changes and lipofuscin deposits. Finally, hypothalamic anomalies consisting of interhypothalamic adhesions, a congenital midline defect usually associated with holoprosencephaly, was detected in 5 cases. CONCLUSION: This is the first report indicating that CDK5RAP2 not only governs brain size but also plays a role in ocular and cochlear development and is necessary for hypothalamic nuclear separation at the midline. Our data indicate that CDK5RAP2 should be considered as a potential gene associated with deafness and forme fruste of holoprosencephaly. These children should be given neurosensory follow-up to prevent additional comorbidities and allow them reaching their full educational potential. TRIAL REGISTRATION NUMBER: NCT01565005.
Asunto(s)
Proteínas de Ciclo Celular/genética , Enfermedades Cocleares/genética , Microcefalia/genética , Proteínas del Tejido Nervioso/genética , Niño , Preescolar , Cóclea/diagnóstico por imagen , Cóclea/metabolismo , Cóclea/patología , Enfermedades Cocleares/diagnóstico por imagen , Enfermedades Cocleares/patología , Anemia de Fanconi/genética , Anemia de Fanconi/patología , Femenino , Humanos , Hipotálamo/diagnóstico por imagen , Hipotálamo/patología , Lactante , Imagen por Resonancia Magnética , Masculino , Microcefalia/diagnóstico por imagen , Microcefalia/patología , Mutación , Neurogénesis/genética , Linaje , Retina/diagnóstico por imagen , Retina/patologíaRESUMEN
OBJECTIVE: Malnutrition is associated with mortality and impaired quality of life (QoL) in systemic immunoglobulin light-chain (AL) amyloidosis. The aim of this study was to determine whether nutritional counseling is beneficial to patients with AL. METHODS: In this intervention study (ClinicalTrials.gov Identifier: NCT02055534), 144 treatment-naïve outpatients with AL were randomized to usual care (UC; n = 72) and nutritional counseling (NC; n = 72). RESULTS: In the randomized population, although patients in the NC group maintained a stable body weight (weight loss [WL] = 0.6 kg; 95% confidence interval [CI], -1.0 to 2.1; P = 0.214), those in the UC group demonstrated a significant decrease (WL = 2.1 kg; 95% CI, 0.2-4.1; P = 0.003). However, the difference in weight between groups was not significant (mean WL difference = 1.6 kg; 95% CI, -0.7 to 3.9; P = 0.179). Patients in the NC group demonstrated more satisfactory energy intake (≥75% of estimated requirements, odds ratio, 2.18; 95% CI, 1.04-4.57; P = 0.048) and a significant increase in the mental component summary of QoL (Short form-36) at 12 mo (mean difference, 8.1; 95% CI, 2.3-13.9; P = 0.007), which was restored to a mean score of 53 (95% CI, 50-53), over the healthy population norms. NC was also associated with better survival (crude hazard ratio, 0.57; 95% CI, 0.35-0.94; P = 0.028). CONCLUSIONS: In outpatients with AL, NC was helpful in preserving body weight, effective in improving mental QoL, and associated with better survival.
Asunto(s)
Amiloidosis/terapia , Consejo Dirigido/métodos , Cadenas Ligeras de Inmunoglobulina , Terapia Nutricional/métodos , Calidad de Vida , Anciano , Amiloidosis/inmunología , Amiloidosis/mortalidad , Amiloidosis/psicología , Peso Corporal , Ingestión de Energía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Pérdida de PesoRESUMEN
BACKGROUND: O2O3 therapy has become a largely diffused treatment for lumbar disk herniation; this procedure is considered generally risk-free. CASE DESCRIPTION: We report a case of ventral and dorsal root injury occurring after transcutaneous intradiscal infiltration of O2O3 for L4-L5 disk herniation. CONCLUSIONS: Until randomized controlled trials on efficacy and short-term safety have been carried out, we think that physicians should be informed about the risk of potential complications when recommending this procedure.