RESUMO
The gold-standard diagnostic test for peroxisomal disorders (PDs) is plasma concentration analysis of very long-chain fatty acids (VLCFAs). However, this method's time-consuming nature and limitations in cases which present normal VLCFA levels necessitates alternative approaches. The analysis of C26:0-lysophosphatydylcholine (C26:0-LPC) in dried blood spot samples by tandem-mass spectrometry (MS/MS) has successfully been implemented in certain newborn screening programs to diagnose X-linked adrenoleukodystrophy (ALD). However, the diagnostic potential of very long-chain LPCs concentrations in plasma remains poorly understood. This study sought to evaluate the diagnostic performance of C26:0-LPC and other very long-chain LPCs, comparing them to VLCFA analysis in plasma. The study, which included 330 individuals affected by a peroxisomal ß-oxidation deficiency and 407 control individuals, revealed that C26:0- and C24:0-LPC concentrations demonstrated the highest diagnostic accuracy (98.8% and 98.4%, respectively), outperforming VLCFA when C26:0/C22:0 and C24:0/C22:0 ratios were combined (98.1%). Combining C24:0- and C26:0-LPC gave the highest sensitivity (99.7%), with ALD females exhibiting notably higher sensitivity compared with the VLCFA ratio combination (98.7% vs. 93.5%, respectively). In contrast, C22:0-LPC exhibited suboptimal performance, primarily due to its low sensitivity (75%), but we identified a potential use to help distinguish between ALD and Zellweger spectrum disorders. In summary, MS/MS analysis of plasma C24:0- and C26:0-LPC concentrations represents a rapid and straightforward approach to diagnose PDs, demonstrating superior diagnostic accuracy, particularly in ALD females, compared with conventional VLCFA biomarkers. We strongly recommend integrating very-long chain LPC plasma analysis in the diagnostic evaluation of individuals suspected of having a PD.
Assuntos
Adrenoleucodistrofia , Lisofosfatidilcolinas , Recém-Nascido , Feminino , Humanos , Espectrometria de Massas em Tandem , Adrenoleucodistrofia/diagnóstico , Triagem Neonatal/métodos , Biomarcadores , Ácidos Graxos não Esterificados , Ácidos GraxosRESUMO
Cerebrospinal fluid opening pressure values are associated with various neurologic diseases; however, numerous factors can modify this measurement. This study aims to describe factors related to modifications in opening pressure measurements in pediatric patients. Methods: A retrospective analysis of lumbar punctures in pediatric patients conducted by the neuropediatrics group with institutional standardization. Bivariate and linear regression analyses were performed to determine the association between opening pressure and variables included in the study. Results: 544 events, median age 107 months, median opening pressure 19.7â cm H2O. Bivariate analysis found no association with medication use; anesthetics that increased opening pressure were remifentanil (P = .02) and propofol (P = .05), along with a positive linear correlation between opening pressure and age (P < .0001). Multiple linear regression analysis revealed that age, BMI, male gender, and remifentanil use were associated with an increase in opening pressure, whereas corticosteroid withdrawal was associated with a reduction in opening pressure. There is an interaction between age and headache, with an association with increased opening pressure up to around 140 months. Conclusion: This study identifies factors associated with changes in opening pressure, crucial for estimating normal opening pressure values in children. Headaches, anesthetic use, and corticosteroid withdrawal are confirmed as significant factors.
Assuntos
Pressão do Líquido Cefalorraquidiano , Cefaleia , Punção Espinal , Humanos , Masculino , Feminino , Criança , Estudos Retrospectivos , Pressão do Líquido Cefalorraquidiano/fisiologia , Pré-Escolar , Adolescente , Cefaleia/fisiopatologia , Lactente , Punção Espinal/métodos , Fatores EtáriosRESUMO
The pathogenesis and clinical significance of cerebral white matter lesions (WML) is poorly understood. Most studies have shown that age and hypertension are the most important factors related to the presence of WML. In addition, there are some evidences suggesting that susceptibility to WML is largely determined by genetic factors. The aim of the present study was to evaluate the possible association between clinical, biological and genetic factors, and the presence of WML in middle-aged, asymptomatic essential hypertensive patients. A total of 71 individuals (43 men, 28 women), aged 50-60 years, with never-treated essential hypertension and without clinical evidence of target organ damage were studied. All patients underwent a 24h-ABPM, an echocardiography, a neuropsychologic test, and a genetic study of renin-angiotensin system polymorphisms. Patients were classified into two groups according to the presence or absence of WML in brain magnetic resonance imaging. A total of 28 (39.4%) hypertensive patients showed WML in brain-resonance. Compared with hypertensives without WML, patients with WML showed significantly higher values of both office and 24h-ABPM systolic, diastolic, and pulse pressure. No differences were observed in either the nocturnal fall of blood pressure, or in blood pressure variability. The prevalence of concentric left ventricular hypertrophy was significantly higher (p = 0.002) in patients with WML (54%) than in hypertensives without WML (11%). Patients with WML exhibited a significantly worse performance on digit span forward, a standardized measure of attention, than hypertensives without WML. The frequency of the DD genotype of the angiotensin converting enzyme (ACE) gene in patients with WML (64%) was significantly higher (p = 0.022) than that observed in patients without WML (28.6%). The presence of WML in middle-aged hypertensive patients is related to the severity of blood pressure elevation, and to concentric left ventricular hypertrophy and also to mild decline in basic attention. The presence of the DD genotype of the ACE gene may be a predisposing factor for developing WML in essential hypertensive patients.
El significado clínico y la patogénesis de las lesiones cerebrales de la sustancia blanca (LSB) no están aclarados. La mayoría de los estudios sugieren que la edad y la hipertensión arterial son los factores más importantes relacionados con la presencia de LSB. También se sugirió la existencia de factores genéticos en la susceptibilidad de desarrollar LSB. El objetivo del presente trabajo es evaluar posibles factores clínicos, biológicos y genéticos relacionados con la presencia de LSB en pacientes de mediana edad afectados por hipertensión arterial esencial. Se incluyeron 71 pacientes con hipertensión esencial de ambos sexos, de edades comprendidas entre 50 y 60 años, nunca tratados y sin evidencia de enfermedad cardiovascular. Se realizaron las siguientes exploraciones: MAPA de 24 horas, ecocardiograma, evaluación neuropsicológica y estudio de los polimorfismos genéticos del sistema renina-angiotensina mediante PCR. A todos los pacientes se les realizó resonancia magnética cerebral para valorar la presencia o ausencia de LSB. Veintiocho (39.4%) de los pacientes hipertensos mostraban LSB en la resonancia. Los pacientes con LSB tenían cifras de presión arterial (PA) sistólica, diastólica y presión de pulso, significativamente mayores que los pacientes hipertensos sin LSB, tanto en la clínica como en la MAPA. No se objetivó asociación entre el perfil circadiano y las LSB, como tampoco con la variabilidad de la PA. La presencia de hipertrofia del ventrículo izquierdo (HVI) concéntrica era significativamente mayor (p = 0.002) en pacientes con LSB (54%) que en hipertensos sin LSB (11%). Los pacientes con LSB mostraron una puntuación significativamente peor en la prueba de la serie de dígitos directa (medida estandarizada de la atención) que los pacientes sin lesiones. En referencia al estudio genético, se objetivó que los pacientes con LSB presentaban mayor frecuencia del genotipo DD del gen de la enzima de conversión de la angiotensina (ECA) (64% versus 28.6%; p = 0.022) en comparación con los pacientes sin LSB. La presencia de LSB en pacientes hipertensos de mediana edad está relacionada con la gravedad de la elevación de la PA y con la existencia de HVI concéntrica. Los pacientes hipertensos con LSB presentan un leve deterioro de la capacidad de atención. La presencia del genotipo DD del gen de la ECA podría ser un factor predisponente para el desarrollo de LSB en pacientes con hipertensión arterial.
Assuntos
Ferimentos e Lesões , Substância Branca , Hipertensão Arterial Pulmonar , Ecocardiografia , Hipertrofia Ventricular Esquerda , Fatores de Risco de Doenças CardíacasRESUMO
Os autores apresentam uma atualização sobre a etiopatogenia, diagnóstico e tratamento do zumbido. Por fim relatam suas experiências com o tratamento cognitivo com o qual curaram 11 pacientes que sofriam de zumbido refratário a vários tipos de tratamento