Synthetic magnetic resonance-based relaxometry and brain volume: cutoff values for predicting neurocognitive outcomes in very preterm infants.

BACKGROUND: Early neurorehabilitation can enhance neurocognitive outcomes in very preterm infants (<32 weeks), and conventional magnetic resonance imaging (MRI) is commonly used to assess neonatal brain injury; however, the predictive value for neurodevelopmental delay is limited. Timely predictive quantitative biomarkers are needed to improve early identification and management of infants at risk of neurodevelopmental delay. OBJECTIVE: To evaluate the potential of quantitative synthetic MRI measurements at term-equivalent age as predictive biomarkers of neurodevelopmental impairment and establish practical cutoff values to guide clinical decision-making. MATERIALS AND METHODS: This retrospective study included 93 very preterm infants who underwent synthetic MRI at term-equivalent age between January 2017 and September 2020. Clinical outcomes were assessed using the Bayley-III scale of infant development (mean age 2.1 years). The predictive value for impaired development was analyzed using receiver operating characteristic curves for synthetic MRI-based volumetry and T1 and T2 relaxation measurements. RESULTS: The T1 relaxation time in the posterior limb of the internal capsule was a potent predictor of severe (sensitivity, 92%; specificity, 80%; area under the curve (AUC), 0.91) and mild or severe (AUC, 0.75) developmental impairment. T2 relaxation time in the posterior limb of the internal capsule was a significant predictor of severe impairment (AUC, 0.76), whereas the brain parenchymal volume was a significant predictor of severe (AUC, 0.72) and mild or severe impairment (AUC, 0.71) outperforming the reported qualitative MRI scores (AUC, 0.66). CONCLUSION: The proposed cutoff values for T1 relaxation time in the posterior limb of the internal capsule and for total brain volume measurements, derived from synthetic MRI, show promise as predictors of both mild and severe neurodevelopmental impairment in very preterm infants.

Congenital Myasthenic Syndromes in Belgium: Genetic and Clinical Characterization of Pediatric and Adult Patients.

BACKGROUND: Congenital myasthenic syndromes (CMS) are a group of genetic disorders characterized by impaired neuromuscular transmission. CMS typically present at a young age with fatigable muscle weakness, often with an abnormal response after repetitive nerve stimulation (RNS). Pharmacologic treatment can improve symptoms, depending on the underlying defect. Prevalence is likely underestimated. This study reports on patients with CMS followed in Belgium in 2022. METHODS: Data were gathered retrospectively from the medical charts. Only likely pathogenic and pathogenic variants were included in the analysis. RESULTS: We identified 37 patients, resulting in an estimated prevalence of 3.19 per 1,000,000. The patients harbored pathogenic variants in CHRNE, RAPSN, DOK7, PREPL, CHRNB1, CHRNG, COLQ, MUSK, CHRND, GFPT1, and GMPPB. CHRNE was the most commonly affected gene. Most patients showed disease onset at birth, during infancy, or during childhood. Symptom onset was at adult age in seven patients, caused by variants in CHRNE, DOK7, MUSK, CHRND, and GMPPB. Severity and distribution of weakness varied, as did the presence of respiratory involvement, feeding problems, and extraneuromuscular manifestations. RNS was performed in 23 patients of whom 18 demonstrated a pathologic decrement. Most treatment responses were predictable based on the genotype. CONCLUSIONS: This is the first pooled characterization of patients with CMS in Belgium. We broaden the phenotypical spectrum of pathogenic variants in CHRNE with adult-onset CMS. Systematically documenting larger cohorts of patients with CMS can aid in better clinical characterization and earlier recognition of this rare disease. We emphasize the importance of establishing a molecular genetic diagnosis to tailor treatment choices.