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Loss-of-function mutations in MECP2 are associated to Rett syndrome (RTT), a severe neurodevelopmental disease. Mainly working as a transcriptional regulator, MeCP2 absence leads to gene expression perturbations resulting in deficits of synaptic function and neuronal activity. In addition, RTT patients and mouse models suffer from a complex metabolic syndrome, suggesting that related cellular pathways might contribute to neuropathogenesis. Along this line, autophagy is critical in sustaining developing neuron homeostasis by breaking down dysfunctional proteins, lipids, and organelles.Here, we investigated the autophagic pathway in RTT and found reduced content of autophagic vacuoles in Mecp2 knock-out neurons. This correlates with defective lipidation of LC3B, probably caused by a deficiency of the autophagic membrane lipid phosphatidylethanolamine. The administration of the autophagy inducer trehalose recovers LC3B lipidation, autophagosomes content in knock-out neurons, and ameliorates their morphology, neuronal activity and synaptic ultrastructure. Moreover, we provide evidence for attenuation of motor and exploratory impairment in Mecp2 knock-out mice upon trehalose administration. Overall, our findings open new perspectives for neurodevelopmental disorders therapies based on the concept of autophagy modulation., Competing Interests: Disclosure and competing interests statement The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Supermicrosurgical lymphaticovenular anastomosis (LVA) is increasingly being recognized as a first-line treatment of limb lymphedema because it is minimally invasive and highly effective. Lymphoscintigraphy and indocyanine green (ICG) lymphography are the two most commonly performed diagnostic imaging examinations to establish the indication and plan the procedure for patients affected by limb lymphedema. In a small group of patients, the information between these two imaging tools can be discordant, showing different anatomical drainage pathways or the absence of drainage and dermal backflow in one examination and valid drainage pathways in the other. The purpose of this study is to examine the types of possible discrepancies between lymphoscintigraphy of the superficial system and ICG lymphography and to describe the surgical outcomes after LVA for patients presenting with such discrepancies., Methods: We retrospectively reviewed the data of all patients who underwent LVA for upper or lower limb lymphedema between July 2015 and July 2023. From this series, we identified a group of patients with nonconcordant imaging results from lymphoscintigraphy and ICG lymphography before lymphatic surgery. Nonconcordant findings were described in terms of "pattern discordance" and "pathway discordance." The surgical outcome was measured by the change in the mean circumference of the limb after surgery. The changes between the preoperative and postoperative limb measures were analyzed using the Student t test. P values < .05 were considered significant., Results: A total of 28 patients with limb lymphedema exhibited inconsistencies between preoperative lymphoscintigraphy of the superficial system and ICG lymphography. Among these patients, 14 experienced pattern discordance, 13 had pathway discordance, and 1 patient had both. After LVA, we observed a significant reduction in the average circumference of the affected limb in the analyzed group., Conclusions: The discrepancy in the information between lymphoscintigraphy and ICG lymphography in the preoperative study of patients affected by limb lymphedema is rare but possible. This phenomenon is still not fully explained; however, our results suggest that it does not correlate with the outcome of supermicrosurgical LVAs., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)