Charcot-Marie-tooth disease type 2A: An update on pathogenesis and therapeutic perspectives.

Mutations in the gene encoding MFN2 have been identified as associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a neurological disorder characterized by a broad clinical phenotype involving the entire nervous system. MFN2, a dynamin-like GTPase protein located on the outer mitochondrial membrane, is well-known for its involvement in mitochondrial fusion. Numerous studies have demonstrated its participation in a network crucial for various other mitochondrial functions, including mitophagy, axonal transport, and its controversial role in endoplasmic reticulum (ER)-mitochondria contacts. Considerable progress has been made in the last three decades in elucidating the disease pathogenesis, aided by the generation of animal and cellular models that have been instrumental in studying disease physiology. A review of the literature reveals that, up to now, no definitive pharmacological treatment for any CMT2A variant has been established; nonetheless, recent years have witnessed substantial progress. Many treatment approaches, especially concerning molecular therapy, such as histone deacetylase inhibitors, peptide therapy to increase mitochondrial fusion, the new therapeutic strategies based on MF1/MF2 balance, and SARM1 inhibitors, are currently in preclinical testing. The literature on gene silencing and gene replacement therapies is still limited, except for a recent study by Rizzo et al.(Rizzo et al., 2023), which recently first achieved encouraging results in in vitro and in vivo models of the disease. The near-future goal for these promising therapies is to progress to the stage of clinical translation.

Neuropathic Pain in the Emergency Setting: Diagnosis and Management.

Neuropathic pain, traditionally considered a chronic condition, is increasingly encountered in the emergency department (ED), accounting for approximately 20% of patients presenting with pain. Understanding the physiology and key clinical presentations of neuropathic pain is crucial for ED physicians to provide optimal treatment. While diagnosing neuropathic pain can be challenging, emphasis should be placed on obtaining a comprehensive medical history and conducting a thorough clinical examination. Patients often describe neuropathic pain as a burning or shock-like sensation, leading them to seek care in the ED after ineffective relief from common analgesics such as paracetamol and NSAIDs. Collaboration between emergency medicine specialists, neurologists, and pain management experts can contribute to the development of evidence-based guidelines specifically tailored for the emergency department setting. This article provides a concise overview of the common clinical manifestations of neuropathic pain that may prompt patients to seek emergency care.