Infections and the neuromuscular junction: From direct neurotoxicity to immune-mediated dysfunction

Infectious diseases and disorders of the neuromuscular junction (NMJ) are linked by complex and heterogeneous mechanisms that extend beyond direct pathogen-mediated injury. While some infectious agents can directly impair neuromuscular transmission, others may act as triggers of autoimmunity or contribute to the exacerbation of pre-existing NMJ disorders. However, the mechanisms underlying these interactions remain incompletely understood. In this narrative review, we summarize the current evidence regarding infections associated with NMJ dysfunction. Available evidence suggests that infections may influence NMJ disorders through multiple pathways, including direct neurotoxicity, immune dysregulation, molecular mimicry, and loss of immune tolerance. While some pathogens have been more consistently associated with NMJ dysfunction, for many others the available evidence remains limited to isolated reports, preventing definitive conclusions regarding causality. Overall, infections represent important contributors to the spectrum of NMJ disorders, acting as direct disruptors of neuromuscular transmission, autoimmune triggers, or disease modifiers. A better understanding of pathogen-host interactions at the NMJ may provide new insights into disease mechanisms and potentially identify novel diagnostic and therapeutic strategies. Future prospective studies integrating clinical, neurophysiological, and immunological approaches are needed to clarify the role of infectious agents in NMJ pathophysiology.