When barriers fail: the role of endothelial dysfunction in rare pediatric neuromuscular diseases.

Rare pediatric neuromuscular diseases represent a heterogeneous group of disorders in which endothelial dysfunction and blood-tissue barrier alterations can contribute to disease onset and progression. The vascular endothelium, which lines blood vessels, plays a central role in regulating blood flow, immune cell trafficking, and maintaining the integrity of both the blood-brain barrier (BBB) and blood-nerve barrier (BNB). While BBB and the BNB share structural similarities, BNB endothelial cells are more restrictive due to a higher density of junctional complex proteins. Dysfunction of these barriers can lead to inadequate perfusion, neuroinflammation, and increased endothelial permeability. Evidence from rare conditions such as Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), Kawasaki Disease (KD), chronic inflammatory demyelinating polyneuropathy (CIDP), and acute inflammatory demyelinating polyradiculoneuropathy (AIDP) suggests that vascular and barrier abnormalities influence disease severity. However, the precise mechanisms underlying BNB disruption remain poorly understood for several disorders. Understanding these processes not only provides insights into disease pathophysiology but also highlights potential diagnostic and therapeutic targets. This review summarizes current knowledge on endothelial and barrier alterations in rare pediatric neuromuscular diseases, emphasizing the need for further studies to elucidate the involvement of BNB and guide future clinical interventions.