Objective:

To summarize current knowledge on endothelial and barrier alterations in rare pediatric neuromuscular diseases, emphasizing the role of endothelial dysfunction in disease progression and highlighting the need for further studies.

Approach:

• Overview of Biological Barriers: Discusses the roles of the blood-brain barrier (BBB) and blood-nerve barrier (BNB) in maintaining neural homeostasis, their structural differences, and implications for disease.
• Neuromuscular Diseases (NMDs): Describes the heterogeneity of pediatric NMDs, their clinical presentations, and the critical role of early diagnosis and multidisciplinary management in improving outcomes.
• Role of Endothelial Dysfunction: Explores how endothelial dysfunction links barrier impairment to NMD progression, with examples of specific disorders affected by these mechanisms.

Key Findings:

• Endothelial dysfunction and blood-tissue barrier alterations contribute to the onset and progression of rare pediatric neuromuscular diseases, influencing clinical outcomes.
• The BNB is structurally more restrictive than the BBB, affecting drug delivery and contributing to peripheral neuropathies, particularly in conditions like Duchenne muscular dystrophy and spinal muscular atrophy.
• Conditions such as Duchenne muscular dystrophy and spinal muscular atrophy show evidence of vascular and barrier abnormalities that correlate with disease severity.

Interpretation:

Understanding the mechanisms of BNB disruption is crucial for insights into disease pathophysiology and potential therapeutic targets.

Limitations:

• The precise mechanisms underlying BNB disruption remain poorly understood for several disorders, including Duchenne muscular dystrophy and spinal muscular atrophy.
• Current literature on CNS-periphery interactions in neuromuscular diseases is limited, highlighting a gap in understanding.

Conclusion:

Further studies are needed to elucidate the involvement of BNB in rare pediatric neuromuscular diseases and guide future clinical interventions.