Degenerative cervical spinal stenosis: biomechanical and molecular foundations of cervical myelopathy pathogenesis

Degenerative cervical spinal stenosis, accompanied by cervical myelopathy, represents a leading cause of spinal cord dysfunction in adults. Contemporary insights into the pathogenesis of this condition, which integrates biomechanical, vascular, and molecular mechanisms, highlight its multifactorial etiology. Chronic spinal cord compression, driven by osteophytes, hypertrophic ligaments, and disc herniations, synergizes withdynamicmechanicalstresses, culminatinginischemia, disruption of the blood-spinal cord barrier (BSCB), and neuroinflammation. Central to the pathogenesis is chronic hypoperfusion, exacerbated by excitotoxicity and activation of matrix metalloproteinases (MMP-9, MMP-2), which degrade the vascular basement membrane. BSCB breakdown facilitates immune cell infiltration, release of pro-inflammatory cytokines (TNF-α, IL-1β), and microglial activation via the CX3CL1-CX3CR1 signaling axis. These processes trigger apoptosis of neurons and oligodendrocytes, leading to demyelination and spinal cord atrophy. Special emphasis is placed on the role of acetylation processes (involving NAT1, NAT2, AANAT, and NAA20 gene expression) in Ligamentum flavum ossification, underscoring the influence of genetic factors and gender disparities. This review addresses unresolved questions, including variability in clinical manifestations, the contribution of metabolic and immune dysregulation, and the urgent need for neuroprotective strategies. The integration of these innovations may bridge current knowledge gaps and improve outcomes for patients with degenerative cervical myelopathy. A systematic literature review (2010–2024) was conducted using PubMed, Scopus, Google Scholar and Cochrane Library. Search terms included degenerative cervical myelopathy, spinal stenosis, BSCB disruption, neuroinflammation and acetylation mechanisms. Inclusion criteria prioritized clinical/preclinical studies and meta-analyses exploring pathophysiology and therapeutic innovations. Data were analyzed thematically. The aim of the study is to analyze and synthesize existing knowledge on the pathogenesis of degenerative cervical myelopathy.

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