Does myelomalacia imply cell death?

Myelomalacia and Cell Death

Yes, myelomalacia definitively implies cell death in the spinal cord tissue. 1 Myelomalacia represents a pathological condition characterized by softening of the spinal cord due to necrosis and irreversible cellular death.

Pathophysiological Mechanisms of Myelomalacia

• Myelomalacia develops through a progressive pathological cascade that culminates in spinal cord cell death through various mechanisms 1:

  • Initial compression or trauma leads to central hemorrhage and spreading ischemia
  • Progressive necrosis develops in affected areas
  • Edema worsens compression and further compromises blood supply
  • Post-traumatic infarction and cavitation develop

• The Nomenclature Committee on Cell Death (NCCD) classifies cell death into two broad categories 2:

  • Accidental cell death (ACD) - caused by severe insults including physical trauma
  • Regulated cell death (RCD) - involves genetically encoded molecular machinery

Types of Cell Death in Myelomalacia

• Necrosis is the predominant form of cell death in myelomalacia 2:

  • Characterized by cytoplasmic swelling
  • Mechanical rupture of the plasma membrane
  • Dilation of cytoplasmic organelles (mitochondria, endoplasmic reticulum, Golgi)
  • Moderate chromatin condensation

• Myelomalacia involves irreversible plasma membrane permeabilization, which the NCCD considers a definitive marker of cell death 2

Vascular Mechanisms Leading to Cell Death

• Spinal cord ischemia is a significant cause of myelomalacia and subsequent cell death 1:

  • Vascular malformations can cause progressive myelopathy through venous hypertension
  • Breakdown of the blood-cord barrier leads to patchy intramedullary enhancement
  • Ischemic damage results in cellular death through oxygen and nutrient deprivation

• Angiodysgenetic myelomalacia involves spinal cord ischemia resulting from degenerative changes in vascular malformations 3

Clinical Evidence of Cell Death in Myelomalacia

• MRI findings in myelomalacia reflect progressive cell death 4:

  • Early stage: high-intensity signal changes on T2-weighted images
  • Intermediate stage: varying degrees of cystic necrosis of central gray matter
  • Late stage: central cystic degeneration, syrinx formation, and atrophy

• Histopathological studies confirm that myelomalacia represents hemorrhagic infarction of the spinal cord 5

• Autopsy findings in traumatic myelomalacia cases reveal total myelomalacia resulting from ischemia and compression, confirming cellular death 6

Progression and Extent of Cell Death

• Myelomalacia may be focal or diffuse 5:

  • Focal myelomalacia: limited cell death in a specific region
  • Diffuse myelomalacia: widespread cell death that can progress cranially ("ascending syndrome")

• Risk factors for progressive myelomalacia (continuing cell death) include 7:

  • Disc extrusions at the lumbar intumescence
  • Surgery performed more than 12 hours after loss of ambulation

Clinical Implications

• The presence of myelomalacia on imaging represents an important prognostic factor for neurosurgical outcomes 1

• Early stage myelomalacia may be reversible depending on the severity of the initial spinal cord injury, suggesting that cell death processes may be interrupted if addressed promptly 4

• The degree of radiographic abnormality may not always match symptom severity, indicating variability in the functional impact of cell death 1