Corticospinal tract degeneration in the progressive muscular atrophy variant of ALS

Neurology. 2003 Apr 22;60(8):1252-8. doi: 10.1212/01.wnl.0000058901.75728.4e.


Objective: Examining the unresolved relationship between the lower motor neuron disorder progressive muscular atrophy (PMA) and ALS is important in clinical practice because of emerging therapies.

Methods: Spinal and brainstem tissues donated from patients with ALS/motor neuron disorder (n = 81) were examined. Using retrospective case note review, the authors assigned patients into three categories: PMA (12), PMA progressing to ALS (6), and ALS ab initio (63). Conventional stains for long tract degeneration and immunocytochemistry for ubiquitin and the macrophage marker CD68 were examined.

Results: Rapid progression and typical ubiquitinated inclusions in lower motor neurons were present in 77 (95%) of the cases. Immunocytochemistry for CD68 was a more sensitive marker of long tract pathology in comparison with conventional stains. Half of the cases with PMA showed corticospinal tract degeneration by CD68.

Conclusion: Patients with PMA frequently have undetected long tract pathology and most have ubiquitinated inclusions typical of ALS. A patient presenting with PMA with rapid clinical evolution likely has the pathology and pathophysiology of ALS whether or not upper motor neuron signs evolve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyotrophic Lateral Sclerosis / classification
  • Amyotrophic Lateral Sclerosis / pathology*
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscular Atrophy, Spinal / pathology*
  • Posterior Horn Cells / pathology
  • Pyramidal Tracts / chemistry
  • Pyramidal Tracts / pathology*
  • Ubiquitin / analysis


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Ubiquitin