A 60-year-old man develops progressive asymmetrical limb weakness without sensory involvement or sphincter disturbance. Over three years he develops fasciculations and bulbar palsy and dies of respiratory failure. Autopsy shows loss of large anterior horn cells and Betz cells with myelin pallor in corticospinal tracts. Cytoplasmic inclusions within surviving anterior horn neurons stain positive for TDP-43. The diagnosis is:

• A Spinal muscular atrophy
• B Hereditary spastic paraplegia
• C Amyotrophic lateral sclerosis ✓
• D Subacute combined degeneration of spinal cord

Explanation

ALS involves both upper and lower motor neurons, explaining the combination of Betz cell loss, corticospinal tract degeneration, and anterior horn cell loss with intact sensation. Most sporadic cases show TDP-43 positive cytoplasmic inclusions; SOD1 familial cases lack them. Subacute combined degeneration affects dorsal and lateral columns with prominent sensory findings, which kills option D.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.