A 60-year-old man presents with a combination of wasting and fasciculations of both hands along with spasticity and brisk reflexes in the lower limbs. Sensory examination is normal. Over four years he develops bulbar weakness and dies of respiratory failure. Autopsy shows loss of anterior horn neurons and lateral corticospinal tract gliosis. Cytoplasmic inclusions in surviving motor neurons stain for which protein?

• A Prion protein (PrP)
• B Alpha-synuclein
• C Tau
• D TDP-43 ✓

Explanation

Amyotrophic lateral sclerosis combines upper motor neuron signs (spasticity, hyperreflexia) and lower motor neuron signs (wasting, fasciculations) with preserved sensation. Pathologically there is loss of anterior horn cells and Betz cells with gliosis of the corticospinal tracts. Most sporadic cases show cytoplasmic inclusions of ubiquitinated TDP-43 within motor neurons, and TDP-43 mutations cause familial forms. Alpha-synuclein defines Lewy body disease, tau defines tauopathies including some familial ALS with C9orf72 overlap, and PrP defines prion disease.

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.