A 65-year-old woman is found dead in her house. The family notes that she had difficulty walking over the past few months. The woman had a history of atrial fibrillation treated with anticoagulation therapy. Autopsy reveals bruising of the scalp. Intracranially, there is a large epidural hemorrhage with brain herniation. In addition, the spinal cord shows symmetric myelin layer vacuolization and axonal degeneration involving the posterior columns and the lateral corticospinal tracts. Which of the following is the most likely cause of this woman's spinal cord findings?
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This woman with recent gait impairment likely died due to a head injury from a fall (scalp bruising); her anticoagulation therapy placed her at increased risk for intracranial hemorrhage and subsequent brain herniation. Evidence of myelin degeneration in the dorsal columns and lateral corticospinal tracts on autopsy is suspicious for vitamin B12 deficiency, the likely cause of her ataxia.
Vitamin B12 deficiency is classically associated with megaloblastic anemia due to impaired DNA synthesis in rapidly dividing hematologic cells. However, vitamin B12 is also essential for myelin generation and maintenance (via methylation of myelin basic protein); deficiency often results in neurologic symptoms due to impaired myelination in the following regions:
Dorsal columns: diminished tactile/vibratory sensation and proprioception, resulting in sensory ataxia (eg, Romberg sign)
Lateral corticospinal tracts: upper motor neuron signs (eg, muscle weakness, spastic paresis), Babinski reflex
Spinocerebellar tracts: ataxia (loss of unconscious proprioception)
Peripheral nerves: numbness, paresthesia, hyporeflexia
The pattern of spinal cord damage is referred to as subacute combined degeneration, given the degeneration of both ascending (dorsal columns, spinocerebellar tracts) and descending (lateral corticospinal tracts) pathways.
(Choice A) Amyotrophic lateral sclerosis is a neurodegenerative disorder that affects upper and lower motor neurons. Damage to the lateral corticospinal tract occurs, but anterior horn damage is also characteristic and not seen in this woman. Moreover, sensory pathways are usually spared, so dorsal column damage would not be expected.
(Choice B) Multiple sclerosis is marked by asymmetric, focal areas of CNS demyelination. This woman's symmetric damage to specific spinal cord tracts would be atypical.
(Choice C) Syringomyelia, a cyst within the spinal cord, can lead to central spinal cord injury involving crossing fibers from the spinothalamic tracts within the anterior white commissure. This woman's autopsy did not reveal a cyst, and extensive dorsal column damage would be unusual.
(Choice D) Tabes dorsales (neurosyphilis) is associated with damage to the dorsal columns and dorsal nerve roots; however, the lateral corticospinal tracts are generally not affected.
(Choice E) Thiamine deficiency causes Wernicke encephalopathy (ataxia, confusion, oculomotor dysfunction). Unlike in this woman, histopathology shows demyelination in the brain (eg, mammillary bodies, thalamus), not the spinal cord.
Educational objective:
Vitamin B12 (cobalamin) deficiency can cause subacute combined degeneration due to impaired myelination in the ascending dorsal columns and spinocerebellar tracts (diminished position/vibration sense, ataxia), as well as the descending lateral corticospinal tracts (eg, muscle weakness, spastic paresis).