What is subacute combined degeneration?

What is Subacute Combined Degeneration?

Subacute combined degeneration (SCD) is a neurological complication of vitamin B12 deficiency characterized by demyelination of the dorsal (posterior) and lateral columns of the spinal cord, resulting in sensory, motor, and sometimes autonomic dysfunction. 1

Pathophysiology and Clinical Features

• SCD represents a degenerative disease affecting both the central and peripheral nervous systems, primarily involving the spinal cord posterior columns, lateral columns, and peripheral nerves. 2, 3

• The condition typically presents with a combination of:

  • Sensory deficits: Loss of proprioception and vibration sense due to dorsal column involvement 4
  • Motor weakness: Spastic paraparesis from lateral column (corticospinal tract) demyelination 4
  • Peripheral neuropathy: Affecting both sensory and motor nerve fibers 3
  • Autonomic dysfunction: Including orthostatic hypotension, postprandial disturbances, and leg edema (less commonly recognized but can be prominent) 4

Diagnostic Characteristics

• Laboratory findings commonly show macrocytic anemia (though not always present), low serum vitamin B12 levels, and elevated methylmalonic acid (MMA) or homocysteine levels. 5, 3

• MRI findings reveal symmetric T2-weighted hyperintensity within the dorsal columns of the spinal cord, with characteristic patterns:

  • "Inverted V" sign on axial images at the cervical spine level 6
  • "Dumbbell" or "binoculars" appearance (bilateral paired nodular hyperintensity) at the thoracic spine level 6

• Note that some patients may present with atypical features, including normal MRI findings, absence of anemia, or normal MMA levels at initial presentation, making diagnosis challenging. 5

Etiology and Risk Factors

• Common causes include:

  • Pernicious anemia (autoimmune gastritis) 3
  • Dietary deficiency (strict vegetarian/vegan diets) 2
  • Malabsorption (gastrectomy, ileal resection, inflammatory bowel disease) 4
  • Nitrous oxide exposure during surgery or recreational use 2

• SCD can develop many years after gastrectomy—cases occurring more than a decade post-surgery have been documented. 4

Prognosis and Reversibility

• SCD is a reversible condition when detected and treated early with vitamin B12 replacement. 2

• Treatment with intramuscular hydroxocobalamin leads to:

  • Clinical improvement of neurological symptoms 2, 4
  • Resolution of MRI abnormalities (typically within 3 months) 2, 6
  • Recovery of autonomic dysfunction 4

• The American College of Radiology emphasizes that misdiagnosis can occur as SCD can mimic other myelopathies, making MRI evaluation of the spinal cord particularly useful. 1

Critical Clinical Pitfall

• Never administer folic acid before treating vitamin B12 deficiency, as it may mask the underlying B12 deficiency and precipitate or worsen subacute combined degeneration of the spinal cord. 1, 7, 8