Merck Manual

Please confirm that you are a health care professional

honeypot link

Subacute Combined Degeneration


Michael Rubin

, MDCM, New York Presbyterian Hospital-Cornell Medical Center

Reviewed/Revised Feb 2023

Subacute combined degeneration refers to degenerative changes in the nervous system due to vitamin B12 deficiency; the degenerative changes affect mostly brain and spinal cord white matter. Demyelinating or axonal peripheral neuropathies can occur.

In the early stages of subacute combined degeneration, decreased position and vibratory sensation in the extremities is accompanied by mild to moderate weakness and hyporeflexia. In later stages, spasticity, hyperreflexia with absent Achilles reflexes (combined central and peripheral findings), extensor plantar responses, greater loss of position and vibratory sensation in the lower extremities, and ataxia develop, sometimes in a stocking-glove distribution.

Tactile, pain, and temperature sensations are usually spared but may be difficult to assess in older people. Some patients are irritable and mildly depressed.

Paranoia (megaloblastic madness), delirium, confusion, and, at times, postural hypotension may occur in advanced cases. The confusion may be difficult to differentiate from age-related dementias, such as Alzheimer disease.

Diagnosis of subacute combined degeneration is based on clinical findings and diagnosis of vitamin B12 deficiency. Diagnosis Dietary vitamin B12 deficiency usually results from inadequate absorption, but deficiency can develop in vegans who do not take vitamin supplements. Deficiency causes megaloblastic anemia, damage... read more A complete blood count is done, and vitamin B12 and folate levels are measured. CT or MRI is done to rule out other causes of the findings.

Neurologic symptoms that persist for months or years become irreversible. Vitamin B12 treatment must be continued for life unless the pathophysiologic mechanism for the deficiency is corrected.

NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz!