CNS nontumor

Toxic and metabolic disorders

Subacute combined degeneration

Last author update: 1 September 2015
Last staff update: 20 June 2023 (update in progress)

Copyright: 2002-2023,, Inc.

PubMed Search: Subacute combined degeneration CNS

Kymberly A. Gyure, M.D.
Page views in 2022: 396
Page views in 2023 to date: 383
Cite this page: Gyure K.A. Subacute combined degeneration. website. Accessed September 30th, 2023.
Definition / general
  • Acquired myelopathy caused by vitamin B12 (cobalamin) deficiency
  • Posterior and lateral columns of spinal cord
  • Adenosylcobalamin and methylcobalamin are metabolites of cobalamin; they are coenzymes in reactions which (a) convert methylmalonyl CoA to succinyl CoA and (b) transfer methyl groups to homocysteine to form methionine, respectively
  • Accumulation of methylmalonyl CoA causes a decrease in normal myelin synthesis and incorporation of abnormal fatty acids into neuronal lipids
  • Cobalamin deficiency: vegetarian diet
  • Impaired absorption of cobalamin intrinsic factor (IF) complex: pernicious anemia / atrophic gastritis, partial gastrectomy, fish tapeworm infection, Imerslund-Gräsbeck syndrome (genetic defect of cobalamin IF complex receptor), Crohn disease
  • Subacute combined degeneration can be triggered by exposure to nitrous oxide in B12 deficient patients
Clinical features
  • Progressive sensory abnormalities, ascending paresthesias, weakness, ataxia, loss of sphincter control and gait impairment
  • Schilling test: radiolabeled cyanocobalamin is administered orally and its excretion is measured in the urine
  • Increased serum methylmalonic acid and homocysteine concentrations
  • Decreased serum cobalamin concentration
  • Macrocytic / megaloblastic anemia
Radiology description
  • Symmetric, increased T2 signal confined to posterior and lateral columns of the cervical and thoracic spinal cord
Radiology images

Images hosted on other servers:
Missing Image

Cervical spinal cord MRI

Missing Image

Brain MRI

Prognostic factors
  • Less severe disease at time of diagnosis, including absence of sensory dermatomal deficits, Romberg sign and Babinski sign, is associated with a higher rate of resolution following cobalamin replacement therapy
Case reports
  • Intramuscular cobalamin injections
Gross description
  • Shrunken spinal cord with discoloration of the posterior and lateral columns
Microscopic (histologic) description
  • Bilaterally symmetric myelin loss and degeneration in the posterior and lateral columns of the spinal cord
  • Dense gliosis in longstanding cases
Microscopic (histologic) images

Contributed by Kymberly A. Gyure, M.D.

Subacute combined degeneration

Peripheral smear images

Images hosted on other servers:
Missing Image

Bone marrow aspiration

Differential diagnosis
  • Tabes dorsalis: does not affect lateral columns of spinal cord
  • Vacuolar myelopathy of acquired immunodeficiency syndrome: thought to be related to abnormal vitamin B12 metabolism but serum B12 levels are typically normal
Back to top
Image 01 Image 02