CNS non tumor
Toxic and metabolic disorders
Subacute combined degeneration

Author: Kymberly A. Gyure, M.D. (see Authors page)

Revised: 24 September 2015, last major update September 2015

Copyright: (c) 2014-2015, PathologyOutlines.com, Inc.

PubMed Search: Subacute combined degeneration [title] CNS
Cite this page: Subacute combined degeneration. PathologyOutlines.com website. http://pathologyoutlines.com/topic/cnssubacutecombined.html. Accessed April 27th, 2017.
Definition / General
  • An acquired myelopathy caused by vitamin B12 (cobalamin) deficiency
  • Sites
  • Posterior and lateral columns of spinal cord
  • Etiology
  • 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
  • Pathophysiology
  • 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
  • Clinical Features
  • Progressive sensory abnormalities, ascending paresthesias, weakness, ataxia, loss of sphincter control, and gait impairment
  • Diagnosis
  • 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 Images
  • Symmetric, increased T2 signal confined to posterior and lateral columns of the cervical and thoracic spinal cord
  • Clinical Images
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    Cervical spinal cord MRI

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    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
  • 23 year old man with vitamin B12 deficiency (BMJ Case Rep 2013;2013:bcr2013200380)
  • 27 year old woman with subacute combined degeneration of the spinal from abusing nitrous oxide (Am J Health Syst Pharm 2015;72:952)
  • Subacute combined degeneration of the spinal cord due to different etiologies (Case Rep Neurol Med 2013;2013:159649)
  • Treatment
  • Intramuscular cobalamin injections
  • Gross Description
  • Shrunken spinal cord with discoloration of the posterior and lateral columns
  • Micro Description
  • Bilaterally symmetric myelin loss and degeneration in the posterior and lateral columns of the spinal cord
  • Dense gliosis in longstanding cases
  • Micro Images
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    Courtesy of Dr. Kymberly Gyure

    Peripheral Smear Images
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    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