Subacute combined degeneration of the spinal cord

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Subacute combined degeneration of the spinal cord (subacute combined degeneration of the cord, subacute combined degeneration, Lichtheim's disease, SACD) is degeneration of the posterior and lateral columns of the spinal cord long associated with anaemia and Addisons disease. The neurological syndrome is produced by either vitamin B12 deficiency (including that induced by nitrous oxide or metformin[1]), vitamin E deficiency, or copper deficiency[2]. There are reports of isolated folate deficiency[3][4] and intrathecal chemotherapy agents affecting folate metabolism such as methotrexate[5] producing SACD.

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  • Always give vitamin B12 first before folic acid in combined deficiency, to prevent SACD by folate converting any remaining B12 into methylcobalamin which then can not partake in fatty acid metabolism
  • Remember the association with pernicious anaemia and then forget it. Only haematologists see SACD always associated with anaemia. The lack of association has been known since at least 1910[6]

It is manifest by:

  1. Distal posterior and lateral column signs
    • Loss vibration sense
    • Loss of position sense
    • Loss of use of the legs
    • Inability to recognise figures drawn on soles of feet
  2. Cervical cord signs
    • Paraesthesiae (legs before arms)
    • In-coordination and gait disorder
    • Rhombergs sign
    • Upgoing plantars
  3. Peripheral/optic nerve involvement
    • Optic nerve involvement is late and may only be in diabetics on metformin[7]
  4. Dementia
    • In advanced B12 deficiency any dementia associated will respond poorly to treatment[8] although acute psychosis can[9].

Investigations

  • FBC, ECr, glucose
  • Serum B12 and folate
  • Consider Vitamin E levels, holotranscobalamin levels, caeruloplasmin, copper and zinc with normal B12 & folate
  • MRI is close to pointless except to exclude structural lesions with normal B12 & folate
    • plain spinal MRI has sensitivity of about 15% for B12 deficiency caused SACD[10]

Treatment

Correct underlying cause

  • If cause Vitamin B12 treatment must be parental

The treatment with liver was described in 1927 but with poor response, but doses were inadequate[11]. The time course of recovery was described well in 1951[12].

It is rare to obtain full recovery of vibration and position sense unless treatment is very early. Other signs such as paraesthesia, upgoing plantars and ataxia generally resolve over months.

References

  1. Liu KW, Dai LK, Jean W. Metformin-related vitamin B12 deficiency. Age and ageing. 2006 Mar; 35(2):200-1.(Link to article – subscription may be required.)
  2. Tsang BK, Crump N, Macdonell RA. Subacute combined degeneration of the spinal cord despite prophylactic vitamin B12 treatment. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2012 Jun; 19(6):908-10.(Link to article – subscription may be required.)
  3. Reynolds EH. The neurology of folic acid deficiency. Handbook of clinical neurology. 2014; 120:927-43.(Link to article – subscription may be required.)
  4. Okada A, Koike H, Nakamura T, Watanabe H, Sobue G. Slowly progressive folate-deficiency myelopathy: report of a case. Journal of the neurological sciences. 2014 Jan 15; 336(1-2):273-5.(Link to article – subscription may be required.)
  5. Satomi K, Yoshida M, Matsuoka K, Okita H, Hosoya Y, Shioda Y, Kumagai MA, Mori T, Morishita Y, Noguchi M, Nakazawa A. Myelopathy mimicking subacute combined degeneration in a Down syndrome patient with methotrexate treatment for B lymphoblastic leukemia: report of an autopsy case. Neuropathology : official journal of the Japanese Society of Neuropathology. 2014 Aug; 34(4):414-9.(Link to article – subscription may be required.)
  6. Bramwell B. REMARKS ON A CASE OF SUBACUTE COMBINED DEGENERATION OF THE SPINAL CORD, SIMULATING DISSEMINATED SCLEROSIS, WITH THE RAPID DEVELOPMENT OF PERNICIOUS ANAEMIA SHORTLY BEFORE DEATH. British medical journal. 1910 Jun 11; 1(2580):1396-8.
  7. Minn YK, Kim SM, Kim SH, Kwon KH, Sunwoo IN. Sequential involvement of the nervous system in subacute combined degeneration. Yonsei medical journal. 2012 Mar; 53(2):276-8.(Link to article – subscription may be required.)
  8. Vitamin B12 and cognitive function: an evidence-based analysis. Ontario health technology assessment series. 2013; 13(23):1-45.(Epub)
  9. Tripathi AK, Verma SP, Himanshu D. Acute psychosis: a presentation of cyanocobalamin deficiency megaloblastic anemia. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion. 2010 Sep; 26(3):99-100.(Link to article – subscription may be required.)
  10. Jain KK, Malhotra HS, Garg RK, Gupta PK, Roy B, Gupta RK. Prevalence of MR imaging abnormalities in vitamin B12 deficiency patients presenting with clinical features of subacute combined degeneration of the spinal cord. Journal of the neurological sciences. 2014 Jul 15; 342(1-2):162-6.(Link to article – subscription may be required.)
  11. Farquharson RF, Graham D. LIVER THERAPY IN THE TREATMENT OF SUBACUTE COMBINED DEGENERATION OF THE CORD. Canadian Medical Association journal. 1930 Aug; 23(2):237-44.
  12. UNGLEY CC, CAMPBELL H. Effect of vitamin B12c in pernicious anemia and subacute combined degeneration of the cord. British medical journal. 1951 Jan 27; 1(4699):152-7.