Subacute Combined Degeneration of the Cord — Presentation and Treatment

Subacute Combined Degeneration of the Cord — Presentation and Treatment Definition and biochemistry

Subacute combined degeneration (SACD) is progressive degeneration — demyelination followed by axonal loss — of the posterior (dorsal) columns and the lateral corticospinal tracts of the spinal cord, caused by vitamin B12 (cobalamin) deficiency.

"Subacute" refers to evolution over weeks to months; "combined" to the involvement of two tract systems. The cervical and upper thoracic cord are preferentially affected.

Vitamin B12 is required for DNA synthesis, mitochondrial function and red blood cell production, and converts folate to its biologically active form; when deficient it can cause a secondary folate deficiency.

Two cobalamin-dependent enzymes explain the pathology: methionine synthase (homocysteine → methionine, required for S-adenosylmethionine and myelin methylation) and methylmalonyl-CoA mutase. Deficiency therefore raises both homocysteine and methylmalonic acid (MMA), and impairs myelin maintenance.

Impaired absorption is the dominant mechanism in the elderly: atrophic gastritis (10–30% of older adults malabsorb food-bound B12), pernicious anaemia (lack of intrinsic factor; 1–2% of older adults), gastrectomy or bariatric surgery, ileal resection, Crohn's disease, intestinal bacterial overgrowth.

Drugs: metformin (long-term users should be screened), proton pump inhibitors and H2 blockers (raised gastric pH prevents release of B12 from animal protein).

Inadequate intake: B12 is found strictly in animal products — red meat, eggs and dairy — making vegetarians and vegans particularly susceptible. This is of major importance in India.

Nitrous oxide exposure or abuse irreversibly oxidises the cobalt ion of cobalamin and inactivates methionine synthase, precipitating SACD even when the serum B12 is normal.

Prevalence of B12 deficiency ranges from 5–40% in older people depending on the cut-off used; 13.8% on nursing-home admission with a 4% new yearly incidence.

Critical exam point: neurological disease may occur in the complete absence of anaemia or macrocytosis — a normal blood count never excludes SACD.

Earliest symptoms are sensory: symmetrical distal paraesthesiae, numbness and tingling in the hands and feet, often affecting the hands before the feet.

Posterior column signs: loss of vibration sense (the earliest and most sensitive sign) and joint position sense, sensory ataxia, a positive Romberg's sign, and unsteadiness that is markedly worse in the dark or with eyes closed.

Corticospinal tract signs: spastic paraparesis, weakness, hyperreflexia and extensor plantar responses.

The classic paradoxical combination: brisk knee jerks with absent ankle jerks and extensor plantars — produced by simultaneous myelopathy and peripheral neuropathy. Always quote this.

Additional features: Lhermitte's phenomenon, gait ataxia, autonomic dysfunction, bladder disturbance late, and optic atrophy with centrocaecal scotoma.

Neuropsychiatric: mood change, depression, irritability, confusion, poor memory, dementia, and psychosis ("megaloblastic madness").

Haematological and mucosal: macrocytic megaloblastic anaemia, hypersegmented neutrophils, glossitis with a beefy-red sore tongue, angular stomatitis, vitiligo, mild jaundice from ineffective erythropoiesis (raised LDH, low haptoglobin), fatigue, weakness, anorexia and weight loss.

Serum B12 is the first test but there is no gold-standard diagnostic test; the diagnosis rests on the clinical picture with a low B12. Serum MMA and homocysteine are both raised and increase diagnostic sensitivity where the B12 is borderline; holotranscobalamin (active B12) is an alternative.

Falsely normal B12 occurs in hepatic and renal disease and myeloproliferative disorders; falsely low B12 occurs in folate deficiency and multiple myeloma.

Additional tests: full blood count and peripheral smear, reticulocytes, LDH, folate, ferritin (coexisting iron deficiency masks macrocytosis), TSH, intrinsic factor antibody (specific but insensitive) and anti-parietal cell antibody (sensitive, non-specific), and upper GI endoscopy for atrophic gastritis.

MRI of the spine: T2 hyperintensity in the dorsal columns of the cervical and upper thoracic cord, producing the classic "inverted V" or "inverted rabbit-ear" sign on axial images. Nerve conduction studies confirm coexisting peripheral neuropathy.

Neurological involvement mandates parenteral replacement. Give hydroxocobalamin 1000 mcg IM on alternate days until there is no further improvement, then 1000 mcg every 2–3 months indefinitely.

Textbook regimen for deficiency without neurological disease: IM B12 1000 mcg weekly for severe deficiency, then monthly for maintenance (10–15% of each injection is absorbed, so stores replenish quickly).

Oral B12 2000 mcg daily is as effective as intramuscular therapy in most cases, is cheaper and easier, and works even with achlorhydria or pernicious anaemia because a small fraction is passively absorbed independent of intrinsic factor. Give once daily only — receptor saturation means more frequent dosing does not improve absorption.

Do not give folate alone — folic acid without B12 corrects the anaemia while allowing the neurological disease to progress. Start B12 first, then replace folate.

Monitoring: reticulocytosis by day 5–7; watch for hypokalaemia in the first week of a brisk haematological response; recheck haemoglobin and B12 at 3 months.

Treatment is lifelong in pernicious anaemia and after gastric or bowel resection, since absorption will remain deficient. Correct coexisting iron and folate deficiency. Review and, where possible, address contributing drugs (metformin, PPIs).

Prognosis is inversely related to the duration of symptoms. Treatment within weeks usually gives complete recovery; after 6–12 months of symptoms, progression is halted but full recovery is unlikely. Sensory symptoms recover better than spastic paraparesis.

Prevention: have a high index of suspicion and screen at-risk individuals annually — those with bowel resection, atrophic gastritis, inflammatory bowel disease, restrictive diets, and users of metformin or acid suppressants. Adults over 50 should meet the RDA mainly through fortified foods or a supplement containing B12, since food-bound B12 is poorly absorbed.