Subacute Combined Degeneration of the Cord

Definition. A vitamin B12 (cobalamin) deficiency myelopathy causing symmetrical demyelination of the dorsal (posterior) columns and lateral corticospinal tracts, chiefly in the cervical and upper thoracic cord. It is frequently combined with a peripheral neuropathy, and occasionally with optic atrophy and dementia — hence “combined”.

Causes in the elderly. Pernicious anaemia (autoimmune atrophic gastritis), food-cobalamin malabsorption from atrophic gastritis (the commonest cause in old age), gastrectomy or bariatric surgery, ileal resection or Crohn’s disease, chronic metformin and proton-pump inhibitor use, strict vegetarian or vegan diet (highly relevant in India), tropical sprue and nitrous oxide exposure.

Clinical features. Symmetrical distal paraesthesiae and numbness first, then sensory ataxia with a positive Romberg sign and loss of vibration and joint-position sense. The classical examination finding is a spastic paraparesis with extensor plantar responses but absent ankle jerks — pyramidal signs coexisting with an abolished reflex because of the accompanying neuropathy. Lhermitte’s phenomenon may occur.

Systemic and neuropsychiatric features. Macrocytic megaloblastic anaemia, glossitis, angular stomatitis and skin hyperpigmentation; and “megaloblastic madness” — irritability, depression, psychosis and reversible dementia. Critically, neurological disease can occur with a normal haemoglobin and a normal MCV, so a normal blood count never excludes SCD.

Investigations. Serum B12 (low or low-normal). If equivocal, measure serum methylmalonic acid and plasma homocysteine — both are raised in B12 deficiency; only homocysteine is raised in folate deficiency. Anti-intrinsic-factor and anti-parietal-cell antibodies for pernicious anaemia. Peripheral smear shows macro-ovalocytes and hypersegmented neutrophils. MRI spine shows T2 hyperintensity of the posterior columns — the “inverted V” or rabbit-ear sign.

Treatment. Parenteral hydroxocobalamin or cyanocobalamin 1000 µg intramuscularly on alternate days for 1–2 weeks, then weekly until no further improvement, then monthly for life. Never give folic acid alone — it corrects the anaemia but precipitates or worsens the myelopathy. Monitor serum potassium during early recovery (hypokalaemia) and co-supplement iron. Recovery takes months and is often incomplete if treatment is delayed beyond 6–12 months, so treat on suspicion.

NICE guideline NG239 — Vitamin B12 deficiency in over-16s (March 2024). Where serum B12 is equivocal, use plasma homocysteine or serum methylmalonic acid as the initial confirmatory test; take all diagnostic samples before starting replacement. Crucially, do not delay B12 replacement while awaiting results in anyone with suspected megaloblastic anaemia or neurological symptoms, especially subacute combined degeneration of the cord. Lifelong intramuscular replacement is advised after total gastrectomy, complete terminal ileal resection, or when autoimmune gastritis is the cause.