Vitamin B12 deficiency:Subacute combined degeneration of the spinal cord is a neurological complication of vitamin B12 (cobalamin) deficiency.
- Nutritional deficiency, vegetarianism and veganism
- Malabsorption: Pernicious anaemia (M/C cause), gastrectomy, intestinal infections, tropical sprue, terminal ileal conditions including Crohn’s disease, and resection
- Pancreatic exocrine insufficiency
- Celiac disease
- Gastric acid suppressants: H2 antagonists and PPIs
- Nitrous oxide
- Fish tapeworm infestation (D. latum)
Myelin synthesis:B12 is a necessary cofactor in the production of myelin in 2 pathways:
- Homocysteine methyltransferase: Conversion of homocysteine to methionine.
- Without adenosylcobalamin, methylmalonyl-CoA builds up and causes a decrease in normal myelin formation, leading to incorporation of abnormal fatty acids into neuronal lipids.
- Methylmalonyl-CoA mutase: Conversion of methylmalonyl-CoA to succinyl-CoA.
- Abnormal DNA synthesis and the role of B12 as a cofactor in the production of tetrahydrofolate (THF), which hinders oligodendrocyte growth, resulting in ineffective myelin production.
Clinically, cobalamin deficiency is manifested mainly by haematological and neuropsychiatric symptoms. In most cases, SAD is restricted to the posterior columns of the upper cervical and thoracic segments associated with tactile sensibility loss and proprioceptive problems
Dorsal column involvement:Presents as subacute/gradual progressive weakness & paresthesias
- Paresthesia (earliest manifestations): Tingling, burning, and sensory loss of the distal extremities
- Lhermitte’s sign
- Loss of proprioception: Difficulty in maintaining balance in the absence of visual cues (e.g., in the dark or with closed eyes)
Lateral corticospinal tract dysfunction:Manifest as signs of upper motor neuron damage such as muscle weakness, hyperreflexia, and spasticity
- Stiffness (initial symptom)
- Spasticity can progress to paraplegia or quadriplegia if the condition remains untreated. Sphincter involvement in advanced cases can lead to bowel and bladder incontinence.
- Diffuse hyperreflexia
- Ankle clonus and Babinski’s sign present
Spinocerebellar tract degeneration:
- Gait abnormalities: Sensory ataxia
- Positive Romberg’s sign
Other clinical findings in B12 deficiency:
- Macrocytic anemia (not always present in B12 deficiency)
- Peripheral neuropathy
- Optic nerve atrophy
- Psychiatric syndromes
Chemiluminescence assay:M/C used assay to measure serum B12 levels. Serum B12 level is not a reliable marker for physiological stores. Most B12 measurement assays only measure the protein-bound form of B12 which is unavailable to tissues. A deficiency is therefore possible with borderline or normal serum B12 levels and requires measurement of metabolite levels.
- 300 pg/mL: Normal
- 200-300 pg/mL: Borderline
- <200 pg/ml: Low/deficient
Cobalamin metabolism intermediates:Measuring MMA and homocysteine is indicated when neurological findings of B12 deficiency are present, but serum B12 levels are either normal or borderline.
- Methylmalonic acid (MMA)
- Inverted V or inverted rabbit ears sign: Demyelination observed as bilateral paired regions of T2 hyperintensity in the dorsal columns of the cervical and upper thoracic spinal cord
- Later stages:
- T2 hyperintensity also seen in lateral columns
- Decreased T1-weighted signal and contrast enhancement of same regions
Differential diagnosis:Other conditions that present with involvement of dorsal and lateral columns and can mimic findings of SCD
- Nutritional/metabolic deficiency or toxicity:
- Copper deficiency
- Vitamin E deficiency
- Methotrexate-induced myelopathy
- Demyelinating myelopathy:
- Transverse myelitis
- Multiple sclerosis
- Infectious myelopathy:
- Vacuolar myelopathy
- Tabes dorsalis (late neurosyphilis)
- Friedreich’s ataxia:
- Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation: Unlike SCD, this condition affects the entire spinal cord and can extend to involve the medulla.
- Other disorders: Sarcoidosis, ischemic lesions, and malignancies
Vitamin B12 supplementation:The dose of vitamin B12, route of administration, and duration of treatment depends on the presenting symptoms, the urgency of treatment, the underlying etiology, and the patient’s preference.