- Patho/Etiology
- Caused by Vitamin B₁₂ (cobalamin) deficiency, which leads to defective myelin synthesis and maintenance.
- The name “combined” refers to the degeneration of multiple spinal cord tracts.
- Affected Tracts:
- Dorsal Columns: Loss of vibration sense, proprioception, and fine touch.
- Lateral Corticospinal Tracts: Spastic paresis, hyperreflexia, and a positive Babinski sign.
- Spinocerebellar Tracts: Ataxia.
- Causes of B₁₂ Deficiency
- Pernicious Anemia: Autoimmune destruction of gastric parietal cells, leading to a lack of intrinsic factor. This is the most common cause.
- Malabsorption: Conditions like Crohn’s disease, celiac disease, or prior gastrectomy/ileal resection.
- Dietary Insufficiency: Rare, but can be seen in strict vegans over many years.
- Other: Diphyllobothrium latum (fish tapeworm) infestation, chronic nitrous oxide abuse.
- Clinical Presentation
- Symmetric and progressive.
- Sensory: Begins with distal, symmetric paresthesias (numbness, tingling) in the feet and hands. Loss of vibration and position sense is often the first sign.
- Motor: Spastic weakness, especially in the lower limbs. An initially flaccid paralysis can become spastic over time.
- Gait: Ataxic gait due to combined sensory and cerebellar tract dysfunction.
- Reflexes: May show a combination of UMN signs (hyperreflexia, Babinski) from corticospinal tract damage and LMN signs (absent Achilles reflex) from a concurrent peripheral neuropathy.
- Neuropsychiatric: Irritability, apathy, “megaloblastic madness” (paranoia, delirium), and cognitive impairment can occur.
- Diagnosis
- Labs:
- Low serum Vitamin B₁₂ level.
- Elevated serum methylmalonic acid (MMA) and homocysteine levels. These are more sensitive than B₁₂ levels alone.
- CBC: May show a megaloblastic anemia (↑ MCV) with hypersegmented neutrophils, but neurologic symptoms can occur without anemia.
- Antibodies against intrinsic factor or parietal cells if pernicious anemia is suspected.
- Imaging:
- MRI of the spinal cord is not usually required for diagnosis but can show T2-weighted hyperintensities in the dorsal columns of the cervical and thoracic spine.
- Management
- Immediate B₁₂ supplementation is crucial to prevent irreversible neurological damage.
- Tx: Intramuscular (IM) or subcutaneous injections of vitamin B₁₂ are standard, especially when neurologic symptoms are present.
- A typical regimen starts with daily or alternate-day injections for 1-2 weeks, followed by weekly, then monthly injections for life (if the underlying cause is irreversible).
- Prognosis: Early treatment (within weeks) can lead to a complete recovery; however, long-standing deficits are often permanent.
- Caution: Never treat megaloblastic anemia with folic acid alone without first ruling out B₁₂ deficiency. Doing so will correct the anemia but will not stop the progression of the potentially irreversible neurologic damage of SCD.