Subacute combined degeneration may also result from nitrous oxide abuse, which leads to inactivation of vitamin B12. A similar syndrome is also seen with copper deficiency, which may be a consequence of total parenteral hyperalimentation, copper deficiency in enteral feeding, malabsorption, gastric surgery, or excessive zinc ingestion, which inhibits the intestinal absorption of copper.
Pathology. The earliest neuropathologic lesion in this disorder is myelin swelling in the thoracic and lower cervical posterior columns. Later, demyelination and axonal destruction occur, and still later, the lateral columns and spinocerebellar tracts are involved. Ascending secondary degeneration may be seen in the posterior columns, and descending degeneration may be seen in the corticospinal tract. Small foci of demyelination are scattered throughout the cerebral white matter and optic (II) nerve. Secondary degeneration of association tracts may be present. Mild changes occur in peripheral nerves, and damage to cortical neurons has been described.
Clinical Manifestations. Fatigue, weight loss, abdominal distress, diarrhea, and sore tongue are the most common general symptoms of pernicious anemia. Examination reveals glossitis and a lemon-yellow tint to the skin.
The most common neurologic symptoms relate to involvement of the posterior columns. Tingling, burning, and numbness of the distal extremities are the earliest symptoms. Depending on the site of initial demyelination, the feet or hands may be involved first, or paresthesias may occur simultaneously in all four extremities. Occasionally, Lhermitte’s sign is present. Due to proprioceptive loss, imbalance, which worsens in the dark, may be an early sign.
Stiffness is often the first sign of lateral column dysfunction but usually occurs after the onset of paresthesias. Later, overt spasticity develops, and if the disease remains untreated, paraplegia with bowel and bladder incontinence ensues.
The cardinal neurologic sign is diminution of vibration sense. Position sense is affected to a lesser degree, but the Romberg sign is often positive. Involvement of the posterior columns and spinocerebellar tract may cause severely disabling sensory ataxia. With extensive spinal cord damage, a sensory level may be noted, usually in the middle or lower thoracic segment. Hyperreflexia, spasticity, clonus, and the Babinski sign signify lateral column damage. A hyperactive bladder may be an associated finding. In severe untreated cases, paraplegia with flexor spasms may develop.
Diagnosis. Subacute combined degeneration is diagnosed clinically by recognition of posterior and lateral column involvement. Determination of the serum vitamin B12 level and the Schilling test are usually sufficient for confirming a diagnosis of pernicious anemia. It has long been recognized that neurologic signs and symptoms may precede the appearance of anemia. The red blood cell count and the mean corpuscular volume, however, are often abnormal in the face of normal hemoglobin and hematocrit values.
Treatment. For patients with a permanent impairment of vitamin B12 absorption (e.g., with pernicious anemia or gastrointestinal resection), treatment will need to be continued indefinitely. Loading doses of intramuscularly administered vitamin B12 are given several times per week for several months, followed by a maintenance dosage of at least 1000 µg/month for life. When the cause of the vitamin B12 deficiency is reversible (e.g., diet, nitrous oxide exposure, certain malabsorption syndromes), treatment can be stopped when the vitamin deficiency is completely reversed and its cause eliminated. In patients with copper deficiency, supplementation may halt disease progression; ingestion of zinc should be discontinued or strictly limited.
Mild paresthesias and mental changes of recent onset may completely resolve with treatment, but when symptoms have been present for several months, complete recovery is unlikely.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
