Weakness almost always begins after sensory loss. Memory difficulties, irritability, and confusion occur in a minority of patients. On examination, patients usually have decreased vibration and position sense, which is worse in the feet than in the hands, and may have spastic paraparesis. Pathological examination reveals symmetric loss of myelin in the posterior and lateral columns of the spinal cord and sometimes patchy demyelination in the cerebral white matter. MRI of the spinal cord often demonstrates white matter lesions, which resolve with treatment.
Diagnosis is made on the basis of the clinical findings and a low serum cobalamin level.
Macrocytosis or anemia is present in most patients but cannot be used in the place of the cobalamin level as a diagnostic measure. For patients who have symptoms and a low-normal cobalamin level, demonstration of elevated levels of serum methylmalonic acid and total homocysteine can confirm the presence of a functionally significant cobalamin deficiency. If cobalamin deficiency is present, the underlying etiology should be investigated. About 80 percent of patients with cobalamin deficiency have pernicious anemia. Administration of cobalamin prevents progression of symptoms and produces clinical improvement in most patients.