A 72-year-old man with hypothyroidism and type 2 diabetes sought care for a 3-year history of slowly progressive, ascending lower limb paresthesias and imbalance. Three months earlier, he noted subacute onset of finger numbness and substantial worsening of imbalance with infrequent falls. He also had a 1-year history of progressive visual decline that persisted despite cataract surgery. Additional symptoms included intermittent light-headedness and confusion.
Laboratory evaluations showed a decreased hemoglobin value and an increased mean corpuscular volume. Macrocytic red blood cells were noted on a peripheral blood smear. Serum vitamin B12 level was less than 70 ng/L. Levels of plasma homocysteine and serum methylmalonic acid were markedly increased to 375 µmol/L and 143 nmol/L, respectively. Serum copper level was normal. Serum parietal cell antibodies were increased to 46 U, and intrinsic factor antibodies were absent. Serum gastrin was markedly increased.
The clinical presentation in this patient suggested a myeloneuropathy. His vitamin B12 level was undetectable and accompanied by a macrocytic anemia and increased methylmalonic acid and homocysteine levels. Even though intrinsic factor antibodies were negative, the clinical picture was supportive of subacute combined degeneration in the setting of pernicious anemia.
The patient was started on vitamin B12 replacement. At 6-month follow-up he had striking improvement in gait and vision. The light-headedness and confusion were no longer present. His examination was remarkable only for mild impairment, with tandem gait and a slightly positive Romberg sign. The lower limb reflexes were reduced. Impaired position perception at the toes persisted, but vibration perception in the lower limbs improved. Laboratory investigations showed normalization of the hemoglobin, vitamin B12, methylmalonic acid, and homocysteine levels. The serum gastrin level had improved but was still increased at 742 pg/mL.
The best-characterized neurologic manifestations of vitamin B12 deficiency include myelopathy and myeloneuropathy. Autonomic neuropathy, optic neuropathy, and neuropsychiatric manifestations have also been reported. Neurologic manifestations may occur without evidence of the characteristic hematologic derangement, megaloblastic anemia. Macrocytosis or hypersegmented neutrophils on peripheral blood smear may be clues.