Vitamin B12 Deficiency Manifested as Psychosis Without Anemia


To the Editor: Vitamin B12 deficiency typically appears as lower-extremity paresthesia or ataxia, most often with concurrent folate deficiency and megaloblastic anemia (1). We report the case of a patient who was deficient in vitamin B12 and was diagnosed with psychosis in the absence of folate deficiency or anemia.

Ms. A was a 52-year-old woman with a 3-month history of acute paralysis of the lower extremities and a 1-month history of paranoid delusions of persecution, delirium, and severe agitation. Ms. A had no significant prior medical or psychiatric history nor any history of drug or alcohol use. Up until 3 months before, she had been in excellent health, happily married, and employed. Ms. A had consulted a neurologist at the onset of her weakness in the lower extremities and was diagnosed with multiple sclerosis. Over the next several weeks, she was placed on a regimen of medications including carbamazepine, amitriptyline, tramadol, diazepam, prednisone, thiamine, and multivitamins. Despite this, her weakness worsened. She required a cane, then a walker, and finally a wheelchair to get around just 3 months after the onset of her symptoms.

In the month preceding our interview, Ms. A’s neurological symptoms had been overshadowed by the acute onset of psychiatric symptoms. She had become increasingly agitated and short tempered with her family, on several occasions throwing furniture at them and once trying to exit a moving car to escape them. She had even called the police several times to report her family for attempting to poison her food. Her family eventually brought her to the emergency room of a state mental health center, where in her first interview with us, she appeared disheveled and uncooperative and had a labile mood and affect. She also showed evidence of delirium, with waxing and waning alertness, anger, and loss of aspects of both her long- and short-term memory.

An examination revealed large bilateral patches of desquamated skin on her feet and normal oral mucosa. Her cranial nerves were intact. Ms. A was, however, unable to stand unassisted. A right Babinski reflex was present, as well as a bilateral loss of proprioception, vibration, and sensation of light touch and pain in the lower extremities. Strength and reflexes in the lower extremities were bilaterally symmetric and grossly diminished. Results of tests of the upper extremities were normal. Ms. A’s CBC results were normal, as were her serum folate and iron levels. Serum vitamin B12 levels were measured and were found to be markedly diminished—less than 9 pg/ml (normal=200–950 pg/ml).

Ms. A was diagnosed with subacute combined spinal cord degeneration and psychosis due to severe vitamin B12 deficiency. She received intramuscular vitamin B12 injections and was transferred to a medical facility. Subsequent test results revealed intrinsic factor and parietal cell antibodies in her serum, as well as elevated levels of methylmalonic acid (23 µmol/liter; normal, <0.4 µmol/liter) and homocysteine (26 µmol/liter; normal, <13 µmol/liter). An endoscopic gastric biopsy revealed atrophic gastritis with prominent intestinal metaplasia.

The etiology of this patient’s vitamin B12 deficiency was classic pernicious anemia; however, when she was seen her most prominent symptom, anemia, was masked. The most likely explanation is that the patient had received folate supplementation during one of her previous emergency room visits or hospitalizations, which corrected for her hematological disease but allowed neurological damage to continue at an accelerated rate. This case reinforced for us the importance of proper follow-up on routine laboratory tests before the implementation of any therapy, even one seemingly as benign as vitamin supplementation (2). In this case, the lack of hematological findings on a routine CBC helped mask what should have been a simple diagnosis of vitamin B12 deficiency. Adding to the confusion over the cause of the psychosis, the patient had a prior diagnosis of multiple sclerosis (which ultimately proved to be inaccurate), as well as a history of recent steroid use.

Several factors, however, should have suggested an organic cause for this patient’s psychosis: her symptoms included disorientation and delirium, had a sudden onset, were accompanied by significant medical morbidity, and were unaccompanied by any history of drug abuse or family or prior history of psychiatric illness. Once the organic nature of her psychiatric illness was realized, the patient was given vitamin B12 supplementation. Within 2 days the strength in her lower extremities had improved. Within 2 months her psychosis was completely resolved, and her only remaining deficit was unilateral weakness of the lower extremities and ataxia, although it was considerably less severe than when she was first seen. We can only assume that had her psychosis been recognized and treated as a symptom of vitamin B12deficiency much earlier, a complete reversal of her symptoms might have been expected (34). As it is, only time will reveal whether her remaining neurological deficits are temporary.

Lindenbaum J, Healton E, Savage D, Brust J, Garrett T, Podell E, Marcell P, Stabler S, Allen R: Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988; 318:1720–  1728
Allen RH, Stabler SP, Savage DG, Lindenbaum J: Metabolic abnormalities in cobalamin (vitamin B12) and folate deficiency. FASEB J 1993; 7:1344–  1353
Hutto B: Folate and cobalamin in psychiatric illness. Compr Psychiatry  1997; 38:305–314
Allen RH, Stabler SP, Lindenbaum J: Relevance of vitamins, homocysteine and other metabolites in neuropsychiatric disorders. Eur J Pediatr 1998; 157(suppl 2):S122–S126

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