Case Presentation: A 79 year old female with a past medical history of type 2 diabetes mellitus, hypertension, coronary artery disease, and prior ischemic stroke presented with a three day history of weakness and confusion. She was oriented to self and location at baseline, without a diagnosis of dementia. Initial investigation revealed an urinalysis with bacteriuria and pyuria. Despite adequate antibiotic treatment, the patient remained encephalopathic. An evaluation for nutritional deficiencies was conducted, which revealed a vitamin B12 level of 160 pg/mL. The patient was initiated on daily 1,000 MCG B12 intramuscular injections and was evaluated for pernicious anemia. Anti-parietal antibody level was elevated at 50.6 units (normal < 20 units) and anti-intrinsic factor antibody was positive. After the eleventh B12 injection, the patient’s neurological symptoms significantly improved and her delirium resolved completely. At discharge, the patient was prescribed weekly B12 injections for four weeks with transition to monthly injection thereafter.
Discussion: Pernicious anemia is a rare autoimmune condition that impairs gastrointestinal absorption of vitamin B12 (cobalamin).1 Autoantibodies against parietal cells leads to decreased intrinsic factor leading to decreased B12 absorption in the ileum.1 Diagnosis can be challenging due to variability in presentation. Neurocognitive impairment, particularly in elderly, can be a subtle manifestation that is difficult to distinguish from other etiologies. Several studies have reported that B12 deficiency is associated with cognitive decline, irritability, delirium and dementia.2 A Swedish study concluded that B12 levels less than 250pg/mL were associated with a twofold increase in Alzheimer’s disease within three years in those 75 years and older.2 Another longitudinal study monitored 1,648 volunteers aged 60 years and older for ten years and found a B12 level of less than 150pg/mL preceded cognitive decline.2 While our patient did not have a confirmed diagnosis of dementia, she did have cognitive impairment at baseline. Cognitive improvement following B12 supplementation in B12 deficiency is usually gradual, however this patient demonstrated rapid neurocognitive recovery.2,3 This underscores the reversibility of B12 related manifestations when promptly recognized and treated.At presentation, serum cobalamin levels are often markedly reduced at less than 200pg/mL. Diagnosis is confirmed by the presence of anti-IF antibodies, which is 40-60% sensitive and almost 100% specific. Anti-parietal cell antibodies, while highly sensitive (approximately 100%), have low specificity (about 14%). When both antibodies are assessed concurrently, diagnostic sensitivity increases to 73% and specificity of 100%.4 Our patient had both positive anti-parietal and anti-IF antibodies with a clinically significant improvement presenting symptoms which all strongly support the diagnosis of pernicious anemia. She will however need a repeat anti-IF level two weeks from the last B12 injection to confirm the initial positive test.
Conclusions: Vitamin B12 deficiency should be considered in elderly patients presenting with cognitive impairment or unexplained delirium. All patients with serum B12 levels less than 200pg/mL and clinically relevant symptoms should be evaluated for pernicious anemia with both anti-IFand anti-parietal antibodies to improve diagnostic sensitivity and specificity.