Case Presentation: A 49-year-old vegetarian male (on supplements with vitamin B12) with recent myocardial infarction (MI) presented with 8-months of worsening neurological symptoms beginning as paresthesias progressing to cognitive decline and gait instability. Physical exam was significant for poor recall, inability to perform basic calculations, impaired proprioception in the right lower extremity, sensory ataxia in the bilateral upper extremities, and inability to ambulate. MRI/MRA of the brain, head, and neck showed mildly enhancing, long segment, dorsal column signal abnormality, suggestive of subacute combined degeneration (SCD) (Figure 1) [1]. Lab studies revealed B12 deficiency (<150 pg/mL, normal 211-946 pg/mL), elevated methylmalonic acid (MMA) (2,520 nmol/L, normal 87-318 nmol/L), severe hyperhomocysteinemia (196.3 umol/L, normal <15 umol/L), as well as positive anti-intrinsic factor antibodies indicative of pernicious anemia. CT abdomen/pelvis and thorax obtained due to concurrent abdominal pain revealed an incidental acute non-occlusive pulmonary embolism (PE).The patient was treated with IM cyanocobalamin and therapeutic anticoagulation with apixaban. He began ambulating with the assistance of a rolling walker and reported improved sensation, memory, and cognition after his first dose of IM cyanocobalamin. He continued to improve throughout his hospital course and was discharged to an acute rehab facility on hospital day 5.

Discussion: Vitamin B12 is an essential cofactor in metabolism and DNA synthesis. It is synthesized only by bacteria found in animal products and stored in the liver for 3-4 years, therefore deficiency secondary to insufficient dietary intake is uncommon. Most deficiencies occur after gastric bypass where intrinsic factor (IF) is low or pernicious anemia where there is immune-mediated destruction of gastric parietal cells and loss of IF necessary for B12 absorption.In the setting of B12 deficiency, serum MMA and homocysteine accumulate as these substrates cannot be further utilized (Figure 2) [2]. MMA disrupts myelin, resulting in degeneration of the dorsal and lateral white matter of the spinal cord, called SCD. Neurologic symptoms of vitamin B12 deficiency include diminished vibration and proprioception sensation, weakness, gait disturbance, and intellectual impairment. These improve with administration of B12, but it is unclear to what extent [3].What is often underappreciated is the relationship between B12 and homocysteine, which directly increases thrombotic risk and may have contributed to the MI and PE in this otherwise healthy patient. Elevated homocysteine increases both cardiovascular-related and overall mortality, and is associated with arterial thrombosis and venous thromboembolism [4-6]. A case-control study involving 326 patients with thrombosis demonstrated that abnormality of B12 and/or renal function was seen in 80% of cases with hyperhomocysteinemia and thrombosis [7]. As homocysteine levels increased by 5 mmol/L, coronary artery disease (CAD) was shown to increase by 20%, independent from other known risk factors of CAD [8].

Conclusions: Vitamin B12 deficiency was the missing link that explained neurological symptoms, MI, and PE in this patient. Although vitamin B12 deficiency is known for presenting with neurological symptoms, providers should also be aware of its association with hyperhomocysteinemia and thrombotic complications.

IMAGE 1: Figure 1: MRI cervical spine Axial T2 showing typical pattern of SCD, known as the “inverted V sign” [1]

IMAGE 2: Figure 2: B12 biochemical pathway [2]