A 37-year-old woman presents to her physician for mood changes and recent falls over the course of 3 months. She feels more irritable with her husband and children and does not find pleasure in creating art anymore. Over the last 2 weeks, she has been sleeping approximately 5 hours a night and had a fall while walking in her home with the lights off. She denies any head trauma or loss of consciousness associated with the fall. She has a medical history of generalized anxiety disorder and hypothyroidism for which she takes escitalopram and levothyroxine. She had a Roux-en-Y gastric bypass 5 years ago. She has been in a monogamous relationship with her husband for the last 15 years and uses a copper intrauterine device. Physical examination is notable for a depressed affect. Pupils are equal, round, and reactive to light and accommodation. She has 4/5 strength in the bilateral lower extremities and brisk patellar reflexes. Which of the following is most likely the cause of this patient's symptoms?
Subtherapeutic levothyroxine dose
Reduced functional parietal cell count
Reduced central nervous system dopamine and serotonin
Poor iron absorption
Reduced functional parietal cell count
This patient's mood changes and findings concerning for subacute combined degeneration (fall in the dark, impaired proprioception, weakness, and brisk patellar reflexes), and history of Roux-en-Y gastric bypass surgery are concerning for vitamin B12 deficiency. Roux-en-y gastric bypass reduces parietal cell count, leading to reduced intrinsic factor secretion, which is needed for vitamin B12 absorption.

Roux-en-Y gastric bypass is a laparoscopic bariatric procedure that creates a small gastric pouch from the stomach with a gastrojejunal and jejunojejunal anastomosis. This causes small volumes of food to be consumed and decreases nutrient absorption. The small gastric pouch contains very few parietal cells, which decreases hydrochloric acid and intrinsic factor secretion. The reduced intrinsic factor secretion impairs the protection of vitamin B12 against HCl and reduces absorption in the ileum. Vitamin B12 deficiency can lead to neuropsychiatric changes (depressed mood, irritability, and insomnia) and subacute combined degeneration (weakness, sensory ataxia, peripheral neuropathy, and upper motor neuron signs). Patients who undergo Roux-en-Y gastric bypass must be given high doses of vitamin B12 (often intramuscularly) in order to prevent deficiency.

Alexandrou et al. review long-term micronutrient deficiencies after sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). The authors find that vitamin B12 deficiency was significantly higher in patients with RYGB compared with sleeve gastrectomy. The authors recommend adherence to supplemental iron and vitamin intake in all patients who undergo bariatric surgery.

Incorrect Answers:
Answer A: Poor iron absorption is a well-known complication of Roux-en-Y gastric bypass surgery due to bypass of the duodenum and proximal jejunum. Poor iron absorption leads to microcytic anemia from iron deficiency and presents with generalized fatigue and conjunctival pallor. Iron deficiency anemia would not present with brisk reflexes and impaired proprioception.

Answer B: Prior Treponema pallidum exposure can result in tabes dorsalis, a neurological complication of syphilis, and is seen in patients with a history of multiple sexual partners who do not use barrier protection. The spirochete leads to disease in the posterior columns (vibration and proprioception sensation). Patients present with sensory ataxia (similar to subacute combined degeneration), lancinating pain (in the limbs, back, or face), and an Argyll-Robertson pupil (impaired pupillary constriction to light but intact pupillary constriction to accommodation).

Answer C: Reduced central nervous system dopamine and serotonin are seen in patients with major depressive disorder which does not cause sensory ataxia with brisk reflexes.

Answer E: Subtherapeutic levothyroxine dose would result in hypothyroidism, which can present with depressed mood, cold intolerance, bradycardia, and delayed relaxation of deep tendon reflexes. Roux-en-Y is an effective means of losing weight, and as the body mass decreases with weight loss, the required dose of levothyroxine is decreased. It would not present with the abnormal neurologic findings seen in this patient.

Bullet Summary:
Roux-en-Y bariatric surgery increases the risk of vitamin B12 deficiency via reduction of food intake, decreased functional parietal cell count, and reduced absorption of vitamin B12 (which may cause subacute combined degeneration).