Gastroenterology Grand Rounds

Final Diagnosis: Polyneuropathy secondary to multivitamin deficiency following gastric bypass surgery

1. Nutrition Implications

Bariatric surgery is an increasingly common surgical procedure for the treatment of morbid obesity. Although the procedure (Roux-en-Y and vertical banded gastroplasty) is considered to carry a relatively low rate of complications, mainly peri-operative, several long-term complications have been described. Cases of peripheral neuropathy, optic atrophy, and Wernicke's encephalopathy have been reported (1). Neurologic symptoms are related to procedure induced malnutrition. The reduction in total caloric intake along with selective food intolerance limits the ability to consume essential nutrients, both macronutrients and micronutrients. Patients are often provided modular protein supplements during the first 6 postoperative months until solid intake increases. Patients also are routinely advised to take a daily multivitamin and mineral supplement. Neuropathy is also associated with infections, Guillain-Barre syndrome or metabolic derangements (2). Both gastric and intestinal surgery may result in inadequate supply of nutrients necessary for normal nerve-tissue function. Nutritional deficit may also result from losses due to vomiting after gastric surgery. (Visual 1)

2. Specific vitamin/nutrient deficiencies that cause polyneuropathy

a. Thiamine (Vitamin B1) deficiency -Wernicke's disease is characterized by the triad of ophthalmoplegia, ataxia, and mental disturbance. The typical findings may present in any order. Ophthalmoplegia is the most consistent. Ataxia can range in severity. In its most severe form, it renders the patient unable to stand or walk. Less severe forms cause a wide-based gait and a slow, short stepped gait. In contrast to stance and gait, individual movement of the limbs are relatively unaffected. Mental disturbance is characterized by a "global confusional state," composed of apathy, impairment of awareness, disorientation, inattention, failure of concentration, and derangement of memory. In addition, 80% of patients with Wernicke's disease will exhibit peripheral neuropathy. Usually, the polyneuropathy is mild and does not account for the ataxia; however, in a small percentage, it can be so severe that stance and gait cannot be tested. Thiamine deficiency can also result in beriberi. The "wet" form is characterized by congestive heart failure and cardiomegaly. The neuropathic form is characterized by progressive weakness of the distal lower extremities, depression of the deep tendon reflexes, atrophy, and sensory alterations. These symptoms may involve the upper extremities later. The sensory findings include pain, paresthesias, and a burning sensation, which primarily affects the soles.

b. Cobalamin (Vitamin B12) deficiency-known to cause a peripheral neuropathy although less common or significant compared with myelopathy of subacute combined degeneration of the spinal cord. Cobalamin deficiency has been reported to occur in 30% of patients after Roux-en-Y gastric bypass (RYGB) (3). Normally, cobalamin-containing foods undergo acid and peptic hydrolysis in the stomach to liberate vitamin B12. Once released, vitamin B12 is avidly bound to R binders, which are glycoproteins. Pancreatic proteases then degrade R binders in the duodenum and permit vitamin B12 to associate to intrinsic factor (IF). The IF-vitamin B12 complex then is bound to receptors in the distal ileum, where absorption occurs. The RYGB procedure disrupts several of these key steps including decreased acid and pepsin digestion of protein-bound cobalamins form foods, incomplete release of vitamin B12 from R binders, and decreased availability of IF to form IF-vitamin B12 complexes. Because the parietal cells, which secrete acid and IF, and chief cells, which secret pepsinogen, are located primarily in the fundus and body of the stomach, the bypass procedure essentially excludes food from the normal gastric digestive process.

c. Pantothenic Acid (Vitamin B5) deficiency-an essential cofactor in many acetylation reactions including tricarboxylic acid, fatty acid synthesis and break down, as well as other mitochondrial and cytosolic reactions. Its biologically active form is Coenzyme A (CoA). Once ingested and broken down, CoA is hydrolyzed in the small intestine to form pantothenic acid. It is then absorbed in the jejunum and secreted into the bloodstream. Clinical manifestations of deficiency include paresthesias and dysesthesias, referred to as "burning feet syndrome."

d. Pyridoxine (Vitamin B6) deficiency-involved in decarboxylation of amino acids, gluconeogenesis, conversion of tryptophan to niacin, sphingolipid biosynthesis, neurotransmitter synthesis, immune function, and steroid hormone modulation. Strictly from a neurologic point of view, deficiencies can result in irritability, confusion, and depression.

e. Biotin (Vitamin B7) deficiency-functions as a cofactor to the carboxylase enzyme. It has an essential role in protein and DNA synthesis and cell replication. Symptoms of deficiency are nonspecific and may include mental status changes, myalgia, dysesthesias, anorexia, and nausea.

f. Trace mineral deficiencies-chromium and selenium can cause peripheral neuropathy

3. Non-specific nutritional polyneuropathies

Nonspecific nutritional polyneuropathies were initially described in the early 1980s. Feit (4) and May (5) separately described a syndrome known as nutritional sensory neuropathy. The disorder bore multiple similarities to patients with Guillain-Barre Syndrome (GBS). It was described initially in two patients who had undergone gastric partitioning and had rapid initial weight loss with severe vomiting. The onset of symptoms was 3-4 months from surgery. It produced severe ataxia, pseudochorea, proprioceptive abnormalities, and hyporeflexia. Severe weakness was not a component in Feit's two patients. Spinal fluid analysis revealed normal cell counts and protein levels. Wernicke's was felt to be unlikely, as patients did not manifest nystagmus or ophthalmoplegia from cranial nerve involvement. Paulson subsequently described six patients with profound weakness, confusion, encephalopathy, and depressed deep tendon reflexes following gastric partitioning (6). All of these patients had severe confusion, psychosis, or coma. All who were tested had EMG evidence of neuropathy. CSF findings were normal in all except one, and all had severe vomiting. The onset of symptoms was 2-4 months form surgery. All had delayed or incomplete recover. Paulson stated that GBS was unlikely, given the extent of encephalopathy and the normal CSF findings. Several other cases have reported similar findings. These reports have found no uniform vitamin deficiency or toxin that might account for the findings.

4. Other vitamin deficiencies (not leading to polyneuropathy)

a. iron deficiency-occurs in 33-50% of patients after RYGB. The pathophysiology of iron deficiency is related to reduced intake of iron and bypassing the acid environment of the stomach and absorptive surface of the duodenum and proximal jejunum.

b. Folate (Vitamin B9) deficiency-occurs with less frequency than vitamin B12 deficiency. It should be considered in patient with anemia. Folate is primarily absorbed from the proximal third of the small intestine, although it can be absorbed from the entire length of the small intestine. Deficiency has been reported in as many as 42 percent of gastric bypass patients.

c. Calcium deficiency-can result from reduced intake of calcium and vitamin D containing foods, bypass of the duodenum, and malabsorption of vitamin D due to mixing of pancreatic and biliary juices