Prevention and Treatment of Peripheral Neuropathy after Bariatric Surgery
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- Rudnicki, S.A. Curr Treat Options Neurol (2010) 12: 29. doi:10.1007/s11940-009-0052-2
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Given the ever-increasing problem of obesity, it is not surprising that the number of patients who undergo bariatric surgery continues to rise. For patients who have gastric banding, the amount of food they can consume is limited, and nausea and vomiting may further limit nutritional intake early on. More extensive procedures, such as the Roux-en-Y or biliopancreatic diversion with or without a duodenal switch, not only restrict intake but also limit absorption in the small intestine. As a result, deficiencies in vitamins, minerals, and trace elements may develop, leading to a variety of neurologic complications. The peripheral neuropathies best described with a clear-cut cause are an acute, frequently painful neuropathy or polyradiculoneuropathy associated with thiamine deficiency, and an isolated neuropathy or myeloneuropathy associated with deficiencies of either vitamin B12 or copper. Thiamine deficiency tends to occur in the first weeks or months after surgery, vitamin B12 deficiency may develop at any time from a few years to many years after surgery, and copper deficiency tends to be a fairly late complication, developing several years to many years following surgery. Patients who have undergone bariatric surgery may also have an increased risk of developing focal neuropathies, though these are less clearly related to specific nutritional deficiencies.
Ideally, one would like to prevent these neuropathies, but there is no consensus of opinion as to what vitamins and micronutrients need to be taken following bariatric surgery. In addition, many patients who take supplements early on fail to maintain the regimen even though some of the neuropathies can occur fairly late. Supplements frequently recommended include a multivitamin, iron, vitamin D, folic acid, calcium citrate, and vitamin B12. Although thiamine is typically included in a multivitamin, the amount is fairly small, so I recommend adding 100 mg daily for at least the first year. Some have suggested zinc supplementation, but this is potentially problematic because exogenous zinc may interfere with copper absorption. Obtaining blood work every 6 months after surgery will help to identify and treat nutritional deficiencies early.
For those patients who have had a bariatric procedure and then develop a neuropathy, evaluating levels of thiamine, copper, vitamin B12, methylmalonic acid, and homocystine is indicated. In addition, since one deficiency is frequently associated with others, obtaining levels of vitamin A, C, D, K, and E, as well as iron, zinc, selenium, and magnesium is worthwhile. Checking total protein, albumin, and cholesterol also gives a sense of general nutritional status. Occasionally, no clear-cut deficiency of a vitamin, mineral, or trace element can be identified in patients with various peripheral nervous system manifestations. Nevertheless, these patients may have at least some recovery with improving nutritional intake and vitamin supplementation, suggesting that we still do not fully understand how nutritional status affects the peripheral nervous system.
Obesity, as defined by the National Institutes of Health, is a body mass index (BMI) of 30 or greater; morbid obesity is a BMI of 40 or greater. It is estimated that 34% of Americans are obese and 5.9% of Americans are morbidly obese . Obesity is an increasing problem not only in adults but also in children. Bariatric surgery provides an option for patients who have been unable to lose weight with dieting and exercise. Patients are considered candidates if their BMI is greater than 40 or if it is greater than 35 with obesity-related disease such as hypertension, sleep apnea, hyperlipidemia, or type II diabetes mellitus . It is estimated that in 2008, 220,000 adults in the United States had bariatric surgery , with 80% of these being women .The preponderance of women is self-selection, as the prevalence of morbid obesity in men is only slightly less than in women. Bariatric surgery is also now being done in children, though not without controversy . It is estimated that 1% of Americans who are eligible have had the surgery, so it is likely that more and more Americans may undertake the procedure in the future .
Bariatric procedures may restrict food intake or may both restrict intake and limit intestinal absorption. Purely restrictive forms of surgery include gastric banding and vertical banding. Procedures that are both restrictive and cause malabsorption are the Roux-en-Y gastric bypass procedure and the biliopancreatic diversion with duodenal switch. The latter procedure bypasses a larger area of the small intestine and thus is associated with a higher incidence of vitamin and micronutrient deficiencies . The procedure chosen is influenced by patient choice, surgeon, associated health problems, and likely also by the degree of obesity, because purely restrictive procedures result in less weight loss than those that also cause malabsorption .
Despite their obesity, patients may have nutritional deficiencies prior to bariatric surgery, including low thiamine, vitamin C , iron, zinc, vitamin B12, and 25-hydroxyvitamin D3 deficiency [7, 8], so preoperative evaluation of nutritional status may be useful. Following surgery, a wide variety of deficiencies have been reported in both retrospective and prospective studies. These studies primarily have focused on patients who underwent Roux-en-Y procedures, but some have included duodenal switch and gastric banding patients. They did not necessarily evaluate the same micronutrients; this difference likely plays a role in the variety of deficiencies reported. Deficiencies found following surgery have included calcium, zinc, selenium, vitamin A, 25-hydroxyvitamin D, and thiamine [6, 9]. In a meta-analysis of nearly 1,000 patients, 25% of the patients were B12-deficient, 20% folate-deficient, and 1% thiamine-deficient .
A variety of peripheral nervous system complications have been described following bariatric surgery. These include acute, subacute, and chronic polyneuropathies; focal entrapment neuropathies; posterior lateral myelopathy associated with a neuropathy; radiculoplexopathy; and burning feet [10–13]. Many reports did not include detailed evaluation of vitamins and micronutrients; in other patients, no clear-cut deficiency was found despite fairly extensive evaluation, making it difficult to know the cause in many of the cases.
Besides the well-known Wernicke’s encephalopathy, thiamine deficiency can also cause a painful acute peripheral neuropathy or polyradiculoneuropathy, which is clinically reminiscent of Guillain-Barré syndrome although axonal in nature; a subacute large-fiber polyneuropathy; and a small-fiber neuropathy primarily causing burning feet. The peripheral nervous system complications may occur in conjunction with the encephalopathy, or either may occur in isolation [10, 11••, 13–15••]. Because thiamine stores may last as few as 20 days , clinical signs of deficiency are most often encountered within months after surgery, though occasionally they may be delayed [15••].
A myeloneuropathy has been described with B12 deficiency or copper deficiency. Patients typically present with a mix of upper and lower motor neuron findings, including spasticity with associated hyperreflexia but absent ankle jerks, as well as the presence of Babinski signs and mild weakness that tends to be worse in the legs and arms. Superimposed upon these findings is a loss of proprioception and vibration sense. Patients also may have urinary symptoms. Electrophysiologic testing frequently shows greater evidence of a mild, length-dependent sensory neuropathy rather than motor neuropathy [11••, 17]. Hematologic changes, which may be noted prior to development of neurologic complaints, have been present in more than half of the reported cases of copper deficiency. Though vitamin B12 deficiency is usually associated with a megaloblastic anemia, copper deficiency also can cause anemia (which can be microcytic, macrocytic, or normocytic), neutropenia, and rarely, pancytopenia [17, 18].
Peripheral nervous system complications following bariatric surgery may be at least partially prevented by postoperative supplements, but the information is mostly empiric rather than evidence-based. Bariatric surgeons vary in their recommendations. A recent guideline statement from the American Association of Clinical Endocrinologists, The Obesity Society, and the American Society for Metabolic and Bariatric Surgery suggested that patients (regardless of the type of procedure) should take multivitamins that contain 400 μg of folate (1 to 2 daily); calcium citrate (1,200–2,000 mg/d); vitamin D (400–800 units per day); elemental iron (40–65 mg/d, particularly for menstruating women); and vitamin B12 (dose and route dependent upon levels). For patients who have had biliopancreatic diversion with or without the duodenal switch, fat-soluble vitamins are also suggested: vitamin A, 5,000 to 10,000 IU daily; vitamin E, 400 IU daily; and vitamin K, 1 mg per day [19••, Class IV].
In addition to supplementation, biochemical surveillance of nutritional status, with treatment when deficiencies are found, is suggested. For those with a Roux-en-Y procedure, the recommendation is a complete blood count, electrolytes, glucose, iron studies, vitamin B12 levels, liver function tests, lipid profile, vitamin D, and optional parathyroid hormone, thiamine, and red blood cell folate every 3 to 6 months for the first year and yearly thereafter. Those with biliopancreatic diversion should have the same tests every 3 to 6 months in perpetuity; they also need to be tested for levels of albumin and prealbumin, fat-soluble vitamins, zinc, and selenium, and should have a metabolic bone evaluation [19••, Class IV]. (Note that copper is not on this list.)
Because deficiencies of thiamine, vitamin B12, and copper are the best described regarding their role in causing peripheral neuropathies in the bariatric surgery population, they will be the focus of the remainder of the discussion.
Diet and lifestyle
Peripheral neuropathies following bariatric surgery are more frequently seen in patients who have rapid and significant early weight loss, diarrhea, dumping syndrome, or nausea and vomiting [12, Class III]. Rapid early weight loss, nausea and vomiting, postoperative loss of appetite, failure to take recommended supplements, and food avoidance have also been associated with the development of thiamine deficiency [15••, Class III].
Small frequent meals without simultaneous consumption of liquids; slow chewing; increased consumption of protein, fiber, and complex carbohydrates; and avoidance of simple sugars lessen gastrointestinal symptoms [19••, 20, Class IV].
Patients who had been dieting before surgery may be at greater risk for developing postoperative deficiencies because of lower reserves.
Compliance with supplement recommendations ranges from 33%  to 90% . Patients who follow up with a nutritionist may have a reduced likelihood of developing neurologic complications [12, Class III], presumably because they are more likely to adhere to vitamin supplementation recommendations and to be reminded of good eating habits. Evaluation by a nutritionist both before and after surgery is suggested [19••, Class IV].
Patients should be cautioned that exogenous zinc consumption may impair copper absorption and lead to hypocupremia . Exogenous zinc may be obtained through zinc supplements, denture cream, and cold remedies containing zinc [22, 23]. Though some recommend zinc supplementation following bariatric surgery , there has been a case report of a patient who developed copper deficiency causing a myeloneuropathy that was felt to be secondary to such supplementation [25, 26]. High doses of iron may also lead to copper deficiency .
- Standard dosage
The standard dose of thiamine for a person with a suspected deficiency causing neurologic disease is 100 mg intravenously (IV), but doses of 100–250 mg daily may not improve thiamine status or the clinical picture [27, 28]. We may need to be more aggressive about replacing thiamine in a patient with neurologic manifestations of deficiency. It was recently proposed that the dose should be 500 mg IV three times a day for 2–3 days, then 250 mg IV daily until improvement is seen [29•, Class IV], followed by an oral dose of 50–100 mg three times a day thereafter, as long as the patient continues to have gastrointestinal complaints [30, Class IV]. Patients with a history of bariatric surgery who present with nausea, vomiting, and diarrhea from any cause, even in the absence of neurologic signs, should prophylactically receive thiamine—prevention is ultimately the best treatment [15••].
- Main drug interactions
Administration of intravenous dextrose can cause the acute development of symptoms of thiamine deficiency. Total parenteral nutrition has also precipitated thiamine deficiency in a patient with depleted reserves.
- Main side effects
Hypersensitivity reactions may occur with repeated IV doses.
- Special points
If the patient has low magnesium levels, this mineral also needs to be replaced, as low magnesium may make the patient resistant to thiamine replacement .
Thirty 100-mg tablets of thiamine cost about $6.00.
There are no recommendations concerning routine copper supplementation following bariatric surgery. The adult RDA for copper is 900 μg.
- Standard dosage
Recommendation for replacement is 6 mg per day of elemental copper for a week, 4 mg per day the next week, and 2 mg daily thereafter. If oral replacement fails to increase copper levels, then IV replacement at a dose of 2 mg per day for 5 days (repeated as necessary) is suggested [25, 26, Class IV]. If elemental copper is difficult to find, copper gluconate can also be given, although this typically requires higher doses than the elemental form.
Supplements can worsen Wilson’s disease and patients with biliary or liver disease may require a lower dose of copper.
- Main drug interactions
Excess zinc can impair copper absorption in the gut, so patients who are taking exogenous zinc should stop. (Low zinc levels may normalize with copper replacement.)
- Main side effects
- Special points
Hematologic problems tend to recover quite quickly, but neurologic deficits do not respond as dramatically or completely. Most patients will have stabilization of their neurologic deficits occasionally they will improve although this improvement tends to be more subjective than objective. Rare patients continue to worsen despite normalization of copper levels [11••, 17, 22, 25, 26, 32–34].
- Standard dosage
For patients who have neurologic symptoms secondary to B12 deficiency, 1,000 μg per day for 5 days (either intramuscularly or deeply subcutaneous), followed by 1,000 μg per month is suggested. In patients who had gastric bypass surgery, 1,000 μg B12 intramuscularly every 3 months or 500 μg intranasally on a weekly basis resulted in a rate of B12 deficiency at 1 year of 3.6% and at 2 years of 2.3% [36, Class III], much less than the 25% found in a meta-analysis . Regardless of the amount and route suggested, B12 levels should be followed and adjustments made as needed [19••, Class IV].
Known hypersensitivity to vitamin B12.
- Main drug interactions
Chloramphenicol may diminish the effectiveness of vitamin B12. H2 blockers may impair the absorption of oral B12.
- Main side effects
Treatment of severe vitamin B12 deficiency with associated megaloblastic anemia may precipitate hypokalemia and thrombocytosis.
- Special points
Replacement of B12 stabilizes but does not necessarily improve neurologic manifestations. Patients without a sensory level, Babinski signs, or cord atrophy on MRI are more likely to improve. Male gender, age under 50 years, and absence of anemia are also associated with a better prognosis .
Ten doses of the injectable form of B12 (1,000-μg dose) is $14.00, 100 tablets of 1,000 μg are approximately $13.00.
If a patient with gastric banding has severe nausea and vomiting, loosening the band to allow more food to pass into the bulk of the stomach will help these symptoms. The band can be tightened later as the patient becomes more tolerant of the small pouch created by the banding.
For patients with a severe neuropathy that has not responded to adequate replacement, revision of the bariatric surgery should be considered [19••, Class IV]. If the patient has continued to have significant neurologic disability even when laboratory values have improved, surgical revision may lead to prompt and remarkable improvement [11••].
No potential conflicts of interest relevant to this article were reported.