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Beriberi after gastric bypass surgery in adolescence
BERIBERI AFTER GASTRIC BYPASS SURGERY IN ADOLESCENCE ALEXANDER TOWBIN, MD, THOMAS H. INGE, MD, PHD, VICTOR F. GARCIA, MD, HELMUT R. ROEHRIG, PHD, RONALD H. CLEMENTS, MD, CARROLL M. HARMON, MD, PHD, AND STEPHEN R. DANIELS, MD, PHD
We report three cases of dry beriberi in adolescents who underwent gastric bypass surgery for clinically severe obesity. The key to successful treatment of this problem lies in prompt recognition and thiamine supplementation. (J Pediatr 2004;145:263-7)
he prevalence and severity of obesity is increasing in children, adolescents, and adults. Bariatric surgery is currently used as a treatment option for selected adolescents with severe obesity and comorbidities. As the number of adolescent patients undergoing this intervention increases, the benefits as well as the adverse effects must be carefully documented. Gastric restrictive and bypass procedures carry a risk of both macronutrient as well as micronutrient deficiency. We present three cases of beriberi after gastric bypass surgery in the adolescent population.
T
CASE DESCRIPTION 1 A 15-year-old female presented to the emergency department at Cincinnati Children’s Hospital with refusal to walk 4 months after laparoscopic Roux-en-Y gastric bypass (RYGBP) surgery for clinically severe obesity. Her neurologic problems began with a fall 2 weeks before admission. She first presented to the emergency department 4 days after the fall with ankle pain. She was diagnosed with a sprained ankle and was discharged with an air cast and crutches. After the initial fall, she continued to fall with increasing frequency, up to 10 to 15 times in the week before admission. She described her falls as collapsing straight down to the ground as a result of weakness. The increasing frequency of falls led her to become fearful of ambulation. The patient denied loss of consciousness or vertigo. The patient further complained of worsening pain extending from the bottom of her feet to her knees and into her thighs, chest pain below her breasts bilaterally and sternally, and numbness and burning of both hands. She described the leg pain as sharp, noting that it lasted only seconds and worsened at night and with use of her legs. The pain was alleviated by acetaminophen with codeine. She denied fever, sore throat, abdominal pain, new rashes, head tilt, nausea, vomiting, or diarrhea. Associated symptoms included hearing loss with tinnitus, dizziness, and diplopia. On admission, her prescribed medications were ranitidine 150 mg twice a day, calcium 1000 mg daily, two chewable multivitamins daily, and ferrous sulfate 325 mg daily. She was also taking 60 gm per day of a liquid protein supplement. The patient’s compliance with her supplement regimen was reportedly incomplete. Her estimated daily caloric intake From the Department of Radiology, University of Pittsburgh Medical Cenwas 300 to 500 kcal with more than half of these calories coming from protein (60-80 g/d). ter, Pittsburgh, Pennsylvania; the DeOn physical examination, she was in no distress and was afebrile with normal vital partments of Surgery and Pediatrics, signs. Her height was 160 cm (35th percentile), and her weight was 102 kg (>97th Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; and the percentile) with a body mass index (BMI) of 39.8 kg/m2 (>97th percentile). This was a 30% Department of Surgery, University of 2 decrease from her preoperative weight and BMI of 146 kg and 56.2 kg/m , respectively. Alabama, and Children’s Hospital of Alabama, Birmingham, Alabama. She had serous fluid behind the left tympanic membrane. She appeared to be able to Submitted for publication Dec 1, 2003; understand conversations, but when asked questions, she stated that she was unable to hear last revision received Mar 10, 2004; them. There was bilateral, end gaze horizontal nystagmus present but no visual field accepted Apr 22, 2004. deficits. The remainder of the cranial nerve and cardiopulmonary examinations were Reprint requests: Dr Thomas H. Inge, 3333 Burnet Ave, Cincinnati, OH normal. The abdomen was obese and nontender with five well-healed surgical trocar site 45229-3039. E-mail: thomas.inge@ scars. She was exquisitely tender to light touch in a stocking distribution from the soles of cchmc.org. 0022-3476/$ - see front matter Copyright ª 2004 Elsevier Inc. All rights reserved. BMI
Body mass index
RYGBP
Roux-en-Y gastric bypass
10.1016/j.jpeds.2004.04.051
263
Table. Lab value comparison Test (normal range)
Case 1
Case 2
Case 3
Height (cm) 160 (35%) 165 (75%) 168 (78%) Pre-bypass weight (kg) 146 (>97 %) 164.1 (>97 %) 179 (>97%) Weight at presentation (kg) 102 (>97%) 108.6 (>97 %) 104 (>97%) Pre-bypass BMI (kg/m2) 56.2 (>97%) 60 (>97%) 63.4 (>97%) BMI at presentation (kg/m2) 39.8 (>97%) 40 (>97%) 36.8 (>97%) AST (10-30 IU/L) 118 24 ALT (5-35 IU/L) 99 23 Alkaline phosphatase 130 59 (65-525 IU/L) GGT (8-78 IU/L) 98 19 Albumin (3.5-5 g/dL) 3.8 3.9 3.8 Prealbumin (16-36 mg/dL) 16.4 10 9.3 Total protein (6.3-8.2 g/dL) 7.3 7.2 6.7 Total bilirubin (0-1.4 mg/dL) 0.4 0.7 1.3 ESR (0-20 mm/hr) 34 20 C-reactive protein 3.8 (<1.0 mg/dL) Serum transferrin 192 237 (197-360 mg/dL) Zinc (670-1240 lg/L) 1007 Vitamin A (200-720 lg/L) 272 149 Vitamin B1 (9-44 nmol/L)* <7 67* <7 11 127* 20 Follow-up vitamin B1 (9-44 mol/L)* Vitamin B2 (6.2-39 nmol/L) 6.3 Vitamin B6 (5-24 nmol/L) <2.5 <2.5 Vitamin B12 (200-1100 1042 1498 pg/mL) Vitamin D-25 OH (9-46 7.2 54.4 ng/mL) Serum folate (>5.4 ng/mL) 10.2 5.3 Antinuclear antibody Negative 1:80 Antinuclear antibody type Anti-ds TSH (0.37-6.00 lU/mL) 3.92 2.78 2.78 Free T4 (5.6-11.7 lg/dL) 12.3 1.25 Urine ketones (negative) $80 mg% 1+ 40 mg% ALT, Alanine aminotransferase; AST, aspartate aminotransferase; ESR, erythrocyte sedimentation rate; GGT, gamma glutamyl transferase; LDH, lactate dehydrogenase; MCV, mean corpuscular volume; TSH, thyroidstimulating hormone. *The normal range for vitamin B1 in case 2 is 87 to 280 nmol/L.
her feet to approximately 10 cm above the ankle bilaterally as well as circumferentially around both knees. Her strength was 4/5 bilaterally throughout with functional give-away weakness. She had bilateral and symmetric 1+ reflexes at her biceps and patellar tendons and decreased vibratory sensation at her fingertips and below her hips. Rapid alternating movements, finger to nose, and heel to shin tests all were normal. The patient’s skin had multiple ecchymoses and abrasions over the lower extremities from falls, keratosis pilaris on the upper extremities, and acanthosis nigricans on the nape of the neck. 264
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Significant laboratory values (Table) included increased aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, erythrocyte sedimentation rate, c-reactive protein, and urine ketones as well as decreased levels of prealbumin, vitamin B1, vitamin B6, and vitamin 25-hydroxyvitamin D. Computed tomography of the brain revealed mild, diffuse, nonspecific cerebral volume loss with poor definition of the cerebral gray/white interface, consistent with chronic illness. An upper gastrointestinal series showed no evidence of gastrojejunal stenosis. The pure tone results suggested mild hearing loss that rose to normal near 3000 Hz in the right ear and moderate hearing loss that rose to normal in the left ear at 8000 Hz. The patient exhibited functional tendencies throughout the test that were inconsistent with the pure tone results. Speech discrimination was described as poor. She complained multiple times that she could not hear spoken words even though they were presented at a supra-threshold level. Otoacoustic evaluation showed normal middle ear pressure and compliance, suggesting normal outer hair cell function and discord with her behavioral results. There was electrodiagnostic evidence of significant peripheral polyneuropathy with ongoing denervation and reinnervation in the distal lower extremity and reinnervation in the distal upper extremity. Nerve conduction studies did not demonstrate any demyelination but did reveal axonal injury at low amplitudes. These findings were consistent with neuropathy as a result of nutritional deficiencies. The patient was diagnosed with vitamin B1 deficiency, or beriberi. She was treated intravenously with 100 mg thiamine and multivitamins for 1 week, followed by 10-mg thiamine orally per day. Her pain was controlled with amitriptyline and gabapentin. The amitriptyline was titrated to a once-daily dose of 25 mg taken at bedtime, and the gabapentin was titrated upward to the point of sedation, beginning with 100 mg three times per day, and increasing by 300 mg daily, divided into three equal doses. Breakthrough pain was controlled with acetaminophen. With vitamin supplementation, pain control, and physical therapy, her symptoms and strength improved to the point that she could walk unassisted and her hearing was unimpaired; she was transferred to an inpatient rehabilitation service for reconditioning before discharge home. Six months following her initial presentation, she had experienced marked reduction of her neuropathic pain and was able to ambulate unassisted.
CASE DESCRIPTION 2 A 14-year-old female presented to the surgery clinic at the University of Alabama, Birmingham, with bilateral foot pain, lower extremity weakness, and numbness in her fingers 5 months after laparoscopic RYGBP surgery. Two months following the operation, she noted increasing vomiting as well as clumsiness and numbness in her feet. After undergoing successful dilation for a gastrojejunal anastomotic stricture, her lower extremity numbness worsened and she developed increasing weakness and progressive burning pain in the soles The Journal of Pediatrics August 2004
of her feet. When she was unable to ambulate without assistance and had numbness in both her hands and fingers, she presented to the surgery clinic. At presentation, she had lost 55.5 kg, or 34% of preoperative weight. Her medications included 600 mg of gabapentin taken three times per day, once-daily doses of 100 mg of vitamin B6, a pediatric multivitamin, a tablet of a B-complex vitamin with vitamin C, two calcium supplement tablets, and acetaminophen as needed. A review of systems revealed a subjective hearing loss, dizziness, and squinting. Her physical exam was remarkable for a weight of 108.6 kg (>97th percentile) and normal extraocular movements with mild nystagmus. The neurologic exam showed that she had normal strength in the upper extremities, decreased strength bilaterally in the calves, decreased pin-prick sensation in both the hands and feet, and decreased vibratory sensation at the great toe. No lower extremity deep tendon reflexes could be elicited, and she had a waddling gait and an inability to toe walk and tandem walk. Significantly decreased laboratory values (Table) included vitamin B1, prealbumin, and free T4. Her antinuclear antibody was positive at 1:80 with normal anti-double stranded DNA. Ketones were present in the urine. Magnetic resonance imaging of the lumbosacral spine was normal. The patient’s electromyogram showed active denervation without evidence of reinnervation in multiple muscle groups. There were small peroneal motor action potentials and absent F waves. The prolonged F waves were seen bilaterally in the posterior tibial nerves. The superficial peroneal sensory nerve conduction was slowed. These findings were consistent with neuropathy as a result of nutritional deficiencies. The patient was diagnosed with vitamin B1 deficiency. She was treated with intravenous thiamine (100mg/day), multivitamins, and hyperalimentation for 1 week. Her foot pain was treated with morphine, promethazine, capsaicin cream, citalopram, and acetaminophen. The pain resolved, and her strength improved throughout the week. She was discharged to home on citalopram, gabapentin, iron complex, a protein supplement, acetaminophen with codeine, vitamin B6, vitamin B complex, a multivitamin, selenium, and capsaicin cream. Four months following discharge, the neuropathy had resolved. Her most recent thiamine level was 127 nmol/L (normal, 87-280 nmol/L) 2 months following discharge.
CASE DESCRIPTION 3 A 17-year-old female presented to her pediatrician with a 2-week history of burning pain in her feet, 6 months after laparoscopic RYGBP surgery for clinically severe obesity at Cincinnati Children’s Hospital. The pain localized primarily in the soles of both feet but extended to the dorsal aspect on the right side. There was no numbness of her feet, nor was there any difficulty with ambulation. The pain was present for the entire day and night but was worse while recumbent at night. Her mother and pediatrician reported that her feet were exquisitely tender to light touch. Her only other neurologic complaint was frequent headaches. The pain was alleviated by acetaminophen with codeine. Her daily medications were Beriberi After Gastric Bypass Surgery in Adolescence
ranitidine, calcium, two chewable multivitamins, potassium chloride, and ferrous fumarate. Her fluid intake was reported to be less than the goal of 64 oz per day; she denied nausea or frequent vomiting. Significantly decreased levels of vitamins B1 and B6 were noted (Table). Her vitamin B12 level was elevated. In addition, her urinary fractional excretion of sodium was 0.15%. The clinical diagnoses of beriberi and dehydration were made. For the beriberi, she was treated as an outpatient with a single parenteral dose of 100 mg thiamine and multivitamins, followed by 10 mg thiamine orally per day. At the time of her surgical follow-up 2 weeks later, her symptoms had nearly completely resolved. She complained only of nighttime pain and only in her toes, which continued to improve daily. The pain was alleviated with acetaminophen. On physical examination, she was in no distress. Her height was 168 cm (78th percentile), and her weight was 104 kg (>97th percentile) with a BMI of 37 kg/m2 (>97th percentile). This was a 42% decrease from her preoperative weight and BMI of 179 kg and 64 kg/m2, respectively. There was no sensory deficit of the lower extremities to sharp stimulus or light touch. Her strength was excellent in all compartments of the upper and lower extremities. Her gait was normal. An upper gastrointestinal contrast study revealed stenosis at the gastro-jejunal anastomosis. The stenosis was treated with four serial endoscopic dilations (every 2 weeks) until the stenosis, dehydration, and hypokalemia had completely resolved.
DISCUSSION Overweight or obesity, defined in children as a BMI $95th percentile for age and sex, has been described by the World Health Organization as ‘‘one of today’s most blatantly visible—yet most neglected—public health problems.’’1 Fifteen percent of all children 6 to 19 years old are overweight.2 Obesity in children has been associated with type II diabetes mellitus,3 hypertension,4 and decreased quality of life.5 As the prevalence and severity of obesity have increased, so too has the need to consider more effective alternatives to standard weight management approaches. In adults, RYGBP typically results in the long-term loss of onethird of body weight and resolution of most comorbid conditions associated with severe obesity.6 During the first year after this procedure, patients typically consume between 500 and 1000 kcal per day and avoid simple carbohydrates because of the risk of dumping syndrome. The effectiveness of bariatric surgery in adults along with the increasing prevalence of clinically severe obesity among adolescents has led to an increase in the use of bariatric procedures for adolescents.7-9 Similar satisfactory outcomes have been observed in this age group10,11 as compared to adults. It is therefore important for pediatricians to recognize the risks, benefits, and potentially predictable side effects of gastric bypass. The differential diagnosis for the patients presented in this series, based on their presenting signs and symptoms, includes peripheral neuropathy as a result of nutritional 265
deficiency or multiple sclerosis; systemic lupus erythematosus; connective tissue disorder; pain amplification syndrome, including reflex sympathetic dystrophy and fibromyalgia; anxiety disorder; and conversion disorder. The diverse studies obtained in these patients allowed the differential diagnosis to be narrowed to a single entity. The response of each case to supplemental thiamine confirms the diagnosis of beriberi. Vitamin and mineral deficiencies have previously been reported with malabsorptive surgical procedures such as gastric bypass.12,13 The most common vitamin deficiencies include hypovitaminosis A, B12, C, D, E, folic acid, and iron.14-19 The likely mechanism for these deficiencies is thought to be malabsorption and/or decreased oral intake, including poor compliance with medications postoperatively. Beriberi is a clinical syndrome of thiamine (vitamin B1) deficiency. Thiamine is absorbed primarily in the jejunum and is required for carbohydrate metabolism. Thus, thiamine levels can be depleted after oral20 or intravenous21 carbohydrate intake. Thiamine deficiency can cause peripheral neurologic, cerebral, cardiologic, and gastrointestinal manifestations. ‘‘Dry’’ beriberi is a disease of bilateral, symmetric, lower extremity paresthesia, dysesthesia, and allodynia with decreased vibratory sensation and reflexes; dry beriberi is seen more commonly in patients with caloric restriction and relative inactivity.22 ‘‘Wet’’ beriberi is characterized by cardiac failure and edema, and is seen in patients with high carbohydrate intake and severe physical exertion. Cerebral beriberi (Wernicke-Korsakoff syndrome) has been reported after prolonged vomiting, starvation, and, most commonly, alcoholism.23,24 Peripheral neuropathy and Wernicke’s encephalopathy secondary to vitamin B1 deficiency have both been described in adults after gastric surgery and protracted vomiting.13,23,25-27 There are no previously reported cases of postsurgical beriberi in the pediatric population. Postsurgical beriberi has been successfully treated with parenteral doses of 50 to 200 mg vitamin B1 daily until symptoms have cleared, followed by daily oral supplementation.12,21 It is not clear in these three cases whether thiamine deficiency developed despite adequate oral intake (malabsorption) or because of inadequate compliance with recommended daily supplementation. In adults with an isocaloric diet, the stores of thiamine have been estimated to last 3 to 6 weeks.28 Deficiency of vitamin B1 has not been described when patients are adequately supplemented. In addition, there are limited data on vitamin stores in the morbidly obese either pre- or postsurgery.29 Thiamine plays a key role in metabolism of both simple sugars and keto acids. Thus, it is possible that patients with already low thiamine levels before surgery (as a result of a diet rich in simple sugars) have increased thiamine demands during their prolonged ketotic state following RYGBP. Vomiting and poor compliance with vitamin supplements after gastric bypass may therefore be important risk factors for depletion of already borderline thiamine stores. Because of these possibilities, our practice is now to begin daily multivitamin supplementation several months prior to gastric bypass, when patients are initially evaluated by the bariatric team. Following 266
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gastric bypass, we have also added a separate vitamin B complex supplement to the prescribed multivitamin and mineral regimen for all patients. The health benefits of significant and sustained weight reduction for the morbidly obese are incontrovertible. Surgical weight loss is, however, associated with some nutritional risks, and it is important for all healthcare workers to recognize the nutritional complications of bariatric surgery. Malnutrition and vitamin deficiencies are easy to overlook in obese persons, but nonetheless they may exist. Because of the possibility of vitamin deficiencies specifically in gastric bypass patients, a targeted review of systems during each visit might bring early attention to a developing micronutrient deficiency. Emphasis on compliance strategies, careful monitoring of vitamin and mineral intake, and periodic laboratory surveillance to detect vitamin deficiency is suggested. Moreover, the observations reported here further suggest that it may be wise to augment thiamine intake in adolescent bariatric patients above the usually recommended daily intake of 1.5 mg/day to further reduce the risk of deficiency syndrome. We acknowledge the expert dietary and nursing care provided to these patients by Shelley Kirk, PhD, RD, Michelle Frank, RD, Jenny Sweeney, MS, PNP, and Beverly Haynes, RN, BSN.
REFERENCES 1. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000;894:i-253. 2. Ogden CL, Flegal KM, Carroll MD, Johnson CL. Prevalence and trends in overweight among US children and adolescents, 1999-2000. JAMA 2002;288:1728-32. 3. Pinhas-Hamiel O, Dolan LM, Daniels SR, Standiford D, Khoury PR, Zeitler P. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr 1996;128:608-15. 4. Must A, Strauss RS. Risks and consequences of childhood and adolescent obesity. Int J Obes Relat Metab Disord 1999;23:S9-11. 5. Schwimmer JB, Burwinkle TM, Varni JW. Health-related quality of life of severely obese children and adolescents. JAMA 2003;289:1813-9. 6. Buchwald H. Overview of bariatric surgery. J Am Coll Surg 2002;194: 367-75. 7. Garcia VF, Langford L, Inge TH. Application of laparoscopy for bariatric surgery in adolescents. Curr Opin Pediatr 2003;15:248-55. 8. Inge TH, Garcia VF, Daniels SR, Langford L, Kirk S, Roehrig H, et al. A multidisciplinary approach to the adolescent bariatric surgical patient. J Pediatr Surg 2004;39:442-7. 9. American Academy of Pediatrics Committees on Nutrition and Gastroenterology. Weighing the consequences: bariatric surgery sometimes considered for obese children, but information lacking on long-term outcomes. AAP News 2003;July:16-8. 10. Sugerman HJ, Sugerman EL, DeMaria EJ, Kellum JM, Kennedy C, Mowery Y, et al. Bariatric surgery for severely obese adolescents. J Gastrointest Surg 2003;7:102-7. 11. Strauss RS, Bradley LJ, Brolin RE. Gastric bypass surgery in adolescents with morbid obesity. J Pediatr 2001;138:499-504. 12. Gollobin C, Marcus WY. Bariatric beriberi. Obes Surg 2002;12:309-11. 13. Chaves LC, Faintuch J, Kahwage S, Alencar FA. A cluster of polyneuropathy and Wernicke-Korsakoff syndrome in a bariatric unit. Obes Surg 2002;12:328-34. 14. Amaral JF, Thompson WR, Caldwell MD, Martin HF, Randall HT. Prospective hematologic evaluation of gastric exclusion surgery for morbid obesity. Ann Surg 1985;201:186-93.
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15. Halverson JD. Vitamin and mineral deficiencies following obesity surgery. Gastroenterol Clin North Am 1987;16:307-15. 16. Halverson JD. Micronutrient deficiencies after gastric bypass for morbid obesity. Am Surg 1986;52:594-8. 17. MacLean LD, Rhode BM, Shizgal HM. Nutrition following gastric operations for morbid obesity. Ann Surg 1983;198:347-55. 18. Mason EE. Starvation injury after gastric reduction for obesity. World J Surg 1998;22:1002-7. 19. Schilling RF, Gohdes PN, Hardie GH. Vitamin B12 deficiency after gastric bypass surgery for obesity. Ann Intern Med 1984;101:501-2. 20. Djoenaidi W, Notermans SL, Verbeek AL. Subclinical beriberi polyneuropathy in the low income group: an investigation with special tools on possible patients with suspected complaints. Eur J Clin Nutr 1996;50:549-55. 21. Hahn JS, Berquist W, Alcorn DM, Chamberlain L, Bass D. Wernicke encephalopathy and beriberi during total parenteral nutrition attributable to multivitamin infusion shortage. Pediatrics 1998;101:E10. 22. Wilson JD. Vitamin deficiency and excess. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison’s principles of internal medicine. 14th ed. New York: McGraw-Hill; 1998;480-9.
Beriberi After Gastric Bypass Surgery in Adolescence
23. Salas-Salvado J, Garcia-Lorda P, Cuatrecasas G, Bonada A, Formiguera X, Del Castillo D, et al. Wernicke’s syndrome after bariatric surgery. Clin Nutr 2000;19:371-3. 24. van den Berg H, van der Gaag M, Hendriks H. Influence of lifestyle on vitamin bioavailability. Int J Vitam Nutr Res 2002;72:53-9. 25. Iwase K, Higaki J, Yoon HE, Mikata S, Miyazaki M, Kamiike W. Reduced thiamine (vitamin B1) levels following gastrectomy for gastric cancer. Gastric Cancer 2002;5:77-82. 26. Maryniak O. Severe peripheral neuropathy following gastric bypass surgery for morbid obesity. Can Med Assoc J 1984;131:119-20. 27. Harwood SC, Chodoroff G, Ellenberg MR. Gastric partitioning complicated by peripheral neuropathy with lumbosacral plexopathy. Arch Phys Med Rehabil 1987;68:310-2. 28. Ziporin ZZ, Nunes WT, Powell RC, Waring PP, Sauberlich HE. Thiamine requirement in the adult human as measured by urinary excretion of thiamine metabolites. J Nutr 1965;85:297-304. 29. Boylan LM, Sugerman HJ, Driskell JA. Vitamin E, vitamin B-6, vitamin B-12, and folate status of gastric bypass surgery patients. J Am Diet Assoc 1988;88:579-85.
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We report three cases of dry beriberi in adolescents who underwent gastric bypass surgery for clinically severe obesity. The key to successful treatment of this problem lies in prompt recognition and thiamine supplementation. (J Pediatr 2004;145:263-7)
he prevalence and severity of obesity is increasing in children, adolescents, and adults. Bariatric surgery is currently used as a treatment option for selected adolescents with severe obesity and comorbidities. As the number of adolescent patients undergoing this intervention increases, the benefits as well as the adverse effects must be carefully documented. Gastric restrictive and bypass procedures carry a risk of both macronutrient as well as micronutrient deficiency. We present three cases of beriberi after gastric bypass surgery in the adolescent population.
T
CASE DESCRIPTION 1 A 15-year-old female presented to the emergency department at Cincinnati Children’s Hospital with refusal to walk 4 months after laparoscopic Roux-en-Y gastric bypass (RYGBP) surgery for clinically severe obesity. Her neurologic problems began with a fall 2 weeks before admission. She first presented to the emergency department 4 days after the fall with ankle pain. She was diagnosed with a sprained ankle and was discharged with an air cast and crutches. After the initial fall, she continued to fall with increasing frequency, up to 10 to 15 times in the week before admission. She described her falls as collapsing straight down to the ground as a result of weakness. The increasing frequency of falls led her to become fearful of ambulation. The patient denied loss of consciousness or vertigo. The patient further complained of worsening pain extending from the bottom of her feet to her knees and into her thighs, chest pain below her breasts bilaterally and sternally, and numbness and burning of both hands. She described the leg pain as sharp, noting that it lasted only seconds and worsened at night and with use of her legs. The pain was alleviated by acetaminophen with codeine. She denied fever, sore throat, abdominal pain, new rashes, head tilt, nausea, vomiting, or diarrhea. Associated symptoms included hearing loss with tinnitus, dizziness, and diplopia. On admission, her prescribed medications were ranitidine 150 mg twice a day, calcium 1000 mg daily, two chewable multivitamins daily, and ferrous sulfate 325 mg daily. She was also taking 60 gm per day of a liquid protein supplement. The patient’s compliance with her supplement regimen was reportedly incomplete. Her estimated daily caloric intake From the Department of Radiology, University of Pittsburgh Medical Cenwas 300 to 500 kcal with more than half of these calories coming from protein (60-80 g/d). ter, Pittsburgh, Pennsylvania; the DeOn physical examination, she was in no distress and was afebrile with normal vital partments of Surgery and Pediatrics, signs. Her height was 160 cm (35th percentile), and her weight was 102 kg (>97th Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; and the percentile) with a body mass index (BMI) of 39.8 kg/m2 (>97th percentile). This was a 30% Department of Surgery, University of 2 decrease from her preoperative weight and BMI of 146 kg and 56.2 kg/m , respectively. Alabama, and Children’s Hospital of Alabama, Birmingham, Alabama. She had serous fluid behind the left tympanic membrane. She appeared to be able to Submitted for publication Dec 1, 2003; understand conversations, but when asked questions, she stated that she was unable to hear last revision received Mar 10, 2004; them. There was bilateral, end gaze horizontal nystagmus present but no visual field accepted Apr 22, 2004. deficits. The remainder of the cranial nerve and cardiopulmonary examinations were Reprint requests: Dr Thomas H. Inge, 3333 Burnet Ave, Cincinnati, OH normal. The abdomen was obese and nontender with five well-healed surgical trocar site 45229-3039. E-mail: thomas.inge@ scars. She was exquisitely tender to light touch in a stocking distribution from the soles of cchmc.org. 0022-3476/$ - see front matter Copyright ª 2004 Elsevier Inc. All rights reserved. BMI
Body mass index
RYGBP
Roux-en-Y gastric bypass
10.1016/j.jpeds.2004.04.051
263
Table. Lab value comparison Test (normal range)
Case 1
Case 2
Case 3
Height (cm) 160 (35%) 165 (75%) 168 (78%) Pre-bypass weight (kg) 146 (>97 %) 164.1 (>97 %) 179 (>97%) Weight at presentation (kg) 102 (>97%) 108.6 (>97 %) 104 (>97%) Pre-bypass BMI (kg/m2) 56.2 (>97%) 60 (>97%) 63.4 (>97%) BMI at presentation (kg/m2) 39.8 (>97%) 40 (>97%) 36.8 (>97%) AST (10-30 IU/L) 118 24 ALT (5-35 IU/L) 99 23 Alkaline phosphatase 130 59 (65-525 IU/L) GGT (8-78 IU/L) 98 19 Albumin (3.5-5 g/dL) 3.8 3.9 3.8 Prealbumin (16-36 mg/dL) 16.4 10 9.3 Total protein (6.3-8.2 g/dL) 7.3 7.2 6.7 Total bilirubin (0-1.4 mg/dL) 0.4 0.7 1.3 ESR (0-20 mm/hr) 34 20 C-reactive protein 3.8 (<1.0 mg/dL) Serum transferrin 192 237 (197-360 mg/dL) Zinc (670-1240 lg/L) 1007 Vitamin A (200-720 lg/L) 272 149 Vitamin B1 (9-44 nmol/L)* <7 67* <7 11 127* 20 Follow-up vitamin B1 (9-44 mol/L)* Vitamin B2 (6.2-39 nmol/L) 6.3 Vitamin B6 (5-24 nmol/L) <2.5 <2.5 Vitamin B12 (200-1100 1042 1498 pg/mL) Vitamin D-25 OH (9-46 7.2 54.4 ng/mL) Serum folate (>5.4 ng/mL) 10.2 5.3 Antinuclear antibody Negative 1:80 Antinuclear antibody type Anti-ds TSH (0.37-6.00 lU/mL) 3.92 2.78 2.78 Free T4 (5.6-11.7 lg/dL) 12.3 1.25 Urine ketones (negative) $80 mg% 1+ 40 mg% ALT, Alanine aminotransferase; AST, aspartate aminotransferase; ESR, erythrocyte sedimentation rate; GGT, gamma glutamyl transferase; LDH, lactate dehydrogenase; MCV, mean corpuscular volume; TSH, thyroidstimulating hormone. *The normal range for vitamin B1 in case 2 is 87 to 280 nmol/L.
her feet to approximately 10 cm above the ankle bilaterally as well as circumferentially around both knees. Her strength was 4/5 bilaterally throughout with functional give-away weakness. She had bilateral and symmetric 1+ reflexes at her biceps and patellar tendons and decreased vibratory sensation at her fingertips and below her hips. Rapid alternating movements, finger to nose, and heel to shin tests all were normal. The patient’s skin had multiple ecchymoses and abrasions over the lower extremities from falls, keratosis pilaris on the upper extremities, and acanthosis nigricans on the nape of the neck. 264
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Significant laboratory values (Table) included increased aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, erythrocyte sedimentation rate, c-reactive protein, and urine ketones as well as decreased levels of prealbumin, vitamin B1, vitamin B6, and vitamin 25-hydroxyvitamin D. Computed tomography of the brain revealed mild, diffuse, nonspecific cerebral volume loss with poor definition of the cerebral gray/white interface, consistent with chronic illness. An upper gastrointestinal series showed no evidence of gastrojejunal stenosis. The pure tone results suggested mild hearing loss that rose to normal near 3000 Hz in the right ear and moderate hearing loss that rose to normal in the left ear at 8000 Hz. The patient exhibited functional tendencies throughout the test that were inconsistent with the pure tone results. Speech discrimination was described as poor. She complained multiple times that she could not hear spoken words even though they were presented at a supra-threshold level. Otoacoustic evaluation showed normal middle ear pressure and compliance, suggesting normal outer hair cell function and discord with her behavioral results. There was electrodiagnostic evidence of significant peripheral polyneuropathy with ongoing denervation and reinnervation in the distal lower extremity and reinnervation in the distal upper extremity. Nerve conduction studies did not demonstrate any demyelination but did reveal axonal injury at low amplitudes. These findings were consistent with neuropathy as a result of nutritional deficiencies. The patient was diagnosed with vitamin B1 deficiency, or beriberi. She was treated intravenously with 100 mg thiamine and multivitamins for 1 week, followed by 10-mg thiamine orally per day. Her pain was controlled with amitriptyline and gabapentin. The amitriptyline was titrated to a once-daily dose of 25 mg taken at bedtime, and the gabapentin was titrated upward to the point of sedation, beginning with 100 mg three times per day, and increasing by 300 mg daily, divided into three equal doses. Breakthrough pain was controlled with acetaminophen. With vitamin supplementation, pain control, and physical therapy, her symptoms and strength improved to the point that she could walk unassisted and her hearing was unimpaired; she was transferred to an inpatient rehabilitation service for reconditioning before discharge home. Six months following her initial presentation, she had experienced marked reduction of her neuropathic pain and was able to ambulate unassisted.
CASE DESCRIPTION 2 A 14-year-old female presented to the surgery clinic at the University of Alabama, Birmingham, with bilateral foot pain, lower extremity weakness, and numbness in her fingers 5 months after laparoscopic RYGBP surgery. Two months following the operation, she noted increasing vomiting as well as clumsiness and numbness in her feet. After undergoing successful dilation for a gastrojejunal anastomotic stricture, her lower extremity numbness worsened and she developed increasing weakness and progressive burning pain in the soles The Journal of Pediatrics August 2004
of her feet. When she was unable to ambulate without assistance and had numbness in both her hands and fingers, she presented to the surgery clinic. At presentation, she had lost 55.5 kg, or 34% of preoperative weight. Her medications included 600 mg of gabapentin taken three times per day, once-daily doses of 100 mg of vitamin B6, a pediatric multivitamin, a tablet of a B-complex vitamin with vitamin C, two calcium supplement tablets, and acetaminophen as needed. A review of systems revealed a subjective hearing loss, dizziness, and squinting. Her physical exam was remarkable for a weight of 108.6 kg (>97th percentile) and normal extraocular movements with mild nystagmus. The neurologic exam showed that she had normal strength in the upper extremities, decreased strength bilaterally in the calves, decreased pin-prick sensation in both the hands and feet, and decreased vibratory sensation at the great toe. No lower extremity deep tendon reflexes could be elicited, and she had a waddling gait and an inability to toe walk and tandem walk. Significantly decreased laboratory values (Table) included vitamin B1, prealbumin, and free T4. Her antinuclear antibody was positive at 1:80 with normal anti-double stranded DNA. Ketones were present in the urine. Magnetic resonance imaging of the lumbosacral spine was normal. The patient’s electromyogram showed active denervation without evidence of reinnervation in multiple muscle groups. There were small peroneal motor action potentials and absent F waves. The prolonged F waves were seen bilaterally in the posterior tibial nerves. The superficial peroneal sensory nerve conduction was slowed. These findings were consistent with neuropathy as a result of nutritional deficiencies. The patient was diagnosed with vitamin B1 deficiency. She was treated with intravenous thiamine (100mg/day), multivitamins, and hyperalimentation for 1 week. Her foot pain was treated with morphine, promethazine, capsaicin cream, citalopram, and acetaminophen. The pain resolved, and her strength improved throughout the week. She was discharged to home on citalopram, gabapentin, iron complex, a protein supplement, acetaminophen with codeine, vitamin B6, vitamin B complex, a multivitamin, selenium, and capsaicin cream. Four months following discharge, the neuropathy had resolved. Her most recent thiamine level was 127 nmol/L (normal, 87-280 nmol/L) 2 months following discharge.
CASE DESCRIPTION 3 A 17-year-old female presented to her pediatrician with a 2-week history of burning pain in her feet, 6 months after laparoscopic RYGBP surgery for clinically severe obesity at Cincinnati Children’s Hospital. The pain localized primarily in the soles of both feet but extended to the dorsal aspect on the right side. There was no numbness of her feet, nor was there any difficulty with ambulation. The pain was present for the entire day and night but was worse while recumbent at night. Her mother and pediatrician reported that her feet were exquisitely tender to light touch. Her only other neurologic complaint was frequent headaches. The pain was alleviated by acetaminophen with codeine. Her daily medications were Beriberi After Gastric Bypass Surgery in Adolescence
ranitidine, calcium, two chewable multivitamins, potassium chloride, and ferrous fumarate. Her fluid intake was reported to be less than the goal of 64 oz per day; she denied nausea or frequent vomiting. Significantly decreased levels of vitamins B1 and B6 were noted (Table). Her vitamin B12 level was elevated. In addition, her urinary fractional excretion of sodium was 0.15%. The clinical diagnoses of beriberi and dehydration were made. For the beriberi, she was treated as an outpatient with a single parenteral dose of 100 mg thiamine and multivitamins, followed by 10 mg thiamine orally per day. At the time of her surgical follow-up 2 weeks later, her symptoms had nearly completely resolved. She complained only of nighttime pain and only in her toes, which continued to improve daily. The pain was alleviated with acetaminophen. On physical examination, she was in no distress. Her height was 168 cm (78th percentile), and her weight was 104 kg (>97th percentile) with a BMI of 37 kg/m2 (>97th percentile). This was a 42% decrease from her preoperative weight and BMI of 179 kg and 64 kg/m2, respectively. There was no sensory deficit of the lower extremities to sharp stimulus or light touch. Her strength was excellent in all compartments of the upper and lower extremities. Her gait was normal. An upper gastrointestinal contrast study revealed stenosis at the gastro-jejunal anastomosis. The stenosis was treated with four serial endoscopic dilations (every 2 weeks) until the stenosis, dehydration, and hypokalemia had completely resolved.
DISCUSSION Overweight or obesity, defined in children as a BMI $95th percentile for age and sex, has been described by the World Health Organization as ‘‘one of today’s most blatantly visible—yet most neglected—public health problems.’’1 Fifteen percent of all children 6 to 19 years old are overweight.2 Obesity in children has been associated with type II diabetes mellitus,3 hypertension,4 and decreased quality of life.5 As the prevalence and severity of obesity have increased, so too has the need to consider more effective alternatives to standard weight management approaches. In adults, RYGBP typically results in the long-term loss of onethird of body weight and resolution of most comorbid conditions associated with severe obesity.6 During the first year after this procedure, patients typically consume between 500 and 1000 kcal per day and avoid simple carbohydrates because of the risk of dumping syndrome. The effectiveness of bariatric surgery in adults along with the increasing prevalence of clinically severe obesity among adolescents has led to an increase in the use of bariatric procedures for adolescents.7-9 Similar satisfactory outcomes have been observed in this age group10,11 as compared to adults. It is therefore important for pediatricians to recognize the risks, benefits, and potentially predictable side effects of gastric bypass. The differential diagnosis for the patients presented in this series, based on their presenting signs and symptoms, includes peripheral neuropathy as a result of nutritional 265
deficiency or multiple sclerosis; systemic lupus erythematosus; connective tissue disorder; pain amplification syndrome, including reflex sympathetic dystrophy and fibromyalgia; anxiety disorder; and conversion disorder. The diverse studies obtained in these patients allowed the differential diagnosis to be narrowed to a single entity. The response of each case to supplemental thiamine confirms the diagnosis of beriberi. Vitamin and mineral deficiencies have previously been reported with malabsorptive surgical procedures such as gastric bypass.12,13 The most common vitamin deficiencies include hypovitaminosis A, B12, C, D, E, folic acid, and iron.14-19 The likely mechanism for these deficiencies is thought to be malabsorption and/or decreased oral intake, including poor compliance with medications postoperatively. Beriberi is a clinical syndrome of thiamine (vitamin B1) deficiency. Thiamine is absorbed primarily in the jejunum and is required for carbohydrate metabolism. Thus, thiamine levels can be depleted after oral20 or intravenous21 carbohydrate intake. Thiamine deficiency can cause peripheral neurologic, cerebral, cardiologic, and gastrointestinal manifestations. ‘‘Dry’’ beriberi is a disease of bilateral, symmetric, lower extremity paresthesia, dysesthesia, and allodynia with decreased vibratory sensation and reflexes; dry beriberi is seen more commonly in patients with caloric restriction and relative inactivity.22 ‘‘Wet’’ beriberi is characterized by cardiac failure and edema, and is seen in patients with high carbohydrate intake and severe physical exertion. Cerebral beriberi (Wernicke-Korsakoff syndrome) has been reported after prolonged vomiting, starvation, and, most commonly, alcoholism.23,24 Peripheral neuropathy and Wernicke’s encephalopathy secondary to vitamin B1 deficiency have both been described in adults after gastric surgery and protracted vomiting.13,23,25-27 There are no previously reported cases of postsurgical beriberi in the pediatric population. Postsurgical beriberi has been successfully treated with parenteral doses of 50 to 200 mg vitamin B1 daily until symptoms have cleared, followed by daily oral supplementation.12,21 It is not clear in these three cases whether thiamine deficiency developed despite adequate oral intake (malabsorption) or because of inadequate compliance with recommended daily supplementation. In adults with an isocaloric diet, the stores of thiamine have been estimated to last 3 to 6 weeks.28 Deficiency of vitamin B1 has not been described when patients are adequately supplemented. In addition, there are limited data on vitamin stores in the morbidly obese either pre- or postsurgery.29 Thiamine plays a key role in metabolism of both simple sugars and keto acids. Thus, it is possible that patients with already low thiamine levels before surgery (as a result of a diet rich in simple sugars) have increased thiamine demands during their prolonged ketotic state following RYGBP. Vomiting and poor compliance with vitamin supplements after gastric bypass may therefore be important risk factors for depletion of already borderline thiamine stores. Because of these possibilities, our practice is now to begin daily multivitamin supplementation several months prior to gastric bypass, when patients are initially evaluated by the bariatric team. Following 266
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gastric bypass, we have also added a separate vitamin B complex supplement to the prescribed multivitamin and mineral regimen for all patients. The health benefits of significant and sustained weight reduction for the morbidly obese are incontrovertible. Surgical weight loss is, however, associated with some nutritional risks, and it is important for all healthcare workers to recognize the nutritional complications of bariatric surgery. Malnutrition and vitamin deficiencies are easy to overlook in obese persons, but nonetheless they may exist. Because of the possibility of vitamin deficiencies specifically in gastric bypass patients, a targeted review of systems during each visit might bring early attention to a developing micronutrient deficiency. Emphasis on compliance strategies, careful monitoring of vitamin and mineral intake, and periodic laboratory surveillance to detect vitamin deficiency is suggested. Moreover, the observations reported here further suggest that it may be wise to augment thiamine intake in adolescent bariatric patients above the usually recommended daily intake of 1.5 mg/day to further reduce the risk of deficiency syndrome. We acknowledge the expert dietary and nursing care provided to these patients by Shelley Kirk, PhD, RD, Michelle Frank, RD, Jenny Sweeney, MS, PNP, and Beverly Haynes, RN, BSN.
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23. Salas-Salvado J, Garcia-Lorda P, Cuatrecasas G, Bonada A, Formiguera X, Del Castillo D, et al. Wernicke’s syndrome after bariatric surgery. Clin Nutr 2000;19:371-3. 24. van den Berg H, van der Gaag M, Hendriks H. Influence of lifestyle on vitamin bioavailability. Int J Vitam Nutr Res 2002;72:53-9. 25. Iwase K, Higaki J, Yoon HE, Mikata S, Miyazaki M, Kamiike W. Reduced thiamine (vitamin B1) levels following gastrectomy for gastric cancer. Gastric Cancer 2002;5:77-82. 26. Maryniak O. Severe peripheral neuropathy following gastric bypass surgery for morbid obesity. Can Med Assoc J 1984;131:119-20. 27. Harwood SC, Chodoroff G, Ellenberg MR. Gastric partitioning complicated by peripheral neuropathy with lumbosacral plexopathy. Arch Phys Med Rehabil 1987;68:310-2. 28. Ziporin ZZ, Nunes WT, Powell RC, Waring PP, Sauberlich HE. Thiamine requirement in the adult human as measured by urinary excretion of thiamine metabolites. J Nutr 1965;85:297-304. 29. Boylan LM, Sugerman HJ, Driskell JA. Vitamin E, vitamin B-6, vitamin B-12, and folate status of gastric bypass surgery patients. J Am Diet Assoc 1988;88:579-85.
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