Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Nutritional Neuropathy Workup

  • Author: Jasvinder Chawla, MD, MBA; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
 
Updated: Dec 28, 2015
 

Laboratory Studies

The neuropathy first must be characterized as a polyneuropathy, mononeuropathy, mononeuropathy multiplex disease, or plexopathy; motor, sensory, sensorimotor, motor-sensory, or autonomic; acute or chronic; and of demyelinating or axonal pathophysiology. Readily apparent clues in the history can often suggest that the peripheral neuropathy might be secondary to nutritional problems; they are as follows:

  • Excessive consumption of alcohol
  • History of bariatric surgery, especially gastrectomy and intestinal shortening
  • History of GI syndromes indicating a predisposition toward malabsorption
  • History of using medications known to be associated with a vitamin deficiency (e.g., isoniazid)

Once the neuropathy is suspected to be nutritional in origin, the physician should first assess a possible vitamin B 12 deficiency (remembering that a CBC is not a good indicator). Documenting other B vitamin deficiencies is not as important because treatment replaces these vitamins anyway.

If history—which is the key to diagnosing a nutritional neuropathy—and physical are unrevealing, check CBC, urinalysis, thyroid-stimulating hormone (TSH), glucose, renal and hepatic functions, vitamin B 12 level, erythrocyte sedimentation rate (ESR), and serum protein electrophoresis, then order other tests, such as copper, as needed. Electrophysiologic findings can confirm the impression of polyneuropathy but rarely provide the diagnosis.

  • Alcohol neuropathy: CBC may show low platelet counts and a megaloblastic anemia due to decreased folate levels.
  • Thiamine (vitamin B 1 ) deficiency: A serum thiamine (vitamin B 1 ) level is not a good index because it responds quickly to dietary supplementation and because it is a poor indicator of total body stores. Urinary excretion of < 65 mg/g of creatinine is abnormal. A pyruvate level of >1 mg/dL is a reliable indicator of deficiency. The best test is erythrocyte transketolase activity; a concentration of < 0.017 U/dL indicates deficiency.
  • Pyridoxine (vitamin B 6 ) deficiency: The CBC shows a microcytic, hypochromic anemia with normal iron levels. Serum pyridoxine levels are < 25 mg/mL, and serum homocysteine and cysathioprine values should be elevated. A tryptophan-loading test (not commonly performed) reveals urinary xanthurenic acid excretion of >50 mg/d.
  • Folate deficiency: Serum folate levels are low.
  • Niacin (vitamin B 3 ) deficiency: Urinary excretion of N -methylnicotinamide + N -methyl-6-pyridone-3-carboxamide is < 2 mg, or urinary excretion of N -methylnicotinamide is < 0.5 mg/g creatinine. Performing a stress test is possible by giving niacin 10 mg and tryptophan 100 mg. If urinary excretion of niacin metabolites is < 3 mg, a deficiency is present.
  • Cyanocobalamin (vitamin B 12 ) deficiency: The CBC may show mean corpuscular volume (MCV) >110 fL (ie, macrocytic anemia), anisocytosis, poikilocytosis, and large and oval erythrocytes with decreased reticulocyte, leukocyte, and platelet counts. However, the neuropathy may precede any hematologic abnormalities in 25% of patients. The serum cobalamin level is < 10 mg/dL but may be normal, even in those with a tissue cobalamin deficit. Serum homocysteine and methylmalonic acid levels are elevated, as is urinary methylmalonic acid excretion. Serum holotranscobalamin II is deficient. Intrinsic factor antibodies are specific for pernicious anemia but not very sensitive (40% negative). The traditional Schilling test is now rarely used.
  • Pantothenic acid deficiency: Excretion is < 1 mg/d.
  • Alpha-tocopherol (vitamin E) deficiency: The serum α -tocopherol (vitamin E) level is low, and the CBC shows acanthocytes. Normal serum α -tocopherol levels in an adult with symptoms consistent with Friedreich ataxia should prompt an investigation for an autosomal recessive defect in the tocopherol transporter protein gene on chromosome 8.
  • Hypophosphatemia: Serum phosphate level is < 1 mg/dL.
  • Gluten-sensitive neuropathy: Anti-gliadin antibodies, either IgM or IgA should be present. 90% have HLA DQ2. Intestinal biopsy is abnormal in only 35%.
Next

Imaging Studies

Imaging studies are generally not useful. In thiamine deficiency, MRIs occasionally show abnormal signal intensity in periaqueductal gray matter and midline structures.

Radiographs of chronic peripheral neuropathies are often consistent with the picture of a diabetic foot.

Previous
Next

Other Tests

Axonal loss manifests as a mild slowing of the nerve conduction velocity (NCV) with a disproportionate loss of amplitude. Demyelination, on the other hand, produces mild loss of amplitude with a disproportionate slowing of the NCV. In affected motor fibers, electromyography (EMG) shows fibrillations, positive sharp waves, and decreased motor unit potentials. EMG and NCV are useful to assess the degree of damage and monitor progression of the neuropathy.

  • Thiamine (vitamin B 1 ) deficiency: EMG and nerve conduction studies reveal a generalized axonal sensorimotor polyneuropathy with denervation of the distal lower extremity musculature; at times some subtle demyelinating features may be present.
  • Niacin (vitamin B 3 ): EMG and NCV show demyelination in mild cases and axonal degeneration in severe cases.
  • Alpha-tocopherol (vitamin E) deficiency: Peripheral nerve conduction findings are normal. Sensory evoked potentials are low or absent. Somatosensory evoked potentials show a delay in central conduction. EMG findings are normal.

Sensorineural hearing loss: Audiometry shows high-tone hearing loss.

Alcohol: The CSF protein level on lumbar puncture is normal or slightly elevated.

Previous
Next

Histologic Findings

A biopsy is not indicated unless the diagnosis is in doubt. If so, biopsy is indicated only if the neuropathy is multifocal or asymmetric, or if the patient has multiple mononeuropathies. The best nerve to biopsy is the sural nerve, lateral to the lateral malleolus. In general, sural nerve biopsy is of limited use in differentiating various types of nutritional neuropathy, but it can help in distinguishing hereditary neuropathy, neuropathy caused by organic solvents, leprosy, amyloidosis, polyarteritis nodosa, or sarcoidosis, and it is occasionally useful in evaluating Guillain-Barré syndrome. Nutritional neuropathies can result in either demyelinating or axonal peripheral nerve pathology.

Previous
 
 
Contributor Information and Disclosures
Author

Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center

Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, MHA, CPE Founding Editor-in-Chief, eMedicine Neurology; Founder and CEO/CMO, PHLT Consultants; Chief Medical Officer, MeMD Inc

Nicholas Lorenzo, MD, MHA, CPE is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American Academy of Neurology

Disclosure: Nothing to disclose.

Additional Contributors

Milind J Kothari, DO Professor, Department of Neurology, Pennsylvania State University College of Medicine; Consulting Staff, Department of Neurology, Penn State Milton S Hershey Medical Center

Milind J Kothari, DO is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Lawrence D Recht, MD Professor of Neurology and Neurosurgery, Department of Neurology and Clinical Neurosciences, Stanford University Medical School

Lawrence D Recht, MD is a member of the following medical societies: American Academy of Neurology, American Association for Cancer Research, American Neurological Association, and Society for Neuroscience

Disclosure: Nothing to disclose.

R Andrew Sewell, MD Associate Research Scientist in Psychiatry and Mental Illness Research, Education,Veterans Affairs Connecticut Health Care System, Yale University School of Medicine

R Andrew Sewell, MD is a member of the following medical societies: American Academy of Neurology, American Headache Society, American Pain Society, and American Psychiatric Association

Disclosure: Nothing to disclose.

References
  1. Poitou Bernert C, Ciangura C, Coupaye M, Czernichow S, Bouillot JL, Basdevant A. Nutritional deficiency after gastric bypass: diagnosis, prevention and treatment. Diabetes Metab. 2007 Feb. 33(1):13-24. [Medline].

  2. Prodan CI, Bottomley SS, Vincent AS, Cowan LD, Greenwood-Van Meerveld B, Holland NR. Copper deficiency after gastric surgery: a reason for caution. Am J Med Sci. 2009 Apr. 337(4):256-8. [Medline].

  3. Menezes MS, Harada KO, Alvarez G. Painful peripheral polyneuropathy after bariatric surgery. Case reports. Rev Bras Anestesiol. 2008 May-Jun. 58(3):252-9. [Medline].

  4. Thaisetthawatkul P, Collazo-Clavell ML, Sarr MG, Norell JE, Dyck PJ. A controlled study of peripheral neuropathy after bariatric surgery. Neurology. 2004 Oct 26. 63(8):1462-70. [Medline].

  5. Becker DA, Balcer LJ, Galetta SL. The Neurological Complications of Nutritional Deficiency following Bariatric Surgery. J Obes. 2012. 2012:608534. [Medline]. [Full Text].

  6. Bibile SW, Lionel ND, Dunuwille R, Perera G. Pantothenol and the burning feet syndrome. Br J Nutr. 1957. 11(4):434-9. [Medline].

  7. Carpenter KJ. The discovery of thiamin. Ann Nutr Metab. 2012. 61(3):219-23. [Medline].

  8. Jolliffe N. The Diagnosis, Treatment, and Prevention of Vitamin B1 Deficiency. Bull N Y Acad Med. 1939 Jul. 15(7):469-78. [Medline]. [Full Text].

  9. Chopra K, Tiwari V. Alcoholic neuropathy: possible mechanisms and future treatment possibilities. Br J Clin Pharmacol. 2012 Mar. 73(3):348-62. [Medline]. [Full Text].

  10. Mellion M, Gilchrist JM, de la Monte S. Alcohol-related peripheral neuropathy: nutritional, toxic, or both?. Muscle Nerve. 2011 Mar. 43(3):309-16. [Medline].

  11. Essa E, Velez MR, Smith S, Giri S, Raman SV, Gumina RJ. Cardiovascular magnetic resonance in wet beriberi. J Cardiovasc Magn Reson. 2011 Aug 12. 13:41. [Medline]. [Full Text].

  12. Hadjivassiliou M, Rao DG, Wharton SB, Sanders DS, Grünewald RA, Davies-Jones AG. Sensory ganglionopathy due to gluten sensitivity. Neurology. 2010 Sep 14. 75(11):1003-8. [Medline].

  13. Shen TC, Lebwohl B, Verma H, Kumta N, Tennyson C, Lewis S, et al. Peripheral neuropathic symptoms in celiac disease and inflammatory bowel disease. J Clin Neuromuscul Dis. 2012 Mar. 13(3):137-45. [Medline].

  14. Gill GV, Bell DR. Persisting nutritional neuropathy amongst former war prisoners. J Neurol Neurosurg Psychiatry. 1982 Oct. 45(10):861-5. [Medline]. [Full Text].

  15. Thaisetthawatkul P, Collazo-Clavell ML, Sarr MG, Norell JE, Dyck PJ. A controlled study of peripheral neuropathy after bariatric surgery. Neurology. 2004 Oct 26. 63(8):1462-70. [Medline].

  16. Kesler A, Pianka P. Toxic optic neuropathy. Curr Neurol Neurosci Rep. 2003 Sep. 3(5):410-4. [Medline].

  17. Kesler A, Pianka P. Toxic optic neuropathy. Curr Neurol Neurosci Rep. 2003 Sep. 3(5):410-4. [Medline].

  18. Chiotoroiu SM, Noaghi M, Stefaniu GI, Secureanu FA, Purcarea VL, Zemba M. Tobacco-alcohol optic neuropathy--clinical challenges in diagnosis. J Med Life. 2014 Oct-Dec. 7 (4):472-6. [Medline].

  19. Chang CG, Adams-Huet B, Provost DA. Acute post-gastric reduction surgery (APGARS) neuropathy. Obes Surg. 2004 Feb. 14(2):182-9. [Medline].

  20. Tanyel MC, Mancano LD. Neurologic findings in vitamin E deficiency. Am Fam Physician. 1997 Jan. 55(1):197-201. [Medline].

  21. Tanyel MC, Mancano LD. Neurologic findings in vitamin E deficiency. Am Fam Physician. 1997 Jan. 55(1):197-201. [Medline].

  22. Diamond I, Messing RO. Neurologic effects of alcoholism. West J Med. 1994 Sep. 161(3):279-87. [Medline].

  23. Erbsloh F, Abel M. Deficiency neuropathies. Bruyn GW, Vinken PJ, eds. Handbook of Clinical Neurology. Vol 7: Diseases of Nerves, Part I. New York: Wiley Interscience Division; 1970. 558-638.

  24. Forbes CD, Jackson WF. A Colour Atlas and Text of Clinical Medicine. Aylesbury: Hazell Books Ltd; 1993: 428.

  25. Gill GV, Bell DR. Persisting nutritional neuropathy amongst former war prisoners. J Neurol Neurosurg Psychiatry. 1982 Oct. 45(10):861-5. [Medline]. [Full Text].

  26. Hattori N, Koike H, Sobue G. [Metabolic and nutritional neuropathy]. Rinsho Shinkeigaku. 2008 Nov. 48(11):1026-7. [Medline].

  27. Koike H, Sobue G. Alcoholic neuropathy. Curr Opin Neurol. 2006 Oct. 19(5):481-6. [Medline].

  28. Kumar N. Copper deficiency myelopathy (human swayback). Mayo Clin Proc. 2006 Oct. 81(10):1371-84. [Medline].

  29. Le Quesne PM. Persisting nutritional neuropathy in former war prisoners. Br Med J (Clin Res Ed). 1983 Mar 19. 286(6369):917-8. [Medline].

  30. Li K, McKay G. Images in clinical medicine. Ischemic retinopathy caused by severe megaloblastic anemia. N Engl J Med. 2000 Mar 23. 342(12):860. [Medline].

  31. Pallis CA. Neurological manifestations of nutritional disorders. Practitioner. 1974 Apr. 212(1270 Spec No):509-17. [Medline].

  32. Theodoropoulos DS. Optic neuropathy in vitamin B12 deficiency [letter; comment]. Lancet. 1998 Jul 11. 352(9122):146-7. [Medline].

  33. Weber GA, Sloan P, Davies D. Nutritionally-induced peripheral neuropathies. Clin Podiatr Med Surg. 1990 Jan. 7(1):107-28. [Medline].

 
Previous
Next
 
Pernicious anemia. Characteristic lemon-yellow–tinged pallor with raw-beef tongue lacking filiform papillae. Used with permission from Forbes and Jackson.
Ischemic retinopathy caused by severe megaloblastic anemia.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.