Screening and assessment of polyneuropathy in adult patients and the effect of folic acid administration on the course of neuropathy

Namrata Pawar, Uma Bhosale


Background: Multiple nerves damage (polyneuropathy) characterized by symmetrical sensory symptoms, such as numbness, paraesthesia, pain, andweakness predominantly in distal parts and pathophysiology depends on the underlying disease. Folic acid, (vitamin B9) deficiency causes many neurodegenerative and cerebrovascular diseases. Supplementation enhances neurodevelopment and provides neuroprotection in someneurological diseases by growth, differentiation and regeneration of the CNS.

Methods: Prospective open-label study included 60 patients visiting at tertiary care hospital of either sex with an age range between 18 to 70 years. We evaluated the role of folic acid in the course of neuropathy in all enrolled patients using various neuropathy scores like diabetic neuropathy symptom questionnaire, survey of autonomic symptoms questionnaire, neuropathy deficit (or disability) score, standardized nerve conduction studies and cardiac autonomic reflex test.

Results: NCV in the diabetic and alcoholic patients was statistically significant in almost all motor and sensory nerves in both upper and lower limb. In epileptic patients, was more significant in the lower limb in both motor and sensory nerves. In nutritional deficient patients was significant in only 2 nerves. In the diabetic patient, we also observed significance in DNS questionnaire (0.017).

Conclusions: Since folate is effective, cheap, treatment and, devoid of apparent toxicity for this obscure, chronic, neurological disorders would be agent justified. A significant improvement in the results was seen majorly in diabetic group, thus can be included for them.


Polyneuropathy, Folic acid, NCV, Diabetes

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England JD, Asbury AK. Peripheral neuropathy. Lancet Lond Engl. 2004;363(9427):2151-61.

Teunissen LL, Eurelings M, Notermans NC, Hop JW, van Gijn J. Quality of life in patients with axonal polyneuropathy. J Neurol. 2000;247(3):195-9.

Hanewinckel R, van Oijen M, Ikram MA, van Doorn PA. The epidemiology and risk factors of chronic polyneuropathy. Eur J Epidemiol. 2016;31(1):5-20.

Kang W-B, Chen Y-J, Lu D-Y, Yan J-Z. Folic acid contributes to peripheral nerve injury repair by promoting Schwann cell proliferation, migration, and secretion of nerve growth factor. Neural Regen Res. 2019;14(1):132-9.

Ma W, Xiang L, Yu H-L, Yuan L-H, Guo A-M, Xiao Y-X, et al. Neuroprotection of soyabean isoflavone co-administration with folic acid against beta-amyloid 1-40-induced neurotoxicity in rats. Br J Nutr. 2009;102(4):502-5.

Manschot SM, Biessels GJ, Rutten GEHM, Kessels RPC, Kessels RCP, Gispen WH, et al. Peripheral and central neurologic complications in type 2 diabetes mellitus: no association in individual patients. J Neurol Sci. 2008;264(1-2):157-62.

Koike H, Takahashi M, Ohyama K, Hashimoto R, Kawagashira Y, Iijima M, et al. Clinicopathologic features of folate-deficiency neuropathy. Neurology. 2015;84(10):1026-33.

Strachan RW, Henderson JG. Dementia and folate deficiency. Q J Med. 1967;36(142):189-204.

Botez MI, Fontaine F, Botez T, Bachevalier J. Folate-responsive neurological and mental disorders: report of 16 cases. Neuropsychological correlates of computerized transaxial tomography and radionuclide cisternography in folic acid deficiencies. Eur Neurol. 1977;16(1-6):230-46.

Reynolds EH, Rothfeld P, Pincus JH. Neurological disease associated with folate deficiency. Br Med J. 1973;2(5863):398–400.

Longo DL, editor. Harrison’s principles of internal medicine. 18th ed. New York: McGraw-Hill; 2012.

Balashova OA, Visina O, Borodinsky LN. Folate action in nervous system development and disease. Dev Neurobiol. 2018;78(4):391-402.

Yilmaz M, Aktug H, Oltulu F, Erbas O. Neuroprotective effects of folic acid on experimental diabetic peripheral neuropathy. Toxicol Ind Health. 2016;32(5):832-40.

Mottaghi T, Khorvash F, Maracy M, Bellissimo N, Askari G. Effect of folic acid supplementation on nerve conduction velocity in diabetic polyneuropathy patients. Neurol Res. 2019;41(4):364-8.

Meijer JWG, Smit AJ, Sonderen EV, Groothoff JW, Eisma WH, Links TP. polyneuropathy in diabetes: the Diabetic Neuropathy Symptom score. Br Med J. 2002;6:52-9.

Zilliox L, Peltier AC, Wren PA, Anderson A, Smith AG, Singleton JR, et al. Assessing autonomic dysfunction in early diabetic neuropathy. Neurology. 2011;76(12):1099-105.

Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993;36(2):150-4.

Abbott CA, Carrington AL, Ashe H, Bath S, Every LC, Griffiths J, et al. The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort. Diabet Med J Br Diabet Assoc. 2002;19(5): 377-84.

Yajnik CS, Kantikar V, Pande A, Deslypere J-P, Dupin J, Calvet J-H, et al. Screening of cardiovascular autonomic neuropathy in patients with diabetes using non-invasive quick and simple assessment of sudomotor function. Diabetes Metab. 2013;39(2):126-31.

Iskandar BJ, Nelson A, Resnick D, Skene JHP, Gao P, Johnson C, et al. Folic acid supplementation enhances repair of the adult central nervous system. Ann Neurol. 2004;56(2):221-7.

Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058-70.

Koike H, Hama T, Kawagashira Y, Hashimoto R, Tomita M, Iijima M, et al. The significance of folate deficiency in alcoholic and nutritional neuropathies: Analysis of a case. Nutrition. 2012;28(7-8):821-4.

Ojeda ML, Rua RM, Nogales F, Díaz-Castro J, Murillo ML, Carreras O. The benefits of administering folic acid in order to combat the oxidative damage caused by binge drinking in adolescent rats. Alcohol Alcohol. 2016;51(3):235-41.

Martinez Figueroa A, Johnson RH, Lambie DG, Shakir RA. The role of folate deficiency in the development of peripheral neuropathy caused by anticonvulsants. J Neurol Sci. 1980;48(3):315-23.

Bhosale UA, Yegnanarayan R, Agrawal A, Patil A. Efficacy study of folic acid supplementation on homocysteine levels in adolescent epileptics taking antiepileptic drugs: a single blind randomized controlled clinical trial. Ann Neurosci. 2019;26(3-4):50-4.

Botez MI, Peyronnard JM, Bachevalier J, Charron L. Polyneuropathy and folate deficiency. Arch Neurol. 1978;35(9):581-4.

Koike H, Takahashi M, Ohyama K, Hashimoto R, Kawagashira Y, Iijima M, et al. Clinicopathologic features of folate-deficiency neuropathy. Neurology. 2015;84(10):1026-33.

Yukawa M, Naka H, Murata Y, Katayama S, Kohriyama T, Mimori Y, et al. Folic acid-responsive neurological diseases in Japan. J Nutr Sci Vitaminol (Tokyo). 2001;47(3):181-7.

Green R, Miller JW. Folate deficiency beyond megaloblastic anemia: hyperhomocysteinemia and other manifestations of dysfunctional folate status. SeminHematol. 1999;36(1):47-64.

Iskandar BJ, Nelson A, Resnick D, Skene JHP, Gao P, Johnson C, et al. Folic acid supplementation enhances repair of the adult central nervous system. Ann Neurol. 2004;56(2):221-7.