How to diagnose neuropathy in diabetes mellitus?

Abstract

Diabetic neuropathy is a common problem and can present various clinical presentations such as cranial neuropathy, radiculopathy, plexopathy, mononeuropathy, polyneuropathy and autonomic neuropathy. Clinical evaluation and use of scoring systems for the evaluation of diabetic polyneuropathy is an important step to get correct diagnosis. New informations about the diagnosis of diabetic neuropathy continue to emerge, which will lead to correct diagnosis and treatment as well. Diabetic length-dependent sensorimotor polyneuropathy (DSPN) and carpal tunnel syndrome are the most common seen problems. While acute and painful situations with motor weakness are mostly transient, sensory fibres are predominantly involved in chronic ones. Nerve conduction studies are needed to confirm diagnosis of any type of diabetic neuropathy, but they are normal in cases with small fiber involvement. The early diagnosis is crucial because it is well-known that subclinical diabetic neuropathy may be reversed or significantly improved with diabetes control. Because neuropathy at the stage in which only small fibers are affected can be reversed, it is important to diagnose DSPN in these stages. Skin biopsy taken from the dermatomal area of sural nerve, laser-doppler-imager flare technique, corneal confocal microscopy are used to assess small fibre dysfunction. The aim of the present review was to evaluate evidence-based diagnosis for any type of neuropathy seen in the patients with diabetes mellitus.

Keywords

• length-dependent sensorimotor polyneuropathy,small fiber,nerve conduction studies,neuropathic pain,scoring systems,diabetes mellitus

References

1. [1] Deli G, Bosnyak E, Pusch G, Komoly S, Feher G. Diabetic neuropathies: diagnosis and management. Neuroendocrinology 2013;98:267-80.
2. [2] Thomas PK. Classification, differential diagnosis and staging of diabetic peripheral neuropathy. Diabetes 1997;46:54-7.
3. [3] Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, et al.; American Diabetes Association. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 2005;28:956-62.
4. [4] Gupta A, Gupta Y. Diabetic neuropathy: Part 1. J Pak Med Assoc 2014;64:714-8.
5. [5] Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 1993;43:817-24.
6. [6] Pasnoor M, Dimachkie MM, Kluding P, Barohn RJ. Diabetic neuropathy part 1: overview and symmetric phenotypes. Neurol Clin 2013;31:425-45.
7. [7] Tesfaye S, Boulton AJM, Dyck PJ, Freeman R, Horowitz M, Kempler P, et al.; Toronto Diabetic Neuropathy Expert Group. Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments. Diabetes Care 2010;33:2285-93.
8. [8] Dyck PJ, Davies JL, Clark VM, Litchy WJ, Dyck PJ, Klein CJ, et al. Modeling chronic glycemic exposure variables as correlates and predictors of microvascular complications of diabetes. Diabetes Care 2006;29:2282-8.

9. [9] Ali A, Iqbal F, Taj A, Iqbal Z, Amin MJ, Iqbal QZ. Prevalence of microvascular complications in newly diagnosed patients with type 2 diabetes. Pak J Med Sci 2013;29: 899-902.
10. [10] Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53.
11. [11] Zilliox L, Russell JW. Treatment of diabetic sensory polyneuropathy. Curr Treat Options Neurol 2011;13:143-59.
12. [12] Smith AG, Russell J, Feldman EL, Goldstein J, Peltier A, Smith S, et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care 2006;29:1294-9.
13. [13] Albers JW, Herman WH, Pop-Busui R, Martin CL, Cleary P, Waberski B; Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) Research Group. Subclinical neuropathy among Diabetes Control and Complications Trial participants without diagnosable neuropathy at trial completion: possible predictors of incident neuropathy? Diabetes Care 2007;30:2613-8.
14. [14] Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008;70:1630-5.
15. [15] Tesfaye S, Selvarajah D. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev 2012;28:8-14.
16. [16] Bril V, Perkins BA. Validation of the Toronto Clinical Scoring System for diabetic polyneuropathy. Diabetes Care 2002;25:2048-52.
17. [17] Meijer JWG, van Sonderen E, Blaauwwiekel EE, Smit AJ, Groothoff JW, Eisma WH, et al. Diabetic neuropathy examination: A hierarchical scoring system to diagnose distal polyneuropathy in diabetes. Diabetes Care 2000;23:750-3.
18. [18] Meijer JW, Smit AJ, Sonderen EV, Groothoff JW, Eisma WH, Links TP. Symptom scoring systems to diagnose distal polyneuropathy in diabetes: The Diabetic Neuropathy Symptom score. Diabet Med 2002;19:962-5.
19. [19] Shehab DK, Al-Jarallah KF, Abraham M, Mojiminiyi OA, Al-Mohamedy H, Abdella NA. Back to basics: ankle reflex in the evaluation of peripheral neuropathy in type 2 diabetes mellitus. QJM 2012;105:315-20.
20. [20] Vrancken AF, Kalmijn S, Brugman F, Rinkel GJ, Notermans NC. The meaning of distal sensory loss and absent ankle reflexes in relation to age: a meta-analysis. J Neurol 2006;253:578-89.
21. [21] Mold JW, Vesely SK, Keyl BA, Schenk JB, Roberts M. The prevalence, predictors, and consequences of peripheral sensory neuropathy in older patients. J Am Board Fam Pract 2004;17:309-18.
22. [22] Siao P, Cros DP. Quantitative sensory testing. Phys Med Rehabil Clin N Am 2003;14:261-86.
23. [23] Perkins BA, Olaleye D, Zinman B, Bril V. Simple screening tests for peripheral neuropathy in the diabetes clinic. Diabetes Care 2001;24:250-6.
24. [24] Krishnan STM, Quattrini C, Jeziorska M, Malik RA, Rayman G. Abnormal LDIflare but Normal Quantitative Sensory Testing and Dermal Nerve Fiber Density in Patients with Painful Diabetic Neuropathy. Diabetes Care 2009;32:451-5.
25. [25] Feng Y, Schlösser FJ, Sumpio BE. The Semmes Weinstein monofilament examination is a significant predictor of the risk of foot ulceration and amputation in patients with diabetes mellitus. J Vasc Surg 2011;53:220-6.
26. [26] Feng Y, Schlösser FJ, Sumpio BE. The Semmes Weinstein monofilament examination as a screening tool for diabetic peripheral neuropathy. J Vasc Surg 2009;50:675-82.
27. [27] Cheng WY, Jiang YD, Chuang LM, Huang CN, Heng LT, Wu HP, et al. Quantitative sensory testing and risk factors of diabetic sensory neuropathy. J Neurol 1999;246:394-8.
28. [28] Smieja M, Hunt DL, Edelman D, Etchells E, Cornuz J, Simel D L.; for the International Cooperative Group for Clinical Examination Research. Clinical examination for the detection of protective sensation in the feet of diabetic patients. J Gen Intern Med 1999;14:418-24.
29. [29] Blankenburg M, Boekens H, Hechler T, Maier C, Krumova E, Scherens A, et al. Reference values for quantitative sensory testing in children and adolescents: developmental and gender differences of somatosensory perception. Pain 2010;149:76-88.
30. [30] Davis EA, Jones TW, Walsh P, Byrne GC. The use of biothesiometry to detect neuropathy in children and adolescents with IDDM. Diabetes Care 1997;20:1448-53.
31. [31] Hirschfeld G, von Glischinski M, Blankenburg M, Zernikow B. Screening for peripheral neuropathies in children with diabetes: a systematic review. Pediatrics 2014;133:1324-30.
32. [32] Kaku M, Vinik A, Simpson DM. Pathways in the diagnosis and management of diabetic polyneuropathy. Curr Diab Rep 2015;15:35.
33. [33] Oyer D, Saxon D, Shah A. Quantitative assessment of diabetic peripheral neuropathy with use of the clanging tuning fork test. Endocr Pract 2007;13:5-10.
34. [34] Rolke R, Baron R, Maier C, Tölle TR, Treede RD, Beyer A, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006;123:231-43.
35. [35] Shukla G, Bhatia M, Behari M. Quantitative thermal sensory testing - value of testing for both cold and warm sensation detection in evaluation of small fiber neuropathy. Clin Neurol Neurosurg 2009;107:486-90.
36. [36] Hoeijmakers JG, Faber CG, Lauria G, Merkies IS, Waxman SG. Small fibre neuropathies--advances in diagnosis, pathophysiology and management. Nat Rev Neurol 2012;8:369-79.
37. [37] Mueller D, Obermann M, Koeppen S, Kavuk I, Yoon MS, Sack F, et al .Electrically evoked nociceptive potentials for early detection of diabetic small-fiber neuropathy. Eur J Neurol 2010;17:834-41.
38. [38] Smieja M, Hunt DL, Edelman D, Etchells E, Cornuz J, Simel DL.; for the International Cooperative Group for Clinical Examination Research. Clinical examination for the detection of protective sensation in the feet of diabetic patients. J Gen Intern Med 1999;14:418-24.
39. [39] Jiang MS, Yuan Y, Gu ZX, Zhuang SL. Corneal confocal microscopy for assessment of diabetic peripheral neuropathy: a meta-analysis. Br J Ophthalmol 2016;100:9-14.
40. [40] Tavakoli M, Petropoulos IN, Malik RA. Assessing corneal nerve structure and function in diabetic neuropathy. Clin Exp Optom 2012;95:338-47.
41. [41] Devigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain 2008;131:1912-25.
42. [42] Lauria G, Cornblath DR, Johansson O, McArthur JC, Mellgren SI, Nolano M, et al. EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol 2005;12:747-58.
43. [43] Gibbons CH, Griffin JW, Polydefkis M, Bonyhay I, Brown A, Hauer PE, et al. The utility of skin biopsy for prediction of progression in suspected small fiber neuropathy. Neurology 2006;66:256-8.
44. [44] Sommer C, Lauria G. Skin biopsy in the management of peripheral neuropathy. Lancet Neurol 2007;6:632-42.
45. [45] Krishnan ST, Rayman G. The LDIflare: a novel test of C-fiber function demonstrates early neuropathy in type 2 diabetes. Diabetes Care 2004;27:2930-5.
46. [46] Votrubec M, Thong I. Neuropathic pain - a management update. Aust Fam Physician 2013;42:92-7.
47. [47] Spallone V, Morganti R, D'Amato C, Greco C, Cacciotti L, Marfia GA. Validation of DN4 as a screening tool for neuropathic pain in painful diabetic polyneuropathy. Diabet Med 2012;29:578-85.
48. [48] Russell JW, Zilliox L. Diabetic neuropathies. Continuum (Minneap Minn) 2014;20:1226-40.
49. [49] Barrett AM, Lucero MA, Le T, Robinson RL, Dworkin RH, Chappell AS. Epidemiology, public health burden, and treatment of diabetic peripheral neuropathic pain: a review. Pain Med 2007;8:50-62.
50. [50] Kaku M, Vinik A, Simpson DM. Pathways in the diagnosis and management of diabetic polyneuropathy. Curr Diab Rep 2015;15:35.
51. [51] Sharma KR, Cross J, Farronay O, Ayyar DR, Shebert RT, Bradley WG. Demyelinating neuropathy in diabetes mellitus. Arch Neurol 2002;59:758-65.
52. [52]Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, et al. Toronto Diabetic Neuropathy Expert Group: Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 2010;33:2285-93.
53. [53] Dyck PJ. Severity and staging of diabetic polyneuropathy. In: Gries FA, Cameron NE, Low PA, et al., eds. Textbook of Diabetic Neuropathy. Stuttgart, Germany: Thieme; 2003;170-5.
54. [54] Vinik AI, Mehrabyan A. Diabetic neuropathies. Med Clin North Am 2004;88:947-99.
55. [55] Hoeijmakers JG, Faber CG, Lauria G, Merkies IS, Waxman SG. Small fibre neuropathies--advances in diagnosis, pathophysiology and management. Nat Rev Neurol 2012;8:369-79.
56. [56] Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA 2005;293:217-28.
57. [57] Edwards JL, Vincent AM, Cheng HT, Feldman EL. Diabetic neuropathy: mechanisms to management. Pharmacol Ther 2008;120:1-34.
58. [58] Tesfaye S. Advances in the management of diabetic peripheral neuropathy. Curr Opin Support Palliat Care 2009;3:136-43.
59. [59] Zilliox LA, Ruby SK, Singh S, Zhan M, Russell JW. Clinical neuropathy scales in neuropathy associated with impaired glucose tolerance. J Diabetes Complications 2015;29:372-7.
60. [60] Boulton AJ, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freeman R, et al.; American Diabetes Association Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 2005;28:956-2.
61. [61] Hartemann A, Attal N, Bouhassira D, Dumont I, Gin H, Jeanne S, Said G, Richard JL; Working Group on the Diabetic Foot from the French-speaking Society of Diabetology: Painful diabetic neuropathy: diagnosis and management. Diabetes Metab 2011;37:377-88.
62. [62] Apfel SC, Asbury AK, Bril V, Burns TM, Campbell JN, Chalk CH, et al. Positive neuropathic sensory symptoms as endpoints in diabetic neuropathy trials. J Neurol Sci 2001;189:3-5.
63. [63] Papanas N, Vinik AI, Ziegler D. Neuropathy in prediabetes: does the clock start ticking early? Nat Rev Endocrinol 2011;7:682-90.
64. [64] Dyck PJ, Albers JW, Andersen H, Arezzo JC, Biessels GJ, Bril V, et al. Toronto Expert Panel on Diabetic Neuropathy. Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev 2011;27:620-8.
65. [65] Pasnoor M, Dimachkie MM, Kluding P, Barohn RJ. Diabetic neuropathy part 1: overview and symmetric phenotypes. Neurol Clin 2013;31:425-45.
66. [66] Said G, Goulon-Goeau C, Slama G, Tchobroutsky G. Severe early-onset polyneuropathy in insulin-dependent diabetes mellitus. A clinical pathological study. N Engl J Med. 1992;326:1257-63.
67. [67] Stewart JD, McKelvey R, Durcan L, Carpenter S, Karpati G. Chronic inflammatory demyelinating polyneuropathy (CIDP) in diabetics. J Neurol Sci 1996;142:59-64.
68. [68] Uncini A, De Angelis MV, Di Muzio A, Callegarini C, Ciucci G, Antonini G, et al. Chronic inflammatory demyelinating polyneuropathy in diabetics: motor conductions are important in the differential diagnosis with diabetic polyneuropathy. Clin Neurophys 1999;110:705-11.
69. [69] Jaradeh SS, Prieto TE, Lobeck LJ. Progressive polyradiculoneuropathy in diabetes: correlation of variables and clinical outcome after immunotherapy. J Neurol Neurosurg Psychiatry 1999;67:607-12.
70. [70] Singleton JR, Bixby B, Russell JW, Feldman EL, Peltier A, Goldstein J, et al. The Utah Early Neuropathy Scale: a sensitive clinical scale for early sensory predominant neuropathy. J Peripher Nerv Syst 2008;13:218-27.
71. [71] Dyck PJ, Davies JL, Litchy WJ, O'Brien PC. Longitudinal assessment of diabetic polyneuropathy using a composite score in the Rochester Diabetic Neuropathy Study cohort. Neurology 1997;49:229-39.
72. [72] Xiong Q, Lu B, Ye H, Wu X, Zhang T, Li Y. The Diagnostic Value of Neuropathy Symptom and Change Score, Neuropathy Impairment Score and Michigan Neuropathy Screening Instrument for Diabetic Peripheral Neuropathy. Eur Neurol 2015;74:323-7.
73. [73] Cruccu G, Sommer C, Anand P, Attal N, Baron R, Garcia-Larrea L, et al. EFNS guidelines on neuropathic pain assessment: revised 2009. Eur J Neurol 2010;17:1010-8.
74. [74] Smith AG, Singleton JR. Diabetic neuropathy. Continuum (Minneap Minn) 2012;18:60-84.
75. [75] Hartemann A, Attal N, Bouhassira D, Dumont I, Gin H, Jeanne S, et al.; Working Group on the Diabetic Foot from the French-speaking Society of Diabetology: Painful diabetic neuropathy: diagnosis and management. Diabetes Metab 2011;37:377-88.
76. [76] Dyck PJ, Lais A, Karnes JL, O'Brien P, Rizza R. Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy. Ann Neurol 1986;19:425-39.
77. [77] Greene DA, Stevens MJ, Feldman EL. Diabetic neuropathy: scope of the syndrome. Am J Med 1999;107(2B):2-8.
78. [78] Tavee J, Zhou L. Small fiber neuropathy: a burning problem. Cleve Clin J Med 2009;76:297-305.
79. [79] Devigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain 2008;131:1912-25.
80. [80] Solomon LR. Diabetes as a cause of clinically significant functional cobalamin deficiency. Diabetes Care 2011;34:1077-80.
81. [81] Bell DS. Metformin-induced vitamin B12 deficiency presenting as a peripheral neuropathy. South Med J 2010;103:265-7.
82. [82] Leishear K, Boudreau RM, Studenski SA, Ferrucci L, Rosano C, de Rekeneire N, et al. Relationship between vitamin B12 and sensory and motor peripheral nerve function in older adults. J Am Geriatr Soc 2012;60:1057-63.
83. [83] Young RJ, Ewing DJ, Clarke BF. Chronic and remitting painful diabetic polyneuropathy. Correlations with clinical features and subsequent changes in neurophysiology. Diabetes Care 1988;11:34-40.
84. [84] England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, et al. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology 2009;72:185-92.
85. [85] D'Costa DF, Price DE, Burden AC. Diabetic neuropathic cachexia associated with malabsorption. Diabetic Med 1992;9:203-5.
86. [86] Wright DL, Shah JH. Diabetic neuropathic cachexia and hypothyroidism in a woman. Mo Med 1987;84:143-5.
87. [87] Gibbons CH, Freeman R. Treatment-induced diabetic neuropathy: a reversible painful autonomic neuropathy. Ann Neurol 2010;67:534-41.
88. [88] Llewelyn JG, Thomas PK, Fonseca V, King RH, Dandona P. Acute painful diabetic neuropathy precipitated by strict glycaemic control. Acta Neuropathol 1986;72:157-63.
89. [89] Bansal V, Kalita J, Misra UK. Diabetic neuropathy. Postgrad Med J 2006;82:95-100.
90. [90] Tracy JA, Dyck PJ. The spectrum of diabetic neuropathies. Phys Med Rehabil Clin N Am 2008;19:1-26.
91. [91] Kelkar P, Parry GJ. Mononeuritis multiplex in diabetes mellitus: evidence for underlying immune pathogenesis. J Neurol Neurosurg Psychiatry 2003;74:803-6.
92. [92] Misra UK, Kalita J, Nair PP. Diagnostic approach to peripheral neuropathy. Ann Indian Acad Neurol 2008;11:89-97.
93. [93] Said G. Focal and multifocal diabetic neuropathies. Arq Neuropsiquiatr 2007;65:1272-8.
94. [94] Keane JR. Third nerve palsy: analysis of 1400 personally-examined inpatients. Can J Neurol Sci 2010;37:662-70.
95. [95] Vinik AI, Erbas T. Diabetic autonomic neuropathy. Hand Clin Neurol 2013;117:279-94.
96. [96] Spallone V, Bellavere F, Scionti L, Maule S, Quadri R, Bax G, et al; Diabetic Neuropathy Study Group of the Italian Society of Diabetology: Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy. Nutr Metab Cardiovasc Dis 2011;21:69-78.
97. [97] Ziegler D. Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. Diabetes Metab Rev 1994;10:339-83.
98. [98] De Souza NM, Vanderlei LCM, Garner DM. Risk evaluation of diabetes mellitus by relation of chaotic globals to HRV. Complexity 2015:20842092.
99. [99] Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care 2003;26:1553-79.
100. [100] Chandrasekharan B, Srinivasan S. Diabetes and the enteric nervous system. Neurogastroenterol Motil 2007;19:951-60.
101. [101] Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The international index of erectile function (IIEF): A multidimensional scale for assessment of erectile dysfunction. Urology 1997;49:822-30.
102. [102] Lowy M, Collins S, Bloch M, Gillman M, Lording D, Sutherland P, et al. Quality of Erection Questionnaire correlates: Change in erection quality with erectile function, hardness, and psychosocial measures in men treated with sildenafil for erectile dysfunction. J Sex Med 2007;4:83-92.
103. [103] Freeman R. Autonomic peripheral neuropathy. Lancet 2005;365:1259-70.
104. [104] Burakgazi AZ, Alsowaity B, Burakgazi ZA, Unal D, Kelly JJ. Bladder dysfunction in peripheral neuropathies. Muscle Nerve 2012;45:2-8.