Neurophysiological assessment of peripheral neuropathy through whole plantar nerve conduction in type 2 diabetes mellitus and healthy control subjects

Abstract

Aim: To neurophysiologically characterize the innervation of the sole and assess the diagnostic efficacy of whole plantar nerve (WPN) conduction study in type 2 diabetes mellitus (T2DM) patients and healthy control subjects.

Methods: This single-center prospective observational case-control study involved 51 individuals with T2DM and 34 healthy controls. All subjects underwent validated screening tests for peripheral neuropathy (PN), including proximal and distal sural nerve conduction study and WPN.

Results: The median amplitude of the compound nerve action potentials (CNAPs) and the sensory conduction velocity (SCV) recorded by WPN conduction were significantly lower in patients with T2DM as compared to healthy controls. Sural nerve conduction revealed that both proximal and distal sensory nerve action potentials amplitude and SCV were significantly lower in subjects with diabetes, as compared to healthy controls. As compared with sural nerve conduction, WPN shows a Sensitivity of 77% and a negative predictive value (NPV) of 77%.

Conclusions: WPN conduction study is helpful in characterizing the most distal nerve fibers in patients with T2DM and healthy controls. WPN may represent a useful tool in the diagnosis of length-dependent diabetic polyneuropathy.

Keywords

Whole plantar nerve conduction study / sural nerve conduction / type 2 diabetes mellitus / peripheral neuropathy

References

[1] Khan MAB,King JK,Mustafa H.Epidemiology of type 2 diabetes - global burden of disease and forecasted trends.J Epidemiol Glob Health2020;10:107-11 PMCID:PMC7310804

[2] American Diabetes Association. 11. Microvascular complications and foot care: Standards of Medical Care in Diabetes-2020.Diabetes Care2020;43:S135-51

[3] Ziegler D,Vinik AI.Chapter 1 - Epidemiology of polyneuropathy in diabetes and prediabetes.Handb Clin Neurol2014;126:3-22

[4] Malik RA,Thompson SD.Endoneurial localisation of microvascular damage in human diabetic neuropathy.Diabetologia1993;36:454-9

[5] Brownlee M.Biochemistry and molecular cell biology of diabetic complications.Nature2001;414:813-20

[6] Boulton AJM, Vinik AI, Arezzo JC, et al; American Diabetes Association. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care 2005;28:956-62.

[7] Pop-Busui R, Lu J, Brooks MM, et al; BARI 2D Study Group. Impact of glycemic control strategies on the progression of diabetic peripheral neuropathy in the bypass angioplasty revascularization investigation 2 diabetes (BARI 2D) cohort. Diabetes Care 2013;36:3208-15. PMCID:PMC3781573

[8] Ang L,Martin C.Glucose control and diabetic neuropathy: lessons from recent large clinical trials.Curr Diab Rep2014;14:528 PMCID:PMC5084623

[9] Martin CL, Albers JW, Pop-Busui R; DCCT/EDIC Research Group. Neuropathy and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care 2014;37:31-8. PMCID:PMC3868000

[10] Smith S,Lane T,Oliver N.Pathogenesis of distal symmetrical polyneuropathy in diabetes.Life2022;12:1074 PMCID:PMC9319251

[11] Ziegler D,Schnell O.Current concepts in the management of diabetic polyneuropathy.J Diabetes Investig2021;12:464-75 PMCID:PMC8015839

[12] Pop-Busui R,Feldman EL.Diabetic neuropathy: a position statement by the American Diabetes Association.Diabetes Care2017;40:136-54 PMCID:PMC6977405

[13] Kamiya H,Himeno T.Point-of-care nerve conduction device predicts the severity of diabetic polyneuropathy: a quantitative, but easy-to-use, prediction model.J Diabetes Investig2021;12:583-91 PMCID:PMC8015817

[14] Hemmi S,Nagai T,Murakami T.Whole plantar nerve conduction study with disposable strip electrodes.Muscle Nerve2016;53:209-13

[15] Galiero R,Pafundi PC.Whole plantar nerve conduction study: a new tool for early diagnosis of peripheral diabetic neuropathy.Diabetes Res Clin Pract2021;176:108856

[16] Frank RN.Diabetic retinopathy.N Engl J Med2004;350:48-58

[17] Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 2013;158:825-30.

[18] Williams B, Mancia G, Spiering W, et al; List of authors/Task Force members. 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens 2018;36:2284-309.

[19] Mach F,Catapano AL.2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS).Eur Heart J2020;41:111-88

[20] Spallone V,D’Amato C,Cacciotti L.Validation of DN4 as a screening tool for neuropathic pain in painful diabetic polyneuropathy.Diabet Med2012;29:578-85

[21] Tesfaye S, Boulton AJ, Dyck PJ, 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. PMCID:PMC2945176

[22] Spallone V.Update on the impact, diagnosis and management of cardiovascular autonomic neuropathy in diabetes: what is defined, what is new, and what is unmet.Diabetes Metab J2019;43:3-30 PMCID:PMC6387879

[23] American Association of Electrodiagnostic Medicine. Guidelines in electrodiagnostic medicine.Muscle Nerve1992;15:229-53

[24] Pop-Busui R, Evans GW, Gerstein HC, et al; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 2010;33:1578-84. PMCID:PMC2890362

[25] Sasso FC,Tranchino G.Cochlear dysfunction in type 2 diabetes: a complication independent of neuropathy and acute hyperglycemia.Metabolism1999;48:1346-50

[26] Narres M,Claessen H.Incidence of lower extremity amputations in the diabetic compared with the non-diabetic population: a systematic review.PLoS One2017;12:e0182081 PMCID:PMC5573217

[27] Lu B,Wen J.Determination of peripheral neuropathy prevalence and associated factors in Chinese subjects with diabetes and pre-diabetes - ShangHai Diabetic neuRopathy Epidemiology and Molecular Genetics Study (SH-DREAMS).PLoS One2013;8:e61053 PMCID:PMC3628856

[28] Herman WH, Pop-Busui R, Braffett BH, et al; DCCT/EDIC Research Group. Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications. Diabet Med 2012;29:937-44. PMCID:PMC3641573

[29] Bril V,Ngo M.Comparison of a neurothesiometer and vibration in measuring vibration perception thresholds and relationship to nerve conduction studies.Diabetes Care1997;20:1360-2

[30] Perkins BA.Diabetic neuropathy: a review emphasizing diagnostic methods.Clin Neurophysiol2003;114:1167-75

[31] Im S,Park JH,Park GY.Assessment of the medial dorsal cutaneous, dorsal sural, and medial plantar nerves in impaired glucose tolerance and diabetic patients with normal sural and superficial peroneal nerve responses.Diabetes Care2012;35:834-9 PMCID:PMC3308311

[32] Kural MA,Pugdahl K,Fuglsang-Frederiksen A.Diagnostic utility of distal nerve conduction studies and sural near-nerve needle recording in polyneuropathy.Clin Neurophysiol2017;128:1590-5

[33] Løseth S,Stålberg E.Medial plantar nerve conduction studies in healthy controls and diabetics.Clin Neurophysiol2007;118:1155-61

[34] Sylantiev C,Chapman J.Medial plantar nerve testing facilitates identification of polyneuropathy.Muscle Nerve2008;38:1595-8

[35] Hemmi S,Murakami T.PO1.18 Comparison of the sensitivities of plantar nerve conduction techniques for early detection of diabetic sensory polyneuropathy.Clin Neurophysiol2009;120:S37

[36] Guiloff RJ.Sensory conduction in medial plantar nerve: normal values, clinical applications, and a comparison with the sural and upper limb sensory nerve action potentials in peripheral neuropathy.J Neurol Neurosurg Psychiatry1977;40:1168-81 PMCID:PMC492940

[37] Ponsford SN.Sensory conduction in medial and lateral plantar nerves.J Neurol Neurosurg Psychiatry1988;51:188-91 PMCID:PMC1031528

[38] Guo Y,Brown XS.Sural and radial sensory responses in patients with sensory polyneuropathy.Clin Med Rev Case Rep2015;2:049 PMCID:PMC4806560

[39] Kellogg AP,Larkin DD,Stevens MJ.Protective effects of cyclooxygenase-2 gene inactivation against peripheral nerve dysfunction and intraepidermal nerve fiber loss in experimental diabetes.Diabetes2007;56:2997-3005

[40] Squintani G,Donato F.Antidromic sensory nerve conduction study of the digital branches of the medial plantar nerve: a novel method to detect early diabetic sensory axonal polyneuropathy.Muscle Nerve2014;50:193-9

[41] Uluc K,Borucu D.Medial plantar and dorsal sural nerve conduction studies increase the sensitivity in the detection of neuropathy in diabetic patients.Clin Neurophysiol2008;119:880-5

[42] Herrmann DN,Pannoni V,Stanton M.Plantar nerve AP and skin biopsy in sensory neuropathies with normal routine conduction studies.Neurology2004;63:879-85

[43] Lai YR,Chiu WC.Sural nerve sensory response in diabetic distal symmetrical polyneuropathy.Muscle Nerve2020;61:88-94

[44] Bril V,Ngo M.Limits of the sympathetic skin response in patients with diabetic polyneuropathy.Muscle Nerve2000;23:1427-30

[45] Oh SJ,Lee DK.Large-fiber neuropathy in distal sensory neuropathy with normal routine nerve conduction.Neurology2001;56:1570-2

[46] Kushnir M,Kimiagar Y,Rabey JM.Medial dorsal superficial peroneal nerve studies in patients with polyneuropathy and normal sural responses.Muscle Nerve2005;31:386-9