Table Info

Table 2.

Blood tests according to clinical suspicion of underlying SFN etiologies

Etiologies associated with SFN	Diseases	Blood tests and other investigations
Metabolic	DM, IFG, IGT, hypertriglyceridemia, hypothyroidism	HbA1C, FG, OGTT, TFT
Nutritional deficiencies	-	vit B1, vit B12
Infectious	HIV, HCV, HBV, Lyme disease	CRP, HIV, Borrelia burgdorferi, HBV, HCV, lumbar puncture
Autoimmune	Vasculitis, SLE, Sjögren’s syndrome (SS), rheumatoid arthritis, connective tissue disease, celiac disease, sarcoidosis	ESR, ANA, anti-ENA, SLE panel, ANCA, anti-transglutaminase antibody, RF, serum ACE, CXR, lumbar puncture
Paraneoplastic	Small cell lung cancer, solid tumors, lymphoma, myeloma, monoclonal gammopathies	Tumor markers, LDH, myeloma screen, SPE, UPE, anti-Hu and anti-CV2/CRMP-5 antibodies, lumbar puncture, whole body PET/CT
Neurotoxins	Metronidazole, alcohol, chemotherapeutic agents, solvents	Urine + blood toxicology, EtOH level, GGT, MCV, screen and review drug history
Hereditary	Fabry disease, HSAN, hATTR, Na_v 1.7, Na_v 1.8 and Na_v 1.9 sodium channelopathies	Leukocyte alpha-galactosidase A and globotriaosylceramide (Gb₃ or GL-3) levels, renal panel, urine protein, genetic testing for TTR, HSAN, SCN9A, SCN10A, SCN11A, skin/nerve/other peripheral fat pad biopsy for congo red staining

IFG: impaired fasting glucose; IGT: impaired glucose tolerance; HbA1C: hemoglobin A1C; FG: fasting glucose; OGTT: oral glucose tolerance test; TFT: thyroid function tests; EtOH: ethanol; GGT: gamma-glutamyl transpeptidase; MCV: mean cell volume; CRP: C-reactive protein; hATTR: hereditary transthyretin amyloidosis; HIV: human immunodeficiency virus; HBV: hepatitis B virus; HCV: hepatitis C virus; SLE: systemic lupus erythematosus; ESR: erythrocyte sedimentation rate; ANA: anti-nuclear antibody; anti-ENA: ant-extractable nuclear antigens; ANCA: anti-neutrophil cytoplasmic antibody; RF: rheumatoid factor; ACE: angiotensin converting enzyme; CXR: chest X-ray; LDH: lactate dehydrogenase; SPE: serum protein electrophoresis; TTR: transthyretin, UPE: urine protein electrophoresis; HSAN: hereditary sensory autonomic neuropathy; Na_v 1.7: SCN subunit 1.7; CV2/CRMP-5: CV2/collapsing response mediator protein 5; Gb3 or GL-3: globotriaosylceramide; -: information not available

Declarations

Author contributions

ACYC, KO, and JV: Conceptualization. KO, ACYC, JV: Writing—original draft, Writing—review & editing. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

ACYC is supported by the Singapore Ministry of Health’s National Medical Research Council [MOH-000437-0] under its NMRC Research Training Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Cazzato D, Lauria G. Small fibre neuropathy. Curr Opin Neurol. 2017;30:490–9. [DOI] [PubMed]

Lauria G, Morbin M, Lombardi R, Capobianco R, Camozzi F, Pareyson D, et al. Expression of capsaicin receptor immunoreactivity in human peripheral nervous system and in painful neuropathies. J Peripher Nerv Syst. 2006;11:262–71. [DOI] [PubMed]

Wilder-Smith EP, Ong WY, Guo Y, Chow AW. Epidermal transient receptor potential vanilloid 1 in idiopathic small nerve fibre disease, diabetic neuropathy and healthy human subjects. Histopathology. 2007;51:674–80. [DOI] [PubMed] [PMC]

Chang CH, Chang YS, Hsieh YL. Transient receptor potential vanilloid subtype 1 depletion mediates mechanical allodynia through cellular signal alterations in small-fiber neuropathy. Pain Rep. 2021;6:e922. [DOI] [PubMed] [PMC]

Peters MJ, Bakkers M, Merkies IS, Hoeijmakers JG, van Raak EP, Faber CG. Incidence and prevalence of small-fiber neuropathy: a survey in the Netherlands. Neurology. 2013;81:1356–60. [DOI] [PubMed]

Kosmidis ML, Koutsogeorgopoulou L, Alexopoulos H, Mamali I, Vlachoyiannopoulos PG, Voulgarelis M, et al. Reduction of intraepidermal nerve fiber density (IENFD) in the skin biopsies of patients with fibromyalgia: a controlled study. J Neurol Sci. 2014;347:143–7. [DOI] [PubMed]

Oaklander AL, Herzog ZD, Downs HM, Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain. 2013;154:2310–6. [DOI] [PubMed] [PMC]

Liu X, Treister R, Lang M, Oaklander AL. IVIg for apparently autoimmune small-fiber polyneuropathy: first analysis of efficacy and safety. Ther Adv Neurol Disord. 2018;11:1756285617744484. [DOI] [PubMed] [PMC]

Basantsova NY, Starshinova AA, Dori A, Zinchenko YS, Yablonskiy PK, Shoenfeld Y. Small-fiber neuropathy definition, diagnosis, and treatment. Neurol Sci. 2019;40:1343–50. [DOI] [PubMed]

10.

de Greef BTA, Hoeijmakers JGJ, Gorissen-Brouwers CML, Geerts M, Faber CG, Merkies ISJ. Associated conditions in small fiber neuropathy - a large cohort study and review of the literature. Eur J Neurol. 2018;25:348–55. [DOI] [PubMed] [PMC]

11.

Chan AC, Wilder-Smith EP. Small fiber neuropathy: getting bigger! Muscle Nerve. 2016;53:671–82. [DOI] [PubMed]

12.

Lang M, Treister R, Oaklander AL. Diagnostic value of blood tests for occult causes of initially idiopathic small-fiber polyneuropathy. J Neurol. 2016;263:2515–27. [DOI] [PubMed] [PMC]

13.

Callaghan BC, Kerber KA, Lisabeth LL, Morgenstern LB, Longoria R, Rodgers A, et al. Role of neurologists and diagnostic tests on the management of distal symmetric polyneuropathy. JAMA Neurol. 2014;71:1143–9. [DOI] [PubMed] [PMC]

14.

FDA-NIH Biomarker Working Group. BEST (biomarkers, endpointS, and other tools) resource. Food and Drug Administration (US); National Institutes of Health (US); 2016.

15.

Bednarik J, Vlckova-Moravcova E, Divisova-Bursova S, Belobradkova J, Dusek L, Sommer C. Etiology of small-fiber neuropathy. J Peripher Nerv Syst. 2009;14:177–83. [DOI] [PubMed]

16.

Low VA, Sandroni P, Fealey RD, Low PA. Detection of small-fiber neuropathy by sudomotor testing. Muscle Nerve. 2006;34:57–61. [DOI] [PubMed]

17.

Oaklander AL, Nolano M. Scientific advances in and clinical approaches to small-fiber polyneuropathy: a review. JAMA Neurol. 2019;76:1240–51. Erratum in: JAMA Neurol. 2019;76:1520. [DOI] [PubMed]

18.

Lauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, et al.; European Federation of Neurological Societies, Peripheral Nerve Society. European federation of neurological societies/peripheral nerve society guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010;17:903–e49. [DOI] [PubMed]

19.

Lacomis D. Small-fiber neuropathy. Muscle Nerve. 2002;26:173–88. [DOI] [PubMed]

20.

Lopate G, Streif E, Harms M, Weihl C, Pestronk A. Cramps and small-fiber neuropathy. Muscle Nerve. 2013;48:252–5. [DOI] [PubMed]

21.

Misery L, Brenaut E, Le Garrec R, Abasq C, Genestet S, Marcorelles P, et al. Neuropathic pruritus. Nat Rev Neurol. 2014;10:408–16. [DOI] [PubMed]

22.

Gemignani F, Giovanelli M, Vitetta F, Santilli D, Bellanova MF, Brindani F, et al. Non-length dependent small fiber neuropathy. a prospective case series. J Peripher Nerv Syst. 2010;15:57–62. [DOI] [PubMed]

23.

Dalla Bella E, Lombardi R, Porretta-Serapiglia C, Ciano C, Gellera C, Pensato V, et al. Amyotrophic lateral sclerosis causes small fiber pathology. Eur J Neurol. 2016;23:416–20. [DOI] [PubMed]

24.

de Araújo DF, de Melo Neto AP, Oliveira ÍS, Brito BS, de Araújo IT, Barros IS, et al. Small (autonomic) and large fiber neuropathy in Parkinson disease and parkinsonism. BMC Neurol. 2016;16:139. [DOI] [PubMed] [PMC]

25.

Khan S, Zhou L. Characterization of non-length-dependent small-fiber sensory neuropathy. Muscle Nerve. 2012;45:86–91. [DOI] [PubMed]

26.

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. Erratum in: Diabetes Care. 2010;33:2725. [DOI] [PubMed] [PMC]

27.

Sousa-Valente J, Brain SD. A historical perspective on the role of sensory nerves in neurogenic inflammation. Semin Immunopathol. 2018;40:229–36. [DOI] [PubMed] [PMC]

28.

Themistocleous AC, Ramirez JD, Shillo PR, Lees JG, Selvarajah D, Orengo C, et al. The pain in neuropathy study (PiNS): a cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy. Pain. 2016;157:1132–45. [DOI] [PubMed] [PMC]

29.

Albrecht PJ, Hou Q, Argoff CE, Storey JR, Wymer JP, Rice FL. Excessive peptidergic sensory innervation of cutaneous arteriole-venule shunts (AVS) in the palmar glabrous skin of fibromyalgia patients: implications for widespread deep tissue pain and fatigue. Pain Med. 2013;14:895–915. [DOI] [PubMed]

30.

Dori A, Lopate G, Keeling R, Pestronk A. Myovascular innervation: axon loss in small-fiber neuropathies. Muscle Nerve. 2015;51:514–21. [DOI] [PubMed]

31.

Joseph P, Sanders J, Oaklander A, Arevalo Rodriguez T, Oliveira R, Faria Urbina M, et al. The pathophysiology of chronic fatigue syndrome: results from an invasive cardiopulmonary exercise laboratory. D60 PULM FUNCT EXERCISE TEST TRAIN. 2019;199:A6902. [DOI]

32.

Selim MM, Wendelschafer-Crabb G, Redmon JB, Khoruts A, Hodges JS, Koch K, et al. Gastric mucosal nerve density: a biomarker for diabetic autonomic neuropathy? Neurology. 2010;75:973–81. [DOI] [PubMed] [PMC]

33.

Oaklander AL, Klein MM. Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes. Pediatrics. 2013;131:e1091–100. [DOI] [PubMed] [PMC]

34.

Poda R, Guaraldi P, Solieri L, Calandra-Buonaura G, Marano G, Gallassi R, et al. Standing worsens cognitive functions in patients with neurogenic orthostatic hypotension. Neurol Sci. 2012;33:469–73. [DOI] [PubMed]

35.

Hsieh PC, Tseng MT, Chao CC, Lin YH, Tseng WI, Liu KH, et al. Imaging signatures of altered brain responses in small-fiber neuropathy: reduced functional connectivity of the limbic system after peripheral nerve degeneration. Pain. 2015;156:904–16. [DOI] [PubMed]

36.

Terkelsen AJ, Karlsson P, Lauria G, Freeman R, Finnerup NB, Jensen TS. The diagnostic challenge of small fibre neuropathy: clinical presentations, evaluations, and causes. Lancet Neurol. 2017;16:934–44. Erratum in: Lancet Neurol. 2017;16:954. [DOI] [PubMed]

37.

Breiner A, Lovblom LE, Perkins BA, Bril V. Does the prevailing hypothesis that small-fiber dysfunction precedes large-fiber dysfunction apply to type 1 diabetic patients? Diabetes Care. 2014;37:1418–24. [DOI] [PubMed]

38.

Gorson KC, Herrmann DN, Thiagarajan R, Brannagan TH, Chin RL, Kinsella LJ, et al. Non-length dependent small fibre neuropathy/ganglionopathy. J Neurol Neurosurg Psychiatry. 2008;79:163–9. [DOI] [PubMed]

39.

Griffin JW, Cornblath DR, Alexander E, Campbell J, Low PA, Bird S, et al. Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjögren’s syndrome. Ann Neurol. 1990;27:304–15. [DOI] [PubMed]

40.

Birnbaum J, Lalji A, Piccione EA, Izbudak I. Magnetic resonance imaging of the spinal cord in the evaluation of 3 patients with sensory neuronopathies: diagnostic assessment, indications of treatment response, and impact of autoimmunity: a case report. Medicine (Baltimore). 2017;96:e8483. [DOI] [PubMed] [PMC]

41.

Birnbaum J, Duncan T, Owoyemi K, Wang KC, Carrino J, Chhabra A. Use of a novel high-resolution magnetic resonance neurography protocol to detect abnormal dorsal root ganglia in Sjögren patients with neuropathic pain: case series of 10 patients and review of the literature. Medicine (Baltimore). 2014;93:121–34. [DOI] [PubMed] [PMC]

42.

West CA, Davies KA, Hart AM, Wiberg M, Williams SR, Terenghi G. Volumetric magnetic resonance imaging of dorsal root ganglia for the objective quantitative assessment of neuron death after peripheral nerve injury. Exp Neurol. 2007;203:22–33. [DOI] [PubMed]

43.

Birnbaum J, Lalji A, Saed A, Baer AN. Biopsy-proven small-fiber neuropathy in primary Sjögren’s syndrome: neuropathic pain characteristics, autoantibody findings, and histopathologic features. Arthritis Care Res (Hoboken). 2019;71:936–48. Erratum in: Arthritis Care Res (Hoboken). 2019;71:1283. [DOI] [PubMed] [PMC]

44.

Gemignani F, Bellanova MF, Saccani E, Pavesi G. Non-length-dependent small fiber neuropathy: not a matter of stockings and gloves. Muscle Nerve. 2022;65:10–28. [DOI] [PubMed]

45.

Oaklander AL. Chapter 10 - Dysimmune small fiber neuropathies. In: Rajabally YA, editor. Dysimmune neuropathies. Academic Press; 2020. pp. 225–47. [DOI]

46.

Bakkers M, Faber CG, Hoeijmakers JG, Lauria G, Merkies IS. Small fibers, large impact: quality of life in small-fiber neuropathy. Muscle Nerve. 2014;49:329–36. [DOI] [PubMed]

47.

Attal N, Bouhassira D, Baron R. Diagnosis and assessment of neuropathic pain through questionnaires. Lancet Neurol. 2018;17:456–66. [DOI] [PubMed]

48.

Visser M, Marinus J, Stiggelbout AM, Van Hilten JJ. Assessment of autonomic dysfunction in Parkinson’s disease: the SCOPA-AUT. Mov Disord. 2004;19:1306–12. [DOI] [PubMed]

49.

Zilliox L, Peltier AC, Wren PA, Anderson A, Smith AG, Singleton JR, et al. Assessing autonomic dysfunction in early diabetic neuropathy: the survey of autonomic symptoms. Neurology. 2011;76:1099–105. [DOI] [PubMed] [PMC]

50.

Solano C, Martinez A, Becerril L, Vargas A, Figueroa J, Navarro C, et al. Autonomic dysfunction in fibromyalgia assessed by the Composite Autonomic Symptoms Scale (COMPASS). J Clin Rheumatol. 2009;15:172–6. [DOI] [PubMed]

51.

Treister R, O’Neil K, Downs HM, Oaklander AL. Validation of the composite autonomic symptom scale 31 (COMPASS-31) in patients with and without small fiber polyneuropathy. Eur J Neurol. 2015;22:1124–30. [DOI] [PubMed] [PMC]

52.

Sun B, Li Y, Liu L, Chen Z, Ling L, Yang F, et al. SFN-SIQ, SFNSL and skin biopsy of 55 cases with small fibre involvement. Int J Neurosci. 2018;128:442–8. [DOI] [PubMed]

53.

Galosi E, Falco P, Di Pietro G, Leone C, Esposito N, De Stefano G, et al. The diagnostic accuracy of the small fiber neuropathy symptoms inventory questionnaire (SFN-SIQ) for identifying pure small fiber neuropathy. J Peripher Nerv Syst. 2022;27:283–90. [DOI] [PubMed]

54.

Hoitsma E, De Vries J, Drent M. The small fiber neuropathy screening list: construction and cross-validation in sarcoidosis. Respir Med. 2011;105:95–100. [DOI] [PubMed]

55.

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. [DOI] [PubMed]

56.

Cheshire WP, Freeman R, Gibbons CH, Cortelli P, Wenning GK, Hilz MJ, et al. Electrodiagnostic assessment of the autonomic nervous system: a consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology. Clin Neurophysiol. 2021;132:666–82. Erratum in: Clin Neurophysiol. 2021;132:1194. [DOI] [PubMed]

57.

Kalliomäki M, Kieseritzky JV, Schmidt R, Hägglöf B, Karlsten R, Sjögren N, et al. Structural and functional differences between neuropathy with and without pain? Exp Neurol. 2011;231:199–206. [DOI] [PubMed]

58.

Namer B, Pfeffer S, Handwerker HO, Schmelz M, Bickel A. Axon reflex flare and quantitative sudomotor axon reflex contribute in the diagnosis of small fiber neuropathy. Muscle Nerve. 2013;47:357–63. [DOI] [PubMed]

59.

Saal DP, Thijs RD, van Dijk JG. Tilt table testing in neurology and clinical neurophysiology. Clin Neurophysiol. 2016;127:1022–30. [DOI] [PubMed]

60.

Wilder-Smith EP. Water immersion wrinkling--physiology and use as an indicator of sympathetic function. Clin Auton Res. 2004;14:125–31. [DOI] [PubMed]

61.

Teoh HL, Chow A, Wilder-Smith EP. Skin wrinkling for diagnosing small fibre neuropathy: comparison with epidermal nerve density and sympathetic skin response. J Neurol Neurosurg Psychiatry. 2008;79:835–7. [DOI] [PubMed]

62.

Wilder-Smith EP, Guo Y, Chow A. Stimulated skin wrinkling for predicting intraepidermal nerve fibre density. Clin Neurophysiol. 2009;120:953–8. [DOI] [PubMed]

63.

Wilder-Smith EP. Stimulated skin wrinkling as an indicator of limb sympathetic function. Clin Neurophysiol. 2015;126:10–6. [DOI] [PubMed]

64.

Thaisetthawatkul P, Fernandes Filho JA, Herrmann DN. Contribution of QSART to the diagnosis of small fiber neuropathy. Muscle Nerve. 2013;48:883–8. [DOI] [PubMed]

65.

Stewart JD, Low PA, Fealey RD. Distal small fiber neuropathy: results of tests of sweating and autonomic cardiovascular reflexes. Muscle Nerve. 1992;15:661–5. [DOI] [PubMed]

66.

Berger MJ, Kimpinski K. Test-retest reliability of quantitative sudomotor axon reflex testing. J Clin Neurophysiol. 2013;30:308–12. [DOI] [PubMed]

67.

Low PA, Denq JC, Opfer-Gehrking TL, Dyck PJ, O’Brien PC, Slezak JM. Effect of age and gender on sudomotor and cardiovagal function and blood pressure response to tilt in normal subjects. Muscle Nerve. 1997;20:1561–8. [DOI]

68.

Billig SCI, Schauermann JC, Rolke R, Katona I, Schulz JB, Maier A. Quantitative sensory testing predicts histological small fiber neuropathy in postural tachycardia syndrome. Neurol Clin Pract. 2020;10:428–34. [DOI] [PubMed] [PMC]

69.

Peltier A, Smith AG, Russell JW, Sheikh K, Bixby B, Howard J, et al. Reliability of quantitative sudomotor axon reflex testing and quantitative sensory testing in neuropathy of impaired glucose regulation. Muscle Nerve. 2009;39:529–35. [DOI] [PubMed] [PMC]

70.

Chong PS, Cros DP. Technology literature review: quantitative sensory testing. Muscle Nerve. 2004;29:734–47. [DOI] [PubMed]

71.

Themistocleous AC, Ramirez JD, Serra J, Bennett DLH. The clinical approach to small fibre neuropathy and painful channelopathy. Pract Neurol. 2014;14:368–79. [DOI] [PubMed] [PMC]

72.

Backonja MM, Attal N, Baron R, Bouhassira D, Drangholt M, Dyck PJ, et al. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain. 2013;154:1807–19. Erratum in: Pain. 2014;155:205. [DOI]

73.

Shy ME, Frohman EM, So YT, Arezzo JC, Cornblath DR, Giuliani MJ, et al. Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2003;60:898–904. [DOI] [PubMed]

74.

Duchesne M, Richard L, Vallat JM, Magy L. Assessing sudomotor impairment in patients with peripheral neuropathy: comparison between electrochemical skin conductance and skin biopsy. Clin Neurophysiol. 2018;129:1341–8. [DOI] [PubMed]

75.

Provitera V, Nolano M, Caporaso G, Stancanelli A, Santoro L, Kennedy WR. Evaluation of sudomotor function in diabetes using the dynamic sweat test. Neurology. 2010;74:50–6. [DOI] [PubMed]

76.

Azmi S, Ferdousi M, Petropoulos IN, Ponirakis G, Alam U, Fadavi H, et al. Corneal confocal microscopy identifies small-fiber neuropathy in subjects with impaired glucose tolerance who develop type 2 diabetes. Diabetes Care. 2015;38:1502–8. [DOI] [PubMed] [PMC]

77.

Sun B, Wang H, Chen Z, Cui F, Yang F, Huang X. Contact heat evoked potentials in China: normal values and reproducibility. Front Hum Neurosci. 2022;15:747553. [DOI] [PubMed] [PMC]

78.

Atherton DD, Facer P, Roberts KM, Misra VP, Chizh BA, Bountra C, et al. Use of the novel Contact Heat Evoked Potential Stimulator (CHEPS) for the assessment of small fibre neuropathy: correlations with skin flare responses and intra-epidermal nerve fibre counts. BMC Neurol. 2007;7:21. [DOI] [PubMed] [PMC]

79.

Lagerburg V, Bakkers M, Bouwhuis A, Hoeijmakers JG, Smit AM, Van Den Berg SJ, et al. Contact heat evoked potentials: normal values and use in small-fiber neuropathy. Muscle Nerve. 2015;51:743–9. [DOI] [PubMed]

80.

Di Stefano G, La Cesa S, Leone C, Pepe A, Galosi E, Fiorelli M, et al. Diagnostic accuracy of laser-evoked potentials in diabetic neuropathy. Pain. 2017;158:1100–7. [DOI] [PubMed]

81.

Provitera V, Gibbons CH, Wendelschafer-Crabb G, Donadio V, Vitale DF, Stancanelli A, et al. A multi-center, multinational age- and gender-adjusted normative dataset for immunofluorescent intraepidermal nerve fiber density at the distal leg. Eur J Neurol. 2016;23:333–8. [DOI] [PubMed]

82.

McArthur JC, Stocks EA, Hauer P, Cornblath DR, Griffin JW. Epidermal nerve fiber density: normative reference range and diagnostic efficiency. Arch Neurol. 1998;55:1513–20. [DOI] [PubMed]

83.

Lauria G, Holland N, Hauer P, Cornblath DR, Griffin JW, McArthur JC. Epidermal innervation: changes with aging, topographic location, and in sensory neuropathy. J Neurol Sci. 1999;164:172–8. [DOI] [PubMed]

84.

Provitera V, Gibbons CH, Wendelschafer-Crabb G, Donadio V, Vitale DF, Loavenbruck A, et al. The role of skin biopsy in differentiating small-fiber neuropathy from ganglionopathy. Eur J Neurol. 2018;25:848–53. Erratum in: Eur J Neurol. 2019;26:202. [DOI] [PubMed]

85.

Walk D, Wendelschafer-Crabb G, Davey C, Kennedy WR. Concordance between epidermal nerve fiber density and sensory examination in patients with symptoms of idiopathic small fiber neuropathy. J Neurol Sci. 2007;255:23–6. [DOI] [PubMed]

86.

Nolano M, Biasiotta A, Lombardi R, Provitera V, Stancanelli A, Caporaso G, et al. Epidermal innervation morphometry by immunofluorescence and bright-field microscopy. J Peripher Nerv Syst. 2015;20:387–91. [DOI] [PubMed]

87.

Manganelli F, Pisciotta C, Provitera V, Taioli F, Iodice R, Topa A, et al. Autonomic nervous system involvement in a new CMT2B family. J Peripher Nerv Syst. 2012;17:361–4. [DOI] [PubMed]

88.

Yoshida T, Nodera H, Kumon Y, Osanai S, Izumi Y, Mizukami H. Detection of nerve enlargement with ultrasound and correlation with skin biopsy findings in painful sensory neuropathy associated with Sjögren’s syndrome. Mod Rheumatol. 2021;31:849–55. [DOI] [PubMed]

89.

Ebadi H, Siddiqui H, Ebadi S, Ngo M, Breiner A, Bril V. Peripheral nerve ultrasound in small fiber polyneuropathy. Ultrasound Med Biol. 2015;41:2820–6. [DOI] [PubMed]

90.

Farhad K, Traub R, Ruzhansky KM, Brannagan TH 3rd. Causes of neuropathy in patients referred as “idiopathic neuropathy”. Muscle Nerve. 2016;53:856–61. [DOI] [PubMed]

91.

Levine TD. Small fiber neuropathy: disease classification beyond pain and burning. J Cent Nerv Syst Dis. 2018;10:1179573518771703. [DOI] [PubMed] [PMC]

92.

Barro C, Chitnis T, Weiner HL. Blood neurofilament light: a critical review of its application to neurologic disease. Ann Clin Transl Neurol. 2020;7:2508–23. [DOI] [PubMed] [PMC]

93.

Sandelius Å, Zetterberg H, Blennow K, Adiutori R, Malaspina A, Laura M, et al. Plasma neurofilament light chain concentration in the inherited peripheral neuropathies. Neurology. 2018;90:e518–24. [DOI] [PubMed] [PMC]

94.

Louwsma J, Brunger AF, Bijzet J, Kroesen BJ, Roeloffzen WWH, Bischof A, et al. Neurofilament light chain, a biomarker for polyneuropathy in systemic amyloidosis. Amyloid. 2021;28:50–5. [DOI] [PubMed]

95.

Kim SH, Kim KH, Hyun JW, Kim JH, Seo SS, Kim HJ, et al. Blood neurofilament light chain as a biomarker for monitoring and predicting paclitaxel-induced peripheral neuropathy in patients with gynecological cancers. Front Oncol. 2022;12:942960. [DOI] [PubMed] [PMC]

96.

Hayashi T, Nukui T, Piao JL, Sugimoto T, Anada R, Matsuda N, et al. Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy. Brain Behav. 2021;11:e02084. [DOI] [PubMed] [PMC]

97.

Celikbilek A, Tanik N, Sabah S, Borekci E, Akyol L, Ak H, et al. Elevated neurofilament light chain (NFL) mRNA levels in prediabetic peripheral neuropathy. Mol Biol Rep. 2014;41:4017–22. [DOI] [PubMed]

98.

Splinter K, Adams DR, Bacino CA, Bellen HJ, Bernstein JA, Cheatle-Jarvela AM, et al.; Undiagnosed Diseases Network. Effect of genetic diagnosis on patients with previously undiagnosed disease. N Engl J Med. 2018;379:2131–9. [DOI] [PubMed] [PMC]

99.

Kamm C, Zettl UK. Autoimmune disorders affecting both the central and peripheral nervous system. Autoimmun Rev. 2012;11:196–202. [DOI] [PubMed]

100.

Oaklander AL. Immunotherapy prospects for painful small-fiber sensory neuropathies and ganglionopathies. Neurotherapeutics. 2016;13:108–17. [DOI] [PubMed] [PMC]

101.

Chan ACY, Wong HY, Chong YF, Lai PS, Teoh HL, Ng AYY, et al. Novel autoantibodies in idiopathic small fiber neuropathy. Ann Neurol. 2022;91:66–77. [DOI] [PubMed] [PMC]

102.

Dabby R, Weimer LH, Hays AP, Olarte MR, Latov N. Antisulfatide antibodies in neuropathy—clinical and electrophysiologic correlates. J Peripher Nerv Syst. 2000;5:240–1. [DOI]

103.

Dabby R, Gilad R, Sadeh M, Lampl Y, Watemberg N. Acute steroid responsive small-fiber sensory neuropathy: a new entity? J Peripher Nerv Syst. 2006;11:47–52. [DOI] [PubMed]

104.

Levine TD, Kafaie J, Zeidman LA, Saperstein DS, Massaquoi R, Bland RJ, et al. Cryptogenic small-fiber neuropathies: serum autoantibody binding to trisulfated heparan disaccharide and fibroblast growth factor receptor-3. Muscle Nerve. 2020;61:512–5. [DOI] [PubMed]

105.

Trevino JA, Novak P. TS-HDS and FGFR3 antibodies in small fiber neuropathy and dysautonomia. Muscle Nerve. 2021;64:70–6. [DOI] [PubMed]

106.

Fujii T, Yamasaki R, Iinuma K, Tsuchimoto D, Hayashi Y, Saitoh BY, et al. A novel autoantibody against plexin D1 in patients with neuropathic pain. Ann Neurol. 2018;84:208–24. [DOI] [PubMed]

107.

Flossdorf P, Haupt WF, Brunn A, Deckert M, Fink GR, Lehmann HC, et al. Long-time course of idiopathic small fiber neuropathy. Eur Neurol. 2018;79:161–5. [DOI] [PubMed]

108.

Fujii T, Lee EJ, Miyachi Y, Yamasaki R, Lim YM, Iinuma K, et al. Antiplexin D1 antibodies relate to small fiber neuropathy and induce neuropathic pain in animals. Neurol Neuroimmunol Neuroinflamm. 2021;8:e1028. [DOI] [PubMed] [PMC]

109.

Yuki N, Chan AC, Wong AHY, Inoue T, Yokai M, Kurihara T, et al. Acute painful autoimmune neuropathy: a variant of Guillain-Barré syndrome. Muscle Nerve. 2018;57:320–4. [DOI] [PubMed]

110.

Duarte JG, Blackburn JM. Advances in the development of human protein microarrays. Expert Rev Proteomics. 2017;14:627–41. [DOI] [PubMed]

111.

Al-Moallem MA, Zaidan RM, Alkali NH. The sympathetic skin response in diabetic neuropathy and its relationship to autonomic symptoms. Saudi Med J. 2008;29:568–72. [PubMed]