Download PDF
Semin Neurol 2025; 45(01): 132-144
DOI: 10.1055/s-0044-1791823
Review Article

The Evolving Landscape of Small Fiber Neuropathy

Grazia Devigili
1   Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta,” Milan, Italy
,
Raffaella Lombardi
2   Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta,” Milan, Italy
,
Giuseppe Lauria
2   Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta,” Milan, Italy
4   Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
,
Daniele Cazzato
3   Clinical Neurophysiology Unit, Fondazione IRCCS Istituto Neurologico “Carlo Besta,” Milan, Italy
› Author Affiliations Funding This work was supported by funding from the Italian Ministry of Health (RRC).
› Further Information
   Permissions and Reprints

Abstract

Small fiber neuropathy (SFN) belongs to a heterogeneous group of disorders in which thinly myelinated Aδ and unmyelinated C-fibers are primarily affected, leading to neuropathic pain and autonomic symptoms. SFN can be associated with systemic conditions such as diabetes, autoimmune diseases, exposure to drugs and toxins, and infection, with the list of associated diseases continuing to expand. Variants in the SCN9A, SCN10A, and SCN11A genes encoding Nav 1.7, Nav 1.8, and Nav 1.9 sodium channel subunits, as well as in the TRPA1 gene, have been found in SFN patients, expanding the spectrum of underlying conditions and enhancing our understanding of pathophysiological mechanisms. There is also growing interest in immune-mediated forms that could help identify potentially treatable subgroups. According to international criteria, diagnosis is established through clinical examination, the assessment of intraepidermal nerve fiber density, and/or quantitative sensory testing. Autonomic functional tests allow for a better characterization of dysautonomia in SFN, which can be subclinical. Other tests can support the diagnosis. Currently, the management of SFN prioritizes treating the underlying condition, if identified, within a multidisciplinary approach that combines symptomatic pain therapy, lifestyle changes, and biopsychological interventions. Emerging insights from the molecular characterization of SFN channelopathies hold promise for improving diagnosis, potentially leading to the discovery of new drugs and refining trial designs in the future. This article reviews the clinical presentation, diagnostic workup, and advancing knowledge of associated conditions and interventional management of SFN.

Keywords

small fiber neuropathy - skin biopsy - neuropathic pain


Publication History

Article published online:
21 October 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Hoeijmakers JG, Faber CG, Lauria G, Merkies IS, Waxman SG. Small-fibre neuropathies – advances in diagnosis, pathophysiology and management. Nat Rev Neurol 2012; 8 (07) 369-379
    CrossrefPubMedSearch in Google Scholar
  • 2 Johnson SA, Shouman K, Shelly S. et al. Small fiber neuropathy incidence, prevalence, longitudinal impairments, and disability. Neurology 2021; 97 (22) e2236-e2247
    CrossrefPubMedSearch in Google Scholar
  • 3 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 (15) 1356-1360
    CrossrefPubMedSearch in Google Scholar
  • 4 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 (02) 348-355
    CrossrefPubMedSearch in Google Scholar
  • 5 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 (10) 2285-2293
    CrossrefPubMedSearch in Google Scholar
  • 6 Devigili G, Tugnoli V, Penza P. et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain 2008; 131 (Pt 7): 1912-1925
    CrossrefPubMedSearch in Google Scholar
  • 7 Oaklander AL, Herzog ZD, Downs HM, Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain 2013; 154 (11) 2310-2316
    CrossrefPubMedSearch in Google Scholar
  • 8 Nolano M, Provitera V, Estraneo A. et al. Sensory deficit in Parkinson's disease: evidence of a cutaneous denervation. Brain 2008; 131 (Pt 7): 1903-1911
    CrossrefPubMedSearch in Google Scholar
  • 9 Ghasemi M, Rajabally YA. Small fiber neuropathy in unexpected clinical settings: a review. Muscle Nerve 2020; 62 (02) 167-175
    CrossrefPubMedSearch in Google Scholar
  • 10 Lumpkin EA, Caterina MJ. Mechanisms of sensory transduction in the skin. Nature 2007; 445 (7130) 858-865
    CrossrefPubMedSearch in Google Scholar
  • 11 Talagas M, Lebonvallet N, Leschiera R. et al. Keratinocytes communicate with sensory neurons via synaptic-like contacts. Ann Neurol 2020; 88 (06) 1205-1219
    CrossrefPubMedSearch in Google Scholar
  • 12 Gemignani F, Vitetta F, Brindani F, Contini M, Negrotti A. Painful polyneuropathy associated with restless legs syndrome. Clinical features and sensory profile. Sleep Med 2013; 14 (01) 79-84
    CrossrefPubMedSearch in Google Scholar
  • 13 Gylfadottir SS, Itani M, Kristensen AG. et al. The characteristics of pain and dysesthesia in patients with diabetic polyneuropathy. PLoS One 2022; 17 (02) e0263831
    CrossrefPubMedSearch in Google Scholar
  • 14 Lopate G, Streif E, Harms M, Weihl C, Pestronk A. Cramps and small-fiber neuropathy. Muscle Nerve 2013; 48 (02) 252-255
    CrossrefPubMedSearch in Google Scholar
  • 15 Shillo P, Sloan G, Greig M. et al. Painful and painless diabetic neuropathies: What is the difference?. Curr Diab Rep 2019; 19 (06) 32
    CrossrefPubMedSearch in Google Scholar
  • 16 Themistocleous AC, Ramirez JD, Shillo PR. 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 (05) 1132-1145
    CrossrefPubMedSearch in Google Scholar
  • 17 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 (05) 1418-1424
    CrossrefPubMedSearch in Google Scholar
  • 18 Gorson KC, Herrmann DN, Thiagarajan R. et al. Non-length dependent small fibre neuropathy/ganglionopathy. J Neurol Neurosurg Psychiatry 2008; 79 (02) 163-169
    CrossrefPubMedSearch in Google Scholar
  • 19 Lauria G, Sghirlanzoni A, Lombardi R, Pareyson D. Epidermal nerve fiber density in sensory ganglionopathies: clinical and neurophysiologic correlations. Muscle Nerve 2001; 24 (08) 1034-1039
    CrossrefPubMedSearch in Google Scholar
  • 20 Provitera V, Gibbons CH, Wendelschafer-Crabb G. et al. The role of skin biopsy in differentiating small-fiber neuropathy from ganglionopathy. Eur J Neurol 2018; 25 (06) 848-853
    CrossrefPubMedSearch in Google Scholar
  • 21 Lauria G, Majorana A, Borgna M. et al. Trigeminal small-fiber sensory neuropathy causes burning mouth syndrome. Pain 2005; 115 (03) 332-337
    CrossrefPubMedSearch in Google Scholar
  • 22 Lauria G, Devigili G. Skin biopsy as a diagnostic tool in peripheral neuropathy. Nat Clin Pract Neurol 2007; 3 (10) 546-557
    CrossrefPubMedSearch in Google Scholar
  • 23 Leone C, Galosi E, Esposito N. et al. Small-fibre damage is associated with distinct sensory phenotypes in patients with fibromyalgia and small-fibre neuropathy. Eur J Pain 2023; 27 (01) 163-173
    CrossrefPubMedSearch in Google Scholar
  • 24 Cazzato D, Castori M, Lombardi R. et al. Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes. Neurology 2016; 87 (02) 155-159
    CrossrefPubMedSearch in Google Scholar
  • 25 Igharo D, Thiel JC, Rolke R. et al. Skin biopsy reveals generalized small fibre neuropathy in hypermobile Ehlers-Danlos syndromes. Eur J Neurol 2023; 30 (03) 719-728
    CrossrefPubMedSearch in Google Scholar
  • 26 Cazzato D, Lauria G. Small fibre neuropathy. Curr Opin Neurol 2017; 30 (05) 490-499
    CrossrefPubMedSearch in Google Scholar
  • 27 Han C, Hoeijmakers JG, Liu S. et al. Functional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy. Brain 2012; 135 (Pt 9): 2613-2628
    CrossrefPubMedSearch in Google Scholar
  • 28 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 (05) 428-434
    CrossrefPubMedSearch in Google Scholar
  • 29 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 (03) 329-336
    CrossrefPubMedSearch in Google Scholar
  • 30 Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol 2014; 13 (09) 924-935
    CrossrefPubMedSearch in Google Scholar
  • 31 Balagny P, Wanono R, d'Ortho MP, Vidal-Petiot E. Reply to validation of the new diagnostic tests for neurogenic orthostatic hypotension. Ann Neurol 2018; 84 (06) 957-958
    CrossrefPubMedSearch in Google Scholar
  • 32 Wilkinson KD, Lee KM, Deshpande S, Duerksen-Hughes P, Boss JM, Pohl J. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science 1989; 246 (4930): 670-673
    CrossrefPubMedSearch in Google Scholar
  • 33 Dalsgaard CJ, Rydh M, Haegerstrand A. Cutaneous innervation in man visualized with protein gene product 9.5 (PGP 9.5) antibodies. Histochemistry 1989; 92 (05) 385-390
    CrossrefPubMedSearch in Google Scholar
  • 34 Joint Task Force of the EFNS and the PNS. 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. J Peripher Nerv Syst 2010; 15 (02) 79-92
    CrossrefPubMedSearch in Google Scholar
  • 35 Lauria G, Bakkers M, Schmitz C. et al. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv Syst 2010; 15 (03) 202-207
    CrossrefPubMedSearch in Google Scholar
  • 36 Provitera V, Gibbons CH, Wendelschafer-Crabb G. 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 (02) 333-338
    CrossrefPubMedSearch in Google Scholar
  • 37 Nolano M, Biasiotta A, Lombardi R. et al. Epidermal innervation morphometry by immunofluorescence and bright-field microscopy. J Peripher Nerv Syst 2015; 20 (04) 387-391
    CrossrefPubMedSearch in Google Scholar
  • 38 Lauria G, Morbin M, Lombardi R. et al. Axonal swellings predict the degeneration of epidermal nerve fibers in painful neuropathies. Neurology 2003; 61 (05) 631-636
    CrossrefPubMedSearch in Google Scholar
  • 39 Nolano M, Provitera V, Caporaso G, Stancanelli A, Vitale DF, Santoro L. Quantification of pilomotor nerves: a new tool to evaluate autonomic involvement in diabetes. Neurology 2010; 75 (12) 1089-1097
    CrossrefPubMedSearch in Google Scholar
  • 40 Gibbons CH, Illigens BM, Wang N, Freeman R. Quantification of sweat gland innervation: a clinical-pathologic correlation. Neurology 2009; 72 (17) 1479-1486
    CrossrefPubMedSearch in Google Scholar
  • 41 Baron R, Maier C, Attal N. et al; German Neuropathic Pain Research Network (DFNS), and the EUROPAIN, and NEUROPAIN consortia. Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain 2017; 158 (02) 261-272
    CrossrefPubMedSearch in Google Scholar
  • 42 Bakkers M, Faber CG, Reulen JP, Hoeijmakers JG, Vanhoutte EK, Merkies IS. Optimizing temperature threshold testing in small-fiber neuropathy. Muscle Nerve 2015; 51 (06) 870-876
    CrossrefPubMedSearch in Google Scholar
  • 43 Backonja MM, Attal N, Baron R. et al. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain 2013; 154 (09) 1807-1819
    CrossrefPubMedSearch in Google Scholar
  • 44 Magerl W, Krumova EK, Baron R, Tölle T, Treede RD, Maier C. Reference data for quantitative sensory testing (QST): refined stratification for age and a novel method for statistical comparison of group data. Pain 2010; 151 (03) 598-605
    CrossrefPubMedSearch in Google Scholar
  • 45 Egenolf N, Zu Altenschildesche CM, Kreß L. et al. Diagnosing small fiber neuropathy in clinical practice: a deep phenotyping study. Ther Adv Neurol Disord 2021; 14: 17 562864211004318
    CrossrefPubMedSearch in Google Scholar
  • 46 Tavakoli M, Ferdousi M, Petropoulos IN. et al. Normative values for corneal nerve morphology assessed using corneal confocal microscopy: a multinational normative data set. Diabetes Care 2015; 38 (05) 838-843
    CrossrefPubMedSearch in Google Scholar
  • 47 Tavakoli M, Marshall A, Pitceathly R. et al. Corneal confocal microscopy: a novel means to detect nerve fibre damage in idiopathic small fibre neuropathy. Exp Neurol 2010; 223 (01) 245-250
    CrossrefPubMedSearch in Google Scholar
  • 48 Gemignani F, Ferrari G, Vitetta F, Giovanelli M, Macaluso C, Marbini A. Non-length-dependent small fibre neuropathy. Confocal microscopy study of the corneal innervation. J Neurol Neurosurg Psychiatry 2010; 81 (07) 731-733
    CrossrefPubMedSearch in Google Scholar
  • 49 Gad H, Petropoulos IN, Khan A. et al. Corneal confocal microscopy for the diagnosis of diabetic peripheral neuropathy: a systematic review and meta-analysis. J Diabetes Investig 2022; 13 (01) 134-147
    CrossrefPubMedSearch in Google Scholar
  • 50 Gylfadottir SS, Itani M, Kristensen AG. et al. Assessing corneal confocal microscopy and other small fiber measures in diabetic polyneuropathy. Neurology 2023; 100 (16) e1680-e1690
    CrossrefPubMedSearch in Google Scholar
  • 51 Cheshire WP, Freeman R, Gibbons CH. 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 (02) 666-682
    CrossrefPubMedSearch in Google Scholar
  • 52 Kaur D, Tiwana H, Stino A, Sandroni P. Autonomic neuropathies. Muscle Nerve 2021; 63 (01) 10-21
    CrossrefPubMedSearch in Google Scholar
  • 53 Gandhi RA, Marques JL, Selvarajah D, Emery CJ, Tesfaye S. Painful diabetic neuropathy is associated with greater autonomic dysfunction than painless diabetic neuropathy. Diabetes Care 2010; 33 (07) 1585-1590
    CrossrefPubMedSearch in Google Scholar
  • 54 Thaisetthawatkul P, Fernandes Filho JA, Herrmann DN. Autonomic evaluation is independent of somatic evaluation for small fiber neuropathy. J Neurol Sci 2014; 344 (1-2): 51-54
    CrossrefPubMedSearch in Google Scholar
  • 55 Rasmussen TK, Karlsson P, Finnerup NB, Jensen TS, Nyengaard JR, Terkelsen AJ. Functional and structural markers of peripheral microvascular autonomic neuropathy. Muscle Nerve 2023; 67 (02) 146-153
    CrossrefPubMedSearch in Google Scholar
  • 56 D'Amato C, Morganti R, Di Gennaro F, Greco C, Marfia GA, Spallone V. A novel association between nondipping and painful diabetic polyneuropathy. Diabetes Care 2014; 37 (09) 2640-2642
    CrossrefPubMedSearch in Google Scholar
  • 57 Thaisetthawatkul P, Fernandes Filho JA, Herrmann DN. Contribution of QSART to the diagnosis of small fiber neuropathy. Muscle Nerve 2013; 48 (06) 883-888
    CrossrefPubMedSearch in Google Scholar
  • 58 Berger MJ, Kimpinski K. Test-retest reliability of quantitative sudomotor axon reflex testing. J Clin Neurophysiol 2013; 30 (03) 308-312
    CrossrefPubMedSearch in Google Scholar
  • 59 Tavee JO, Polston D, Zhou L, Shields RW, Butler RS, Levin KH. Sural sensory nerve action potential, epidermal nerve fiber density, and quantitative sudomotor axon reflex in the healthy elderly. Muscle Nerve 2014; 49 (04) 564-569
    CrossrefPubMedSearch in Google Scholar
  • 60 Tsapas A, Liakos A, Paschos P. et al. A simple plaster for screening for diabetic neuropathy: a diagnostic test accuracy systematic review and meta-analysis. Metabolism 2014; 63 (04) 584-592
    CrossrefPubMedSearch in Google Scholar
  • 61 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 (01) 50-56
    CrossrefPubMedSearch in Google Scholar
  • 62 Gibbons CH, Illigens BM, Centi J, Freeman R. QDIRT: quantitative direct and indirect test of sudomotor function. Neurology 2008; 70 (24) 2299-2304
    CrossrefPubMedSearch in Google Scholar
  • 63 Sopacua M, Gorissen-Brouwers CML, de Greef BTA. et al. The applicability of the digit wrinkle scan to quantify sympathetic nerve function. Clin Neurophysiol Pract 2022; 7: 115-119
    CrossrefPubMedSearch in Google Scholar
  • 64 Abraham A, Alabdali M, Alsulaiman A. et al. Laser Doppler flare imaging and quantitative thermal thresholds testing performance in small and mixed fiber neuropathies. PLoS One 2016; 11 (11) e0165731
    CrossrefPubMedSearch in Google Scholar
  • 65 Hijazi MM, Buchmann SJ, Sedghi A. et al. Assessment of cutaneous axon-reflex responses to evaluate functional integrity of autonomic small nerve fibers. Neurol Sci 2020; 41 (07) 1685-1696
    CrossrefPubMedSearch in Google Scholar
  • 66 Devigili G, Rinaldo S, Lombardi R. et al. Diagnostic criteria for small fibre neuropathy in clinical practice and research. Brain 2019; 142 (12) 3728-3736
    CrossrefPubMedSearch in Google Scholar
  • 67 IDF Diabetes Atlas. 2024. Accessed September 27, 2024 at: https://diabetesatlas.org/
    PubMed
  • 68 Russell JW, Zilliox LA. Diabetic neuropathies. Continuum (Minneapolis, Minn) 2014; 20 (5 Peripheral Nervous System Disorders): 1226-1240
    PubMedSearch in Google Scholar
  • 69 Zhou L, Li J, Ontaneda D, Sperling J. Metabolic syndrome in small fiber sensory neuropathy. J Clin Neuromuscul Dis 2011; 12 (04) 235-243
    CrossrefPubMedSearch in Google Scholar
  • 70 Kazamel M, Stino AM, Smith AG. Metabolic syndrome and peripheral neuropathy. Muscle Nerve 2021; 63 (03) 285-293
    CrossrefPubMedSearch in Google Scholar
  • 71 Isomaa B, Henricsson M, Almgren P, Tuomi T, Taskinen MR, Groop L. The metabolic syndrome influences the risk of chronic complications in patients with type II diabetes. Diabetologia 2001; 44 (09) 1148-1154
    CrossrefPubMedSearch in Google Scholar
  • 72 Callaghan BC, Xia R, Reynolds E. et al. Association between metabolic syndrome components and polyneuropathy in an obese population. JAMA Neurol 2016; 73 (12) 1468-1476
    CrossrefPubMedSearch in Google Scholar
  • 73 Callaghan BC, Xia R, Banerjee M. et al; Health ABC Study. Metabolic syndrome components are associated with symptomatic polyneuropathy independent of glycemic status. Diabetes Care 2016; 39 (05) 801-807
    CrossrefPubMedSearch in Google Scholar
  • 74 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 (01) 10-28
    CrossrefPubMedSearch in Google Scholar
  • 75 Gendre T, Lefaucheur JP, Nordine T. et al. Characterizing acute-onset small fiber neuropathy. Neurol Neuroimmunol Neuroinflamm 2024; 11 (02) e200195
    CrossrefPubMedSearch in Google Scholar
  • 76 Liampas A, Parperis K, Erotocritou MF. et al. Primary Sjögren syndrome-related peripheral neuropathy: a systematic review and meta-analysis. Eur J Neurol 2023; 30 (01) 255-265
    CrossrefPubMedSearch in Google Scholar
  • 77 Descamps E, Henry J, Labeyrie C. et al. Small fiber neuropathy in Sjögren syndrome: comparison with other small fiber neuropathies. Muscle Nerve 2020; 61 (04) 515-520
    CrossrefPubMedSearch in Google Scholar
  • 78 Tavee J. Peripheral neuropathy in sarcoidosis. J Neuroimmunol 2022; 368: 577864
    CrossrefPubMedSearch in Google Scholar
  • 79 Gavrilova N, Starshinova A, Zinchenko Y. et al. Small fiber neuropathy in sarcoidosis. Pathophysiology 2021; 28 (04) 544-550
    CrossrefPubMedSearch in Google Scholar
  • 80 Levine TD, Kafaie J, Zeidman LA. et al. Cryptogenic small-fiber neuropathies: serum autoantibody binding to trisulfated heparin disaccharide and fibroblast growth factor receptor-3. Muscle Nerve 2020; 61 (04) 512-515
    CrossrefPubMedSearch in Google Scholar
  • 81 Pestronk A, Schmidt RE, Choksi RM, Sommerville RB, Al-Lozi MT. Clinical and laboratory features of neuropathies with serum IgM binding to TS-HDS. Muscle Nerve 2012; 45 (06) 866-872
    CrossrefPubMedSearch in Google Scholar
  • 82 Pestronk A, Choksi R, Logigian E, Al-Lozi MT. Sensory neuropathy with monoclonal IgM binding to a trisulfated heparin disaccharide. Muscle Nerve 2003; 27 (02) 188-195
    CrossrefPubMedSearch in Google Scholar
  • 83 Antoine JC, Boutahar N, Lassablière F. et al. Antifibroblast growth factor receptor 3 antibodies identify a subgroup of patients with sensory neuropathy. J Neurol Neurosurg Psychiatry 2015; 86 (12) 1347-1355
    CrossrefPubMedSearch in Google Scholar
  • 84 Daifallah O, Farah A, Dawes JM. A role for pathogenic autoantibodies in small fiber neuropathy?. Front Mol Neurosci 2023; 16: 1254854
    CrossrefPubMedSearch in Google Scholar
  • 85 Fujii T, Lee EJ, Miyachi Y. et al. Antiplexin D1 antibodies relate to small fiber neuropathy and induce neuropathic pain in animals. Neurol Neuroimm 2021; 8 (05) e1028
    CrossrefPubMedSearch in Google Scholar
  • 86 Ramanathan S, Tseng M, Davies AJ. et al. Leucine-rich glioma-inactivated 1 versus contactin-associated protein-like 2 antibody neuropathic pain: clinical and biological comparisons. Ann Neurol 2021; 90 (04) 683-690
    CrossrefPubMedSearch in Google Scholar
  • 87 Di Giacomo R, Rossi Sebastiano D, Cazzato D. et al. Expanding clinical spectrum of Caspr2 antibody-associated disease: warning on brainstem involvement and respiratory failure. J Neurol Sci 2020; 413: 116865
    CrossrefPubMedSearch in Google Scholar
  • 88 Chan ACY, Wong HY, Chong YF. et al. Novel autoantibodies in idiopathic small fiber neuropathy. Ann Neurol 2022; 91 (01) 66-77
    CrossrefPubMedSearch in Google Scholar
  • 89 Shikuma CM, Bennett K, Ananworanich J. et al; SEARCH 003 Protocol Team. Distal leg epidermal nerve fiber density as a surrogate marker of HIV-associated sensory neuropathy risk: risk factors and change following initial antiretroviral therapy. J Neurovirol 2015; 21 (05) 525-534
    CrossrefPubMedSearch in Google Scholar
  • 90 Mariotto S, Ferrari S, Monaco S. HCV-related central and peripheral nervous system demyelinating disorders. Inflamm Allergy Drug Targets 2014; 13 (05) 299-304
    CrossrefPubMedSearch in Google Scholar
  • 91 Leng A, Shah M, Ahmad SA. et al. Pathogenesis underlying neurological manifestations of long COVID syndrome and potential therapeutics. Cells 2023; 12 (05) 816
    CrossrefPubMedSearch in Google Scholar
  • 92 Negrut N, Menegas G, Kampioti S. et al. The multisystem impact of long COVID: a comprehensive review. Diagnostics (Basel, Switzerland) 2024; 14 (03) 244
    PubMedSearch in Google Scholar
  • 93 Hoeijmakers JGJ, Merkies ISJ, Faber CG. Small fiber neuropathies: expanding their etiologies. Curr Opin Neurol 2022; 35 (05) 545-552
    PubMedSearch in Google Scholar
  • 94 Abrams RMC, Simpson DM, Navis A, Jette N, Zhou L, Shin SC. Small fiber neuropathy associated with SARS-CoV-2 infection. Muscle Nerve 2022; 65 (04) 440-443
    CrossrefPubMedSearch in Google Scholar
  • 95 Oaklander AL, Mills AJ, Kelley M. et al. Peripheral neuropathy evaluations of patients with prolonged long COVID. Neurol Neuroimmunol Neuroinflamm 2022; 9 (03) e1146
    CrossrefPubMedSearch in Google Scholar
  • 96 Shouman K, Vanichkachorn G, Cheshire WP. et al. Autonomic dysfunction following COVID-19 infection: an early experience. Clin Auton Res 2021; 31 (03) 385-394
    CrossrefPubMedSearch in Google Scholar
  • 97 Finsterer J, Scorza FA, Scorza CA, de Almeida AG. Small fiber neuropathy with long-term, multifocal paresthesias after a SARS-CoV-2 vaccination. Clinics (Sao Paulo) 2023; 78: 100186
    CrossrefPubMedSearch in Google Scholar
  • 98 Faber CG, Hoeijmakers JG, Ahn HS. et al. Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. Ann Neurol 2012; 71 (01) 26-39
    CrossrefPubMedSearch in Google Scholar
  • 99 Faber CG, Lauria G, Merkies IS. et al. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc Natl Acad Sci U S A 2012; 109 (47) 19444-19449
    CrossrefPubMedSearch in Google Scholar
  • 100 Huang J, Han C, Estacion M. et al; PROPANE Study Group. Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy. Brain 2014; 137 (Pt 6): 1627-1642
    CrossrefPubMedSearch in Google Scholar
  • 101 Alsaloum M, Estacion M, Almomani R. et al; Propane Study Group. A gain-of-function sodium channel β2-subunit mutation in painful diabetic neuropathy. Mol Pain 2019; 15: 17 44806919849802
    CrossrefPubMedSearch in Google Scholar
  • 102 Alsaloum M, Labau JIR, Sosniak D. et al. A novel gain-of-function sodium channel β2 subunit mutation in idiopathic small fiber neuropathy. J Neurophysiol 2021; 126 (03) 827-839
    CrossrefPubMedSearch in Google Scholar
  • 103 Hoeijmakers JG, Han C, Merkies IS. et al. Small nerve fibres, small hands and small feet: a new syndrome of pain, dysautonomia and acromesomelia in a kindred with a novel NaV1.7 mutation. Brain 2012; 135 (Pt 2): 345-358
    CrossrefPubMedSearch in Google Scholar
  • 104 Waxman SG, Merkies ISJ, Gerrits MM. et al. Sodium channel genes in pain-related disorders: phenotype-genotype associations and recommendations for clinical use. Lancet Neurol 2014; 13 (11) 1152-1160
    CrossrefPubMedSearch in Google Scholar
  • 105 Marchi M, Salvi E, Andelic M. et al. TRPA1 rare variants in chronic neuropathic and nociplastic pain patients. Pain 2023; 164 (09) 2048-2059
    CrossrefPubMedSearch in Google Scholar
  • 106 Masuda T, Ueda M, Suenaga G. et al. Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy. Neurology 2017; 88 (23) 2192-2197
    CrossrefPubMedSearch in Google Scholar
  • 107 Leonardi L, Adam C, Beaudonnet G. et al. Skin amyloid deposits and nerve fiber loss as markers of neuropathy onset and progression in hereditary transthyretin amyloidosis. Eur J Neurol 2022; 29 (05) 1477-1487
    CrossrefPubMedSearch in Google Scholar
  • 108 Chan ACY, Kumar S, Tan G. et al. Expanding the genetic causes of small-fiber neuropathy: SCN genes and beyond. Muscle Nerve 2023; 67 (04) 259-271
    CrossrefPubMedSearch in Google Scholar
  • 109 Devigili G, De Filippo M, Ciana G. et al. Chronic pain in Gaucher disease: skeletal or neuropathic origin?. Orphanet J Rare Dis 2017; 12 (01) 148
    CrossrefPubMedSearch in Google Scholar
  • 110 Farschtschi SC, Mainka T, Glatzel M. et al. C-fiber loss as a possible cause of neuropathic pain in Schwannomatosis. Int J Mol Sci 2020; 21 (10) 3569
    CrossrefPubMedSearch in Google Scholar
  • 111 Barnett C, Alon T, Abraham A. et al. Evidence of small-fiber neuropathy in neurofibromatosis type 1. Muscle Nerve 2019; 60 (06) 673-678
    CrossrefPubMedSearch in Google Scholar
  • 112 Tagliapietra M, Incensi A, Ferrarini M. et al. Clinical and pathology characterization of small nerve fiber neuro(no)pathy in cerebellar ataxia with neuropathy and vestibular areflexia syndrome. Eur J Neurol 2023; 30 (12) 3834-3841
    CrossrefPubMedSearch in Google Scholar
  • 113 Dalla Bella E, Lombardi R, Porretta-Serapiglia C. et al. Amyotrophic lateral sclerosis causes small fiber pathology. Eur J Neurol 2016; 23 (02) 416-420
    CrossrefPubMedSearch in Google Scholar
  • 114 Grayston R, Czanner G, Elhadd K. et al. A systematic review and meta-analysis of the prevalence of small fiber pathology in fibromyalgia: implications for a new paradigm in fibromyalgia etiopathogenesis. Semin Arthritis Rheum 2019; 48 (05) 933-940
    CrossrefPubMedSearch in Google Scholar
  • 115 Smith AG, Russell J, Feldman EL. et al. Lifestyle intervention for pre-diabetic neuropathy. Diabetes Care 2006; 29 (06) 1294-1299
    CrossrefPubMedSearch in Google Scholar
  • 116 Finnerup NB, Attal N, Haroutounian S. et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14 (02) 162-173
    CrossrefPubMedSearch in Google Scholar
  • 117 Attal N, de Andrade DC, Adam F. et al. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2016; 15 (06) 555-565
    CrossrefPubMedSearch in Google Scholar
  • 118 McDonnell A, Collins S, Ali Z. et al. Efficacy of the Nav1.7 blocker PF-05089771 in a randomised, placebo-controlled, double-blind clinical study in subjects with painful diabetic peripheral neuropathy. Pain 2018; 159 (08) 1465-1476
    CrossrefPubMedSearch in Google Scholar
  • 119 Labau JIR, Estacion M, Tanaka BS. et al. Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy. Brain 2020; 143 (03) 771-782
    CrossrefPubMedSearch in Google Scholar
  • 120 de Greef BTA, Hoeijmakers JGJ, Geerts M. et al. Lacosamide in patients with Nav1.7 mutations-related small fibre neuropathy: a randomized controlled trial. Brain 2019; 142 (02) 263-275
    CrossrefPubMedSearch in Google Scholar
  • 121 Oaklander AL, Klein MM. Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes. Pediatrics 2013; 131 (04) e1091-e1100
    CrossrefPubMedSearch in Google Scholar
  • 122 Gaillet A, Champion K, Lefaucheur JP, Trout H, Bergmann JF, Sène D. Intravenous immunoglobulin efficacy for primary Sjögren's syndrome associated small fiber neuropathy. Autoimmun Rev 2019; 18 (11) 102387
    CrossrefPubMedSearch in Google Scholar
  • 123 Tavee JO, Karwa K, Ahmed Z, Thompson N, Parambil J, Culver DA. Sarcoidosis-associated small fiber neuropathy in a large cohort: clinical aspects and response to IVIG and anti-TNF alpha treatment. Respir Med 2017; 126: 135-138
    CrossrefPubMedSearch in Google Scholar
  • 124 Gibbons CH, Rajan S, Senechal K, Hendry E, McCallister B, Levine TD. A double-blind placebo-controlled pilot study of immunoglobulin for small fiber neuropathy associated with TS-HDS and FGFR-3 autoantibodies. Muscle Nerve 2023; 67 (05) 363-370
    CrossrefPubMedSearch in Google Scholar
  • 125 Geerts M, de Greef BTA, Sopacua M. et al. Intravenous immunoglobulin therapy in patients with painful idiopathic small fiber neuropathy. Neurology 2021; 96 (20) e2534-e2545
    CrossrefPubMedSearch in Google Scholar
  • 126 van Beek M, Geurts JW, Slangen R. et al. Severity of neuropathy is associated with long-term spinal cord stimulation outcome in painful diabetic peripheral neuropathy: five-year follow-up of a prospective two-center clinical trial. Diabetes Care 2018; 41 (01) 32-38
    CrossrefPubMedSearch in Google Scholar
  • 127 Weisman A, Quintner J. On “a mechanism-based approach to physical therapist management of pain.” . Phys Ther 2018; 98 (09) 817
    PubMedSearch in Google Scholar
  • 128 Damci A, Schruers KRJ, Leue C, Faber CG, Hoeijmakers JGJ. Anxiety and depression in small fiber neuropathy. J Peripher Nerv Syst 2022; 27 (04) 291-301
    CrossrefPubMedSearch in Google Scholar
  • 129 Telesca A, Soldini E, Devigili G. et al. Cognitive, behavioral, and psychological phenotypes in small fiber neuropathy: a case-control study. Cortex 2024; 173: 208-221
    CrossrefPubMedSearch in Google Scholar
  • 130 Pindi Sala T, Villedieu M, Damian L. et al. Long-term efficacy of immunoglobulins in small fiber neuropathy related to Sjögren's syndrome. J Neurol 2020; 267 (12) 3499-3507
    CrossrefPubMedSearch in Google Scholar
  • 131 Khoshnoodi MA, Truelove S, Burakgazi A, Hoke A, Mammen AL, Polydefkis M. Longitudinal assessment of small fiber neuropathy: evidence of a non-length-dependent distal axonopathy. JAMA Neurol 2016; 73 (06) 684-690
    CrossrefPubMedSearch in Google Scholar
  • 132 Flossdorf P, Haupt WF, Brunn A. et al. Long-time course of idiopathic small fiber neuropathy. Eur Neurol 2018; 79 (3-4): 161-165
    CrossrefPubMedSearch in Google Scholar
  • 133 MacDonald S, Sharma TL, Li J, Polston D, Li Y. Longitudinal follow-up of biopsy-proven small fiber neuropathy. Muscle Nerve 2019; 60 (04) 376-381
    CrossrefPubMedSearch in Google Scholar
  • 134 Shouman K, Sandroni P. Antibody testing for suspected autoimmune autonomic dysfunction and small fiber neuropathies. J Clin Neurophysiol 2021; 38 (04) 274-278
    CrossrefPubMedSearch in Google Scholar
  • 135 de Greef BT, Hoeijmakers JG, Wolters EE. et al. No Fabry disease in patients presenting with isolated small fiber neuropathy. PLoS One 2016; 11 (02) e0148316
    CrossrefPubMedSearch in Google Scholar