Manifestaciones clínicas, causas y examen físico | 20 MAY 18

Neuropatía de fibras pequeñas: un reto diagnóstico

La neuropatía de fibras pequeñas continua siendo de causa desconocida en hasta el 50% de los casos.
Autor/a: Terkelsen AJ, Karlsson P, Lauria G Lancet Neurol 2017; 16: 934–44
INDICE:  1. Página 1 | 2. Referencias bibliográficas
Referencias bibliográficas

1 Oaklander AL. Immunotherapy prospects for painful small-fiber sensory neuropathies and ganglionopathies. Neurotherapeutics 2016; 13: 108–17.

2 Themistocleous AC, Ramirez JD, Serra J, Bennett DL. The clinical approach to small fibre neuropathy and painful channelopathy. Pract Neurol 2014; 14: 368–79.

3 Peters MJ, Bakkers M, Merkies IS, et al. Incidence and prevalence of small-fiber neuropathy: a survey in the Netherlands. Neurology 2013; 81: 1356–60.

4 Uceyler N, Zeller D, Kahn AK, et al. Small fibre pathology in patients with fibromyalgia syndrome. Brain 2013; 136: 1857–67.

5 Dalla Bella E, Lombardi R, Porretta-Serapiglia C, et al. Amyotrophic lateral sclerosis causes small fiber pathology. Eur J Neurol 2016; 23: 416–20.

6 Cazzato D, Castori M, Lombardi R, et al. Small fiber neuropathy is a common feature of Ehlers–Danlos syndromes. Neurology 2016; 87: 155–59.

7 de Araujo DF, de Melo Neto AP, Oliveira IS, et al. Small (autonomic) and large fiber neuropathy in Parkinson disease and parkinsonism. BMC Neurol 2016; 16: 139.

8 Thaisetthawatkul P, Fernandes Filho JA, Herrmann DN. Autonomic evaluation is independent of somatic evaluation for small fiber neuropathy. J Neurol Sci 2014; 344: 51–54.

9 Hoeijmakers JG, Faber CG, Lauria G, et al. Small-fibre neuropathies—advances in diagnosis, pathophysiology and management. Nat Rev Neurol 2012; 8: 369–79.

10 Brouwer BA, Bakkers M, Hoeijmakers JG, et al. Improving assessment in small fiber neuropathy. J Periph Nerv Syst 2015; 20: 333–40.

11 Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 162–73.

12 McArthur JC. Painful small fiber neuropathies. Continuum 2012; 18: 106–25.

13 Mathias CJ, Bannister R. Autonomic failure: a textbook of clinical disorders of the autonomic nervous system, 5th edn. Oxford: Oxford University Press, 2013.

14 Khoshnoodi MA, Truelove S, Burakgazi A, et al. Longitudinal assessment of small fiber neuropathy: evidence of a non-lengthdependent distal axonopathy. JAMA Neurol 2016; 73: 684–90.

15 Pop-Busui R, Boulton AJ, Feldman EL, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care 2017; 40: 136–54.

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: 1132–45.

17 Bansal N. Prediabetes diagnosis and treatment: a review. World J Diabetes 2015; 6: 296–303.

18 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.

19 Waheed W, Boyd J, Khan F, et al. Double trouble: para-neoplastic anti-PCA-2 and CRMP-5-mediated small fibre neuropathy followed by chorea associated with small cell lung cancer and evolving radiological features. BMJ Case Rep 2016; 2016: bcr2016215158.

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

21 Gwathmey KG. Sensory neuronopathies. Muscle Nerve 2016; 53: 8–19.

22 Tomita M, Koike H, Kawagashira Y, et al. Clinicopathological features of neuropathy associated with lymphoma. Brain 2013; 136: 2563–78.

23 Puhakka A, Forssell H, Soinila S, et al. Peripheral nervous system involvement in primary burning mouth syndrome—results of a pilot study. Oral Dis 2016; 22: 338–44.

24 Lauria G, Lombardi R. Skin biopsy: a new tool for diagnosing peripheral neuropathy. BMJ 2007; 334: 1159–62.

25 Nolano M, Crisci C, Santoro L, et al. Absent innervation of skin and sweat glands in congenital insensitivity to pain with anhidrosis. Clin Neurophysiol 2000; 111: 1596–601.

26 Doppler K, Rittner HL, Deckart M, Sommer C. Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia. Pain 2015; 156: 2319–325.

27 Serra J, Collado A, Sola R, et al. Hyperexcitable C nociceptors in fibromyalgia. Ann Neurol 2014; 75: 196–208.

28 Oaklander AL, Herzog ZD, Downs HM, Klein MM. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain 2013; 154: 2310–16.

29 Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol 2014; 13: 924–35. Vol 16 November 2017 943 Review

30 Waxman SG. Painful Na-channelopathies: an expanding universe.Trends Mol Med 2013; 19: 406–09.

31 Zhao M, Isami K, Nakamura S, et al. Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice. Mol Pain 2012; 8: 55.

32 Faber CG, Hoeijmakers JG, Ahn HS, et al. Gain of function Nanu1.7 mutations in idiopathic small fiber neuropathy. Ann Neurol 2012; 71: 26–39.

33 Heij L, Niesters M, Swartjes M, et al. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med 2012; 18: 1430–36.

34 Treister R, Lodahl M, Lang M, et al. Initial development and validation of a patient-reported symptom survey for small-fiber polyneuropathy. J Pain 2017; 18: 556–63.

35 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.

36 Anish L, Nagappa M, Mahadevan A, Taly AB. Neuropathy in elderly: lessons learnt from nerve biopsy. Age Ageing 2015; 44: 312–17.

37 Rolke R, Baron R, Maier C, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006; 123: 231–43.

38 Thaisetthawatkul P, Fernandes Filho JA, Herrmann DN. Contribution of QSART to the diagnosis of small fiber neuropathy. Muscle Nerve 2013; 48: 883–88.

39 Petropoulos IN, Alam U, Fadavi H, et al. Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care 2013; 36: 3646–51.

40 Serra J. Microneurography: towards a biomarker of spontaneous pain. Pain 2012; 153: 1989–90.

41 Di Stefano G, La Cesa S, Leone C, et al. Diagnostic accuracy of laser evoked potentials in diabetic neuropathy. Pain 2017; 158: 1100–07.

42 Madsen CS, Johnsen B, Fuglsang-Frederiksen A, et al. The effect of nerve compression and capsaicin on contact heat-evoked potentials related to Aδ- and C-fibers. Neuroscience 2012; 223: 92–101.

43 Singleton JR, Bixby B, Russell JW, et al. The Utah Early Neuropathy Scale: a sensitive clinical scale for early sensory predominant neuropathy. J Peripher Nerv Syst 2008; 13: 218–227.

44 Herman WH, Pop-Busui R, Braffett BH, et al. 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.

45 Ziegler D, Edmundson S, Gurieva I, et al. Predictors of response to treatment with actovegin for 6 months in patients with type 2 diabetes and symptomatic polyneuropathy. J Diabetes Complications 2017; 31: 1181–87.

46 Zilliox LA, Ruby SK, Singh S, et al. Clinical neuropathy scales in neuropathy associated with impaired glucose tolerance. J Diabetes Complications 2015; 29: 372–77.

47 Devigili G, Tugnoli V, Penza P, et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain 2008; 131: 1912–25.

48 Backonja MM, Attal N, Baron R, et al. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain 2013; 154: 1807–19.

49 Baron R, Maier C, Attal N, et al. Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles. Pain 2016; 158: 261–72.

50 Freeman R, Baron R, Bouhassira D, et al. Sensory profiles of patients with neuropathic pain based on the neuropathic pain symptoms and signs. Pain 2014; 155: 367–76.

51 Kural MA, Pugdahl K, Fuglsang-Frederiksen A, et al. Near-nerve needle technique versus surface electrode recordings in electrodiagnosis of diabetic polyneuropathy. J Clin Neurophysiol 2016; 33: 346–49.

52 Siepmann T, Gibbons CH, Illigens BM, et al. Quantitative pilomotor axon-reflex test—a novel test of pilomotor function. Arch Neurol 2012; 69: 1488–92.

53 Sharma S, Venkitaraman R, Vas PR, Rayman G. Assessment of chemotherapy-induced peripheral neuropathy using the LDIFLARE technique: a novel technique to detect neural small fiber dysfunction. Brain Behav 2015; 5: e00354.

54 Uceyler N, Geng A, Reiners K, et al. Non-systemic vasculitic neuropathy: single-center follow-up of 60 patients. J Neurol 2015; 262: 2092–100.

55 Mantyh WG, Dyck PJ, Dyck PJ, et al. Epidermal nerve fiber quantification in patients with erythromelalgia. JAMA Dermatol 2017; 153: 162–67.

56 Lauria G, Bakkers M, Schmitz C, et al. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv System 2010; 15: 202–07.

57 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: 333–38.

58 Nolano M, Biasiotta A, Lombardi R, et al. Epidermal innervation morphometry by immunofluorescence and bright-field microscopy. J Peripher Nerv Syst 2015; 20: 387–91.

59 Lauria G, Dacci P, Lombardi R, et al. Side and time variability of intraepidermal nerve fiber density. Neurology 2015; 84: 2368–71.

60 Pan B, Byrnes K, Schwartz M, et al. Peripheral neuropathic changes in pachyonychia congenita. Pain 2016; 157: 2843–53.

61 Karlsson P, Moller AT, Jensen TS, Nyengaard JR. Epidermal nerve fiber length density estimation using global spatial sampling in healthy subjects and neuropathy patients. J Neuropathol Exp Neurol 2013; 72: 186–93.

62 Karlsson P, Porretta-Serapiglia C, Lombardi R, et al. Dermal innervation in healthy subjects and small fiber neuropathy patients: a stereological reappraisal. J Peripher Nerv Syst 2013; 18: 48–53.

63 Liu Y, Billiet J, Ebenezer GJ, et al. Factors influencing sweat gland innervation in diabetes. Neurology 2015; 84: 1652–59.

64 Cheng HT, Dauch JR, Porzio MT, et al. Increased axonal regeneration and swellings in intraepidermal nerve fibers characterize painful phenotypes of diabetic neuropathy. J Pain 2013; 14: 941–47.

65 Casanova-Molla J, Morales M, Planas-Rigol E, et al. Epidermal Langerhans cells in small fiber neuropathies. Pain 2012; 153: 982–89.

66 Schley M, Bayram A, Rukwied R, et al. Skin innervation at different depths correlates with small fibre function but not with pain in neuropathic pain patients. Eur J Pain 2012; 16: 1414–25.

67 Blackmore D, Siddiqi ZA. Diagnostic criteria for small fiber neuropathy. J Clin Neuromusc Dis 2017; 18: 125–31.

68 Freeman R, Chapleau MW. Testing the autonomic nervous system. Handb Clin Neurol 2013; 115: 115–36.

69 Ang L, Jaiswal M, Callaghan B, et al. Sudomotor dysfunction as a measure of small fiber neuropathy in type 1 diabetes. Auton Neurosci 2017; 205: 87–92.

70 Petropoulos IN, Alam U, Fadavi H, et al. Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy. Invest Ophthalmol Vis Sci 2014; 55: 2071–78.

71 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: 838–43.

72 Ahmed A, Bril V, Orszag A, et al. Detection of diabetic sensorimotor polyneuropathy by corneal confocal microscopy in type 1 diabetes: a concurrent validity study. Diabetes Care 2012; 35: 821–28.

73 Ziegler D, Papanas N, Zhivov A, et al. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes 2014; 63: 2454–63.

74 Azmi S, Ferdousi M, Petropoulos IN, et al. Corneal confocal microscopy shows an improvement in small-fiber neuropathy in subjects with type 1 diabetes on continuous subcutaneous insulin infusion compared with multiple daily injection. Diabetes Care 2015;

38: e3–4.

75 Bucher F, Schneider C, Blau T, et al. Small-fiber neuropathy is associated with corneal nerve and dendritic cell alterations: an in vivo confocal microscopy study. Cornea 2015; 34: 1114–19.

76 Gibbons CH. Small fiber neuropathies. Continuum 2014; 20: 1398–412.

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

78 Freeman R. Diabetic autonomic neuropathy. Handb Clin Neurol 2014; 126: 63–79.

79 Shikuma CM, Bennett K, Ananworanich J, et al. 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: 525–34.

80 Coutinho BM, Bordalo E, Nascimento OJ. Autonomic evaluation of hepatitis C virus infected patients. Arq Neuropsiquiatr 2013; 71: 537–39.

81 Ghosh PS, Mitra S, Fealey RD. Generalized anhidrosis in a child following presumptive H1N1 influenza. Clin Auton Res 2012; 22: 109–12.

82 Makonahalli R, Seneviratne J, Seneviratne U. Acute small fiber neuropathy following mycoplasma infection: a rare variant of Guillain-Barre syndrome. J Clin Neuromusc Dis 2014; 15: 147–51.

83 Mellion ML, Silbermann E, Gilchrist JM, et al. Small-fiber degeneration in alcohol-related peripheral neuropathy. Alcohol Clin Exp Res 2014; 38: 1965–72.

84 Saad M, Tafani C, Psimaras D, Ricard D. Chemotherapy-induced peripheral neuropathy in the adult. Curr Opin Oncol 2014; 26: 634–41.

85 Adams D, Suhr OB, Hund E, et al. First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy. Curr Opin Neurol 2016; 29 (suppl 1): S14–26.

86 de Greef BT, Hoeijmakers JG, Wolters EE, et al. No Fabry disease in patients presenting with isolated small fiber neuropathy. PLoS One 2016; 11: e0148316.

87 Fridman V, Oaklander AL, David WS, et al. Natural history and biomarkers in hereditary sensory neuropathy type 1. Muscle Nerve 2015; 51: 489–95.

88 Faber CG, Lauria G, Merkies IS, et al. Gain-of-function Nav1.8 mutations in painful neuropathy. Proc Natl Acad Sci USA 2012; 109: 19444–49.

89 Huang J, Han C, Estacion M, et al. Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy. Brain 2014; 137: 1627–42.

90 Han C, Yang Y, de Greef BT, et al. The domain II S4-S5 linker in Nav1.9: a missense mutation enhances activation, impairs fast inactivation, and produces human painful neuropathy. Neuromolecular Med 2015; 17: 158–69.

91 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: 2613–28.

92 Rolyan H, Liu S, Hoeijmakers JG, et al. A painful neuropathy associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels. Mol Pain 2016; 12: 1744806916674472.

93 Dib-Hajj SD, Geha P, Waxman SG. Sodium channels in pain disorders: pathophysiology and prospects for treatment. Pain 2017; 158 (suppl 1): s97–107.

94 Brouwer BA, Merkies IS, Gerrits MM, et al. Painful neuropathies: the emerging role of sodium channelopathies. J Peripher Nerv Syst 2014; 19: 53–65.

95 Waxman SG, Merkies IS, Gerrits MM, et al. Sodium channel genes in pain-related disorders: phenotype-genotype associations and recommendations for clinical use. Lancet Neurol 2014; 13: 1152–60.

96 Kapetis D, Sassone J, Yang Y, et al. Network topology of NaV1.7 mutations in sodium channel-related painful disorders. BMC Syst Biol 2017; 11: 28.

97 England JD, Gronseth GS, Franklin G, et al. Practice parameter: the evaluation of distal symmetric polyneuropathy: the role of laboratory and genetic testing (an evidence-based review). Report of the American Academy of Neurology, the American Association of

Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. PM R 2009; 1: 5–13.

98 Callaghan BC, Price RS, Feldman EL. Distal symmetric polyneuropathy: a review. JAMA 2015; 314: 2172–81.

99 Tesfaye S, Boulton AJ, Dyck PJ, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 2010; 33: 2285–93.

100 Malik RA, Veves A, Tesfaye S, et al. Small fibre neuropathy: role in the diagnosis of diabetic sensorimotor polyneuropathy. Diabetes Metab Res Rev 2011; 27: 678–84.

101 van Hecke O, Kamerman PR, Attal N, et al. Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic studies: a NeuPSIG systematic review, Delphi survey, and expert panel recommendations. Pain 2015; 156: 2337–5


Usted debe ingresar al sitio con su cuenta de usuario IntraMed para ver los comentarios de sus colegas o para expresar su opinión. Si ya tiene una cuenta IntraMed o desea registrase, ingrese aquí

Términos y condiciones de uso | Todos los derechos reservados | Copyright 1997-2020