Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec 1;142(12):3728-3736.
doi: 10.1093/brain/awz333.

Diagnostic criteria for small fibre neuropathy in clinical practice and research

Grazia Devigili  1 , Sara Rinaldo  1 , Raffaella Lombardi  2 , Daniele Cazzato  2 , Margherita Marchi  2 , Erika Salvi  2 , Roberto Eleopra  1 , Giuseppe Lauria  2   3
Affiliations

Diagnostic criteria for small fibre neuropathy in clinical practice and research

Grazia Devigili et al. Brain. .

Abstract

The diagnostic criteria for small fibre neuropathy are not established, influencing the approach to patients in clinical practice, their access to disease-modifying and symptomatic treatments, the use of healthcare resources, and the design of clinical trials. To address these issues, we performed a reappraisal study of 150 patients with sensory neuropathy and a prospective and follow-up validation study of 352 new subjects with suspected sensory neuropathy. Small fibre neuropathy diagnostic criteria were based on deep clinical phenotyping, quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD). Small fibre neuropathy was ruled out in 5 of 150 patients (3.3%) of the reappraisal study. Small fibre neuropathy was diagnosed at baseline of the validation study in 149 of 352 patients (42.4%) based on the combination between two clinical signs and abnormal QST and IENFD (69.1%), abnormal QST alone (5.4%), or abnormal IENFD alone (20.1%). Eight patients (5.4%) had abnormal QST and IENFD but no clinical signs. Further, 38 patients complained of sensory symptoms but showed no clinical signs. Of those, 34 (89.4%) had normal QST and IENFD, 4 (10.5%) had abnormal QST and normal IENFD, and none had abnormal IENFD alone. At 18-month follow-up, 19 of them (56%) reported the complete recovery of symptoms and showed normal clinical, QST and IENFD findings. None of those with one single abnormal test (QST or IENFD) developed clinical signs or showed abnormal findings on the other test. Conversely, all eight patients with abnormal QST and IENFD at baseline developed clinical signs at follow-up. The combination of clinical signs and abnormal QST and/or IENFD findings can more reliably lead to the diagnosis of small fibre neuropathy than the combination of abnormal QST and IENFD findings in the absence of clinical signs. Sensory symptoms alone should not be considered a reliable screening feature. Our findings demonstrate that the combined clinical, functional and structural approach to the diagnosis of small fibre neuropathy is reliable and relevant both for clinical practice and clinical trial design.

Keywords: diagnostic criteria; neuropathic pain; quantitative sensory testing; skin biopsy; small fibre neuropathy.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Flow-chart of the diagnostic assessment of patients included in the validation study.
See this image and copyright information in PMC

References

    1. Alsaloum M, Estacion M, Almomani R, Gerrits M, Bonhof G, Ziegler D, et al.A gain-of-function sodium channel beta2 subunit mutation in painful diabetic neuropathy. Mol Pain 2019; 15: 1744806919849802. - PMC - PubMed
    1. 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. - PubMed
    1. 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. - PubMed
    1. Bartesaghi L, Wang Y, Fontanet P, Wanderoy S, Berger F, Wu H, et al.PRDM12 is required for initiation of the nociceptive neuron lineage during neurogenesis. Cell Rep 2019; 26: 3484–92e4. - PMC - PubMed
    1. Bennett DL, Woods CG. Painful and painless channelopathies. Lancet Neurol 2014; 13: 587–99. - PubMed

Publication types