Small Fiber Neuropathy – The Under-Diagnosed Peripheral Neuropathy

In an interview with Harvard Medical School’s Harvard Health, Dr. Khosro Farhad, a neuropathy expert at Harvard-affiliated Massachusetts General Hospital, noted that small-fiber neuropathy is generally underdiagnosed because routine neurological exams and tests cannot accurately discriminate between large-fiber and small-fiber neuropathy.

In a literature review of diabetic peripheral neuropathy diagnostic and screening technologies in the Journal of Diabetes Science and Technology, Kelley Newlin Lew et al pointed out that the body of research backs up the assertion that distal symmetrical peripheral neuropathy – including both small- and large-fiber neuropathy – is underdiagnosed in primary care (1).

The article points out:

Small- and large-nerve fiber DSPN (distal symmetrical peripheral neuropathy) may present exclusively or together while each subtype may increase risk for foot ulceration due to reduced sensory function, and thereby heightened risk for lower extremity amputations. According to the ADA, the clinical history and physical examination often are sufficient for diagnosis of DSPN. Yet, up to 50% of individuals with DSPN may be asymptomatic.

Small-fiber DSPN typically precedes large-fiber neuropathy. Small-fiber DSPN impairs functional integrity of the small thinly myelinated Aδ and unmyelinated C fibers. These small, peripheral nerve fibers prominently convey pain to the central nervous system. In DSPN, they may stimulate profound pain. Small-fiber DSPN may also adversely affect local autonomic (eg, decreased sweating, dry skin, impaired vasomotion) and thermoreceptor (cold, warm sensations) functions.

Often, pain and other symptoms and signs first manifest in the feet and progress proximally to the lower extremities and, in some cases, to the hands with a stocking and glove pattern. However, some with small-fiber DSPN may not experience pain. A proportion of patients with small-fiber neuropathy may present with little evidence of the disease, which may delay DSPN diagnosis.

The primary care practitioner’s toolbox for diagnosing diabetic peripheral neuropathy has been very limited to date, with tools such as temperature and pin-prick sensation, 128-Hz tuning fork, and 10-g monofilament that are neither quantifiable nor reproducible and are prone to human error. Further, since the ADA Standards of Care only call for annual foot exams for people with a diagnosis of diabetes, a large number of patients with pre-diabetes accompanied by the onset of small fiber neuropathy, miss the chance for an early diagnosis (2,3).

Withings is focused intently on this deficit in detection technologies in primary care and other frontline environments. As Newlin Lew points out in the Journal of Diabetes Science and Technology article, the Sudoscan® Electrochemical Skin Conductance (ESC) technology being used in our Body Pro 2 device, and that has been used in clinical settings for nearly a decade, could play an important role in improving detection and monitoring:

When considered with respect to past and more recent research, Sudoscan has substantial evidence revealing it may potentially identify early DSPN (although this is not its main use) and monitor DSPN progression over time. Sudoscan also has adequate reproducibility and repeatability. Sudoscan is approved by the FDA and may be reimbursed through proper billing. Sudoscan is thus a POCD [point of care device] worthy of clinical adoption to detect and monitor DSPN in clinical settings.

Newlin Lew K, Arnold T, Cantelmo C, Jacque F, Posada-Quintero H, Luthra P, Chon KH. Diabetes Distal Peripheral Neuropathy: Subtypes and Diagnostic and Screening Technologies. Journal of Diabetes Science and Technology. 2022 Mar;16(2):295-320. doi: 10.1177/19322968211035375. Epub 2022 Jan 7. PMID: 34994241; PMCID: PMC8861801.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861801/Williams SM, Eleftheriadou A, Alam U, Cuthbertson DJ, Wilding JPH. Cardiac Autonomic Neuropathy in Obesity, the Metabolic Syndrome and Prediabetes: A Narrative Review. Diabetes Ther. 2019 Dec;10(6):1995-2021. doi: 10.1007/s13300-019-00693-0. Epub 2019 Sep 24. Erratum in: Diabetes Ther. 2019 Oct 4;: PMID: 31552598; PMCID: PMC6848658. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848658/Burgess J, Frank B, Marshall A, Khalil RS, Ponirakis G, Petropoulos IN, Cuthbertson DJ, Malik RA, Alam U. Early Detection of Diabetic Peripheral Neuropathy: A Focus on Small Nerve Fibres. Diagnostics (Basel). 2021 Jan 24;11(2):165. doi: 10.3390/diagnostics11020165. PMID: 33498918; PMCID: PMC7911433. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911433/

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