Evaluation of dermal myelinated nerve fibers in diabetes mellitus

Peltier, Amanda; Myers, M. Iliza; Artibee, Kay; Hamilton, Audra; Yan, Qing; Guo, Jiasong; Shi, Yaping; Wang, Lily; Li, Jun

doi:10.1111/jns5.12027

Cited by 19 publications

(25 citation statements)

References 30 publications

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“…13, 14, 33, 34 Changes in MC densities correlate with changes in axon terminals of both myelinated and unmyelinated fibers. 11, 16, 17 Therefore, it stands to reason that MC density in the skin would be a useful marker of early diabetic DSP, a conclusion supported by biopsy studies and expanded upon with the present study. 11, 16, 17 …”

Section: Discussionsupporting

confidence: 77%

“…11, 16, 17 Therefore, it stands to reason that MC density in the skin would be a useful marker of early diabetic DSP, a conclusion supported by biopsy studies and expanded upon with the present study. 11, 16, 17 …”

Section: Discussionsupporting

confidence: 77%

“…4, 10, 11, 17, 24, 28–32 The earliest neuropathic changes in diabetic DSP are seen in the skin at the distal nerve terminals, which explains why NCS are not optimally sensitive for the detection of early diabetic DSP. 8, 28, 29 Meissner’s corpuscles are composed of axon terminals of A-β (myelinated) and C fiber (unmyelinated) sensory afferents and play a role in touch-pressure perception and possibly mechanical nociception.…”

Section: Discussionmentioning

confidence: 99%

“…13, 14 Glabrous skin biopsy studies have identified MC density (MC/mm 2 ) at the fingertip as a sensitive measure of diabetic DSP. 11, 13–17 However, MC density has not been widely used as a DSP marker, as glabrous skin biopsies are invasive, and not suitable for serial monitoring.…”

Section: Introductionmentioning

confidence: 99%

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In-vivo reflectance confocal microscopy of Meissner's corpuscles in diabetic distal symmetric polyneuropathy

Creigh

McDermott

Sowden

et al. 2017

Journal of the Neurological Sciences

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Objective To evaluate in-vivo reflectance confocal microscopy (RCM) of Meissner’s corpuscles (MC) in diabetic distal symmetric polyneuropathy (DSP). Methods Forty-three adults with diabetes and 21 control subjects underwent RCM of MC density at the fingertip of digit V, thenar eminence (TE), and arch of the foot, ankle skin biopsy for epidermal nerve fiber density (ENFD), electrophysiological studies, monofilament threshold testing, and timed vibration at the toe. Subjects with diabetes were subdivided into groups with and without clinical DSP using the American Academy of Neurology (AAN) case definition and neuropathy outcomes were compared across groups. Results Both diabetic groups (with and without AAN clinical DSP criteria) had objective evidence of peripheral sensory involvement using conventional sensory measures, although those with clinical DSP criteria had greater abnormalities. MC densities were lower in the entire diabetic group at the TE and digit V relative to controls. MC densities at all imaging sites were associated with corresponding conventional sensory measures. MC densities were reduced in subjects without AAN clinical DSP criteria at the TE and digit V compared to controls whereas conventional upper limb sensory measures did not differ between these groups. Conclusions In-vivo RCM of MC density at digit V is a non-invasive, painless, objective marker in diabetes that offers a window into early large fiber sensory nerve terminal loss. Further studies are needed to determine whether RCM of MCs can identify quantitative changes in DSP associated with disease progression or treatment.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In-vivo reflectance confocal microscopy of Meissner's corpuscles in diabetic distal symmetric polyneuropathy

Creigh

McDermott

Sowden

et al. 2017

Journal of the Neurological Sciences

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“…Analysis of pathologic changes in dermal myelinated fibers and MCs is an excellent diagnostic tool for assessing nerve degeneration in both hereditary and acquired peripheral neuropathies. A recent study of the nodal architecture has provided further insights into the pathologic processes underlying nerve pathology .…”

mentioning

confidence: 99%

A Model to Study Myelinated Fiber Degeneration and Regeneration in Human Skin

Provitera

Piscosquito

Manganelli

et al. 2020

Annals of Neurology

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Objective To describe morphological changes associated with degeneration and regeneration of large fibers in the skin using a model of chronic compression of the median nerve. Methods We studied cutaneous innervation in 30 patients with chronic compression of the median nerve at the wrist. Before surgery, we assessed the symptom severity and performed neurography, quantitative sensory testing, and analysis of nerve morphology and morphometry in skin biopsies from the third digit fingertip. Fifteen patients repeated all tests 12 months after the surgery. Thirty age‐ and sex‐matched healthy subjects were included in the study. Results Clinical and neurophysiological basal assessment showed a moderate involvement of the median nerve. Quantitative sensory testing showed abnormal findings. The density of intraepidermal nerve fibers and intrapapillary myelinated endings was reduced. Myelinated fibers showed caliber reduction and nodal elongation. Meissner corpuscles had normal density but were located deeper in the dermis and their capsule appeared partially empty. During follow‐up, patients exhibited a positive clinical and neurophysiological outcome. Quantitative sensory testing improved. Intraepidermal nerve fibers and intrapapillary myelinated endings remained unchanged, but the caliber of intrapapillary myelinated endings was increased. The neural component of the Meissner corpuscle filled the capsule of the mechanoreceptors that remained deeper in the dermis. The position of vasoactive intestinal peptide–immunoreactive fibers was more superficial compared to the basal assessment and controls. Interpretation We recognized and quantified the pathological changes associated with nerve degeneration and regeneration in skin and proposed new parameters that may increase the diagnostic yield of skin biopsy in clinical practice. Ann Neurol 2020;87:456–465

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Selecting a prospective test for early detection of diabetic polyneuropathy

et al. 2015

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Microneurolysis of entrapped peripheral nerve has the best chance of success when compression has not created significant axonal loss. The purpose of this study is to learn the best way to identify potential surgical candidates at the earliest time for intervention, by examining patients in a clinical setting using objective, electrodiagnostic nerve conduction studies (NCS), and subjective touch threshold studies, Semmes-Weinstein monofilaments (SWM) and Pressure-Specified Sensory Device™ (PSSD). Fifty-five patients with diabetic polyneuropathy over the age of 30 years were included. Neuropathy symptom score was the gold standard for statistical calculation, with a prevalence of 70%. In the symptomatic population, prevalence was 64% for NCS (n = 25), 59% for SWM (n = 43), and 88% for PSSD (n = 51). In the asymptomatic population, prevalence was 70% for NCS, 27% for SWM, and 92% for PSSD. It is concluded that the PSSD is the most sensitive device of those tested for identifying peripheral neuropathy in an at risk population of patients.

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Evaluation of dermal myelinated nerve fibers in diabetes mellitus

Cited by 19 publications

References 30 publications

In-vivo reflectance confocal microscopy of Meissner's corpuscles in diabetic distal symmetric polyneuropathy

In-vivo reflectance confocal microscopy of Meissner's corpuscles in diabetic distal symmetric polyneuropathy

A Model to Study Myelinated Fiber Degeneration and Regeneration in Human Skin

Selecting a prospective test for early detection of diabetic polyneuropathy

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