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

Abstract

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.

Measuring peripheral nerve involvement in Friedreich’s ataxia

“…Among the measures evaluated, our data provide evidence for the potential utility of MC densities via in‐vivo RCM, ENFD, and QST thresholds as sensory markers in FRDA. This compliments prior studies supporting MC imaging via RCM as a noninvasive and objective measure of sensory neuropathies …”

“…In‐vivo RCM of MCs was performed on the palmar surface of the distal phalanx of digit V, the midpoint of the thenar eminence (TE), and midpoint of the medial sole (arch) of the foot on the nondominant side . MC imaging was performed by a trained microscopist using the Vivascope 3000 (Caliber I.D.…”

“…Vibration detection thresholds and cooling detection thresholds, expressed as just noticeable differences (JND), were assessed using the Case IV system (WR Medical Electronics Company, Maplewood, Minnesota) and a 4‐2‐1 algorithm . Timed vibration sensation thresholds using a 128 Hz tuning fork were also determined . Vibration thresholds were assessed at the first interphalangeal joints of the great toe and index finger and cooling thresholds were assessed over the dorsal surfaces of the hand and foot, on the nondominant side.…”

“…Analysis of covariance (ANCOVA) based on ranks was used to compare MC density, diameter, and area between individuals with FRDA and unaffected controls at each imaging site with a two‐tailed significance level of 5% . Models for hand digit V and thenar eminence were adjusted for age, sex, and hand surface area and those for the arch were adjusted for age, sex, and foot surface area …”

“…Meissner’s corpuscle (MC) densities, the main touch‐pressure sensory receptor in glabrous skin (hands and feet), are also reduced in FRDA, but have not been widely measured, as glabrous skin biopsies are invasive and not suitable for serial monitoring . In‐vivo reflectance confocal microscopy (RCM) of skin is a noninvasive way to quantify MC density, which has recently emerged as a sensitive measure of sensory polyneuropathies and has potential utility as a marker of large sensory nerve fiber involvement in FRDA …”