In Vivo Reflectance Microscopy of Meissner Corpuscles and Bedside Measures of Large Fiber Sensory Function: A Normative Data Cohort

Abstract

Background and objectives: The goal of this work was to establish age-, sex-, and body dimension-adjusted normal cutoff values for Meissner corpuscle (MC) densities via in vivo reflectance confocal microscopy (RCM), timed vibration sensory thresholds with a 128-Hz tuning fork, and touch-pressure sensory thresholds with standardized monofilaments for clinical and research application.

Methods: Seventy-seven prospectively recruited individuals without signs or symptoms of peripheral neuropathy or a condition or neurotoxin exposure that can alter sensory function underwent cross-sectional evaluation of MC densities via in vivo RCM, monofilament touch-pressure sensory thresholds, and timed vibration sensory thresholds in nondominant upper and lower extremities. Age-, sex-, and body dimension (e.g., height)-adjusted normal values were developed. The fifth percentile for MC densities and timed vibration thresholds and 95th percentile for MF touch-pressure thresholds were selected as normal cutoff points.

Results: Participants were 9 to 89 years of age. Age and sex were uniformly distributed. Timed vibration and touch-pressure thresholds were less sensitive with increasing age and were more sensitive in the hand than in the leg or foot within individuals. Timed vibration thresholds did not differ by sex or body dimensions. Touch-pressure thresholds were lower (more sensitive) at the thenar eminence and digit V in the hand in women compared to men but otherwise did not differ by sex at other measurement locations. Body dimensions did not affect touch-pressure thresholds. There were no apparent age-related floor effects for the 5th and 95th percentile normal cutoff values for timed vibration or touch-pressure thresholds, respectively. MC densities also declined with age and were highest at digit V and lowest at the arch within individuals. MC densities were affected by sex or body dimensions at all imaging sites, with lower densities seen in male participants or larger individuals. MC densities were quantifiable in the hand of all participants and were associated with touch-pressure thresholds at all locations.

Discussion: This study establishes age-, sex-, and body dimension-adjusted normal cutoff values for 2 easily applied measures of large fiber sensory function and RCM assessment of MC densities for multiple limb locations. These results will aid in the detection and monitoring of peripheral sensory nerve disorders.

Figure 1. Scatterplots of Timed Vibration Sensory Thresholds at the Index Finger (Digit II), Great Toe, Tibial Tuberosity, Medial Malleolus, and Metatarsophalangeal Joint (MTP) With Adjusted 95th and 5th Percentiles by Age

Figure 2. Scatterplots of Meissner Corpuscle (MC) Densities and Monofilament (MF) Touch-Pressure Sensory Thresholds at Digit V of the Hand, Thenar Eminence (TE), and Foot Arch With Adjusted 95th and 5th Percentiles by Age

Figure 3. Scatterplots of Monofilament (MF) Touch-Pressure Sensory Thresholds at the Palmar Surface of the Distal Phalanx of the Index Finger (Digit II) and Great Toe With Adjusted 95th and 5th Percentiles by Age

Figure 4. In Vivo RCM Images of MC

Representative 0.75 × 0.75–mm images obtained from the palmar surface of the distal phalanx of digit V using in vivo reflectance confocal microscopy (RCM) in a (A) 19-year-old, (B) 55-year-old, and (C) 82-year-old. White arrows highlight Meissner corpuscles (MC).