The Value of In Vivo Reflectance Confocal Microscopy as an Assessment Tool in Chemotherapy-Induced Peripheral Neuropathy: A Pilot Study

Abstract

Background There is a lack of standardized objective and reliable assessment tools for chemotherapy-induced peripheral neuropathy (CIPN). In vivo reflectance confocal microscopy (RCM) imaging offers a non-invasive method to identify peripheral neuropathy markers, namely Meissner’s corpuscles (MC). This study investigated the feasibility and value of RCM in CIPN. Patients and Methods Reflectance confocal microscopy was performed on the fingertip to evaluate MC density in 45 healthy controls and 9 patients with cancer (prior, during, and post-chemotherapy). Quantification was completed by 2 reviewers (one blinded), with maximum MC count/3 × 3 mm image reported. Quantitative Sensory Testing (QST; thermal and mechanical detection thresholds), Grooved pegboard test, and patient-reported outcomes measures (PROMS) were conducted for comparison. Results In controls (25 females, 20 males; 24-81 years), females exhibited greater mean MC density compared with males (49.9 ± 7.1 vs 30.9 ± 4.2 MC/3 × 3 mm; P = .03). Differences existed across age by decade (P < .0001). Meissner’s corpuscle density was correlated with mechanical detection (ρ = −0.51), warm detection (ρ = −0.47), cold pain (ρ = 0.49) thresholds (P < .01); and completion time on the Grooved pegboard test in both hands (P ≤ .02). At baseline, patients had reduced MC density vs age and gender-matched controls (P = .03). Longitudinal assessment of MC density revealed significant relationships with QST and PROMS. Inter-rater reliability of MC count showed an intraclass correlation of 0.96 (P < .0001). Conclusions The findings support the clinical utility of RCM in CIPN as it provides meaningful markers of sensory nerve dysfunction. Novel, prospective assessment demonstrated the ability to detect subclinical deficits in patients at risk of CIPN and potential to monitor neuropathy progression.

Bilateral deficiency of Meissner corpuscles and papillary microvessels in patients with acute complex regional pain syndrome

“…This might be explained by the slightly different location of the investigated region because QST was measured on the back of the hand and at the base of the thumb, depending on the QST parameter. In other studies, a loss of Meissner corpuscles correlated with mechanical, vibration, or thermal thresholds in QST, 16,45 but there is no clear assignment of Meissner corpuscles to a specific tactile quality.…”

“…Miswiring of Meissner corpuscles after nerve injury in preclinical models by sprouting nociceptors could explain tactile allodynia caused by light touch. 22 Multiple studies described reduced Meissner corpuscles in other pain conditions, including diabetic, HIV, and chemotherapy-induced neuropathy, 11 , 16 , 23 , 42 , 45 but only one study investigated Meissner corpuscles in CRPS. 2 The authors showed disorganized Meissner corpuscles with disruption of Aβ-innervation in skin samples from amputated extremities of 2 patients.…”

The Role of Quantitative Sensory Testing in Clinical Medicine and Research

“…Given limitations around CCM, some are looking for alternative PN biomarkers. Reflective confocal microscopy, for example, is a relatively new technology that measures the density of Meissner corpuscles in patients' fingertips and may be used to identify various forms of PN [8].…”

“…While estimates vary widely by diagnostic criteria and population studied, PN likely affects between 21% and 50% of patients with HIV or diabetes during the course of their disease, a significant proportion of patients with pre-diabetes, and at least 40% of patients exposed to neurotoxic chemotherapeutic agents. PN may also be idiopathic [3][4][5][6][7][8].…”