Subclinical Peripheral Neuropathy in Patients With Multiple Myeloma Before Chemotherapy Is Correlated With Decreased Fingertip Innervation Density

Purpose The goal in this study was to determine the incidence of subclinical neuropathy in treatment-naive patients with multiple myeloma (MM) with no history of peripheral neuropathy using quantitative sensory tests (QSTs) and its correlation with innervation density of the extremities using noninvasive laser reflectance confocal microscopy. Patients and Methods QST results were collected for 27 patients with a diagnosis of MM and compared with data collected from 30 age- and sex-matched healthy volunteers. Skin temperature, sensorimotor function (grooved pegboard test), and detection thresholds for temperature, sharpness, and low-threshold mechanical stimuli (von Frey monofilaments and bumps detection test) were measured. Meissner's corpuscle (MC) density in the fingertips was assessed using in vivo laser reflectance confocal microscopy. Results Patients showed a high incidence (> 80%) of ≥ one subclinical QST deficit. These included increased von Frey, bumps, and warmth detection thresholds as compared with healthy volunteers. Patients also showed increases in cold pain, sensorimotor deficits (grooved pegboard test), and higher overall neuropathy scores. MC density was significantly lower in patients than controls and showed significant inverse correlation with bumps detection threshold. Conclusion Patients with MM commonly present with sensory and sensorimotor deficits before undergoing treatment, and these deficits seem to result from disease-related decreases in peripheral innervation density.

Download Full-text

Is in vivo reflectance confocal microscopy a useful assessment tool in chemotherapy-induced peripheral neuropathy (CIPN)?

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e23088 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e23088-e23088

Author(s):

Sabrina Ramnarine ◽

Roman Rolke ◽

Patrick M. Dougherty ◽

Linda J Williams ◽

Christi Alessi Fox ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Confocal Microscopy ◽

Cancer Patients ◽

Sensorimotor Function ◽

Dominant Hand ◽

Healthy Controls ◽

Detection Thresholds ◽

Mechanical Detection ◽

Grooved Pegboard Test

e23088 Background: The lack of standardized diagnostic or assessment tools in CIPN pose an unmet need for objective and reliable measures. Advances in non-invasive, in vivo reflectance confocal microscopy (RCM) offer a painless method to identify markers of peripheral neuropathy such as loss of Meissner’s corpuscles (MC). This study aims to investigate the feasibility of RCM in CIPN by assessing MC density in healthy controls compared to cancer patients. Methods: RCM imaging (Vivascope 1500) was performed on the fingertip (digit V) to evaluate MC density in 45 healthy controls and 9 cancer patients prior to starting chemotherapy. Quantification was completed by two reviewers, one being blinded to achieve unbiased identification as the maximum MC count/6x6 mm image. Quantitative Sensory Testing (thermal and mechanical detection thresholds) along with the grooved pegboard test (sensorimotor function) were conducted for comparison with MC density. Spearman’s correlation coefficients were used to determine associations. Results: In healthy controls (25 females, 20 males; mean age 58.9, range 24-81 years), females exhibited a greater mean MC density compared with males (49.9 ± 7.1 MC vs 30.9 ± 4.2 MC; p = 0.03). Variances were observed across age range by decade (p < 0.0001). MC density was inversely correlated with mechanical detection (ρ = -0.51) and warm detection thresholds (ρ = -0.47) in contrast to cold pain threshold (ρ = 0.49). All correlations were significant (p < 0.01). Time to complete the grooved pegboard test correlated with MC density in the dominant hand (p = 0.02) and non-dominant hand (p < 0.01). Compared with age and gender matched controls, cancer patients had reduced MC density (22.0 ± 9.3 vs 35.4 ± 14.1; p = 0.03), mirroring deficits in cold detection threshold and the grooved pegboard test. Inter-rater reliability of MC density count showed an intraclass correlation of 0.96 (p < 0.0001). Conclusions: The findings from this study support the clinical utility of RCM in CIPN. Assessment of MC density using RCM may provide meaningful markers of sensory loss, sensorimotor function and an ability to detect possible subclinical deficits in patients at risk of CIPN prior to initiating chemotherapy.

Download Full-text

The subjective sensation induced by various thermal pulse stimulation in healthy volunteers

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2017.04.039 ◽

2017 ◽

Vol 16 (1) ◽

pp. 177-178

Author(s):

Y. Oono ◽

H. Kubo ◽

T. Imamura ◽

K. Matsumoto ◽

S. Uchida ◽

...

Keyword(s):

Healthy Volunteers ◽

Thermal Sensation ◽

Heat Pulse ◽

Peltier Element ◽

Cold Pain ◽

Thermal Pulse ◽

Heat Sensation ◽

Thermal Stimulator ◽

Subjective Sensation ◽

Pulse Stimulation

AbstractAimsNovel quantitative thermal stimulator devices (QTSDs) have been developed to deliver thermal pulse stimulation with regulated constant temperatures (0–45°C) with a Peltier element probe (16 cm2). The aim of this study was to investigate subjective sensation induced by the interaction between simultaneously applied painful cold and heat stimuli in various sites.MethodsTwenty healthy subjects (12 men and 8 women, age range: 25–45 years) participated. The intensity of cold pain (CP) and heat pain (HP) stimuli were assessed by visual analogue scale (VAS) and adjusted to elicit approximately 70/100 mm. Alternately pulse stimulations (pulse duration of 40 s; 0.025 Hz) which consisted of CP, HP, or neutral temperature (32°C) were applied. Four conditions were tested and subjective sensations were assessed: (1) one QTSD was applied to non-dominant forearm and cold-heat pulse stimulation was applied.Two QTSDs were applied to (2) non-dominant ipsilateral forearm with 5 cm apart, (3) non-dominant and contralateral forearms, (4) non-dominant forearm and ipsilateral thigh, respectively. In conditions of (2)–(4), CP-neutral pulse stimulation (C-Neutral) and neutral-HP pulse stimulation (Neutral-H) were applied simultaneously with opposite phase, respectively.ResultsCP and HP were 3.9±1.0°C (mean±SD) and 43.6±0.9°C (mean±SD), respectively. The VAS values for CP and HP were 73.4±2.0 mm (mean±SD) and 76.4 ±4.8 mm (mean±SD), respectively. Some subjects could not discriminate cold or heat sensation and some felt cold as heat (paradoxical sensation). The number of subjects with such paradoxical sensation in (1), (2), (3), (4) were 9 (45%), 2 (10%), 0 (0%) and 3 (15%), respectively.ConclusionsIn healthy volunteers, simultaneous alternately cold-heat pulse stimulation on one site triggered paradoxical thermal sensation, which to a much less degree is triggered when C-Neutral and Neutral-H were applied to different dermatomes. This suggests that the mechanism is primarily triggered peripherally.

Download Full-text