Maria Nolano1, Fiore Manganelli2, Vincenzo Provitera2, Chiara Pisciotta2, Annamaria Stancanelli2, Giuseppe Caporaso2, Rosa Iodice2, Michael E Shy2, Lucio Santoro2. 1. From the Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurosciences, Reproductive and Odontostomatological Sciences (F.M., C.P., R.I., L.S.), University Federico II of Naples, Italy; and the Department of Neurology (M.E.S.), University of Iowa, Iowa City. maria.nolano@fsm.it. 2. From the Neurology Division (M.N., V.P., A.S., G.C.), "Salvatore Maugeri" Foundation, Institute of Telese Terme; the Department of Neurosciences, Reproductive and Odontostomatological Sciences (F.M., C.P., R.I., L.S.), University Federico II of Naples, Italy; and the Department of Neurology (M.E.S.), University of Iowa, Iowa City.
Abstract
OBJECTIVE: To assess the involvement of small nerve fibers in Charcot-Marie-Tooth type 1A (CMT1A). METHODS: We used indirect immunofluorescence and confocal microscopy on punch biopsies from glabrous (fingertip) and hairy (thigh and leg) skin of 20 unrelated patients with CMT1A to quantify somatic and autonomic nerve fibers. In particular, we quantified epidermal nerve fibers (ENF), Meissner corpuscles (MC), intrapapillary myelinated endings (IME), and sudomotor nerves. We correlated morphologic data with findings from quantitative sensory testing, sudomotor output, sympathetic skin response, and cardiovascular reflexes. A control population of healthy age- and sex-matched controls was included with a matching ratio of 1:2. RESULTS: We found a length-dependent loss of ENFs that worsened with aging. We also observed a loss of MCs, IMEs, and sudomotor nerves. The loss of ENF at distal leg correlated with the increase in heat-pain thresholds (p < 0.05) and with tactile thresholds (p < 0.05). Sudomotor nerve fiber loss correlated with ENF density (p < 0.05) and sweating output (p < 0.001). CONCLUSIONS: We demonstrated through morphologic, physical, and psychophysical testing that small somatic and autonomic fibers are abnormal and cause symptoms in patients with CMT1A. Awareness of such symptoms by the clinician could lead to better treatment.
OBJECTIVE: To assess the involvement of small nerve fibers in Charcot-Marie-Tooth type 1A (CMT1A). METHODS: We used indirect immunofluorescence and confocal microscopy on punch biopsies from glabrous (fingertip) and hairy (thigh and leg) skin of 20 unrelated patients with CMT1A to quantify somatic and autonomic nerve fibers. In particular, we quantified epidermal nerve fibers (ENF), Meissner corpuscles (MC), intrapapillary myelinated endings (IME), and sudomotor nerves. We correlated morphologic data with findings from quantitative sensory testing, sudomotor output, sympathetic skin response, and cardiovascular reflexes. A control population of healthy age- and sex-matched controls was included with a matching ratio of 1:2. RESULTS: We found a length-dependent loss of ENFs that worsened with aging. We also observed a loss of MCs, IMEs, and sudomotor nerves. The loss of ENF at distal leg correlated with the increase in heat-pain thresholds (p < 0.05) and with tactile thresholds (p < 0.05). Sudomotor nerve fiber loss correlated with ENF density (p < 0.05) and sweating output (p < 0.001). CONCLUSIONS: We demonstrated through morphologic, physical, and psychophysical testing that small somatic and autonomic fibers are abnormal and cause symptoms in patients with CMT1A. Awareness of such symptoms by the clinician could lead to better treatment.
Authors: M Nolano; V Provitera; C Crisci; A M Saltalamacchia; G Wendelschafer-Crabb; W R Kennedy; A Filla; L Santoro; G Caruso Journal: Ann Neurol Date: 2001-07 Impact factor: 10.422
Authors: Maria Nolano; Vincenzo Provitera; Claudio Crisci; Annamaria Stancanelli; Gwen Wendelschafer-Crabb; William Robert Kennedy; Lucio Santoro Journal: Ann Neurol Date: 2003-08 Impact factor: 10.422
Authors: K M Krajewski; R A Lewis; D R Fuerst; C Turansky; S R Hinderer; J Garbern; J Kamholz; M E Shy Journal: Brain Date: 2000-07 Impact factor: 13.501
Authors: C Haney; G J Snipes; E M Shooter; U Suter; C Garcia; J W Griffin; B D Trapp Journal: J Neuropathol Exp Neurol Date: 1996-03 Impact factor: 3.685
Authors: John Svaren; John J Moran; Xingyao Wu; Riccardo Zuccarino; Chelsea Bacon; Yunhong Bai; Raghu Ramesh; Laurie Gutmann; Daniel M Anderson; Derek Pavelec; Michael E Shy Journal: Ann Neurol Date: 2019-04-22 Impact factor: 10.422