title: Small nerve fiber involvement in CMT1A.
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.
authors.affiliation: 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.
authors.forename: Maria
authors.initials: M
authors.lastname: Nolano
authors.affiliation: 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.
authors.forename: Fiore
authors.initials: F
authors.lastname: Manganelli
authors.affiliation: 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.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Provitera
authors.affiliation: 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.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pisciotta
authors.affiliation: 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.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Stancanelli
authors.affiliation: 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.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caporaso
authors.affiliation: 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.
authors.forename: Rosa
authors.initials: R
authors.lastname: Iodice
authors.affiliation: 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.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Shy
authors.affiliation: 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.
authors.forename: Lucio
authors.initials: L
authors.lastname: Santoro
mesh_terms: D000328:Adult; D000367:Age Factors; D002607:Charcot-Marie-Tooth Disease / Q000473:pathology* / Q000503:physiopathology*; D004817:Epidermis / Q000294:innervation; D005260:Female; D006801:Humans; D008297:Male; D008465:Mechanoreceptors / Q000473:pathology; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D012867:Skin / Q000294:innervation* / Q000473:pathology; D013545:Sweat Glands / Q000294:innervation