title: Cutaneous sensory and autonomic denervation in CADASIL.
abstract: OBJECTIVE
  To assess the involvement of the peripheral nervous system in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) by means of immunofluorescence and confocal analysis of punch skin biopsies.
  
  
  METHODS
  We recruited 14 unrelated patients with CADASIL (M/F = 9/5; age 53.9 ± 10.5 years) and 52 healthy controls (M/F = 31/21; age 53.8 ± 9.8). Patients underwent clinical and neuroradiologic assessment. Three-millimeter punch skin biopsies were taken from the fingertip, the thigh, and the distal leg and processed using indirect immunofluorescence and a panel of primary antibodies to mark vessels and sensory and autonomic nerve fibers. Intraepidermal nerve fibers (IENF), Meissner corpuscles (MC), and sudomotor, vasomotor, and pilomotor nerves were assessed using confocal microscopy.
  
  
  RESULTS
  In patients, compared to controls, we found a severe loss of IENF at the distal leg (p < 0.01), at the thigh (p < 0.01), and at the fingertip (p < 0.01) with a non-length-dependent pattern and a loss of MC (p < 0.01). A severe sudomotor, vasomotor, and pilomotor nerve fiber loss was found by semiquantitative evaluation. Along with nerve loss, a severe derangement of the vascular bed was observed. In our patient population, sensory and autonomic denervation did not correlate with age, sex, type of mutation, or MRI involvement.
  
  
  CONCLUSIONS
  We found an involvement of the peripheral nervous system in patients with CADASIL through the assessment of cutaneous somatic and autonomic nerves. The neurovascular derangement observed in the skin may reflect, although to a lesser extent, what happens in the CNS.
authors.affiliation: From the Neurology Department (M.N., V.P., G.C., A.S., F.C.), "Salvatore Maugeri" Foundation, IRCCS, Institute of Telese Terme; IRCCS Istituto delle Scienze Neurologiche (V.D., R.L.), Bologna; Molecular Medicine Laboratory (L.P.), Mazzoni Hospital, Ascoli Piceno; Department of Neurosciences, Reproductive Sciences and Odontostomatology (L.S.), University Federico II of Naples; and Division of Neurology (M.R.), Madonna del Soccorso Hospital, ASUR AV5, San Benedetto del Tronto, Italy. maria.nolano@fsm.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Nolano
authors.affiliation: From the Neurology Department (M.N., V.P., G.C., A.S., F.C.), "Salvatore Maugeri" Foundation, IRCCS, Institute of Telese Terme; IRCCS Istituto delle Scienze Neurologiche (V.D., R.L.), Bologna; Molecular Medicine Laboratory (L.P.), Mazzoni Hospital, Ascoli Piceno; Department of Neurosciences, Reproductive Sciences and Odontostomatology (L.S.), University Federico II of Naples; and Division of Neurology (M.R.), Madonna del Soccorso Hospital, ASUR AV5, San Benedetto del Tronto, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Provitera
authors.affiliation: From the Neurology Department (M.N., V.P., G.C., A.S., F.C.), "Salvatore Maugeri" Foundation, IRCCS, Institute of Telese Terme; IRCCS Istituto delle Scienze Neurologiche (V.D., R.L.), Bologna; Molecular Medicine Laboratory (L.P.), Mazzoni Hospital, Ascoli Piceno; Department of Neurosciences, Reproductive Sciences and Odontostomatology (L.S.), University Federico II of Naples; and Division of Neurology (M.R.), Madonna del Soccorso Hospital, ASUR AV5, San Benedetto del Tronto, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Donadio
authors.affiliation: From the Neurology Department (M.N., V.P., G.C., A.S., F.C.), "Salvatore Maugeri" Foundation, IRCCS, Institute of Telese Terme; IRCCS Istituto delle Scienze Neurologiche (V.D., R.L.), Bologna; Molecular Medicine Laboratory (L.P.), Mazzoni Hospital, Ascoli Piceno; Department of Neurosciences, Reproductive Sciences and Odontostomatology (L.S.), University Federico II of Naples; and Division of Neurology (M.R.), Madonna del Soccorso Hospital, ASUR AV5, San Benedetto del Tronto, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caporaso
authors.affiliation: From the Neurology Department (M.N., V.P., G.C., A.S., F.C.), "Salvatore Maugeri" Foundation, IRCCS, Institute of Telese Terme; IRCCS Istituto delle Scienze Neurologiche (V.D., R.L.), Bologna; Molecular Medicine Laboratory (L.P.), Mazzoni Hospital, Ascoli Piceno; Department of Neurosciences, Reproductive Sciences and Odontostomatology (L.S.), University Federico II of Naples; and Division of Neurology (M.R.), Madonna del Soccorso Hospital, ASUR AV5, San Benedetto del Tronto, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Stancanelli
authors.affiliation: From the Neurology Department (M.N., V.P., G.C., A.S., F.C.), "Salvatore Maugeri" Foundation, IRCCS, Institute of Telese Terme; IRCCS Istituto delle Scienze Neurologiche (V.D., R.L.), Bologna; Molecular Medicine Laboratory (L.P.), Mazzoni Hospital, Ascoli Piceno; Department of Neurosciences, Reproductive Sciences and Odontostomatology (L.S.), University Federico II of Naples; and Division of Neurology (M.R.), Madonna del Soccorso Hospital, ASUR AV5, San Benedetto del Tronto, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Califano
authors.affiliation: From the Neurology Department (M.N., V.P., G.C., A.S., F.C.), "Salvatore Maugeri" Foundation, IRCCS, Institute of Telese Terme; IRCCS Istituto delle Scienze Neurologiche (V.D., R.L.), Bologna; Molecular Medicine Laboratory (L.P.), Mazzoni Hospital, Ascoli Piceno; Department of Neurosciences, Reproductive Sciences and Odontostomatology (L.S.), University Federico II of Naples; and Division of Neurology (M.R.), Madonna del Soccorso Hospital, ASUR AV5, San Benedetto del Tronto, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Pianese
authors.affiliation: From the Neurology Department (M.N., V.P., G.C., A.S., F.C.), "Salvatore Maugeri" Foundation, IRCCS, Institute of Telese Terme; IRCCS Istituto delle Scienze Neurologiche (V.D., R.L.), Bologna; Molecular Medicine Laboratory (L.P.), Mazzoni Hospital, Ascoli Piceno; Department of Neurosciences, Reproductive Sciences and Odontostomatology (L.S.), University Federico II of Naples; and Division of Neurology (M.R.), Madonna del Soccorso Hospital, ASUR AV5, San Benedetto del Tronto, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Liguori
authors.affiliation: From the Neurology Department (M.N., V.P., G.C., A.S., F.C.), "Salvatore Maugeri" Foundation, IRCCS, Institute of Telese Terme; IRCCS Istituto delle Scienze Neurologiche (V.D., R.L.), Bologna; Molecular Medicine Laboratory (L.P.), Mazzoni Hospital, Ascoli Piceno; Department of Neurosciences, Reproductive Sciences and Odontostomatology (L.S.), University Federico II of Naples; and Division of Neurology (M.R.), Madonna del Soccorso Hospital, ASUR AV5, San Benedetto del Tronto, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Santoro
authors.affiliation: From the Neurology Department (M.N., V.P., G.C., A.S., F.C.), "Salvatore Maugeri" Foundation, IRCCS, Institute of Telese Terme; IRCCS Istituto delle Scienze Neurologiche (V.D., R.L.), Bologna; Molecular Medicine Laboratory (L.P.), Mazzoni Hospital, Ascoli Piceno; Department of Neurosciences, Reproductive Sciences and Odontostomatology (L.S.), University Federico II of Naples; and Division of Neurology (M.R.), Madonna del Soccorso Hospital, ASUR AV5, San Benedetto del Tronto, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Ragno
mesh_terms: D000328:Adult; D000368:Aged; D017763:Autonomic Denervation; D046589:CADASIL / Q000175:diagnosis* / Q000503:physiopathology*; D004817:Epidermis / Q000294:innervation* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D055815:Young Adult