Cutaneous sensory and autonomic denervation in CADASIL

Maria Nolano, Vincenzo Provitera, Vincenzo Donadio, Giuseppe Caporaso, Annamaria Stancanelli, Francesca Califano, Luigi Pianese, Rocco Liguori, Lucio Santoro, Michele Ragno

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1039-1044
Number of pages6
JournalNeurology
Volume86
Issue number11
DOIs
Publication statusPublished - Mar 15 2016

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Autonomic Denervation
CADASIL
Nerve Fibers
Skin
Autonomic Pathways
Mechanoreceptors
Peripheral Nervous System
Thigh
Leg
Biopsy
Indirect Fluorescent Antibody Technique
Confocal Microscopy
Fluorescent Antibody Technique
Blood Vessels
Mutation
Antibodies
Population

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Cutaneous sensory and autonomic denervation in CADASIL. / Nolano, Maria; Provitera, Vincenzo; Donadio, Vincenzo; Caporaso, Giuseppe; Stancanelli, Annamaria; Califano, Francesca; Pianese, Luigi; Liguori, Rocco; Santoro, Lucio; Ragno, Michele.

In: Neurology, Vol. 86, No. 11, 15.03.2016, p. 1039-1044.

Research output: Contribution to journalArticle

Nolano, Maria ; Provitera, Vincenzo ; Donadio, Vincenzo ; Caporaso, Giuseppe ; Stancanelli, Annamaria ; Califano, Francesca ; Pianese, Luigi ; Liguori, Rocco ; Santoro, Lucio ; Ragno, Michele. / Cutaneous sensory and autonomic denervation in CADASIL. In: Neurology. 2016 ; Vol. 86, No. 11. pp. 1039-1044.
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AU - Nolano, Maria

AU - Provitera, Vincenzo

AU - Donadio, Vincenzo

AU - Caporaso, Giuseppe

AU - Stancanelli, Annamaria

AU - Califano, Francesca

AU - Pianese, Luigi

AU - Liguori, Rocco

AU - Santoro, Lucio

AU - Ragno, Michele

PY - 2016/3/15

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N2 - 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.

AB - 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.

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