Nonmotor involvement in amyotrophic lateral sclerosis: New insight from nerve and vessel analysis in skin biopsy

M. Nolano, V. Provitera, F. Manganelli, R. Iodice, G. Caporaso, A. Stancanelli, K. Marinou, B. Lanzillo, L. Santoro, G. Mora

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18 Citations (Scopus)

Abstract

Aims: To assess cutaneous sensory and autonomic nerves and the vascular bed in amyotrophic lateral sclerosis (ALS). Methods: We enrolled 41 patients (M = 20, aged 63.5 ± 11.8 years), and 41 age- and gender-matched healthy volunteers (M = 20, aged 63.5 ± 11.8 years). Disease severity and sensory and autonomic symptoms were scored using dedicated rating scales. Skin biopsies obtained from thigh, leg and fingertip were processed using indirect immunofluorescence. Intraepidermal nerve fibres, Meissner corpuscles (MCs), intrapapillary myelinated endings, cholinergic and noradrenergic pilomotor nerves and dermal vessels were quantified on confocal images. Intraepidermal nerve fibres, pilomotor nerves and vessels were also assessed on distal leg skin samples of 10 spinal cord injury patients to compare our findings with those of a chronic hypomobility condition. Results: Compared to healthy controls skin biopsies showed: (i) non-length-dependent loss of intraepidermal nerve fibres (P <0.01) and loss of MCs (P <0.01); (ii) reduced (P <0.01) density of pilomotor nerves involving cholinergic and noradrenergic fibres and (iii) a reduced (P <0.01) vascular bed. Autonomic nerve and dermal vessel densities were higher in patients with higher disease progression rate (P <0.01). Moreover, we observed signs of nerve regeneration coexisting with nerve degeneration and increased complexity of the dermal vessels. In patients with posttraumatic spinal cord injury, the density of intraepidermal nerve fibres, pilomotor nerves and of the vascular bed did not differ from controls (P > 0.05). Conclusions: We demonstrated a cutaneous sensory and autonomic denervation in ALS and a previously undescribed relationship between autonomic and vascular involvement that appeared to be linked to the disease progression rate.

Original languageEnglish
JournalNeuropathology and Applied Neurobiology
DOIs
Publication statusPublished - May 2017

Fingerprint

Amyotrophic Lateral Sclerosis
Biopsy
Skin
Nerve Fibers
Blood Vessels
Autonomic Denervation
Leg
Autonomic Pathways
Mechanoreceptors
Indirect Fluorescent Antibody Technique
Thigh
Spinal Cord Injuries
Cholinergic Agents
Disease Progression
Healthy Volunteers

Keywords

  • Amyotrophic lateral sclerosis
  • Autonomic nervous system
  • Epidermal nerve fibres
  • Skin biopsy

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neurology
  • Histology
  • Physiology (medical)

Cite this

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title = "Nonmotor involvement in amyotrophic lateral sclerosis: New insight from nerve and vessel analysis in skin biopsy",
abstract = "Aims: To assess cutaneous sensory and autonomic nerves and the vascular bed in amyotrophic lateral sclerosis (ALS). Methods: We enrolled 41 patients (M = 20, aged 63.5 ± 11.8 years), and 41 age- and gender-matched healthy volunteers (M = 20, aged 63.5 ± 11.8 years). Disease severity and sensory and autonomic symptoms were scored using dedicated rating scales. Skin biopsies obtained from thigh, leg and fingertip were processed using indirect immunofluorescence. Intraepidermal nerve fibres, Meissner corpuscles (MCs), intrapapillary myelinated endings, cholinergic and noradrenergic pilomotor nerves and dermal vessels were quantified on confocal images. Intraepidermal nerve fibres, pilomotor nerves and vessels were also assessed on distal leg skin samples of 10 spinal cord injury patients to compare our findings with those of a chronic hypomobility condition. Results: Compared to healthy controls skin biopsies showed: (i) non-length-dependent loss of intraepidermal nerve fibres (P <0.01) and loss of MCs (P <0.01); (ii) reduced (P <0.01) density of pilomotor nerves involving cholinergic and noradrenergic fibres and (iii) a reduced (P <0.01) vascular bed. Autonomic nerve and dermal vessel densities were higher in patients with higher disease progression rate (P <0.01). Moreover, we observed signs of nerve regeneration coexisting with nerve degeneration and increased complexity of the dermal vessels. In patients with posttraumatic spinal cord injury, the density of intraepidermal nerve fibres, pilomotor nerves and of the vascular bed did not differ from controls (P > 0.05). Conclusions: We demonstrated a cutaneous sensory and autonomic denervation in ALS and a previously undescribed relationship between autonomic and vascular involvement that appeared to be linked to the disease progression rate.",
keywords = "Amyotrophic lateral sclerosis, Autonomic nervous system, Epidermal nerve fibres, Skin biopsy",
author = "M. Nolano and V. Provitera and F. Manganelli and R. Iodice and G. Caporaso and A. Stancanelli and K. Marinou and B. Lanzillo and L. Santoro and G. Mora",
year = "2017",
month = "5",
doi = "10.1111/nan.12332",
language = "English",
journal = "Neuropathology and Applied Neurobiology",
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TY - JOUR

T1 - Nonmotor involvement in amyotrophic lateral sclerosis

T2 - New insight from nerve and vessel analysis in skin biopsy

AU - Nolano, M.

AU - Provitera, V.

AU - Manganelli, F.

AU - Iodice, R.

AU - Caporaso, G.

AU - Stancanelli, A.

AU - Marinou, K.

AU - Lanzillo, B.

AU - Santoro, L.

AU - Mora, G.

PY - 2017/5

Y1 - 2017/5

N2 - Aims: To assess cutaneous sensory and autonomic nerves and the vascular bed in amyotrophic lateral sclerosis (ALS). Methods: We enrolled 41 patients (M = 20, aged 63.5 ± 11.8 years), and 41 age- and gender-matched healthy volunteers (M = 20, aged 63.5 ± 11.8 years). Disease severity and sensory and autonomic symptoms were scored using dedicated rating scales. Skin biopsies obtained from thigh, leg and fingertip were processed using indirect immunofluorescence. Intraepidermal nerve fibres, Meissner corpuscles (MCs), intrapapillary myelinated endings, cholinergic and noradrenergic pilomotor nerves and dermal vessels were quantified on confocal images. Intraepidermal nerve fibres, pilomotor nerves and vessels were also assessed on distal leg skin samples of 10 spinal cord injury patients to compare our findings with those of a chronic hypomobility condition. Results: Compared to healthy controls skin biopsies showed: (i) non-length-dependent loss of intraepidermal nerve fibres (P <0.01) and loss of MCs (P <0.01); (ii) reduced (P <0.01) density of pilomotor nerves involving cholinergic and noradrenergic fibres and (iii) a reduced (P <0.01) vascular bed. Autonomic nerve and dermal vessel densities were higher in patients with higher disease progression rate (P <0.01). Moreover, we observed signs of nerve regeneration coexisting with nerve degeneration and increased complexity of the dermal vessels. In patients with posttraumatic spinal cord injury, the density of intraepidermal nerve fibres, pilomotor nerves and of the vascular bed did not differ from controls (P > 0.05). Conclusions: We demonstrated a cutaneous sensory and autonomic denervation in ALS and a previously undescribed relationship between autonomic and vascular involvement that appeared to be linked to the disease progression rate.

AB - Aims: To assess cutaneous sensory and autonomic nerves and the vascular bed in amyotrophic lateral sclerosis (ALS). Methods: We enrolled 41 patients (M = 20, aged 63.5 ± 11.8 years), and 41 age- and gender-matched healthy volunteers (M = 20, aged 63.5 ± 11.8 years). Disease severity and sensory and autonomic symptoms were scored using dedicated rating scales. Skin biopsies obtained from thigh, leg and fingertip were processed using indirect immunofluorescence. Intraepidermal nerve fibres, Meissner corpuscles (MCs), intrapapillary myelinated endings, cholinergic and noradrenergic pilomotor nerves and dermal vessels were quantified on confocal images. Intraepidermal nerve fibres, pilomotor nerves and vessels were also assessed on distal leg skin samples of 10 spinal cord injury patients to compare our findings with those of a chronic hypomobility condition. Results: Compared to healthy controls skin biopsies showed: (i) non-length-dependent loss of intraepidermal nerve fibres (P <0.01) and loss of MCs (P <0.01); (ii) reduced (P <0.01) density of pilomotor nerves involving cholinergic and noradrenergic fibres and (iii) a reduced (P <0.01) vascular bed. Autonomic nerve and dermal vessel densities were higher in patients with higher disease progression rate (P <0.01). Moreover, we observed signs of nerve regeneration coexisting with nerve degeneration and increased complexity of the dermal vessels. In patients with posttraumatic spinal cord injury, the density of intraepidermal nerve fibres, pilomotor nerves and of the vascular bed did not differ from controls (P > 0.05). Conclusions: We demonstrated a cutaneous sensory and autonomic denervation in ALS and a previously undescribed relationship between autonomic and vascular involvement that appeared to be linked to the disease progression rate.

KW - Amyotrophic lateral sclerosis

KW - Autonomic nervous system

KW - Epidermal nerve fibres

KW - Skin biopsy

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