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 language | English |
|---|---|
| Journal | Neuropathology and Applied Neurobiology |
| DOIs | |
| Publication status | Published - May 2017 |
Fingerprint
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
Nonmotor involvement in amyotrophic lateral sclerosis : New insight from nerve and vessel analysis in skin biopsy. / Nolano, M.; Provitera, V.; Manganelli, F.; Iodice, R.; Caporaso, G.; Stancanelli, A.; Marinou, K.; Lanzillo, B.; Santoro, L.; Mora, G.
In: Neuropathology and Applied Neurobiology, 05.2017.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=84978036324&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978036324&partnerID=8YFLogxK
U2 - 10.1111/nan.12332
DO - 10.1111/nan.12332
M3 - Article
AN - SCOPUS:84978036324
JO - Neuropathology and Applied Neurobiology
JF - Neuropathology and Applied Neurobiology
SN - 0305-1846
ER -