{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:01:50Z","timestamp":1790834510197,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T00:00:00Z","timestamp":1467849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF\u2010MAU\u20102007\u2010643050"],"award-info":[{"award-number":["RF\u2010MAU\u20102007\u2010643050"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To assess cutaneous sensory and autonomic nerves and the vascular bed in amyotrophic lateral sclerosis (ALS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled 41 patients (<jats:italic>M<\/jats:italic> = 20, aged 63.5 \u00b1 11.8 years), and 41 age\u2010 and gender\u2010matched healthy volunteers (<jats:italic>M<\/jats:italic> = 20, aged 63.5 \u00b1 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to healthy controls skin biopsies showed: (i) non\u2013length\u2010dependent loss of intraepidermal nerve fibres (<jats:italic>P<\/jats:italic> &lt; 0.01) and loss of MCs (<jats:italic>P<\/jats:italic> &lt; 0.01); (ii) reduced (<jats:italic>P<\/jats:italic> &lt; 0.01) density of pilomotor nerves involving cholinergic and noradrenergic fibres and (iii) a reduced (<jats:italic>P<\/jats:italic> &lt; 0.01) vascular bed. Autonomic nerve and dermal vessel densities were higher in patients with higher disease progression rate (<jats:italic>P<\/jats:italic> &lt; 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 (<jats:italic>P<\/jats:italic> &gt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12332","type":"journal-article","created":{"date-parts":[[2016,6,11]],"date-time":"2016-06-11T14:36:43Z","timestamp":1465655803000},"page":"119-132","source":"Crossref","is-referenced-by-count":63,"title":["Non\u2010motor involvement in amyotrophic lateral sclerosis: new insight from nerve and vessel analysis in skin biopsy"],"prefix":"10.1111","volume":"43","author":[{"given":"M.","family":"Nolano","sequence":"first","affiliation":[{"name":"Neurology 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