Loss of cutaneous large and small fibers in naive and l-dopa-treated PD patients

Maria Nolano, Vincenzo Provitera, Fiore Manganelli, Rosa Iodice, Annamaria Stancanelli, Giuseppe Caporaso, Annamaria Saltalamacchia, Francesca Califano, Bernardo Lanzillo, Marina Picillo, Paolo Barone, Lucio Santoro

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: To study small and large fiber pathology in drug-naive and l-dopa-treated patients affected by Parkinson disease (PD) in early phases, before the occurrence of neuropathic electrophysiologic abnormalities.

METHODS: We enrolled 85 patients with idiopathic PD (male/female 49/36, age 61.3 ± 9.7 years) without electrophysiologic signs of neuropathy, including 48 participants naive to l-dopa treatment. All patients underwent clinical, functional, and morphologic assessment of sensory and autonomic nerves through dedicated questionnaires, quantitative sensory testing, sympathetic skin response, dynamic sweat test, and punch biopsies from glabrous and hairy skin. Sensory and autonomic innervation was visualized with specific antibodies and analyzed by confocal microscopy. Data were compared with those obtained from sex- and age-comparable healthy controls. In 35 patients, skin biopsies were performed bilaterally to evaluate side-to-side differences.

RESULTS: Intraepidermal nerve fiber density was lower in patients compared to controls in all the examined sites (p < 0.001). The loss was higher in the more affected side (p < 0.01). A loss of autonomic nerves to vessels, sweat glands, and arrector pili muscles and of Meissner corpuscles and their myelinated endings in glabrous skin was found (p < 0.001). Patients showed increased tactile and thermal thresholds, impairment of mechanical pain perception, and reduced sweat output (p < 0.001). The naive and l-dopa-treated groups differed only for Meissner corpuscle density (p < 0.001).

CONCLUSIONS: Both large and small fiber pathology occurs in the early stages of PD and may account for the sensory and autonomic impairment. l-Dopa affects the 2 populations of fibers differently.

Original languageEnglish
Pages (from-to)776-784
Number of pages9
JournalNeurology
Volume89
Issue number8
DOIs
Publication statusPublished - Aug 22 2017

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Dihydroxyphenylalanine
Parkinson Disease
Skin
Autonomic Pathways
Mechanoreceptors
Sweat
Pathology
Biopsy
Sweat Glands
Pain Perception
Touch
Nerve Fibers
Confocal Microscopy
Hot Temperature
Muscles
Antibodies
Pharmaceutical Preparations
Population

Keywords

  • Antiparkinson Agents
  • Autonomic Pathways
  • Female
  • Fingers
  • Functional Laterality
  • Humans
  • Leg
  • Levodopa
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Parkinson Disease
  • Sensation Disorders
  • Sensory Receptor Cells
  • Skin
  • Journal Article

Cite this

Loss of cutaneous large and small fibers in naive and l-dopa-treated PD patients. / Nolano, Maria; Provitera, Vincenzo; Manganelli, Fiore; Iodice, Rosa; Stancanelli, Annamaria; Caporaso, Giuseppe; Saltalamacchia, Annamaria; Califano, Francesca; Lanzillo, Bernardo; Picillo, Marina; Barone, Paolo; Santoro, Lucio.

In: Neurology, Vol. 89, No. 8, 22.08.2017, p. 776-784.

Research output: Contribution to journalArticle

Nolano, Maria ; Provitera, Vincenzo ; Manganelli, Fiore ; Iodice, Rosa ; Stancanelli, Annamaria ; Caporaso, Giuseppe ; Saltalamacchia, Annamaria ; Califano, Francesca ; Lanzillo, Bernardo ; Picillo, Marina ; Barone, Paolo ; Santoro, Lucio. / Loss of cutaneous large and small fibers in naive and l-dopa-treated PD patients. In: Neurology. 2017 ; Vol. 89, No. 8. pp. 776-784.
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T1 - Loss of cutaneous large and small fibers in naive and l-dopa-treated PD patients

AU - Nolano, Maria

AU - Provitera, Vincenzo

AU - Manganelli, Fiore

AU - Iodice, Rosa

AU - Stancanelli, Annamaria

AU - Caporaso, Giuseppe

AU - Saltalamacchia, Annamaria

AU - Califano, Francesca

AU - Lanzillo, Bernardo

AU - Picillo, Marina

AU - Barone, Paolo

AU - Santoro, Lucio

N1 - © 2017 American Academy of Neurology.

PY - 2017/8/22

Y1 - 2017/8/22

N2 - OBJECTIVE: To study small and large fiber pathology in drug-naive and l-dopa-treated patients affected by Parkinson disease (PD) in early phases, before the occurrence of neuropathic electrophysiologic abnormalities.METHODS: We enrolled 85 patients with idiopathic PD (male/female 49/36, age 61.3 ± 9.7 years) without electrophysiologic signs of neuropathy, including 48 participants naive to l-dopa treatment. All patients underwent clinical, functional, and morphologic assessment of sensory and autonomic nerves through dedicated questionnaires, quantitative sensory testing, sympathetic skin response, dynamic sweat test, and punch biopsies from glabrous and hairy skin. Sensory and autonomic innervation was visualized with specific antibodies and analyzed by confocal microscopy. Data were compared with those obtained from sex- and age-comparable healthy controls. In 35 patients, skin biopsies were performed bilaterally to evaluate side-to-side differences.RESULTS: Intraepidermal nerve fiber density was lower in patients compared to controls in all the examined sites (p < 0.001). The loss was higher in the more affected side (p < 0.01). A loss of autonomic nerves to vessels, sweat glands, and arrector pili muscles and of Meissner corpuscles and their myelinated endings in glabrous skin was found (p < 0.001). Patients showed increased tactile and thermal thresholds, impairment of mechanical pain perception, and reduced sweat output (p < 0.001). The naive and l-dopa-treated groups differed only for Meissner corpuscle density (p < 0.001).CONCLUSIONS: Both large and small fiber pathology occurs in the early stages of PD and may account for the sensory and autonomic impairment. l-Dopa affects the 2 populations of fibers differently.

AB - OBJECTIVE: To study small and large fiber pathology in drug-naive and l-dopa-treated patients affected by Parkinson disease (PD) in early phases, before the occurrence of neuropathic electrophysiologic abnormalities.METHODS: We enrolled 85 patients with idiopathic PD (male/female 49/36, age 61.3 ± 9.7 years) without electrophysiologic signs of neuropathy, including 48 participants naive to l-dopa treatment. All patients underwent clinical, functional, and morphologic assessment of sensory and autonomic nerves through dedicated questionnaires, quantitative sensory testing, sympathetic skin response, dynamic sweat test, and punch biopsies from glabrous and hairy skin. Sensory and autonomic innervation was visualized with specific antibodies and analyzed by confocal microscopy. Data were compared with those obtained from sex- and age-comparable healthy controls. In 35 patients, skin biopsies were performed bilaterally to evaluate side-to-side differences.RESULTS: Intraepidermal nerve fiber density was lower in patients compared to controls in all the examined sites (p < 0.001). The loss was higher in the more affected side (p < 0.01). A loss of autonomic nerves to vessels, sweat glands, and arrector pili muscles and of Meissner corpuscles and their myelinated endings in glabrous skin was found (p < 0.001). Patients showed increased tactile and thermal thresholds, impairment of mechanical pain perception, and reduced sweat output (p < 0.001). The naive and l-dopa-treated groups differed only for Meissner corpuscle density (p < 0.001).CONCLUSIONS: Both large and small fiber pathology occurs in the early stages of PD and may account for the sensory and autonomic impairment. l-Dopa affects the 2 populations of fibers differently.

KW - Antiparkinson Agents

KW - Autonomic Pathways

KW - Female

KW - Fingers

KW - Functional Laterality

KW - Humans

KW - Leg

KW - Levodopa

KW - Male

KW - Microscopy, Confocal

KW - Middle Aged

KW - Parkinson Disease

KW - Sensation Disorders

KW - Sensory Receptor Cells

KW - Skin

KW - Journal Article

U2 - 10.1212/WNL.0000000000004274

DO - 10.1212/WNL.0000000000004274

M3 - Article

C2 - 28747449

VL - 89

SP - 776

EP - 784

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 8

ER -