Postganglionic Sudomotor Assessment in Early Stage of Multiple System Atrophy and Parkinson Disease: A Morpho-functional Study.

Aged Autonomic Nervous System Diseases / diagnosis Humans Hypohidrosis Middle Aged Multiple System Atrophy / diagnosis Parkinson Disease / complications Prospective Studies

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
22 03 2022
Historique:
received: 22 06 2021
accepted: 27 12 2021
pubmed: 13 1 2022
medline: 7 4 2022
entrez: 12 1 2022
Statut: ppublish

Résumé

Sudomotor impairment has been recognized as a key feature in differentiating Parkinson disease (PD) and multiple system atrophy-parkinsonian type (MSA-P), with the latter characterized by diffuse anhidrosis in prospective study, including patients in late stage of disease. We aimed to evaluate morphologic and functional postganglionic sudomotor involvement in patients with newly diagnosed MSA-P and PD to identify possible biomarkers that might be of help in differentiating the 2 conditions in the early stage. One hundred patients with parkinsonism within 2 years from onset of motor symptoms were included in the study. At the time of recruitment, questionnaires to assess nonmotor, autonomic, and small fiber symptoms were administered, and patients underwent postganglionic sudomotor function assessment by the dynamic sweat test and punch skin biopsy from the distal leg. Skin samples were processed for indirect immunofluorescence with a panel of antibodies, including noradrenergic and cholinergic markers. The density of intraepidermal, sudomotor, and pilomotor nerve fibers was measured on confocal images with dedicated software. A follow-up visit 12 months after recruitment was performed to confirm the diagnosis. We recruited 57 patients with PD (M/F 36/21, age 63.5 ± 9.4 years) and 43 patients with MSA-P (M/F 27/16, age 62.3 ± 9.0 years). Clinical scales and questionnaires showed a more severe clinical picture in patients with MSA-P compared to those with PD. Sweating output and intraepidermal, pilomotor, and sudomotor nerve densities, compared to controls, were lower in both groups but with a greater impairment in patients with MSA-P. Pilomotor and sudomotor nerve density correlated with sweating function and with nonmotor clinical symptoms. A composite sudomotor parameter defined as the arithmetic product of sweat production multiplied by the density of sudomotor fibers efficiently separated the 2 populations; the receiver operating characteristics curve showed an area under the curve of 0.83. Dynamic sweat test and the quantification of cutaneous autonomic nerves proved to be a sensitive morpho-functional approach to assess the postganglionic component of the sudomotor pathway, revealing a more severe involvement in MSA-P than in PD early in the disease course. This approach can be applied to differentiate the 2 conditions early. This study provides Class II evidence that postganglionic sudomotor morpho-functional assessment accurately distinguish patients with PD from patients with MSA-P.

Sections du résumé

BACKGROUND AND OBJECTIVES
Sudomotor impairment has been recognized as a key feature in differentiating Parkinson disease (PD) and multiple system atrophy-parkinsonian type (MSA-P), with the latter characterized by diffuse anhidrosis in prospective study, including patients in late stage of disease. We aimed to evaluate morphologic and functional postganglionic sudomotor involvement in patients with newly diagnosed MSA-P and PD to identify possible biomarkers that might be of help in differentiating the 2 conditions in the early stage.
METHODS
One hundred patients with parkinsonism within 2 years from onset of motor symptoms were included in the study. At the time of recruitment, questionnaires to assess nonmotor, autonomic, and small fiber symptoms were administered, and patients underwent postganglionic sudomotor function assessment by the dynamic sweat test and punch skin biopsy from the distal leg. Skin samples were processed for indirect immunofluorescence with a panel of antibodies, including noradrenergic and cholinergic markers. The density of intraepidermal, sudomotor, and pilomotor nerve fibers was measured on confocal images with dedicated software. A follow-up visit 12 months after recruitment was performed to confirm the diagnosis.
RESULTS
We recruited 57 patients with PD (M/F 36/21, age 63.5 ± 9.4 years) and 43 patients with MSA-P (M/F 27/16, age 62.3 ± 9.0 years). Clinical scales and questionnaires showed a more severe clinical picture in patients with MSA-P compared to those with PD. Sweating output and intraepidermal, pilomotor, and sudomotor nerve densities, compared to controls, were lower in both groups but with a greater impairment in patients with MSA-P. Pilomotor and sudomotor nerve density correlated with sweating function and with nonmotor clinical symptoms. A composite sudomotor parameter defined as the arithmetic product of sweat production multiplied by the density of sudomotor fibers efficiently separated the 2 populations; the receiver operating characteristics curve showed an area under the curve of 0.83.
DISCUSSION
Dynamic sweat test and the quantification of cutaneous autonomic nerves proved to be a sensitive morpho-functional approach to assess the postganglionic component of the sudomotor pathway, revealing a more severe involvement in MSA-P than in PD early in the disease course. This approach can be applied to differentiate the 2 conditions early.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that postganglionic sudomotor morpho-functional assessment accurately distinguish patients with PD from patients with MSA-P.

Identifiants

DOI: 10.1212/WNL.0000000000013300 PMID: 35017309 PMC: PMC8967330
pubmed: 35017309
pii: WNL.0000000000013300
doi: 10.1212/WNL.0000000000013300
pmc: PMC8967330
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1282-e1291

Subventions

Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

© 2022 American Academy of Neurology.

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Auteurs

Vincenzo Provitera (V)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy. vincenzo.provitera@icsmaugeri.it.
ORCID: 0000-0003-1230-942X

Valeria Iodice (V)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Fiore Manganelli (F)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Stefania Mozzillo (S)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Giuseppe Caporaso (G)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.
ORCID: 0000-0001-5822-7505

Annamaria Stancanelli (A)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Ilaria Borreca (I)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Marcello Esposito (M)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Raffaele Dubbioso (R)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Rosa Iodice (R)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Floriana Vitale (F)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Shiwen Koay (S)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.
ORCID: 0000-0002-0860-9211

Ekawat Vichayanrat (E)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Fernanda Valerio (F)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Lucio Santoro (L)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

Maria Nolano (M)

From the Neurology Department (V.P., S.M., G.C., A.S., I.B., M.N.), Skin Biopsy Laboratory, Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy; Department of Brain, Repair and Rehabilitation (V.I., S.K.), University College London Queen Square Institute of Neurology; Autonomic Unit (V.I., S.K., E.V., F. Valerio), National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurosciences, Reproductive Sciences and Odontostomatology (F.M., R.D., R.I., F. Vitale, L.S., M.N.), University Federico II of Naples; and Clinical Neurophysiology Unit (M.E.), Cardarelli Hospital, Naples, Italy.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Postganglionic Sudomotor Assessment in Early...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux autonome › Postganglionic Sudomotor Assessment in Early...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Postganglionic Sudomotor Assessment in Early...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies des glandes sudoripares › Hypohidrose › Postganglionic Sudomotor Assessment in Early...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Postganglionic Sudomotor Assessment in Early...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Atrophie multisystématisée › Postganglionic Sudomotor Assessment in Early...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Maladie de Parkinson › Postganglionic Sudomotor Assessment in Early...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Postganglionic Sudomotor Assessment in Early...