Increased intraepidermal nerve fiber degeneration and impaired regeneration relate to symptoms and deficits in Parkinson's disease

Maria Jeziorska, Andrew Atkinson, Lewis Kass-Iliyya, Saad Javed, Christopher Kobylecki, David Gosal, Andrew Marshall, Monty Silverdale, Rayaz Malik

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Abstract

Background: Previous studies have shown cutaneous small fiber pathology in patients with Parkinson's disease (PD). These studies have focused on nerve degeneration, but recent reports suggest that nerve regeneration may also be important in PD pathology. Objective: To establish the extent of intraepidermal nerve fiber (IENF) degeneration and regeneration and its relationship to clinical and neurological deficits in Parkinson's disease (PD). Methods: Twenty-three PD patients and 10 age-matched controls underwent skin biopsy and assessment of somatic and autonomic symptoms and deficits. We have assessed Intraepidermal Nerve Fiber Density (IENFD) using standard PGP9.5 staining and GAP-43 to assess Mean Axonal Length (MAL) and Intraepidermal Total Nerve Fiber Length (IETNFL). Results: IENFD (p < 0.0001), MAL (p < 0.0001), IETNFL/Area (p = 0.009), and IETNFL/Length (p = 0.04) were significantly reduced in patients with PD compared to controls. IENFD correlated significantly with disease duration (p = 0.03), cumulative levodopa dose (p = 0.02), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (p = 0.01), Schwab and England Activities of Daily Living (ADL) (p = 0.03), NSP (p = 0.03), and 30:15 ratio (p = 0.03). IETNFL/Area correlated with the Autonomic Scale for Outcomes in Parkinson's Disease (SCOPA-AUT) (p = 0.03) and Diabetic Neuropathy Symptom score (DNS) (p = 0.04) and IETNFL/Length correlated with DNS (p = 0.03). MAL correlated with SCOPA-AUT (p = 0.01), DNS (p = 0.02), and DB-HRV (p = 0.02). Conclusion: Increased IENF degeneration and impaired regeneration correlates with somatic and autonomic symptoms and deficits in patients with PD.

Original languageEnglish
Article number111
JournalFrontiers in Neurology
Volume10
Issue numberFEB
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

Nerve Degeneration
Nerve Fibers
Parkinson Disease
Regeneration
Diabetic Neuropathies
Nerve Regeneration
Pathology
GAP-43 Protein
Skin
Levodopa
Activities of Daily Living
England
Staining and Labeling
Biopsy

Keywords

  • Autonomic
  • Intraepidermal nerve
  • Motor
  • Parkinson's disease
  • Skin biopsy
  • Small fiber neuropathy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Increased intraepidermal nerve fiber degeneration and impaired regeneration relate to symptoms and deficits in Parkinson's disease. / Jeziorska, Maria; Atkinson, Andrew; Kass-Iliyya, Lewis; Javed, Saad; Kobylecki, Christopher; Gosal, David; Marshall, Andrew; Silverdale, Monty; Malik, Rayaz.

In: Frontiers in Neurology, Vol. 10, No. FEB, 111, 01.01.2019.

Research output: Contribution to journalArticle

Jeziorska, M, Atkinson, A, Kass-Iliyya, L, Javed, S, Kobylecki, C, Gosal, D, Marshall, A, Silverdale, M & Malik, R 2019, 'Increased intraepidermal nerve fiber degeneration and impaired regeneration relate to symptoms and deficits in Parkinson's disease', Frontiers in Neurology, vol. 10, no. FEB, 111. https://doi.org/10.3389/fneur.2019.00111
Jeziorska, Maria ; Atkinson, Andrew ; Kass-Iliyya, Lewis ; Javed, Saad ; Kobylecki, Christopher ; Gosal, David ; Marshall, Andrew ; Silverdale, Monty ; Malik, Rayaz. / Increased intraepidermal nerve fiber degeneration and impaired regeneration relate to symptoms and deficits in Parkinson's disease. In: Frontiers in Neurology. 2019 ; Vol. 10, No. FEB.
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abstract = "Background: Previous studies have shown cutaneous small fiber pathology in patients with Parkinson's disease (PD). These studies have focused on nerve degeneration, but recent reports suggest that nerve regeneration may also be important in PD pathology. Objective: To establish the extent of intraepidermal nerve fiber (IENF) degeneration and regeneration and its relationship to clinical and neurological deficits in Parkinson's disease (PD). Methods: Twenty-three PD patients and 10 age-matched controls underwent skin biopsy and assessment of somatic and autonomic symptoms and deficits. We have assessed Intraepidermal Nerve Fiber Density (IENFD) using standard PGP9.5 staining and GAP-43 to assess Mean Axonal Length (MAL) and Intraepidermal Total Nerve Fiber Length (IETNFL). Results: IENFD (p < 0.0001), MAL (p < 0.0001), IETNFL/Area (p = 0.009), and IETNFL/Length (p = 0.04) were significantly reduced in patients with PD compared to controls. IENFD correlated significantly with disease duration (p = 0.03), cumulative levodopa dose (p = 0.02), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (p = 0.01), Schwab and England Activities of Daily Living (ADL) (p = 0.03), NSP (p = 0.03), and 30:15 ratio (p = 0.03). IETNFL/Area correlated with the Autonomic Scale for Outcomes in Parkinson's Disease (SCOPA-AUT) (p = 0.03) and Diabetic Neuropathy Symptom score (DNS) (p = 0.04) and IETNFL/Length correlated with DNS (p = 0.03). MAL correlated with SCOPA-AUT (p = 0.01), DNS (p = 0.02), and DB-HRV (p = 0.02). Conclusion: Increased IENF degeneration and impaired regeneration correlates with somatic and autonomic symptoms and deficits in patients with PD.",
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AU - Jeziorska, Maria

AU - Atkinson, Andrew

AU - Kass-Iliyya, Lewis

AU - Javed, Saad

AU - Kobylecki, Christopher

AU - Gosal, David

AU - Marshall, Andrew

AU - Silverdale, Monty

AU - Malik, Rayaz

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N2 - Background: Previous studies have shown cutaneous small fiber pathology in patients with Parkinson's disease (PD). These studies have focused on nerve degeneration, but recent reports suggest that nerve regeneration may also be important in PD pathology. Objective: To establish the extent of intraepidermal nerve fiber (IENF) degeneration and regeneration and its relationship to clinical and neurological deficits in Parkinson's disease (PD). Methods: Twenty-three PD patients and 10 age-matched controls underwent skin biopsy and assessment of somatic and autonomic symptoms and deficits. We have assessed Intraepidermal Nerve Fiber Density (IENFD) using standard PGP9.5 staining and GAP-43 to assess Mean Axonal Length (MAL) and Intraepidermal Total Nerve Fiber Length (IETNFL). Results: IENFD (p < 0.0001), MAL (p < 0.0001), IETNFL/Area (p = 0.009), and IETNFL/Length (p = 0.04) were significantly reduced in patients with PD compared to controls. IENFD correlated significantly with disease duration (p = 0.03), cumulative levodopa dose (p = 0.02), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (p = 0.01), Schwab and England Activities of Daily Living (ADL) (p = 0.03), NSP (p = 0.03), and 30:15 ratio (p = 0.03). IETNFL/Area correlated with the Autonomic Scale for Outcomes in Parkinson's Disease (SCOPA-AUT) (p = 0.03) and Diabetic Neuropathy Symptom score (DNS) (p = 0.04) and IETNFL/Length correlated with DNS (p = 0.03). MAL correlated with SCOPA-AUT (p = 0.01), DNS (p = 0.02), and DB-HRV (p = 0.02). Conclusion: Increased IENF degeneration and impaired regeneration correlates with somatic and autonomic symptoms and deficits in patients with PD.

AB - Background: Previous studies have shown cutaneous small fiber pathology in patients with Parkinson's disease (PD). These studies have focused on nerve degeneration, but recent reports suggest that nerve regeneration may also be important in PD pathology. Objective: To establish the extent of intraepidermal nerve fiber (IENF) degeneration and regeneration and its relationship to clinical and neurological deficits in Parkinson's disease (PD). Methods: Twenty-three PD patients and 10 age-matched controls underwent skin biopsy and assessment of somatic and autonomic symptoms and deficits. We have assessed Intraepidermal Nerve Fiber Density (IENFD) using standard PGP9.5 staining and GAP-43 to assess Mean Axonal Length (MAL) and Intraepidermal Total Nerve Fiber Length (IETNFL). Results: IENFD (p < 0.0001), MAL (p < 0.0001), IETNFL/Area (p = 0.009), and IETNFL/Length (p = 0.04) were significantly reduced in patients with PD compared to controls. IENFD correlated significantly with disease duration (p = 0.03), cumulative levodopa dose (p = 0.02), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (p = 0.01), Schwab and England Activities of Daily Living (ADL) (p = 0.03), NSP (p = 0.03), and 30:15 ratio (p = 0.03). IETNFL/Area correlated with the Autonomic Scale for Outcomes in Parkinson's Disease (SCOPA-AUT) (p = 0.03) and Diabetic Neuropathy Symptom score (DNS) (p = 0.04) and IETNFL/Length correlated with DNS (p = 0.03). MAL correlated with SCOPA-AUT (p = 0.01), DNS (p = 0.02), and DB-HRV (p = 0.02). Conclusion: Increased IENF degeneration and impaired regeneration correlates with somatic and autonomic symptoms and deficits in patients with PD.

KW - Autonomic

KW - Intraepidermal nerve

KW - Motor

KW - Parkinson's disease

KW - Skin biopsy

KW - Small fiber neuropathy

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