Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study

Lewis Kass-Iliyya, Saad Javed, David Gosal, Christopher Kobylecki, Andrew Marshall, Ioannis N. Petropoulos, Georgios Ponirakis, Mitra Tavakoli, Maryam Ferdousi, Kallol Ray Chaudhuri, Maria Jeziorska, Rayaz Malik, Monty A. Silverdale

Research output: Contribution to journalArticle

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Abstract

Autonomic and somatic denervation is well established in Parkinson's disease (PD). Objectives: (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Methods: Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. Results: PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. Conclusion: CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD.

Original languageEnglish
Pages (from-to)1454-1460
Number of pages7
JournalParkinsonism and Related Disorders
Volume21
Issue number12
DOIs
Publication statusPublished - 1 Dec 2015

Fingerprint

Nerve Fibers
Confocal Microscopy
Parkinson Disease
Levodopa
Small Fiber Neuropathy
Autonomic Denervation
Respiration
Heart Rate
Pathology
Peripheral Nerves
Foot
Biopsy
Pain
Skin

Keywords

  • Confocal microscopy
  • Cornea
  • Intraepidermal nerve fiber density
  • Parkinson's disease
  • Small fiber neuropathy

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Kass-Iliyya, L., Javed, S., Gosal, D., Kobylecki, C., Marshall, A., Petropoulos, I. N., ... Silverdale, M. A. (2015). Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study. Parkinsonism and Related Disorders, 21(12), 1454-1460. https://doi.org/10.1016/j.parkreldis.2015.10.019

Small fiber neuropathy in Parkinson's disease : A clinical, pathological and corneal confocal microscopy study. / Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N.; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz; Silverdale, Monty A.

In: Parkinsonism and Related Disorders, Vol. 21, No. 12, 01.12.2015, p. 1454-1460.

Research output: Contribution to journalArticle

Kass-Iliyya, L, Javed, S, Gosal, D, Kobylecki, C, Marshall, A, Petropoulos, IN, Ponirakis, G, Tavakoli, M, Ferdousi, M, Chaudhuri, KR, Jeziorska, M, Malik, R & Silverdale, MA 2015, 'Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study', Parkinsonism and Related Disorders, vol. 21, no. 12, pp. 1454-1460. https://doi.org/10.1016/j.parkreldis.2015.10.019
Kass-Iliyya, Lewis ; Javed, Saad ; Gosal, David ; Kobylecki, Christopher ; Marshall, Andrew ; Petropoulos, Ioannis N. ; Ponirakis, Georgios ; Tavakoli, Mitra ; Ferdousi, Maryam ; Chaudhuri, Kallol Ray ; Jeziorska, Maria ; Malik, Rayaz ; Silverdale, Monty A. / Small fiber neuropathy in Parkinson's disease : A clinical, pathological and corneal confocal microscopy study. In: Parkinsonism and Related Disorders. 2015 ; Vol. 21, No. 12. pp. 1454-1460.
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AU - Kass-Iliyya, Lewis

AU - Javed, Saad

AU - Gosal, David

AU - Kobylecki, Christopher

AU - Marshall, Andrew

AU - Petropoulos, Ioannis N.

AU - Ponirakis, Georgios

AU - Tavakoli, Mitra

AU - Ferdousi, Maryam

AU - Chaudhuri, Kallol Ray

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N2 - Autonomic and somatic denervation is well established in Parkinson's disease (PD). Objectives: (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Methods: Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. Results: PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. Conclusion: CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD.

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KW - Intraepidermal nerve fiber density

KW - Parkinson's disease

KW - Small fiber neuropathy

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