Objective: In a longitudinal manner explore possible diagnostic and prognostic properties of determining intraepidermal nerve fiber density (IENFD), by means of skin punch biopsy, in patients with Parkinson’s disease (PD) and atypical parkinsonism.

Background: The presence of cutaneous small fiber neuropathy in PD has been demonstrated in several studies, including associations with clinical measures of disease burden [1, 2]. Together with the detection of phosphorylated alpha-synuclein in dermal nerve fibers, the notion of peripheral neurodegeneration in PD has been suggested [3].

Some studies have demonstrated cutaneous denervation, together with alpha-synuclein deposits, also in multiple system atrophy (MSA) [4, 5], but less data exist with regard to the four-repeat tauopathies corticobasal degeneration and progressive supranuclear palsy.

Method: In an ongoing longitudinal study, controls and patients with PD, MSA and four-repeat tauopathies were prospectively included. Assessments included clinical rating scales, questionnaires and quantification of IENFD from 3 mm skin punch biopsies taken from the neck, proximal and distal leg. Assessments were repeated after one year.

Non-parametric testing was performed to explore group differences and associations at baseline, and associations between IENFD at baseline and one-year changes in clinical rating scores.

Results: An overview of the study population (n=63) is shown in Table 1 [table1]. At baseline, no significant group differences were seen with regard to IENFD [figure1]. No significant associations between clinical rating scores and IENFD were demonstrated in patients at baseline.

56 participants completed the one-year follow-up, with drop-outs (n=7) owing to death and severe clinical deterioration. In MSA, strong associations were demonstrated between one-year changes in clinical rating scores and baseline IENFD at all three biopsy sites [table2]. No significant associations were demonstrated in the other disease groups.

Conclusion: IENFD at baseline may be negatively associated with the rate of clinical disease progression in MSA over a one-year period. Longer follow-up is needed to explore possible similar associations in PD, given its slower rate of progression. In contrast to previous studies, no cross-sectional discriminative properties of IENFD were demonstrated in this cohort.

Table 1.

Figure 1.

Table 2.

References: [1] Nolano, M., et al., Sensory deficit in Parkinson’s disease: evidence of a cutaneous denervation. Brain, 2008. 131(Pt 7): p. 1903-11.

[2] Nolano, M., et al., Small fiber pathology parallels disease progression in Parkinson disease: a longitudinal study. Acta Neuropathol, 2018. 136(3): p. 501-503.

[3] Doppler, K., et al., Cutaneous neuropathy in Parkinson’s disease: a window into brain pathology. Acta Neuropathol, 2014. 128(1): p. 99-109.

[4] Vacchi, E., et al., Alpha-synuclein oligomers and small nerve fiber pathology in skin are potential biomarkers of Parkinson’s disease. NPJ Parkinsons Dis, 2021. 7(1): p. 119.

[5] Provitera, V., et al., Postganglionic Sudomotor Assessment in Early Stage of Multiple System Atrophy and Parkinson Disease: A Morpho-functional Study. Neurology, 2022. 98(12): p. e1282-e1291.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/intraepidermal-nerve-fiber-density-at-baseline-associates-with-one-year-clinical-disease-progression-in-multiple-system-atrophy/