scholarly journals Alpha-synuclein oligomers and small nerve fiber pathology in skin are potential biomarkers of Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Elena Vacchi ◽  
Camilla Senese ◽  
Giacomo Chiaro ◽  
Giulio Disanto ◽  
Sandra Pinton ◽  
...  
Keyword(s):  
Skin Biopsy ◽  
Nerve Fiber ◽  
Temporal Dynamics ◽  
Alpha Synuclein ◽  
Small Fiber Neuropathy ◽  
Proximity Ligation Assay ◽  
Anatomical Site ◽  
Small Fiber ◽  
Intraepidermal Nerve Fiber Density ◽  
Small Nerve

AbstractThe proximity ligation assay (PLA) is a specific and sensitive technique for the detection of αSyn oligomers (αSyn-PLA), early and toxic species implicated in the pathogenesis of PD. We aimed to evaluate by skin biopsy the diagnostic and prognostic capacity of αSyn-PLA and small nerve fiber reduction in PD in a longitudinal study. αSyn-PLA was performed in the ankle and cervical skin biopsies of PD (n = 30), atypical parkinsonisms (AP, n = 23) including multiple system atrophy (MSA, n = 12) and tauopathies (AP-Tau, n = 11), and healthy controls (HC, n = 22). Skin biopsy was also analyzed for phosphorylated αSyn (P-αSyn) and 5G4 (αSyn-5G4), a conformation-specific antibody to aggregated αSyn. Intraepidermal nerve fiber density (IENFD) was assessed as a measure of small fiber neuropathy. αSyn-PLA signal was more expressed in PD and MSA compared to controls and AP-Tau. αSyn-PLA showed the highest diagnostic accuracy (PD vs. HC sensitivity 80%, specificity 77%; PD vs. AP-Tau sensitivity 80%, specificity 82%), however, P-αSyn and 5G4, possible markers of later phases, performed better when considering the ankle site alone. A small fiber neuropathy was detected in PD and MSA. A progression of denervation not of pathological αSyn was detected at follow-up and a lower IENFD at baseline was associated with a greater cognitive and motor decline in PD. A skin biopsy-derived compound marker, resulting from a linear discrimination analysis model of αSyn-PLA, P-αSyn, αSyn-5G4, and IENFD, stratified patients with accuracy (77.8%), including the discrimination between PD and MSA (84.6%). In conclusion, the choice of pathological αSyn marker and anatomical site influences the diagnostic performance of skin biopsy and can help in understanding the temporal dynamics of αSyn spreading in the peripheral nervous system during the disease. Skin denervation, not pathological αSyn is a potential progression marker for PD.

scholarly journals Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?

2021 ◽  
Vol 29 (1) ◽  
pp. 1-8
Author(s):  
Mariia V. Lukashenko ◽  
Natalia Y. Gavrilova ◽  
Anna V. Bregovskaya ◽  
Lidiia A. Soprun ◽  
Leonid P. Churilov ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Skin Biopsy ◽  
Nerve Fiber ◽  
Small Fiber Neuropathy ◽  
Fiber Damage ◽  
Advantages And Disadvantages ◽  
Small Fiber ◽  
Corneal Confocal Microscopy ◽  
Common Causes ◽  
Small Nerve

Chronic pain may affect 30–50% of the world’s population and an important cause is small fiber neuropathy (SFN). Recent research suggests that autoimmune diseases may be one of the most common causes of small nerve fiber damage. There is low awareness of SFN among patients and clinicians and it is difficult to diagnose as routine electrophysiological methods only detect large fiber abnormalities, and specialized small fiber tests, like skin biopsy and quantitative sensory testing, are not routinely available. Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible method for quantifying small nerve fiber degeneration and regeneration, and could be an important tool for diagnosing SFN. This review considers the advantages and disadvantages of CCM and highlights the evolution of this technique from a research tool to a diagnostic test for small fiber damage, which can be a valuable contribution to the study and management of autoimmune disease.

Small Fiber Neuropathy

2019 ◽  
Vol 39 (05) ◽  
pp. 570-577 ◽  
Author(s):  
Lan Zhou
Keyword(s):  
Skin Biopsy ◽  
Lifestyle Modification ◽  
Specific Treatment ◽  
Small Fiber Neuropathy ◽  
Fiber Density ◽  
Small Fiber ◽  
Intraepidermal Nerve Fiber Density ◽  
Associated Conditions ◽  
Density Evaluation

AbstractSmall fiber neuropathy (SFN) is common, and can be associated with many medical conditions. The majority of the patients with SFN suffer from painful paresthesia which can negatively impact their quality of life. Skin biopsy with intraepidermal nerve fiber density evaluation is the gold standard diagnostic test. Autonomic function testing is useful when autonomic symptoms are present. Screening for associated conditions should be done in every patient, even when a known underlying associated condition is present, before the neuropathy evaluation. Etiology-specific treatment, lifestyle modification, and pain control are the key elements of SFN management. This article will review the clinical presentation, skin biopsy procedure, utility of diagnostic tests, associated conditions, management, and prognosis of SFN.

scholarly journals Presence of Decreased Intraepidermal Nerve Fiber Density Consistent with Small Fiber Neuropathy in Patients with Central Post-Stroke Pain

Pain Medicine ◽  
2016 ◽  
Vol 17 (8) ◽  
pp. 1569-1571 ◽  
Author(s):  
Yefim Cavalier ◽  
Phillip J. Albrecht ◽  
Colum Amory ◽  
Gary L. Bernardini ◽  
Charles E. Argoff
Keyword(s):  
Nerve Fiber ◽  
Small Fiber Neuropathy ◽  
Fiber Density ◽  
Post Stroke ◽  
Small Fiber ◽  
Intraepidermal Nerve Fiber Density ◽  
Nerve Fiber Density ◽  
Intraepidermal Nerve Fiber

Characterization of small nerve fibers in painful distal symmetric polyneuropathy and healthy controls

2015 ◽  
Vol 8 (1) ◽  
pp. 51
Author(s):  
P. Karlsson ◽  
S. Haroutounian ◽  
M. Polydefkis ◽  
J.R. Nyengaard ◽  
T.S. Jensen
Keyword(s):  
Nerve Fiber ◽  
Quantitative Sensory Testing ◽  
Nerve Fibers ◽  
Healthy Controls ◽  
Sensory Testing ◽  
Fiber Morphology ◽  
Small Fiber ◽  
Intraepidermal Nerve Fiber Density ◽  
Distal Symmetric Polyneuropathy ◽  
Small Nerve

AbstractAimsThe introduction of skin biopsies to examine small nerve fiber morphology together with functional measures such as quantitative sensory testing (QST) has led to an improvement in diagnosing patients with small fiber neuropathy (SFN). Quantification of intraepidermal nerve fiber density (IENFD) is an important measure in SFN. However, the relationship between structure and function is not straightforward and the morphological and functional fiber characteristics are still unclear. This study aimed to combine structural and functional measurements to improve the diagnosis of distal symmetric polyneuropathy and small fiber involvement. Additionally, we investigated whether patients and healthy controls have differential patterns of correlations between structural and functional nerve measurements.Methods17 patients with painful distal symmetric polyneu-ropathy (DSP) and 19 controls underwent comprehensive small fiber assessments that included quantitative sensory testing, response to topical capsaicin and analysis of skin biopsy samples (IENFD, epidermal and dermal nerve fiber length densities (eNFLD, dNFLD) and swellings).ResultsDSP patients had reduced sensitivity to cold and heat, diminished capsaicin response, and lower IENFD, eNFLD and dNFLD (all p < 0.0003).The correlation between structural and functional parameters was better in controls than in DSP. A diagnostic approach of combined IENFD and eNFLD utilization, increased DSP diagnostic sensitivity from 82.0% to 100% and specificity from 84.0% to 89.5%.ConclusionsA correlation is found between functional and structural small fiber parameters for DSP and controls, and an approach to improve diagnostic accuracy in DSP is suggested.

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