Skin biopsy and I‐123 MIBG scintigraphy findings in idiopathic Parkinson's disease and parkinsonism: A comparative study

Giannoccaro, Maria Pia; Donadio, Vincenzo; Incensi, Alex; Pizza, Fabio; Cason, Ernesto; Stasi, Vitantonio Di; Martinelli, Paolo; Scaglione, Cesa; Capellari, Sabina; Treglia, Giorgio; Liguori, Rocco

doi:10.1002/mds.26189

Cited by 24 publications

(14 citation statements)

References 21 publications

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“…A reduction of epidermal and autonomic innervation has recently been reported in patients with iPD, compared to other forms of parkinsonism. 11 However, our data suggest to differentiate between MSA and other forms of parkinsonism when studying PNS involvement. Given that our study was a premortem study, diagnosis was based on clinical symptoms and diagnostic accuracy is therefore limited.…”

Section: Discussionmentioning

confidence: 69%

Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy

et al. 2015

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Background MSA is characterized by deposition of alpha‐synuclein (α‐Syn) in oligodendrocytes and central nervous system (CNS) neurons. After recently detecting phospho‐α‐Syn (p‐α‐Syn) in dermal nerve fibers of patients with Parkinson's disease (PD), we assessed skin biopsies from patients with MSA to evaluate its potential role as a biomarker. Methods Skin biopsies of patients with MSA (n = 12), idiopathic PD (n = 30), tauopathies (n = 15), and normal controls (n = 39) were analyzed. P‐α‐Syn within dermal nerves was detected by immunofluorescence staining. Results p‐α‐Syn was found in 67% of patients with MSA and Parkinson's disease, but not in patients with tauopathy or controls when analyzing 15 consecutive sections. Sensitivity could be increased to 75% and 73%, respectively, by analyzing serial sections. In contrast to PD, where p‐α‐Syn clustered in autonomic fibers, deposits were mainly found in unmyelinated somatosensory fibers in MSA. Conclusion α‐Syn pathology in MSA is not restricted to the CNS, and skin biopsy may be useful for the premortem study of p‐α‐Syn. © 2015 International Parkinson and Movement Disorder Society

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Section: Discussionmentioning

confidence: 69%

Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy

et al. 2015

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“…Reported prevalence of SFN, as this was determined by the intra-epidermal nerve fiber density, ranges from 37% [20] to 91% [21]. The pooled estimate of the prevalence of small fiber neuropathy based on the skin biopsy as this has been reported in 3 studies of a total of 72 patients with PD is 56.9% [20 -22].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Wang et al studied the α-synuclein deposition in cutaneous sensory nerves and showed that is increased in cutaneous sympathetic adrenergic and sympathetic cholinergic fibers but not sensory fibers of patients with PD compared to controls [21]. Donadio et al showed that neuritic α-synuclein inclusions are correlated with a small-fiber neuropathy suggesting a possible direct role of phosphorylated αsynuclein in peripheral nerve fiber damage [33].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Such reports of patients with PD with coincident autoimmune diseases[26] suggest a possible role of the immune system in the pathogenesis of at least some cases of neuropathy in PD who developed acute motor axonal neuropathy (AMAN) following Campylobacter jejuni infection. Acute inflammatory demyelinating polyneuropathy (classical Guillain-Barre syndrome) with positive anti-ganglioside antibodies has been reported by Galazky et al during intrajejunal levodopa infusion therapy[28].Small fiber density is reduced in PD compared with healthy controls[15, 18 -21] and patients with parkinsonism[17,21] suggesting than skin biopsy may be also contribute to the differential diagnosis of IPD and parkinsonism[21].…”

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confidence: 99%

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Peripheral neuropathy in idiopathic Parkinson's disease: A systematic review

Zis

Grünewald

Chaudhuri

et al. 2017

Journal of the Neurological Sciences

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“…Two promising studies have shown that dermal p‐ α Syn can be detected in a subgroup of patients with REM‐sleep behavioral disturbances (RBD), potentially representing prodromal PD . Another important point emerging from these studies is that most PD patients displayed cutaneous somatic and autonomic denervation . However, the potential relationship between pathological α ‐Syn deposits and the loss of small nerve fibers is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Cervical skin denervation associates with alpha‐synuclein aggregates in Parkinson disease

Melli

Vacchi

Biemmi

et al. 2018

Ann Clin Transl Neurol

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ObjectiveAutonomic nervous system is involved at the onset of Parkinson disease (PD), and alpha‐synuclein (α‐Syn) and its phosphorylated form (p‐αSyn) have been detected in dermal autonomic nerve fibers of PD. We assessed disease specific conformation variant of α‐Syn immunoreactivity in cutaneous nerves and characterized skin denervation patterns in PD and atypical parkinsonism (AP).MethodsWe enrolled 49 subjects, 19 with PD, 17 age‐matched healthy controls, and 13 with AP. The manifestations of disease were rated on clinical scales. Skin biopsies from ankle, thigh, and neck were analyzed by immunofluorescence for p‐αSyn, 5G4 as a conformation specific antibody to pathogenic α‐Syn and PGP9.5 as axonal marker. Intraepidermal nerve fiber density was measured in all anatomical sites as marker of neurodegeneration. Thirteen of the 19 PD underwent a 1 year follow‐up visit plus skin biopsies.ResultsPD subjects displayed more severe cervical skin denervation (P < 0.03), which correlated to disease duration and worsened between initial and follow‐up examination (P < 0.001). p‐αSyn and 5G4 were equally sensitive and specific for the diagnosis of PD (area under the ROC was 0.839 for p‐αSyn and 0.886 for 5G4). PD and AP with possible alpha‐synucleinopathies share the features of marked cervical denervation and the presence of 5G4. In contrast AP with possible tauopathies were normal.InterpretationConformational specific forms of α‐Syn are detectable in skin biopsy by immunofluorescence in PD, with a promising diagnostic efficiency similar to p‐αSyn. Cervical cutaneous denervation correlates with disease duration and increases over time standing out as a potential biomarker of PD progression.

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Skin biopsy and I‐123 MIBG scintigraphy findings in idiopathic Parkinson's disease and parkinsonism: A comparative study

Abstract: (1) Skin biopsy and (123) I-MIBG scintigraphy provide comparable results; (2) in IPD, autonomic dysfunctions are often simultaneously widespread at cardiac and skin branches. © 2015 International Parkinson and Movement Disorder Society.

Cited by 24 publications

References 21 publications

Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy

Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy

Peripheral neuropathy in idiopathic Parkinson's disease: A systematic review

Cervical skin denervation associates with alpha‐synuclein aggregates in Parkinson disease

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