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Vincenzo Donadio - One of the best experts on this subject based on the ideXlab platform.

  • Skin Nerve phosphorylated α-synuclein deposits in Parkinson’s disease with orthostatic hypotension
    Clinical Neurophysiology, 2019
    Co-Authors: Vincenzo Donadio, Alex Incensi, Giovanni Rizzo, F. Del Sorbo, Cesa Scaglione, Antonio E. Elia, Rossella Infante, Nicola Modugno, E. Fileccia, Federica Cencini
    Abstract:

    To investigate phosphorylated α -synuclein (p-syn) deposits in Skin Nerves of Parkinson’s disease (PD) patients with neurogenic orthostatic hypotension (OH) and a PD matched group without dysautonomia. We enrolled 28 idiopathic PD patients with abnormal nigro-striatal DatScan and cardiac MIBG: (1) 14 of them complained of neurogenic OH (PD + OH); and (2) 14 matched patients did not complain of autonomic dysfunctions (PD-OH); 7 of them were re-evaluated over a follow-up (4 ± 2 years). Patients underwent Skin biopsy in proximal (i.e. C7 paravertebral spine region) and distal (i.e. thigh and leg) sites. PD + OH showed a higher p-syn deposition than PD-OH with a widespread autonomic cholinergic and adrenergic Skin Nerves involvement. Over the follow-up PD-OH patients showed a marked increase in motor dysfunctions scores without autonomic symptoms and a slight increase of Skin p-syn deposition but still lower than PD + OH. PD + OH showed a wide involvement of p-syn deposits in autonomic cholinergic and adrenergic Skin Nerves Skin; (2) PD-OH showed a lower load of Skin p-syn mainly restricted to adrenergic fibers of Skin vessels, still persisting over a follow-up. These data supported a different pathogenesis between PD + OH and PD-OH and may help to identify a specific diagnostic trait for PD + OH patients.

  • Skin Nerve α-synuclein deposits in Parkinson's disease and other synucleinopathies: a review.
    Clinical autonomic research : official journal of the Clinical Autonomic Research Society, 2018
    Co-Authors: Vincenzo Donadio
    Abstract:

    Purpose The in vivo diagnosis of synucleinopathies is an important research aim since clinical diagnostic criteria show low accuracy. The Skin innervation, especially the autonomic subdivision, is a useful region to search for abnormal α-syn aggregates in synucleinopathies since the peripheral sympathetic Nerves can be the earliest-affected neural region and autonomic symptoms may precede the classical symptoms of these disorders.

  • Skin Nerve α-synuclein deposits in Parkinson's disease and other synucleinopathies: a review.
    Clinical autonomic research : official journal of the Clinical Autonomic Research Society, 2018
    Co-Authors: Vincenzo Donadio
    Abstract:

    The in vivo diagnosis of synucleinopathies is an important research aim since clinical diagnostic criteria show low accuracy. The Skin innervation, especially the autonomic subdivision, is a useful region to search for abnormal α-syn aggregates in synucleinopathies since the peripheral sympathetic Nerves can be the earliest-affected neural region and autonomic symptoms may precede the classical symptoms of these disorders. The major advantages of Skin biopsy as an in vivo diagnostic tool for synucleinopathies are that it is an inexpensive and easy-to-perform technique requiring only limited facilities, and that it is repeatable in long-term studies as it causes only minor discomfort to the patient. This review analyzes current progress in this area of research that may facilitate the standardization of this method, potentially eliminating differences among laboratories in the implementation of the method. The most suitable and commonly used technique for identifying in vivo α-syn aggregates in Skin Nerves is indirect immunofluorescence, although several aspects of this approach need to be standardized, particularly when synucleinopathies without autonomic failure present a patchy distribution of abnormal α-syn aggregates in Skin Nerves. By contrast, synucleinopathies with autonomic failure may present widespread diffusion of abnormal aggregates in autonomic Skin Nerves.

  • Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study.
    Scientific reports, 2018
    Co-Authors: Vincenzo Donadio, Alex Incensi, Omar M. A. El-agnaf, Giovanni Rizzo, Nishant N. Vaikath, F. Del Sorbo, Cesa Scaglione, Sabina Capellari, Antonio E. Elia, M. Stanzani Maserati
    Abstract:

    We aimed to characterize in vivo α-synuclein (α-syn) aggregates in Skin Nerves to ascertain: 1) the optimal marker to identify them; 2) possible differences between synucleinopathies that may justify the clinical variability. We studied multiple Skin Nerve α-syn deposits in 44 patients with synucleinopathy: 15 idiopathic Parkinson’s disease (IPD), 12 dementia with Lewy Bodies (DLB), 5 pure autonomic failure (PAF) and 12 multiple system atrophy (MSA). Ten healthy subjects were used as controls. Antibodies against native α-syn, C-terminal α-syn epitopes such as phosphorylation at serine 129 (p-syn) and to conformation-specific for α-syn mature amyloid fibrils (syn-F1) were used. We found that p-syn showed the highest sensitivity and specificity in disclosing Skin α-syn deposits. In MSA abnormal deposits were only found in somatic fibers mainly at distal sites differently from PAF, IPD and DLB displaying α-syn deposits in autonomic fibers mainly at proximal sites. PAF and DLB showed the highest p-syn load with a widespread involvement of autonomic Skin Nerve fibers. In conclusion: 1) p-syn in Skin Nerves was the optimal marker for the in vivo diagnosis of synucleinopathies; 2) the localization and load differences of aggregates may help to identify specific diagnostic traits and support a different pathogenesis among synucleinopathies.

  • Skin Nerve Phosphorylated α-Synuclein Deposits in Parkinson Disease With Orthostatic Hypotension.
    Journal of neuropathology and experimental neurology, 2018
    Co-Authors: Vincenzo Donadio, Alex Incensi, Giovanni Rizzo, Cesa Scaglione, Antonio E. Elia, Francesca Del Sorbo, Rossella Infante, Nicola Modugno, E. Fileccia, Federica Cencini
    Abstract:

    This study aimed to investigate phosphorylated α-synuclein (p-syn) in autonomic Skin Nerves of Parkinson disease (PD) patients with and without orthostatic hypotension (OH). We studied 28 PD patients with normal corrected Mini-Mental State Examination including 14 patients with neurogenic OH (PD + OH) and 14 matched patients did not complain of OH (PD - OH); 7 of whom were re-evaluated over a follow-up period (4 ± 2 years). Skin biopsy was performed in proximal and distal sites. PD + OH patients showed a higher p-syn deposition than PD - OH, with widespread autonomic cholinergic and adrenergic Skin Nerve involvement. Over the follow-up period, PD - OH patients showed an increase in motor dysfunction scores without autonomic symptoms and a slight increase of Skin p-syn deposition but still lower than PD + OH, mainly restricted to adrenergic fibers of Skin vessels (SV). In summary, PD + OH patients showed a wide involvement of p-syn deposits in autonomic cholinergic and adrenergic Skin Nerves compared with PD - OH, and PD - OH patients showed a lower load of Skin p-syn restricted to adrenergic fibers of SV still persisting over the follow-up period. The data supported a different pathogenesis between PD + OH and PD - OH and may help to identify a specific diagnostic trait for PD + OH.

Rocco Liguori - One of the best experts on this subject based on the ideXlab platform.

  • Skin Nerve phosphorylated α synuclein deposits in idiopathic rem sleep behavior disorder
    Neurology, 2017
    Co-Authors: Elena Antelmi, Vincenzo Donadio, Alex Incensi, Giuseppe Plazzi, Rocco Liguori
    Abstract:

    Objective: To test if phosphorylated α-synuclein (p-α-syn) deposits can be detected by means of Skin biopsy in patients with idiopathic REM sleep behavior disorder (iRBD) as a potential early histopathologic marker of impending synucleinopathy. Methods: Proximal (cervical) and distal (legs) samples of Skin biopsy were obtained from 12 patients with polysomnographically confirmed iRBD and 55 sex- and age-matched healthy controls (HC). P-α-syn deposits were assessed with a monoclonal antibody against p-α-syn at serine 129, disclosed by an immunofluorescence method. In addition, patients underwent an extensive workup in order to search for nonmotor symptoms and neuroimaging findings usually associated with impending neurodegeneration and to exclude subtle motor or cognitive signs. Results: P-α-syn deposits were detected in 9 (75%) out of 12 patients with iRBD and none of the HC. In iRBD, the sensitivity of the test was higher at the cervical site (67%) when compared to the leg site (58%). Conclusions: Our preliminary findings suggest that Skin biopsy in patients with iRBD might be a safe and sensitive procedure to be further tested in order to detect p-α-syn deposits in the premotor stage of synucleinopathies. Classification of evidence: This study provides Class III evidence that p-α-syn Skin deposits identify patients with iRBD.

  • Skin Nerve misfolded α-synuclein in pure autonomic failure and Parkinson disease.
    Annals of neurology, 2015
    Co-Authors: Alex Incensi, Cristina Piccinini, Rocco Liguori
    Abstract:

    OBJECTIVE To characterize the expression in Skin Nerves of native (n-syn) and misfolded phosphorylated (p-syn) α-synucleins in pure autonomic failure (PAF) and idiopathic Parkinson disease (IPD). The specific aims were to (1) define the importance of n-syn and p-syn as disease biomarkers and (2) ascertain differences in abnormal synuclein Skin Nerve deposits. METHODS We studied 30 patients, including 16 well-characterized IPD patients and 14 patients fulfilling PAF diagnostic criteria, and 15 age-matched controls. Subjects underwent Skin biopsy from proximal (ie, cervical) and distal (ie, thigh and leg) sites to study small Nerve fiber and intraneural n-syn and p-syn. RESULTS PAF and IPD showed length-dependent somatic and autonomic small fiber loss, more severely expressed in patients with higher p-syn load. n-syn was similarly expressed in both groups of patients and controls. By contrast, p-syn was not evident in any Skin sample of controls but was found in all PAF and IPD patients, although with different Skin innervation. In addition, abnormal α-synuclein deposits were found in all analyzed Skin samples in PAF but in only 49% of samples with a higher positivity rate at the proximal site in IPD. INTERPRETATION (1) Intraneural p-syn was a reliable in vivo marker of PAF and IPD; (2) neuritic p-syn inclusions differed in PAF and IPD, suggesting a different underlying pathogenesis; (3) when searching for abnormal p-syn deposits in Skin Nerves, the site of analysis is irrelevant in PAF but it is critical in IPD.

  • 83. Skin Nerve α-synuclein deposits: A biomarker for idiopathic Parkinson’s disease
    Clinical Neurophysiology, 2015
    Co-Authors: Vincenzo Donadio, V Leta, Maria Pia Giannoccaro, Patrizia Avoni, Agostino Baruzzi, A. Incensi, C. Scaglione, S. Cappellari, Rocco Liguori
    Abstract:

    (1) Whether phosphorylated α-synuclein deposits in Skin Nerve fibers might represent a useful biomarker for idiopathic Parkinson’s disease (IPD). (2) The underlying pathogenesis of peripheral neuropathy associated with IPD. We studied 21 well-characterized IPD patients, 20 with parkinsonisms assumed not to have α-synuclein deposits (PAR: 10 vascular parkinsonism, 6 taupathies and 4 parkin mutations) and 30 controls. Subjects underwent: Nerve conduction velocities from the leg to evaluate large Nerve fibers; Skin biopsy from proximal (i.e. cervical) and distal (i.e. thigh and distal leg) sites to study small Nerve fibers and deposits of phosphorylated α-synuclein. IPD patients showed a small Nerve fiber neuropathy prevalent in the leg with preserved large Nerve fibers. PAR patients showed normal large and small Nerve fibers. Phosphorylated α-synuclein was not found in any Skin sample in PAR patients and controls but it was found in all IPD patients in the cervical Skin site. Abnormal deposits were correlated with leg epidermal denervation. Phosphorylated α-synuclein in proximal peripheral Nerves is a sensitive biomarker for IPD diagnosis helping to differentiate IPD from other parkinsonisms. Neuritic inclusions of α-synuclein were correlated with a small fiber neuropathy suggesting their direct role in peripheral Nerve fiber damage.

  • Skin Nerve α synuclein deposits a biomarker for idiopathic parkinson disease
    Neurology, 2014
    Co-Authors: Vincenzo Donadio, Alex Incensi, Cesa Scaglione, Sabina Capellari, V Leta, Maria Pia Giannoccaro, P Martinelli, Patrizia Avoni, Agostino Baruzzi, Rocco Liguori
    Abstract:

    Objective: To investigate (1) whether phosphorylated α-synuclein deposits in Skin Nerve fibers might represent a useful biomarker for idiopathic Parkinson disease (IPD), and (2) the underlying pathogenesis of peripheral neuropathy associated with IPD. Methods: Twenty-one well-characterized patients with IPD were studied together with 20 patients with parkinsonisms assumed not to have α-synuclein deposits (PAR; 10 patients fulfilling clinical criteria for vascular parkinsonism, 6 for tauopathies, and 4 with parkin mutations) and 30 controls. Subjects underwent Nerve conduction velocities from the leg to evaluate large Nerve fibers and Skin biopsy from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small Nerve fibers and deposits of phosphorylated α-synuclein considered the pathologic form of α-synuclein. Results: Patients with IPD showed a small Nerve fiber neuropathy prevalent in the leg with preserved large Nerve fibers. PAR patients showed normal large and small Nerve fibers. Phosphorylated α-synuclein was not found in any Skin sample in PAR patients and controls, but it was found in all patients with IPD in the cervical Skin site. Abnormal deposits were correlated with leg epidermal denervation. Conclusions: The search for phosphorylated α-synuclein in proximal peripheral Nerves is a sensitive biomarker for IPD diagnosis, helping to differentiate IPD from other parkinsonisms. Neuritic inclusions of α-synuclein were correlated with a small-fiber neuropathy, suggesting their direct role in peripheral Nerve fiber damage. Classification of evidence: This study provides Class III evidence that the presence of phosphorylated α-synuclein in Skin Nerve fibers on Skin biopsy accurately distinguishes IPD from other forms of parkinsonism.

  • Somatic and autonomic small fiber neuropathy induced by bortezomib therapy: an immunofluorescence study
    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2011
    Co-Authors: Maria Pia Giannoccaro, Vincenzo Donadio, Carolina Gomis Pèrez, Walter Borsini, Vitantonio Di Stasi, Rocco Liguori
    Abstract:

    Bortezomib is a new chemotherapeutic agent approved for the treatment of relapsed/refractory and newly diagnosed multiple myeloma. One of the major side effects of bortezomib is a peripheral length-dependent sensory axonal neuropathy and, less frequently, a small fiber neuropathy. Autonomic symptoms like postural dizziness, syncope, diarrhoea, ileus, impotence and urinary disturbances have been reported, nevertheless, autonomic neuropathy has never been characterized. We describe by means of immunofluorescence, the involvement of autonomic Skin Nerve fibers in three patients with small fiber neuropathy induced by bortezomib treatment.

Alex Incensi - One of the best experts on this subject based on the ideXlab platform.

  • Skin Nerve phosphorylated α-synuclein deposits in Parkinson’s disease with orthostatic hypotension
    Clinical Neurophysiology, 2019
    Co-Authors: Vincenzo Donadio, Alex Incensi, Giovanni Rizzo, F. Del Sorbo, Cesa Scaglione, Antonio E. Elia, Rossella Infante, Nicola Modugno, E. Fileccia, Federica Cencini
    Abstract:

    To investigate phosphorylated α -synuclein (p-syn) deposits in Skin Nerves of Parkinson’s disease (PD) patients with neurogenic orthostatic hypotension (OH) and a PD matched group without dysautonomia. We enrolled 28 idiopathic PD patients with abnormal nigro-striatal DatScan and cardiac MIBG: (1) 14 of them complained of neurogenic OH (PD + OH); and (2) 14 matched patients did not complain of autonomic dysfunctions (PD-OH); 7 of them were re-evaluated over a follow-up (4 ± 2 years). Patients underwent Skin biopsy in proximal (i.e. C7 paravertebral spine region) and distal (i.e. thigh and leg) sites. PD + OH showed a higher p-syn deposition than PD-OH with a widespread autonomic cholinergic and adrenergic Skin Nerves involvement. Over the follow-up PD-OH patients showed a marked increase in motor dysfunctions scores without autonomic symptoms and a slight increase of Skin p-syn deposition but still lower than PD + OH. PD + OH showed a wide involvement of p-syn deposits in autonomic cholinergic and adrenergic Skin Nerves Skin; (2) PD-OH showed a lower load of Skin p-syn mainly restricted to adrenergic fibers of Skin vessels, still persisting over a follow-up. These data supported a different pathogenesis between PD + OH and PD-OH and may help to identify a specific diagnostic trait for PD + OH patients.

  • Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study.
    Scientific reports, 2018
    Co-Authors: Vincenzo Donadio, Alex Incensi, Omar M. A. El-agnaf, Giovanni Rizzo, Nishant N. Vaikath, F. Del Sorbo, Cesa Scaglione, Sabina Capellari, Antonio E. Elia, M. Stanzani Maserati
    Abstract:

    We aimed to characterize in vivo α-synuclein (α-syn) aggregates in Skin Nerves to ascertain: 1) the optimal marker to identify them; 2) possible differences between synucleinopathies that may justify the clinical variability. We studied multiple Skin Nerve α-syn deposits in 44 patients with synucleinopathy: 15 idiopathic Parkinson’s disease (IPD), 12 dementia with Lewy Bodies (DLB), 5 pure autonomic failure (PAF) and 12 multiple system atrophy (MSA). Ten healthy subjects were used as controls. Antibodies against native α-syn, C-terminal α-syn epitopes such as phosphorylation at serine 129 (p-syn) and to conformation-specific for α-syn mature amyloid fibrils (syn-F1) were used. We found that p-syn showed the highest sensitivity and specificity in disclosing Skin α-syn deposits. In MSA abnormal deposits were only found in somatic fibers mainly at distal sites differently from PAF, IPD and DLB displaying α-syn deposits in autonomic fibers mainly at proximal sites. PAF and DLB showed the highest p-syn load with a widespread involvement of autonomic Skin Nerve fibers. In conclusion: 1) p-syn in Skin Nerves was the optimal marker for the in vivo diagnosis of synucleinopathies; 2) the localization and load differences of aggregates may help to identify specific diagnostic traits and support a different pathogenesis among synucleinopathies.

  • Skin Nerve Phosphorylated α-Synuclein Deposits in Parkinson Disease With Orthostatic Hypotension.
    Journal of neuropathology and experimental neurology, 2018
    Co-Authors: Vincenzo Donadio, Alex Incensi, Giovanni Rizzo, Cesa Scaglione, Antonio E. Elia, Francesca Del Sorbo, Rossella Infante, Nicola Modugno, E. Fileccia, Federica Cencini
    Abstract:

    This study aimed to investigate phosphorylated α-synuclein (p-syn) in autonomic Skin Nerves of Parkinson disease (PD) patients with and without orthostatic hypotension (OH). We studied 28 PD patients with normal corrected Mini-Mental State Examination including 14 patients with neurogenic OH (PD + OH) and 14 matched patients did not complain of OH (PD - OH); 7 of whom were re-evaluated over a follow-up period (4 ± 2 years). Skin biopsy was performed in proximal and distal sites. PD + OH patients showed a higher p-syn deposition than PD - OH, with widespread autonomic cholinergic and adrenergic Skin Nerve involvement. Over the follow-up period, PD - OH patients showed an increase in motor dysfunction scores without autonomic symptoms and a slight increase of Skin p-syn deposition but still lower than PD + OH, mainly restricted to adrenergic fibers of Skin vessels (SV). In summary, PD + OH patients showed a wide involvement of p-syn deposits in autonomic cholinergic and adrenergic Skin Nerves compared with PD - OH, and PD - OH patients showed a lower load of Skin p-syn restricted to adrenergic fibers of SV still persisting over the follow-up period. The data supported a different pathogenesis between PD + OH and PD - OH and may help to identify a specific diagnostic trait for PD + OH.

  • a new potential biomarker for dementia with lewy bodies Skin Nerve α synuclein deposits
    Neurology, 2017
    Co-Authors: Vincenzo Donadio, Alex Incensi, Giovanni Rizzo, Sabina Capellari, R Pantieri, Michelangelo Stanzani Maserati, Grazia Devigili, Roberto Eleopra, Giovanni Defazio, Federico Montini
    Abstract:

    Objective: To investigate whether (1) phosphorylated α-synuclein (p-syn) deposits in Skin Nerves could be useful in differentiating dementia with Lewy bodies (DLB) from different forms of dementia and (2) small fiber neuropathy (SFN) is associated with DLB. Methods: We studied 18 well-characterized patients with DLB (11 with autonomic dysfunction), 23 patients with nonsynucleinopathy dementia (NSD; 13 with young-onset Alzheimer disease dementia, 6 frontotemporal dementia, and 4 vascular dementia), and 25 healthy controls. All participants underwent Skin biopsies from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small Nerve fibers and deposits of p-syn, considered the pathologic form of α-synuclein. Results: No p-syn was detected in any Skin sample in patients with NSD and controls but was found in all patients with DLB. SFN was found in patients with DLB and the autonomic denervation of Skin was more severe in patients with autonomic dysfunctions. Conclusions: (1) In autonomic Skin Nerves, p-syn is a sensitive biomarker for DLB diagnosis, helping to differentiate DLB from other forms of dementia, although this needs to be confirmed in a larger, more representative sample; and (2) Skin autonomic neuropathy is part of the DLB pathology and may contribute to autonomic symptoms. Classification of evidence: This study provides Class III evidence that p-syn in Skin Nerve fibers on Skin biopsy accurately distinguishes DLB from other forms of dementia.

  • Skin Nerve phosphorylated α synuclein deposits in idiopathic rem sleep behavior disorder
    Neurology, 2017
    Co-Authors: Elena Antelmi, Vincenzo Donadio, Alex Incensi, Giuseppe Plazzi, Rocco Liguori
    Abstract:

    Objective: To test if phosphorylated α-synuclein (p-α-syn) deposits can be detected by means of Skin biopsy in patients with idiopathic REM sleep behavior disorder (iRBD) as a potential early histopathologic marker of impending synucleinopathy. Methods: Proximal (cervical) and distal (legs) samples of Skin biopsy were obtained from 12 patients with polysomnographically confirmed iRBD and 55 sex- and age-matched healthy controls (HC). P-α-syn deposits were assessed with a monoclonal antibody against p-α-syn at serine 129, disclosed by an immunofluorescence method. In addition, patients underwent an extensive workup in order to search for nonmotor symptoms and neuroimaging findings usually associated with impending neurodegeneration and to exclude subtle motor or cognitive signs. Results: P-α-syn deposits were detected in 9 (75%) out of 12 patients with iRBD and none of the HC. In iRBD, the sensitivity of the test was higher at the cervical site (67%) when compared to the leg site (58%). Conclusions: Our preliminary findings suggest that Skin biopsy in patients with iRBD might be a safe and sensitive procedure to be further tested in order to detect p-α-syn deposits in the premotor stage of synucleinopathies. Classification of evidence: This study provides Class III evidence that p-α-syn Skin deposits identify patients with iRBD.

Peter Novak - One of the best experts on this subject based on the ideXlab platform.

  • Electrochemical Skin Conductance Correlates with Skin Nerve Fiber Density.
    Frontiers in aging neuroscience, 2016
    Co-Authors: Peter Novak
    Abstract:

    Purpose: Electrochemical Skin conductance (ESC) using reverse iontophoresis and chronoamperometry has been used to evaluate abnormal function of small fibers. How ESC correlates with loss of small fibers in Skin is unclear. Methods: This was a prospective, blinded study. The primary outcome measure was the correlation between ESC at the feet and results of Skin biopsies including epidermal Nerve fiber density (ENFD) and sweat gland Nerve fiber density (SGNFD) at the distal leg. ESC, ENFD and SGNFD data were normalized by adjusting for weight. The secondary outcome measures were the correlation between ESC and the following variables: quantitative sudomotor axon reflex test (QSART) and symptom scales (neuropathy, pain and autonomic). Results: 81 patients ((mean±sd): age=53.3±17.3, men/women=25/56 were enrolled in the study. ESC was reduced in subjects with abnormally low ENFD (ENFD normal/abnormal, ESC = 1.17±0.27/0.87±0.34 µSiemens/kg, p

  • electrochemical Skin conductance correlates with Skin Nerve fiber density
    Frontiers in Aging Neuroscience, 2016
    Co-Authors: Peter Novak
    Abstract:

    Purpose: Electrochemical Skin conductance (ESC) using reverse iontophoresis and chronoamperometry has been used to evaluate abnormal function of small fibers. How ESC correlates with loss of small fibers in Skin is unclear. Methods: This was a prospective, blinded study. The primary outcome measure was the correlation between ESC at the feet and results of Skin biopsies including epidermal Nerve fiber density (ENFD) and sweat gland Nerve fiber density (SGNFD) at the distal leg. ESC, ENFD and SGNFD data were normalized by adjusting for weight. The secondary outcome measures were the correlation between ESC and the following variables: quantitative sudomotor axon reflex test (QSART) and symptom scales (neuropathy, pain and autonomic). Results: 81 patients ((mean±sd): age=53.3±17.3, men/women=25/56 were enrolled in the study. ESC was reduced in subjects with abnormally low ENFD (ENFD normal/abnormal, ESC = 1.17±0.27/0.87±0.34 µSiemens/kg, p<0.0008) and abnormally low SGNFD (SGNFD normal/abnormal ESC=1.09±0.34/,0.78±0.3 µSiemens/kg,p<0.0003). ESC correlated with ENFD (ρ=0.73, p=0.0001) and SGNFD (ρ=0.64, p=0.0001). ESC did not correlate with symptom scales. Conclusion: ESC is diminished in subjects who have a reduced number of small fibers in the Skin and the ESC reduction is proportional to ENFD and SGNFD. ESC can be useful in detecting loss of small Nerve fibers.

Giovanni Rizzo - One of the best experts on this subject based on the ideXlab platform.

  • Skin Nerve phosphorylated α-synuclein deposits in Parkinson’s disease with orthostatic hypotension
    Clinical Neurophysiology, 2019
    Co-Authors: Vincenzo Donadio, Alex Incensi, Giovanni Rizzo, F. Del Sorbo, Cesa Scaglione, Antonio E. Elia, Rossella Infante, Nicola Modugno, E. Fileccia, Federica Cencini
    Abstract:

    To investigate phosphorylated α -synuclein (p-syn) deposits in Skin Nerves of Parkinson’s disease (PD) patients with neurogenic orthostatic hypotension (OH) and a PD matched group without dysautonomia. We enrolled 28 idiopathic PD patients with abnormal nigro-striatal DatScan and cardiac MIBG: (1) 14 of them complained of neurogenic OH (PD + OH); and (2) 14 matched patients did not complain of autonomic dysfunctions (PD-OH); 7 of them were re-evaluated over a follow-up (4 ± 2 years). Patients underwent Skin biopsy in proximal (i.e. C7 paravertebral spine region) and distal (i.e. thigh and leg) sites. PD + OH showed a higher p-syn deposition than PD-OH with a widespread autonomic cholinergic and adrenergic Skin Nerves involvement. Over the follow-up PD-OH patients showed a marked increase in motor dysfunctions scores without autonomic symptoms and a slight increase of Skin p-syn deposition but still lower than PD + OH. PD + OH showed a wide involvement of p-syn deposits in autonomic cholinergic and adrenergic Skin Nerves Skin; (2) PD-OH showed a lower load of Skin p-syn mainly restricted to adrenergic fibers of Skin vessels, still persisting over a follow-up. These data supported a different pathogenesis between PD + OH and PD-OH and may help to identify a specific diagnostic trait for PD + OH patients.

  • Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study.
    Scientific reports, 2018
    Co-Authors: Vincenzo Donadio, Alex Incensi, Omar M. A. El-agnaf, Giovanni Rizzo, Nishant N. Vaikath, F. Del Sorbo, Cesa Scaglione, Sabina Capellari, Antonio E. Elia, M. Stanzani Maserati
    Abstract:

    We aimed to characterize in vivo α-synuclein (α-syn) aggregates in Skin Nerves to ascertain: 1) the optimal marker to identify them; 2) possible differences between synucleinopathies that may justify the clinical variability. We studied multiple Skin Nerve α-syn deposits in 44 patients with synucleinopathy: 15 idiopathic Parkinson’s disease (IPD), 12 dementia with Lewy Bodies (DLB), 5 pure autonomic failure (PAF) and 12 multiple system atrophy (MSA). Ten healthy subjects were used as controls. Antibodies against native α-syn, C-terminal α-syn epitopes such as phosphorylation at serine 129 (p-syn) and to conformation-specific for α-syn mature amyloid fibrils (syn-F1) were used. We found that p-syn showed the highest sensitivity and specificity in disclosing Skin α-syn deposits. In MSA abnormal deposits were only found in somatic fibers mainly at distal sites differently from PAF, IPD and DLB displaying α-syn deposits in autonomic fibers mainly at proximal sites. PAF and DLB showed the highest p-syn load with a widespread involvement of autonomic Skin Nerve fibers. In conclusion: 1) p-syn in Skin Nerves was the optimal marker for the in vivo diagnosis of synucleinopathies; 2) the localization and load differences of aggregates may help to identify specific diagnostic traits and support a different pathogenesis among synucleinopathies.

  • Skin Nerve Phosphorylated α-Synuclein Deposits in Parkinson Disease With Orthostatic Hypotension.
    Journal of neuropathology and experimental neurology, 2018
    Co-Authors: Vincenzo Donadio, Alex Incensi, Giovanni Rizzo, Cesa Scaglione, Antonio E. Elia, Francesca Del Sorbo, Rossella Infante, Nicola Modugno, E. Fileccia, Federica Cencini
    Abstract:

    This study aimed to investigate phosphorylated α-synuclein (p-syn) in autonomic Skin Nerves of Parkinson disease (PD) patients with and without orthostatic hypotension (OH). We studied 28 PD patients with normal corrected Mini-Mental State Examination including 14 patients with neurogenic OH (PD + OH) and 14 matched patients did not complain of OH (PD - OH); 7 of whom were re-evaluated over a follow-up period (4 ± 2 years). Skin biopsy was performed in proximal and distal sites. PD + OH patients showed a higher p-syn deposition than PD - OH, with widespread autonomic cholinergic and adrenergic Skin Nerve involvement. Over the follow-up period, PD - OH patients showed an increase in motor dysfunction scores without autonomic symptoms and a slight increase of Skin p-syn deposition but still lower than PD + OH, mainly restricted to adrenergic fibers of Skin vessels (SV). In summary, PD + OH patients showed a wide involvement of p-syn deposits in autonomic cholinergic and adrenergic Skin Nerves compared with PD - OH, and PD - OH patients showed a lower load of Skin p-syn restricted to adrenergic fibers of SV still persisting over the follow-up period. The data supported a different pathogenesis between PD + OH and PD - OH and may help to identify a specific diagnostic trait for PD + OH.

  • a new potential biomarker for dementia with lewy bodies Skin Nerve α synuclein deposits
    Neurology, 2017
    Co-Authors: Vincenzo Donadio, Alex Incensi, Giovanni Rizzo, Sabina Capellari, R Pantieri, Michelangelo Stanzani Maserati, Grazia Devigili, Roberto Eleopra, Giovanni Defazio, Federico Montini
    Abstract:

    Objective: To investigate whether (1) phosphorylated α-synuclein (p-syn) deposits in Skin Nerves could be useful in differentiating dementia with Lewy bodies (DLB) from different forms of dementia and (2) small fiber neuropathy (SFN) is associated with DLB. Methods: We studied 18 well-characterized patients with DLB (11 with autonomic dysfunction), 23 patients with nonsynucleinopathy dementia (NSD; 13 with young-onset Alzheimer disease dementia, 6 frontotemporal dementia, and 4 vascular dementia), and 25 healthy controls. All participants underwent Skin biopsies from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small Nerve fibers and deposits of p-syn, considered the pathologic form of α-synuclein. Results: No p-syn was detected in any Skin sample in patients with NSD and controls but was found in all patients with DLB. SFN was found in patients with DLB and the autonomic denervation of Skin was more severe in patients with autonomic dysfunctions. Conclusions: (1) In autonomic Skin Nerves, p-syn is a sensitive biomarker for DLB diagnosis, helping to differentiate DLB from other forms of dementia, although this needs to be confirmed in a larger, more representative sample; and (2) Skin autonomic neuropathy is part of the DLB pathology and may contribute to autonomic symptoms. Classification of evidence: This study provides Class III evidence that p-syn in Skin Nerve fibers on Skin biopsy accurately distinguishes DLB from other forms of dementia.

  • 3. Immunofluorescence characterization of Skin Nerve misfolded α-synuclein in different synucleinopathies: A confocal study
    Clinical Neurophysiology, 2017
    Co-Authors: V. Donadio, Omar M. A. El-agnaf, Giovanni Rizzo, Nishant N. Vaikath, Sabina Capellari, M. Stanzani Maserati, A. Incensi, C. Scaglione, R Pantieri, R. Liguori
    Abstract:

    Intraneural misfolded α-synuclein (syn) characterized different synucleinopathies such as pure autonomic failure (PAF), idiopathic Parkinson disease (IPD) and dementia with Lewy Bodies (DLB). The aim of this study is to characterize by immunofluorescence the Skin intraneural α-synuclein (syn) deposits in PAF, IPD and DLB to ascertain conformation-specific differences which may justify a different clinical phenotype. We identified a total of 21 Skin intraneural abnormal syn deposits in PAF (3 patients), 22 in IPD (8 patients) and 40 in DLB (7 patients). Ten healthy subjects were used controls. Skin biopsy was performed on proximal (C7 paravertebral) and distal (thigh and leg) sites. To characterize abnormal syn deposits we used primary antibodies against native α-synuclein (NAC) and against C-terminal α-synuclein epitopes involved in post-translational modifications such as phosphorylation at serine 129 (pS129) and tyrosine 125 (pY125), nitrate α-synuclein at tyr125-133 (nY125-133) and advanced glycation end products (AGEs). Furthermore, the mature amyloid α-synuclein fibrils were characterized by using a non-commercial antibody (Syn-F) and ubiquitin deposits were identified by a specific antibody (UBI). Antibody raised against pS129 disclosed abnormal Skin Nerves syn deposits in all patients and never in the control group. Abnormal pS129 syn deposits were often (80–90% of all analysed deposits) stained by the antibody recognizing a fibril conformation, seldom (around 40%) by native antibodies and very occasionally by antibodies against nY125-133. Furthermore, abnormal syn deposits were not stained by antibodies against pY125, AGEs and UBI. The immunofluorescence characterization of abnormal syn deposits showed similar findings in IPD, PAF and DLB although in these latter abnormal deposits were quantitatively higher than in IPD. Phosphorylation at serine 129 was the most sensitive and specific epitope to identify Skin Nerves abnormal syn deposits for the in vivo diagnosis of synucleinopathies; (2) Skin syn neuritis showed no relevant immunofluorescence differences in PAF, IPD and DLB suggesting a similar conformation among different clinical phenotypes.