41.
Brain Interstitial Nociceptin/Orphanin FQ Levels are Elevated in Parkinson's Disease
Marti, Matteo; Sarubbo, Silvio; Latini, Francesco ...
Movement disorders,
15 August 2010, Letnik:
25, Številka:
11
Journal Article
Expression and release of nociceptin/orphanin FQ (N/OFQ) are elevated in the substantia nigra reticulata of 6‐hydroxydopamine‐hemilesioned rats, suggesting a pathogenic role for N/OFQ in Parkinson's ...
disease. In this study, we investigated whether elevation of N/OFQ expression in 6‐hydroxydopamine‐hemilesioned rats selectively occurs in substantia nigra and whether hypomotility following acute haloperidol administration is accompanied by a rise in nigral N/OFQ levels. Moreover, to prove a link between N/OFQ and idiopathic Parkinson's disease in humans, we measured N/OFQ levels in the cerebrospinal fluid of parkinsonian patients undergoing surgery for deep brain stimulation. In situ hybridization demonstrated that dopamine depletion was associated with increase of N/OFQ expression in substantia nigra (compacta +160%, reticulata +105%) and subthalamic nucleus (+45%), as well as reduction in caudate putamen (−20%). No change was observed in globus pallidus, nucleus accumbens, thalamus, and motor cortex. Microdialysis coupled to the bar test allowed to demonstrate that acute administration of haloperidol (0.8 and 3 mg/kg) increased nigral N/OFQ levels (maximally of +47% and +53%, respectively) in parallel with akinesia. A correlation with preclinical studies was found by analyzing N/OFQ levels in humans. Indeed, N/OFQ levels were found to be ∼3.5‐fold elevated in the cerebrospinal fluid of parkinsonian patients (148 fmol/ml) compared with nonparkinsonian neurologic controls (41 fmol/ml). These data represent the first clinical evidence linking N/OFQ to idiopathic Parkinson's disease in humans. They strengthen the pathogenic role of N/OFQ in the modulation of parkinsonism across species and provide a rationale for developing N/OFQ receptor antagonists as antiparkinsonian drugs. © 2010 Movement Disorder Society
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42.
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43.
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44.
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45.
Bilateral striatal necrosis, dystonia and multiple mitochondrial DNA deletions: Case study and effect of deep brain stimulation
Aniello, Maria Stella; Martino, Davide; Petruzzella, Vittoria ...
Movement disorders,
January 2008, Letnik:
23, Številka:
1
Journal Article
Bilateral striatal necrosis (BSN) is relatively rare and has been related to a wide array of causes, including nuclear and mitochondrial DNA mutations. We report the clinical vignette of a patient ...
with a 37 years‐history of generalized dystonia secondary to BSN associated with multiple mitochondrial DNA deletions of undefined origin. Globus pallidus interna deep brain stimulation produced sustained benefit, with predominant improvements in disability. © 2007 Movement Disorder Society
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46.
Telemedicine for parkinsonism: A two-step model based on the COVID-19 experience in Milan, Italy
Cilia, Roberto; Mancini, Francesca; Bloem, Bastiaan R. ...
Parkinsonism & related disorders,
June 2020, 2020-06-00, 20200601, Letnik:
75
Journal Article
•Telehealth keeps patients with parkinsonism safe from traveling to in-person care site during the COVID-19 mitigation phase.•During the COVID-19 crisis, a telemedicine program for patients with ...
parkinsonism was boosted in Milan, Italy.•This two-step model integrates a telenursing forward triage followed by video-consultations by experienced neurologists.
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47.
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48.
A new potential biomarker for dementia with Lewy bodies: Skin nerve α-synuclein deposits
Donadio, Vincenzo; Incensi, Alex; Rizzo, Giovanni ...
Neurology,
2017-July-25, 2017-Jul-25, 2017-07-25, 20170725, Letnik:
89, Številka:
4
Journal Article
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.
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49.
Skin Biopsy May Help to Distinguish Multiple System Atrophy–Parkinsonism from Parkinson's Disease With Orthostatic Hypotension
Donadio, Vincenzo; Incensi, Alex; Rizzo, Giovanni ...
Movement disorders,
September 2020, Letnik:
35, Številka:
9
Journal Article
ABSTRACT
Background
The differential diagnosis between multiple system atrophy parkinsonism type (MSA‐P) and Parkinson's disease with orthostatic hypotension (PD+OH) is difficult because the 2 ...
diseases have a similar clinical picture. The aim of this study is to distinguish MSA‐P from PD+OH by immunostaining for abnormal phosphorylated α‐synuclein at serine 129 (p‐syn) in cutaneous nerves.
Method
We recruited 50 patients with parkinsonism and chronic orthostatic hypotension: 25 patients fulfilled the diagnostic criteria for MSA‐P and 25 patients for PD+OH. The patients underwent a skin biopsy from the cervical area, thigh, and leg to analyze somatic and autonomic skin innervation and p‐syn in skin nerves.
Results
Intraneural p‐syn positivity was found in 72% of patients with MSA‐P, mainly in distal skin sites. More important, p‐syn deposits in MSA‐P differed from PD+OH because they were mainly found in somatic fibers of subepidermal plexi, whereas scant autonomic fiber involvement was found in only 3 patients. All patients with PD+OH displayed widely distributed p‐syn deposits in the autonomic skin fibers of proximal and distal skin sites, whereas somatic fibers were affected only slightly in 4 patients with PD+OH. Skin innervation mirrored p‐syn deposits because somatic innervation was mainly reduced in MSA‐P. Sympathetic innervation was damaged in PD+OH but fairly preserved in MSA‐P.
Conclusions
The p‐syn in cutaneous nerves allows the differentiation of MSA‐P from PD+OH; MSA‐P mainly shows somatic fiber involvement with relatively preserved autonomic innervation; and by contrast, PD+OH displays prevalent abnormal p‐syn deposits and denervation in autonomic postganglionic nerves. © 2020 International Parkinson and Movement Disorder Society
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50.
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