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author:("paves, Nicola")
1.  Age at onset and Parkinson disease phenotype 
Neurology  2016;86(15):1400-1407.
Objective:
To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD.
Methods:
We have analyzed baseline data from the Parkinson's Progression Markers Initiative database. Four hundred twenty-two patients with a diagnosis of PD confirmed by DaTSCAN imaging were divided into 4 groups according to age at onset (onset younger than 50 years, 50–59 years, 60–69 years, and 70 years or older) and investigated for differences in side, type and localization of symptoms, occurrence/severity of motor and nonmotor features, nigrostriatal function, and CSF biomarkers.
Results:
Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF α-synuclein and total tau. The most common presentation was the combination of 2 or 3 motor symptoms (bradykinesia, resting tremor, and rigidity) with rigidity being more common in the young-onset group. In about 80% of the patients with localized onset, the arm was the most affected part of the body, with no difference across subgroups.
Conclusions:
Although the presentation of PD symptoms is similar across age subgroups, the severity of motor and nonmotor features, the impairment of striatal binding, and the levels of CSF biomarkers increase with age at onset. The variability of imaging and nonimaging biomarkers in patients with PD at different ages could hamper the results of future clinical trials.
doi:10.1212/WNL.0000000000002461
PMCID: PMC4831034  PMID: 26865518
2.  Imaging acetylcholinesterase density in peripheral organs in Parkinson's disease with 11C-donepezil PET 
Brain  2014;138(3):653-663.
See Stoessl (doi: 10:1093/awu392) for a scientific commentary on this article.
Parkinson's disease is associated with early parasympathetic dysfunction. Using 5-[11C]-methoxy-donepezil PET, Gjerløff et al. demonstrate reduced acetylcholinesterase binding in the small intestine and pancreas of 12 patients with Parkinson's disease compared to matched controls. [11C]donepezil PET could thus have validity for in vivo imaging of systemic parasympathetic function.
Parkinson's disease is associated with early parasympathetic dysfunction leading to constipation and gastroparesis. It has been suggested that pathological α-synuclein aggregations originate in the gut and ascend to the brainstem via the vagus. Our understanding of the pathogenesis and time course of parasympathetic denervation in Parkinson's disease is limited and would benefit from a validated imaging technique to visualize the integrity of parasympathetic function. The positron emission tomography tracer 5-[11C]-methoxy-donepezil was recently validated for imaging acetylcholinesterase density in the brain and peripheral organs. Donepezil is a high-affinity ligand for acetylcholinesterase—the enzyme that catabolizes acetylcholine in cholinergic synapses. Acetylcholinesterase histology has been used for many years for visualizing cholinergic neurons. Using 5-[11C]-methoxy-donepezil positron emission tomography, we studied 12 patients with early-to-moderate Parkinson's disease (three female; age 64 ± 9 years) and 12 age-matched control subjects (three female; age 62 ± 8 years). We collected clinical information about motor severity, constipation, gastroparesis, and other parameters. Heart rate variability measurements and gastric emptying scintigraphies were performed in all subjects to obtain objective measures of parasympathetic function. We detected significantly decreased 11C-donepezil binding in the small intestine (−35%; P = 0.003) and pancreas (−22%; P = 0.001) of the patients. No correlations were found between the 11C-donepezil signal and disease duration, severity of constipation, gastric emptying time, and heart rate variability. In Parkinson's disease, the dorsal motor nucleus of the vagus undergoes severe degeneration and pathological α-synuclein aggregations are also seen in nerve fibres innervating the gastro-intestinal tract. In contrast, the enteric nervous system displays little or no loss of cholinergic neurons. Decreases in 11C-donepezil binding may, therefore, represent a marker of parasympathetic denervation of internal organs, but further validation studies are needed.
doi:10.1093/brain/awu369
PMCID: PMC4408425  PMID: 25539902
autonomic nervous system; positron emission tomography; Parkinson's disease; parasympathetic nervous system; acetylcholinesterase
4.  Benefits of putaminal GDNF infusion in Parkinson disease are maintained after GDNF cessation 
Neurology  2013;81(13):1176-1178.
We previously reported clinical improvement, increase in putamen [18F]-dopa uptake on PET imaging, and neuropathologic evidence of sprouting of dopaminergic fibers following chronic intraputaminal delivery of glial cell line–derived neurotrophic factor (GDNF) in idiopathic Parkinson disease (PD).1–3 We now provide clinical and PET evidence of persistent efficacy lasting for at least 3 years following cessation of GDNF infusion in a patient with PD. This is a single-case observational study, providing Class IV evidence.
doi:10.1212/WNL.0b013e3182a55ea5
PMCID: PMC3795600  PMID: 23946313
5.  Acute HCV/HIV Coinfection Is Associated with Cognitive Dysfunction and Cerebral Metabolite Disturbance, but Not Increased Microglial Cell Activation 
PLoS ONE  2012;7(7):e38980.
Background
Microglial cell activation and cerebral function impairment are described in both chronic hepatitis C viral (HCV) and Human-Immune-Deficiency viral (HIV) infections. The aim of this study was to investigate the effect of acute HCV infection upon cerebral function and microglial cell activation in HIV-infected individuals.
Methods
A case-control study was conducted. Subjects with acute HCV and chronic HIV coinfection (aHCV) were compared to matched controls with chronic HIV monoinfection (HIVmono). aHCV was defined as a new positive plasma HCV RNA within 12 months of a negative RNA test. Subjects underwent neuro-cognitive testing (NCT), cerebral proton magnetic resonance spectroscopy (1H-MRS) and positron emission tomography (PET) using a 11C-radiolabeled ligand (PK11195), which is highly specific for translocator protein 18 kDA receptors on activated microglial cells. Differences between cases and controls were assessed using linear regression modelling.
Results
Twenty-four aHCV cases completed NCT and 1H-MRS, 8 underwent PET. Of 57 HIVmono controls completing NCT, 12 underwent 1H-MRS and 8 PET. Subjects with aHCV demonstrated on NCT, significantly poorer executive function (mean (SD) error rate 26.50(17.87) versus 19.09(8.12), p = 0.001) and on 1H-MRS increased myo-inositol/creatine ratios (mI/Cr, a marker of cerebral inflammation) in the basal ganglia (ratio of 0.71(0.22) versus 0.55(0.23), p = 0.03), compared to subjects with HIVmono. On PET imaging, no difference in 11C-PK11195 binding potential (BP) was observed between study groups (p>0.10 all cerebral locations), however lower BPs were associated with combination antiretroviral therapy (cART) use in the parietal (p = 0.01) and frontal (p = 0.03) cerebral locations.
Discussion
Poorer cognitive performance and disturbance of cerebral metabolites are observed in subjects with aHC,V compared to subjects with HIVmono. Higher 11C-PK11195 BP was not observed in subjects with aHCV, but was observed in subjects not on cART.
doi:10.1371/journal.pone.0038980
PMCID: PMC3395624  PMID: 22808022
6.  Recent imaging advances in the diagnosis and management of Parkinson’s disease 
In this review we report novel sensitive imaging biomarkers for Parkinson’s disease (PD) and its atypical variants. Diffusion tensor imaging and transcranial brain sonography are potentially promising techniques that can differentiate typical PD from atypical variants (multiple system atrophy and progressive supranuclear palsy) and from benign tremor disorders. Non-motor symptoms, such as dementia, depression, and sleep disruption, are often more distressing to PD patients than their slowness and stiffness. Dopamine replacement treatment can also lead to complications such as dyskinesias, impulse control disorders, and psychosis. Recent positron emission tomography studies have helped to clarify the physiopathological mechanisms underlying dementia and compulsive gambling in PD and provide a rationale for therapeutic strategies.
doi:10.3410/M1-82
PMCID: PMC2948338  PMID: 20948696

Results 1-6 (6)