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Parkinson Disease: HELP
Articles from University of Chieti
Based on 70 articles published since 2010
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These are the 70 published articles about Parkinson Disease that originated from University of Chieti during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial The democratic aspect of machine learning: Limitations and opportunities for Parkinson's disease. 2019

Bonanni, Laura. ·Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy. ·Mov Disord · Pubmed #30597623.

ABSTRACT: -- No abstract --

2 Review The Pharmacology of Visual Hallucinations in Synucleinopathies. 2019

Russo, Mirella / Carrarini, Claudia / Dono, Fedele / Rispoli, Marianna Gabriella / Di Pietro, Martina / Di Stefano, Vincenzo / Ferri, Laura / Bonanni, Laura / Sensi, Stefano Luca / Onofrj, Marco. ·Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy. · Behavioral Neurology and Molecular Neurology Units, Center of Excellence on Aging and Translational Medicine-CeSI-MeT, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy. · Departments of Neurology and Pharmacology, Institute for Mind Impairments and Neurological Disorders-iMIND, University of California, Irvine, Irvine, CA, United States. ·Front Pharmacol · Pubmed #31920635.

ABSTRACT: Visual hallucinations (VH) are commonly found in the course of synucleinopathies like Parkinson's disease and dementia with Lewy bodies. The incidence of VH in these conditions is so high that the absence of VH in the course of the disease should raise questions about the diagnosis. VH may take the form of early and simple phenomena or appear with late and complex presentations that include hallucinatory production and delusions. VH are an unmet treatment need. The review analyzes the past and recent hypotheses that are related to the underlying mechanisms of VH and then discusses their pharmacological modulation. Recent models for VH have been centered on the role played by the decoupling of the default mode network (DMN) when is released from the control of the fronto-parietal and salience networks. According to the proposed model, the process results in the perception of priors that are stored in the unconscious memory and the uncontrolled emergence of intrinsic narrative produced by the DMN. This DMN activity is triggered by the altered functioning of the thalamus and involves the dysregulated activity of the brain neurotransmitters. Historically, dopamine has been indicated as a major driver for the production of VH in synucleinopathies. In that context, nigrostriatal dysfunctions have been associated with the VH onset. The efficacy of antipsychotic compounds in VH treatment has further supported the notion of major involvement of dopamine in the production of the hallucinatory phenomena. However, more recent studies and growing evidence are also pointing toward an important role played by serotonergic and cholinergic dysfunctions. In that respect,

3 Review A Stage-Based Approach to Therapy in Parkinson's Disease. 2019

Carrarini, Claudia / Russo, Mirella / Dono, Fedele / Di Pietro, Martina / Rispoli, Marianna G / Di Stefano, Vincenzo / Ferri, Laura / Barbone, Filomena / Vitale, Michela / Thomas, Astrid / Sensi, Stefano Luca / Onofrj, Marco / Bonanni, Laura. ·Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, 66100 Chieti, Italy. · Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, 66100 Chieti, Italy. l.bonanni@unich.it. ·Biomolecules · Pubmed #31434341.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD.

4 Review Hallucinations, somatic-functional disorders of PD-DLB as expressions of thalamic dysfunction. 2019

Onofrj, Marco / Espay, Alberto J / Bonanni, Laura / Delli Pizzi, Stefano / Sensi, Stefano L. ·Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Italy. · Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA. · Departments of Neurology and Pharmacology, Institute for Mind Impairments and Neurological Disorders, University of California - Irvine, Irvine, California, USA. ·Mov Disord · Pubmed #31307115.

ABSTRACT: Hallucinations, delusions, and functional neurological manifestations (conversion and somatic symptom disorders) of Parkinson's disease (PD) and dementia with Lewy bodies increase in frequency with disease progression, predict the onset of cognitive decline, and eventually blend with and are concealed by dementia. These symptoms share the absence of reality constraints and can be considered comparable elements of the PD-dementia with Lewy bodies psychosis. We propose that PD-dementia with Lewy bodies psychotic disorders depend on thalamic dysfunction promoting a theta burst mode and subsequent thalamocortical dysrhythmia with focal cortical coherence to theta electroencephalogram rhythms. This theta electroencephalogram activity, also called fast-theta or pre-alpha, has been shown to predict cognitive decline and fluctuations in Parkinson's disease with dementia and dementia with Lewy bodies. These electroencephalogram alterations are now considered a predictive marker for progression to dementia. The resulting thalamocortical dysrhythmia inhibits the frontal attentional network and favors the decoupling of the default mode network. As the default mode network is involved in integration of self-referential information into conscious perception, unconstrained default mode network activity, as revealed by recent imaging studies, leads to random formation of connections that link strong autobiographical correlates to trivial stimuli, thereby producing hallucinations, delusions, and functional neurological disorders. The thalamocortical dysrhythmia default mode network decoupling hypothesis provides the rationale for the design and testing of novel therapeutic pharmacological and nonpharmacological interventions in the context of PD, PD with dementia, and dementia with Lewy bodies. © 2019 International Parkinson and Movement Disorder Society.

5 Review Role of Dietary Supplements in the Management of Parkinson's Disease. 2019

Ciulla, Michele / Marinelli, Lisa / Cacciatore, Ivana / Stefano, Antonio Di. ·Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, via dei Vestini 31, 66100 Chieti Scalo (CH), Italy. · Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, via dei Vestini 31, 66100 Chieti Scalo (CH), Italy. antonio.distefano@unich.it. ·Biomolecules · Pubmed #31295842.

ABSTRACT: The use of food supplements or functional food has significantly increased in the past decades, especially to compensate both the modern lifestyle and the food shortages of the industrialized countries. Despite food supplements are habitually intended to correct nutritional deficiencies or to support specific physiological functions, they are often combined with common drug therapies to improve the patient's health and/or mitigate the symptoms of many chronic diseases such as cardiovascular diseases, cystic fibrosis, cancer, liver and gastrointestinal diseases. In recent years, increased attentions are given to the patient's diet, and the use of food supplements and functional food rich in vitamins and antioxidants plays a very important role in the treatment and prevention of neurodegenerative diseases such as Parkinson's disease (PD). Natural compounds, phytochemicals, vitamins, and minerals can prevent, delay, or alleviate the clinical symptoms of PD in contrast to some of the main physiopathological mechanisms involved in the development of the disease, like oxidative stress, free radical formation, and neuroinflammation. The purpose of this review is to collect scientific evidences which support the use of specific biomolecules and biogenic elements commonly found in food supplements or functional food to improve the clinical framework of patients with PD.

6 Review Clinimetric approach to rating scales for the assessment of apathy in Parkinson's disease: A systematic review. 2019

Carrozzino, Danilo. ·Department of Psychological, Health, and Territorial Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini no. 31, 66100 Chieti, Italy. Electronic address: danilo.carrozzino@unich.it. ·Prog Neuropsychopharmacol Biol Psychiatry · Pubmed #31059722.

ABSTRACT: A number of rating scales for the assessment of apathy in Parkinson's disease (PD) were developed. Unfortunately, previous studies focused mainly on psychometric criteria rather than on clinimetric principles to develop these assessment instruments. In the clinimetric approach, the clinical validity of a rating scale, rather than its statistical significance, has the priority. The aim of the present systematic review was to capture the clinimetric properties of these rating scales and to identify the measures, which display clinical validity for the assessment of apathy in PD. The systematic search was conducted on Scopus, PsycINFO, PubMed, Web of Science, ScienceDirect, and Medline following the PRISMA guidelines. A total of 44 studies were included and analyzed in this systematic review. The apathy rating scales, which were found to be psychometrically robust and reliable, were actually clinically questionable. The apathy measures, which displayed clinimetric properties, were the Starkstein Apathy Scale (SAS), the 5-item version of the World Health Organization Well-Being Index (WHO-5), the Neurasthenia Scale and the Lille Apathy Rating Scale (LARS). The SAS was found to be clinically valid at a macro-analytic level, particularly when used either to exclude the presence of symptoms of apathy or to evaluate the side effects of medications. The WHO-5 and the Neurasthenia Scale were found to be clinically valid only at a micro-analytic level and can be used as screening measures for the assessment of the severity of symptoms of apathy. The LARS was a clinically valid instrument to be used for the diagnosis of apathy.

7 Review IFCN-endorsed practical guidelines for clinical magnetoencephalography (MEG). 2018

Hari, Riitta / Baillet, Sylvain / Barnes, Gareth / Burgess, Richard / Forss, Nina / Gross, Joachim / Hämäläinen, Matti / Jensen, Ole / Kakigi, Ryusuke / Mauguière, François / Nakasato, Nobukatzu / Puce, Aina / Romani, Gian-Luca / Schnitzler, Alfons / Taulu, Samu. ·Department of Art, Aalto University, Helsinki, Finland. Electronic address: riitta.hari@aalto.fi. · McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. · Wellcome Centre for Human Neuroimaging, University College of London, London, UK. · Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA. · Clinical Neuroscience, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. · Centre for Cognitive Neuroimaging, University of Glasgow, Glasgow, UK; Institute for Biomagnetism and Biosignalanalysis, University of Muenster, Germany. · Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA; NatMEG, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. · Centre for Human Brain Health, University of Birmingham, Birmingham, UK. · Department of Integrative Physiology, National Institute of Physiological Sciences, Okazaki, Japan. · Department of Functional Neurology and Epileptology, Neurological Hospital & University of Lyon, Lyon, France. · Department of Epileptology, Tohoku University, Sendai, Japan. · Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA. · Department of Neuroscience, Imaging and Clinical Sciences, Università degli Studi G. D'Annunzio, Chieti, Italy. · Institute of Clinical Neuroscience and Medical Psychology, and Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany. · Institute for Learning & Brain Sciences, University of Washington, Seattle, WA, USA; Department of Physics, University of Washington, Seattle, WA, USA. ·Clin Neurophysiol · Pubmed #29724661.

ABSTRACT: Magnetoencephalography (MEG) records weak magnetic fields outside the human head and thereby provides millisecond-accurate information about neuronal currents supporting human brain function. MEG and electroencephalography (EEG) are closely related complementary methods and should be interpreted together whenever possible. This manuscript covers the basic physical and physiological principles of MEG and discusses the main aspects of state-of-the-art MEG data analysis. We provide guidelines for best practices of patient preparation, stimulus presentation, MEG data collection and analysis, as well as for MEG interpretation in routine clinical examinations. In 2017, about 200 whole-scalp MEG devices were in operation worldwide, many of them located in clinical environments. Yet, the established clinical indications for MEG examinations remain few, mainly restricted to the diagnostics of epilepsy and to preoperative functional evaluation of neurosurgical patients. We are confident that the extensive ongoing basic MEG research indicates potential for the evaluation of neurological and psychiatric syndromes, developmental disorders, and the integrity of cortical brain networks after stroke. Basic and clinical research is, thus, paving way for new clinical applications to be identified by an increasing number of practitioners of MEG.

8 Review Advances in prodrug design for Parkinson's disease. 2018

Cacciatore, Ivana / Ciulla, Michele / Marinelli, Lisa / Eusepi, Piera / Di Stefano, Antonio. ·a Department of Pharmacy , University 'G. D'Annunzio' Chieti-Pescara , Chieti , Italy. ·Expert Opin Drug Discov · Pubmed #29361853.

ABSTRACT: INTRODUCTION: Parkinson's Disease (PD) is a neurodegenerative disorder of the central nervous system (CNS) characterized by motor dysfunctions, such as bradykinesia, rigidity, neuropsychiatric symptoms, and others. The pharmacological treatment of the disease is only symptomatic since, to date, there is no treatment to stop or slow PD. Currently, L-Dopa (LD) remains the gold standard therapy even though it undergoes peripheral metabolism causing several side effects, such as nausea, vomiting and orthostatic hypotension. Areas covered: This review is focused on recent developments in strategies involving prodrugs to enhance DA and/or LD absorption, their chemical and enzymatic stabilities, and selective targeting to the central nervous system. Expert opinion: The prodrug strategy remains one of the most promising approaches to improve pharmaceutical, pharmacokinetic, and pharmacodynamic properties of hydrophilic compounds, such as anti-Parkinson drugs (DA and LD). Prodrugs developed in recent years have demonstrated good pharmacokinetic profiles, affording a sustained release of LD and reducing its plasma level fluctuations. The development of new prodrugs that may reach the BBB unaltered and with a good ADME (Absorption, Distribution, Metabolism, Elimination) profile and pharmacological efficacy represents an exciting challenge for medicinal chemists.

9 Review MAO inhibitors and their wider applications: a patent review. 2018

Carradori, Simone / Secci, Daniela / Petzer, Jacques P. ·a Department of Pharmacy , "G. d'Annunzio" University of Chieti-Pescara , Chieti , Italy. · b Dipartimento di Chimica e Tecnologie del Farmaco , Sapienza University of Rome , Rome , Italy. · c Pharmaceutical Chemistry and Centre of Excellence for Pharmaceutical Sciences , North-West University , Potchefstroom , South Africa. ·Expert Opin Ther Pat · Pubmed #29324067.

ABSTRACT: INTRODUCTION: Monoamine oxidase (MAO) inhibitors, after the initial 'golden age', are currently used as third-line antidepressants (selective MAO-A inhibitors) or clinically enrolled as co-adjuvants for neurodegenerative diseases (selective MAO-B inhibitors). However, the research within this field is always increasing due to their pivotal role in modulating synaptic functions and monoamines metabolism. AREAS COVERED: In this paper, MAO inhibitors (2015-2017) are disclosed ordering all the patents according to their chemical scaffold. Structure-activity relationships (SARs) are extrapolated for the most investigated chemotypes (coumarins, pyrazole/oxazepinones, (hetero)arylamides). 108 Compounds are divided into two main groups: newly synthesized molecules and naturally-occurring metabolites. Finally, new therapeutic options are outlined to ensure a more complete view on the potential of these inhibitors. EXPERT OPINION: New proposed MAO inhibitors are endowed with a marked isoform selectivity, with innovative therapeutic potential toward other targets (gliomas, inflammation, muscle dystrophies, migraine, chronic pain, pseudobulbar affect), and with a promising ability to address multi-faceted pathologies such as Alzheimer's disease. The increasing number of patents is analyzed collecting data from 2002 to 2017.

10 Review Psychosis in parkinsonism: an unorthodox approach. 2017

Onofrj, Marco / Carrozzino, Danilo / D'Amico, Aurelio / Di Giacomo, Roberta / Delli Pizzi, Stefano / Thomas, Astrid / Onofrj, Valeria / Taylor, John-Paul / Bonanni, Laura. ·Department of Neuroscience Imaging and Clinical Sciences, University "G. d'Annunzio" of Chieti-Pescara. · CE.S.I. University Foundation. · Department of Psychological, Health, and Territorial Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. · Psychiatric Research Unit, Psychiatric Centre North Zealand, Copenhagen University Hospital, Hillerød, Denmark. · Department of Bioimaging, University Cattolica del Sacro Cuore, Rome, Italy. · Institute of Neuroscience, Campus for Ageing and Vitality Newcastle University Newcastle upon Tyne, Newcastle upon Tyne, UK. ·Neuropsychiatr Dis Treat · Pubmed #28553118.

ABSTRACT: Psychosis in Parkinson's disease (PD) is currently considered as the occurrence of hallucinations and delusions. The historical meaning of the term psychosis was, however, broader, encompassing a disorganization of both consciousness and personality, including behavior abnormalities, such as impulsive overactivity and catatonia, in complete definitions by the International Classification of Diseases-10 (ICD-10) and the

11 Review Somatization in Parkinson's Disease: A systematic review. 2017

Carrozzino, Danilo / Bech, Per / Patierno, Chiara / Onofrj, Marco / Morberg, Bo Mohr / Thomas, Astrid / Bonanni, Laura / Fulcheri, Mario. ·Psychiatric Research Unit, Psychiatric Centre North Zealand, Copenhagen University Hospital, Hillerød, Denmark; Department of Psychological, Health, and Territorial Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. Electronic address: danilo.carrozzino@unich.it. · Psychiatric Research Unit, Psychiatric Centre North Zealand, Copenhagen University Hospital, Hillerød, Denmark. · Department of Psychological, Health, and Territorial Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; Department of Dynamic and Clinical Psychology, Sapienza University of Rome, Rome, Italy. · Department of Neuroscience and Imaging, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. · Department of Psychological, Health, and Territorial Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy. ·Prog Neuropsychopharmacol Biol Psychiatry · Pubmed #28522290.

ABSTRACT: The current systematic review study is aimed at critically analyzing from a clinimetric viewpoint the clinical consequence of somatization in Parkinson's Disease (PD). By focusing on the International Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive electronic literature research strategy on ISI Web-of-Science, PsychINFO, PubMed, EBSCO, ScienceDirect, MEDLINE, Scopus, and Google Scholar databases. Out of 2.926 initial records, only a total of 9 studies were identified as clearly relevant and analyzed in this systematic review. The prevalence of somatization in PD has been found to range between 7.0% and 66.7%, with somatoform disorders acting as clinical factor significantly contributing to predict a progressive cognitive impairment. We highlighted that somatization is a highly prevalent comorbidity affecting PD. However, the clinical consequence of such psychiatric symptom should be further evaluated by replacing the clinically inadequate diagnostic label of psychogenic parkinsonism with the psychosomatic concept of persistent somatization as conceived by the Diagnostic Criteria for Psychosomatic Research (DCPR).

12 Review Solid lipid nanoparticles as a drug delivery system for the treatment of neurodegenerative diseases. 2016

Cacciatore, Ivana / Ciulla, Michele / Fornasari, Erika / Marinelli, Lisa / Di Stefano, Antonio. ·a Department of Pharmacy , University 'G. D'Annunzio' Chieti-Pescara , Chieti , Italy. ·Expert Opin Drug Deliv · Pubmed #27073977.

ABSTRACT: INTRODUCTION: The failure of many molecules as CNS bioactive compounds is due to many restrictions: poor water solubility, intestinal absorption, in vivo stability, bioavailability, therapeutic effectiveness, side effects, plasma fluctuations, and difficulty crossing physiological barriers, like the brain blood barrier (BBB), to deliver the drug directly to the site of action. AREA COVERED: Nanotechnology-based approaches with the employment of liposomes, micelles, dendrimers, and solid lipid nanoparticles (SLN) as drug delivery systems, are used to overcome the above reported limitations. Here, we focus on the delivery of drugs based on SLN formulation to treat neurodegenerative diseases. Notably, SLN have the ability to protect drugs from chemical and enzymatic degradation, direct the active compound towards the target site with a substantial reduction of toxicity for the adjacent tissues, and pass physiological barriers increasing bioavailability without resorting to high dosage forms. EXPERT OPINION: We believe that SLN could represent a suitable tool to pass the BBB and permit drugs to reach damaged areas of the CNS in patients affected by neurodegenerative pathologies, such as Alzheimer's and Parkinson's diseases.

13 Review Neurophysiological biomarkers for Lewy body dementias. 2016

Cromarty, Ruth A / Elder, Greg J / Graziadio, Sara / Baker, Mark / Bonanni, Laura / Onofrj, Marco / O'Brien, John T / Taylor, John-Paul. ·Institute of Neuroscience, Campus for Aging and Vitality, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. Electronic address: r.a.cromarty@ncl.ac.uk. · Institute of Neuroscience, Campus for Aging and Vitality, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. · Institute of Neuroscience, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. · Clinica Neurologica, Dipartimento di Neuroscienze e Imaging, Università "G.D'Annunzio" Chieti-Pescara, Italy. · Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0SP, UK. ·Clin Neurophysiol · Pubmed #26183755.

ABSTRACT: OBJECTIVE: Lewy body dementias (LBD) include both dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), and the differentiation of LBD from other neurodegenerative dementias can be difficult. Currently, there are few biomarkers which might assist early diagnosis, map onto LBD symptom severity, and provide metrics of treatment response. Traditionally, biomarkers in LBD have focussed on neuroimaging modalities; however, as biomarkers need to be simple, inexpensive and non-invasive, neurophysiological approaches might also be useful as LBD biomarkers. METHODS: In this review, we searched PubMED and PsycINFO databases in a semi-systematic manner in order to identify potential neurophysiological biomarkers in the LBDs. RESULTS: We identified 1491 studies; of these, 37 studies specifically examined neurophysiological biomarkers in LBD patients. We found that there was substantial heterogeneity with respect to methodologies and patient cohorts. CONCLUSION: Generally, many of the findings have yet to be replicated, although preliminary findings reinforce the potential utility of approaches such as quantitative electroencephalography and motor cortical stimulation paradigms. SIGNIFICANCE: Various neurophysiological techniques have the potential to be useful biomarkers in the LBDs. We recommend that future studies focus on maximising the diagnostic specificity and sensitivity of the most promising neurophysiological biomarkers.

14 Review Polyneuropathy associated with duodenal infusion of levodopa in Parkinson's disease: features, pathogenesis and management. 2015

Uncini, Antonino / Eleopra, Roberto / Onofrj, Marco. ·Department of Neuroscience and Imaging, University "G. d'Annunzio", Chieti-Pescara, Italy. · Neurology Unit, Department of Neurosciences, Santa Maria della Misericordia University Hospital, Udine, Italy. ·J Neurol Neurosurg Psychiatry · Pubmed #25168395.

ABSTRACT: Patients with Parkinson's disease (PD) treated with oral levodopa have a higher prevalence of chronic, prevalently sensory, usually mild axonal polyneuropathy (PNP). Several studies showed a positive association among PNP, cumulative levodopa dosage, low serum B12 and high-homocysteine and methylmalonic acid level. Anecdotal severe acute or subacute PNPs thought to be Guillain-Barré syndrome have been reported in patients receiving continuous intraduodenal infusion of levodopa/carbidopa intestinal gel (LCIG). We report an additional acute case and by a systematic literature search we also reviewed the clinical and laboratory features of 13 other acute and 21 subacute PNP cases occurring during LCIG treatment. In series with at least nine patients, the mean frequency of acute and subacute PNP is 13.6% and the mortality rate at 6 months in acute cases is 14%. The great majority of PNP cases displayed axonal sensory-motor and reduced vitamin B12 levels, and alterations of metabolites of 1-carbon pathway were found in most patients. We discuss the possible role of high-levodopa dosage, vitamin B12, B6 and folate deficiency and accumulation of homocysteine and methylmalonic acid in the pathogenesis to conclude that there is enough, although circumstantial, evidence that alterations of 1-carbon pathway are implicated also in acute and subacute PNP during LCIG usage. There is no solid proof for a dysimmune pathogenesis and in our opinion acute, subacute and chronic PNP, either after oral levodopa or LCIG, represent a continuum. Finally, we propose recommendations for prevention and management of PNP occurring during LCIG treatment.

15 Review Visual hallucinations in PD and Lewy body dementias: old and new hypotheses. 2013

Onofrj, M / Taylor, J P / Monaco, D / Franciotti, R / Anzellotti, F / Bonanni, L / Onofrj, V / Thomas, A. ·Department of Neuroscience and Imaging, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy Aging Research Center, "G. d'Annunzio" University Foundation, Chieti, Italy. ·Behav Neurol · Pubmed #23242366.

ABSTRACT: Visual Hallucinations (VH) are a common non-motor symptom of Parkinson's Disease (PD) and the Lewy body dementias (LBD) of Parkinson's disease with dementia (PDD) and Dementia with Lewy Bodies (DLB). The origin of VH in PD and LBD is debated: earlier studies considered a number of different possible mechanisms underlying VH including visual disorders, Rapid Eye Movement (REM) Sleep Intrusions, dysfunctions of top down or bottom up visual pathways, and neurotransmitter imbalance. More recently newer hypotheses introduce, among the possible mechanisms of VH, the role of attention networks (ventral and dorsal) and of the Default Mode Network (DMN) a network that is inhibited during attentional tasks and becomes active during rest and self referential imagery. Persistent DMN activity during active tasks with dysfunctional imbalance of dorsal and ventral attentional networks represents a new hypothesis on the mechanism of VH. We review the different methods used to classify VH and discuss reports supporting or challenging the different hypothetical mechanisms of VH.

16 Review Designing prodrugs for the treatment of Parkinson's disease. 2012

Sozio, Piera / Cerasa, Laura Serafina / Abbadessa, Anna / Di Stefano, Antonio. ·School of Pharmacy, Department of Drug Sciences, G. d'Annunzio University, Via dei Vestini 31, Chieti, Italy. ·Expert Opin Drug Discov · Pubmed #22494466.

ABSTRACT: INTRODUCTION: Current Parkinson's disease (PD) therapy is essentially symptomatic, and l-Dopa (LD), is the treatment of choice in more advanced stages of the disease. However, motor complications often develop after long-term treatment, and at this point physicians usually prescribe adjuvant therapy with other classes of antiparkinsonian drugs, including dopamine (DA) agonists, catechol-O-methyl transferase (COMT) or monoamine oxidase (MAO)-B inhibitors. In order to improve bioavailability, the prodrug approach appeared to be the most promising, and some antiparkinsonian prodrugs have been prepared in an effort to solve these problems. AREAS COVERED: This review discusses the evidence of progress in PD therapy, mainly focused on prodrug approach for treatment of this neurological disorder. Several derivatives were studied with the aim of enhancing its chemical stability, water or lipid solubility, as well as diminishing the susceptibility to enzymatic degradation. Chemical structures mainly related to LD, DA and dopaminergic agonists are also reviewed in this paper. EXPERT OPINION: In order to strengthen the pharmacological activity of antiparkinsonian drugs, enhancing their penetration of the blood-brain barrier (BBB), different approaches are possible. Among these, the prodrug approach appeared to be the most promising, and many prodrugs have been prepared in an effort to optimize physicochemical characteristics. In addition, novel therapeutic strategies based on formulations linking dopaminergic drugs with neuroprotective agents, increasing LD striatal levels and offering sustained release of the drug without any fluctuation of brain concentration, offer promising avenues for development of other effective new treatments for PD.

17 Review Mitochondria as an easy target to oxidative stress events in Parkinson's disease. 2012

Reale, Marcella / Pesce, Mirko / Priyadarshini, Medha / Kamal, Mohammad A / Patruno, Antonia. ·Department of Biomedical Sciences, University "G. d'Annunzio" of Chieti-Pescara, Italy. mreale@unich.it ·CNS Neurol Disord Drug Targets · Pubmed #22483310.

ABSTRACT: Parkinson's disease (PD) is related to excess production of reactive oxygen species (ROS) or inadequate and impaired detoxification by endogenous antioxidants, alterations in catecholamine metabolism, alterations in mitochondrial electron transfer function, and enhanced iron deposition in the substantia nigra. The concept that oxidative stress is an important mechanism underlying the degeneration of dopaminergic (DAergic) neurons is reinforced by data documenting that high levels of lipid peroxidation, increased oxidation of proteins and DNA and depletion of glutathione are observed in postmortem studies of brain tissues of PD patients. Tyrosine hydroxylase (TH) is an important neuronal enzyme that, in the presence of tetrahydrobiopterin, catalyzes the initial and rate-limiting step in the biosynthesis of the catecholamine neurotransmitters dopamine (DA) and norepinephrine, and is frequently used as a marker of DAergic neuronal loss in animal models of PD. The role for TH as generators of ROS are highly relevant to PD because ROS have been proposed to contribute to the neurodegeneration of DA neurons. Oxidants and superoxide radicals are produced as byproducts of oxidative phosphorylation, making mitochondria the main site of ROS generation within the cell and the site of the first line of defence against oxidative stress. ROS can affect mitochondrial DNA (mtDNA) causing modulation in synthesis of electron transport chain (ETC) components, decreased ATP production, and increased leakage of ROS.

18 Review L-Dopa prodrugs: an overview of trends for improving Parkinson's disease treatment. 2011

Di Stefano, Antonio / Sozio, Piera / Cerasa, Laura Serafina / Iannitelli, Antonio. ·Department of Drug Sciences,G. d'Annunzio University, Faculty of Pharmacy, Chieti, Italy. adistefano@unich.it ·Curr Pharm Des · Pubmed #22074421.

ABSTRACT: L-Dopa is the mainstay of Parkinson's disease therapy; this drug is usually administered orally, but it is extensively metabolized in the gastrointestinal tract, so that relatively little arrives in the bloodstream as intact L-Dopa. The peripheral conversion of L-Dopa by amino acid decarboxylase to dopamine is responsible for the typical gastrointestinal and cardiovascular side effects. To minimize the conversion to dopamine outside the central nervous system, L-Dopa is usually given in combination with peripheral inhibitors of amino acid decarboxylase. In spite of that, other central nervous side effects such as dyskinesia, on-off phenomenon and end-of-dose deterioration still remain. The main factors responsible for the poor bioavailability are the drug's physical-chemical properties: low water and lipid solubility, resulting in unfavorable partition, and the high susceptibility to chemical and enzymatic degradation. Starting from these considerations the prodrug approach has been applied to L-Dopa in order to overcome its metabolism problems and to improve its bioavailability. The goal of this paper is to provide the reader with a critical overview on L-Dopa prodrugs here classified according to the nature of the main chemical modification on L-Dopa backbone that led to the formation of the desired derivative.

19 Clinical Trial Pathological gambling in Parkinson disease is reduced by amantadine. 2010

Thomas, Astrid / Bonanni, Laura / Gambi, Francesco / Di Iorio, Angelo / Onofrj, Marco. ·Department of Neurology, University G. d'Annunzio, Chieti and Pescara, Italy. ·Ann Neurol · Pubmed #20687121.

ABSTRACT: To investigate the possible efficacy of amantadine in the control of pathological gambling (PG) associated with Parkinson disease (PD), 17 PD patients with PG were randomly selected for a double-blind crossover study with amantadine 200mg/day versus placebo and an open follow-up. Assessments included PG-specific scales (Yale-Brown Obsessive-Compulsive Scale for PG, Gambling-Symptom Assessment Scale, South Oaks Gambling Screen) and assessment of expenditures and time spent gambling. Amantadine abolished or reduced PG in all treated patients, as confirmed by scale score and daily expenditure reduction. Amantadine might be useful to treat PG. The effect of amantadine, acting as an antiglutamatergic agent, also opens new insights into the pathogenesis of PG.

20 Article Inhibitory Effects Induced by 2019

Orlando, Giustino / Chiavaroli, Annalisa / Leone, Sheila / Brunetti, Luigi / Politi, Matteo / Menghini, Luigi / Recinella, Lucia / Ferrante, Claudio. ·Department of Pharmacy, Università degli Studi "Gabriele d'Annunzio", via dei Vestini 31, 66100 Chieti, Italy. ·Antioxidants (Basel) · Pubmed #31795449.

ABSTRACT: BACKGROUND: Parkinson's disease (PD) is the most common and progressive neurodegenerative and oxidative stress-related disorder, characterized by a dramatic loss of dopamine (DA) neurons in the nigrostriatal tissue. The first-line drug for PD treatment is represented by l-dopa, although clinical and preclinical studies pointed out the potential efficacy of medicinal plant- and food-derived antioxidants as brain protective agents. In this regard, the potential application of METHODS: The protective effects of RESULTS: The pharmacological association of the extracts was the most effective in contrasting the upregulated LDH and nitrite levels and in reducing striatal DA turnover. CONCLUSION: The present findings corroborate the rational for the traditional use of

21 Article Functional and Brain Activation Changes Following Specialized Upper-Limb Exercise in Parkinson's Disease. 2019

Messa, Luca Valerio / Ginanneschi, Federica / Momi, Davide / Monti, Lucia / Battisti, Carla / Cioncoloni, David / Pucci, Barbara / Santarnecchi, Emiliano / Rossi, Alessandro. ·Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy. · Siena Brain Investigation and Neuromodulation Lab, Department of Medicine, Surgery and Neurological Sciences, University of Siena, Siena, Italy. · Department of Neuroscience, Imaging and Clinical Sciences, University of Chieti-Pescara, Chieti, Italy. · Unit of Neuroimaging and Neurointervention, Department of Neurological and Neurosensorial Sciences, Azienda Ospedaliera Universitaria Senese, Siena, Italy. · U.O.P. Professioni della Riabilitazione, Azienda Ospedaliera Universitaria Senese, Siena, Italy. · Berenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States. · The Center for Complex Network Research, Department of Physics, Northeastern University, Boston, MA, United States. ·Front Hum Neurosci · Pubmed #31749690.

ABSTRACT: For the management of Parkinson's disease (PD), the concept of forced exercise (FE) has drawn interest. In PD subjects, the FE executed with lower limbs has been shown to lessen symptoms and to promote brain adaptive changes. Our study is aimed to investigate the effect of an upper-limb exercise, conceptually comparable with the FE, in PD. Upper-limb exercise was achieved in a sitting position by using a specially designed device (Angel's Wings

22 Article Postural Abnormalities in Parkinson's Disease: An Epidemiological and Clinical Multicenter Study. 2019

Tinazzi, Michele / Gandolfi, Marialuisa / Ceravolo, Roberto / Capecci, Marianna / Andrenelli, Elisa / Ceravolo, Maria Gabriella / Bonanni, Laura / Onofrj, Marco / Vitale, Michela / Catalan, Mauro / Polverino, Paola / Bertolotti, Claudio / Mazzucchi, Sonia / Giannoni, Sara / Smania, Nicola / Tamburin, Stefano / Vacca, Laura / Stocchi, Fabrizio / Radicati, Fabiana G / Artusi, Carlo Alberto / Zibetti, Maurizio / Lopiano, Leonardo / Fasano, Alfonso / Geroin, Christian. ·Neurology Unit, Movement Disorders Division, Department of Neurosciences, Biomedicine and Movement Sciences University of Verona Verona Italy. · Neuromotor and Cognitive Rehabilitation Research Center, Department of Neurosciences, Biomedicine and Movement Sciences University of Verona Verona Italy. · Neurorehabilitation Unit Azienda Ospedaliera Universitaria Integrata Verona Italy. · Department of Clinical and Experimental Medicine University of Pisa Pisa Italy. · Department of Experimental and Clinical Medicine Neurorehabilitation Clinic, "Politecnica delle Marche" University Ancona Italy. · Department of Neuroscience, Imaging and Clinical Sciences University G. d'Annunzio of Chieti-Pescara Chieti-Pescara Italy. · Clinical Neurology Unit, Department of Medical, Surgical and Health Services University of Trieste Trieste Italy. · University and Institute for Research and Medical Care, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Roma Italy. · Department of Neuroscience "Rita Levi Montalcini," University of Torino Torino Italy. · Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital University Health Network, Division of Neurology, University of Toronto Toronto Ontario Canada. · Krembil Brain Institute Toronto Ontario Canada. ·Mov Disord Clin Pract · Pubmed #31538092.

ABSTRACT: Introduction: The overall frequency of postural abnormalities (PA) in Parkinson's disease (PD) is unknown. We evaluated the overall prevalence of PA and assessed the association with demographic and clinical variables. Methods: For this multicenter, cross-sectional study, consecutive PD outpatients attending 7 tertiary Italian centers were enrolled. Patients were evaluated and compared for the presence of isolated PA such as camptocormia, Pisa syndrome, and anterocollis and for combined forms (ie, camptocormia + Pisa syndrome) together with demographic and clinical variables. Results: Of the total 811 PD patients enrolled, 174 (21.5%; 95% confidence interval [CI], 18.6%-24.3%) presented PA, 144 of which had isolated PA and 30 had combined PA. The prevalence of camptocormia was 11.2% (95% CI, 9%-13.3%), Pisa syndrome 8% (95% CI, 6.2%-9.9%), and anterocollis 6.5% (95% CI, 4.9%-8.3%). Patients with PA were more often male and older with longer disease duration, more advanced disease stage, more severe PD symptoms, a bradykinetic/rigid phenotype, and poorer quality of life. They were initially treated with l Conclusions: PA are frequent and disabling complications in PD, especially in the advanced disease stages.

23 Article Somatic symptoms disorders in Parkinson's disease are related to default mode and salience network dysfunction. 2019

Franciotti, Raffaella / Delli Pizzi, Stefano / Russo, Mirella / Carrarini, Claudia / Carrozzino, Danilo / Perfetti, Bernardo / Onofrj, Marco / Bonanni, Laura. ·Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy. · Department of Psychological Sciences, Health and Territorial Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy. · Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy. Electronic address: l.bonanni@unich.it. ·Neuroimage Clin · Pubmed #31491814.

ABSTRACT: BACKGROUND: Somatic Symptoms Disorder (SSD) has been shown to have a clinically very high prevalence in Parkinson's Disease (PD) with frequencies ranging from 7.0% to 66.7%, higher than in the general population (10%- 25%). SSD has been associated with dysfunction in Default Mode and Salience network. AIM: With the present study we aim to verify by means of resting state functional MRI whether possible specific abnormalities in the activation and functional connectivity of the default mode network (DMN) and salience network in cognitively intact PD patients may be more prominent in PD patients with somatic symptoms (SSD-PD) as compared with patients without SSD (PD). METHODS: Eighteen SSD-PD patients (61% male), 18 PD patients (83% male) and 22 healthy age-matched subjects (59% male) were enrolled in the study and underwent resting state functional MRI. RESULTS: fractional amplitude of low-frequency fluctuation (fALFF) showed reduced activity in bilateral lateral parietal cortex and in left anterior insula in both SSD-PD and PD compared to control group. Functional connectivity (FC) values in the DMN areas and between DMN and salience network areas were found to be lower in SSD-PD than in control group and PD. No significant correlation was found between fMRI results and demographic and clinical variables, excluding the effect of possible confounders on fMRI results. The present study, showing reduced activity in bilateral parietal areas and in the left anterior insula as compared to healthy controls, suggests a dysfunction of the DMN and salience network in PD, either with or without SSD. The FC reduction within DMN areas and between DMN and salience network areas in SSD-PD patients suggests a role of dysfunctional connectivity in the resting state network of patients with SSD.

24 Article Modulation of Apoptotic Cell Death and Neuroprotective Effects of Glutathione-L-Dopa Codrug Against H 2019

Franceschelli, Sara / Lanuti, Paola / Ferrone, Alessio / Gatta, Daniela Maria Pia / Speranza, Lorenza / Pesce, Mirko / Grilli, Alfredo / Cacciatore, Ivana / Ricciotti, Emanuela / Di Stefano, Antonio / Miscia, Sebastiano / Felaco, Mario / Patruno, Antonia. ·Department of Psychological, Health and Territorial Sciences, University "G. D'Annunzio", 66100 Chieti-Pescara, Italy. · Department of Medicine and Science of Aging, University "G. D'Annunzio", 66100 Chieti-Pescara, Italy. · Department of Pharmacy, University "Gabriele D'Annunzio" of Chieti-Pescara, 66100 Chieti-Pescara, Italy. · Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA. · Department of Medicine and Science of Aging, University "G. D'Annunzio", 66100 Chieti-Pescara, Italy. antoniapatruno@unich.it. ·Antioxidants (Basel) · Pubmed #31430883.

ABSTRACT: The L-3,4-dihydroxyphenylalanine (LD) is the gold standard drug currently used to manage Parkinson's disease (PD) and to control its symptoms. However, LD could cause disease neurotoxicity due to the generation of pro-oxidant intermediates deriving from its autoxidation. In order to overcome this limitation, we have conjugated LD to the natural antioxidant glutathione (GSH) to form a codrug (GSH-LD). Here we investigated the effect of GSH-LD on H

25 Article Benzo[ 2019

Guglielmi, Paolo / Secci, Daniela / Petzer, Anél / Bagetta, Donatella / Chimenti, Paola / Rotondi, Giulia / Ferrante, Claudio / Recinella, Lucia / Leone, Sheila / Alcaro, Stefano / Zengin, Gokhan / Petzer, Jacobus P / Ortuso, Francesco / Carradori, Simone. ·a Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome , Rome , Italy. · b Pharmaceutical Chemistry, School of Pharmacy, Centre of Excellence for Pharmaceutical Sciences, North-West University , Potchefstroom , South Africa. · c Dipartimento di Scienze della Salute, "Magna Graecia" University of Catanzaro, Campus Universitario "S. Venuta", Viale Europa Loc. Germaneto , Catanzaro , Italy. · d Net4Science Academic Spin-Off, Campus Universitario "S. Venuta", Viale Europa Loc. Germaneto, "Magna Graecia" University of Catanzaro , Catanzaro , Italy. · e Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara , Chieti , Italy. · f Department of Biology, Science Faculty, Selcuk University , Konya , Turkey. ·J Enzyme Inhib Med Chem · Pubmed #31422706.

ABSTRACT: A series of benzo[

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