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Brain Sciences
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Updates in Parkinson's Disease
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Updates in Parkinson's Disease

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neurodegenerative Diseases".

Deadline for manuscript submissions: closed (22 December 2023) | Viewed by 34299

Special Issue Editors

Prof. Dr. Massimo Filippi

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Guest Editor
Neurology Unit, Neurophysiology Service and Neurorehabilitation Unit, and Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy
Interests: Parkinson’s disease; multiple sclerosis; Alzheimer’s disease; amyotrophic lateral sclerosis; neuroimaging
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Federica Agosta

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Co-Guest Editor
Neuroimaging Research Unit, Division of Neuroscience and Neurology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy
Interests: Parkinson’s disease; Alzheimer’s disease; amyotrophic lateral sclerosis; neuroimaging; neuroreha-bilitation
Elisabetta Sarasso

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Guest Editor Assistant
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy
Interests: Parkinson’s disease; movement disorders; neuroimaging; neurorehabilitation; motor learning

Special Issue Information

Dear Colleagues,

Parkinson’s disease is one of the most common neurodegenerative disorders and, despite the presence of effective symptomatic therapies for several motor and non-motor signs and symptoms, the disease has a high impact on quality of life. To date, researchers are mainly focused on studying the prodromal phase of the disease, searching biomarkers to predict and monitor disease progression and finding innovative pharmacological and non-pharmacological treatments to improve patients’ quality of life.

This Special Issue aims to collect research contributions covering salient and novel topics on Parkinson’s disease in humans in order to provide an updated state of the art on the disease. We welcome original research and review articles covering, but not limited to, the following themes: etiology, genetics, epidemiology and pathophysiology of Parkinson’s disease, novel biomarkers to monitor and predict Parkinson’s disease progression, innovative pharmacological, non-pharmacological and surgical approaches, and novel outcome measures to assess the efficacy of treatments. 

Prof. Dr. Massimo Filippi
Prof. Dr. Federica Agosta
Guest Editors

Elisabetta Sarasso
Guest Editor Assistant

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Parkinson’s disease
  • pathophysiology
  • biomarkers
  • treatment
  • outcome measures

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Published Papers (7 papers)

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Research

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17 pages, 2436 KiB  
Article
Sensorimotor Network Segregation Predicts Long-Term Learning of Writing Skills in Parkinson’s Disease
by Nicholas D’Cruz, Joni De Vleeschhauwer, Martina Putzolu, Evelien Nackaerts, Moran Gilat and Alice Nieuwboer
Brain Sci. 2024, 14(4), 376; https://doi.org/10.3390/brainsci14040376 - 12 Apr 2024
Viewed by 1479
Abstract
The prediction of motor learning in Parkinson’s disease (PD) is vastly understudied. Here, we investigated which clinical and neural factors predict better long-term gains after an intensive 6-week motor learning program to ameliorate micrographia. We computed a composite score of learning through principal [...] Read more.
The prediction of motor learning in Parkinson’s disease (PD) is vastly understudied. Here, we investigated which clinical and neural factors predict better long-term gains after an intensive 6-week motor learning program to ameliorate micrographia. We computed a composite score of learning through principal component analysis, reflecting better writing accuracy on a tablet in single and dual task conditions. Three endpoints were studied—acquisition (pre- to post-training), retention (post-training to 6-week follow-up), and overall learning (acquisition plus retention). Baseline writing, clinical characteristics, as well as resting-state network segregation were used as predictors. We included 28 patients with PD (13 freezers and 15 non-freezers), with an average disease duration of 7 (±3.9) years. We found that worse baseline writing accuracy predicted larger gains for acquisition and overall learning. After correcting for baseline writing accuracy, we found female sex to predict better acquisition, and shorter disease duration to help retention. Additionally, absence of FOG, less severe motor symptoms, female sex, better unimanual dexterity, and better sensorimotor network segregation impacted overall learning positively. Importantly, three factors were retained in a multivariable model predicting overall learning, namely baseline accuracy, female sex, and sensorimotor network segregation. Besides the room to improve and female sex, sensorimotor network segregation seems to be a valuable measure to predict long-term motor learning potential in PD. Full article
(This article belongs to the Special Issue Updates in Parkinson's Disease)
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Review

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15 pages, 740 KiB  
Review
Imaging Markers in Genetic Forms of Parkinson’s Disease
by Amgad Droby, Avner Thaler and Anat Mirelman
Brain Sci. 2023, 13(8), 1212; https://doi.org/10.3390/brainsci13081212 - 16 Aug 2023
Cited by 1 | Viewed by 2151
Abstract
Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by motor symptoms such as bradykinesia, rigidity, and resting tremor. While the majority of PD cases are sporadic, approximately 15–20% of cases have a genetic component. Advances in neuroimaging techniques have provided valuable insights [...] Read more.
Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by motor symptoms such as bradykinesia, rigidity, and resting tremor. While the majority of PD cases are sporadic, approximately 15–20% of cases have a genetic component. Advances in neuroimaging techniques have provided valuable insights into the pathophysiology of PD, including the different genetic forms of the disease. This literature review aims to summarize the current state of knowledge regarding neuroimaging findings in genetic PD, focusing on the most prevalent known genetic forms: mutations in the GBA1, LRRK2, and Parkin genes. In this review, we will highlight the contributions of various neuroimaging modalities, including positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI), in elucidating the underlying pathophysiological mechanisms and potentially identifying candidate biomarkers for genetic forms of PD. Full article
(This article belongs to the Special Issue Updates in Parkinson's Disease)
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13 pages, 989 KiB  
Review
Microglia and Astrocytes Dysfunction and Key Neuroinflammation-Based Biomarkers in Parkinson’s Disease
by Kun Chen, Haoyang Wang, Iqra Ilyas, Arif Mahmood and Lijun Hou
Brain Sci. 2023, 13(4), 634; https://doi.org/10.3390/brainsci13040634 - 7 Apr 2023
Cited by 20 | Viewed by 4447
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease, with symptoms such as tremor, bradykinesia with rigidity, and depression appearing in the late stage of life. The key hallmark of PD is the loss or death of dopaminergic neurons in the region [...] Read more.
Parkinson’s disease (PD) is the second most common neurodegenerative disease, with symptoms such as tremor, bradykinesia with rigidity, and depression appearing in the late stage of life. The key hallmark of PD is the loss or death of dopaminergic neurons in the region substantia nigra pars compacta. Neuroinflammation plays a key role in the etiology of PD, and the contribution of immunity-related events spurred the researchers to identify anti-inflammatory agents for the treatment of PD. Neuroinflammation-based biomarkers have been identified for diagnosing PD, and many cellular and animal models have been used to explain the underlying mechanism; however, the specific cause of neuroinflammation remains uncertain, and more research is underway. So far, microglia and astrocyte dysregulation has been reported in PD. Patients with PD develop neural toxicity, inflammation, and inclusion bodies due to activated microglia and a-synuclein–induced astrocyte conversion into A1 astrocytes. Major phenotypes of PD appear in the late stage of life, so there is a need to identify key early-stage biomarkers for proper management and diagnosis. Studies are under way to identify key neuroinflammation-based biomarkers for early detection of PD. This review uses a constructive analysis approach by studying and analyzing different research studies focused on the role of neuroinflammation in PD. The review summarizes microglia, astrocyte dysfunction, neuroinflammation, and key biomarkers in PD. An approach that incorporates multiple biomarkers could provide more reliable diagnosis of PD. Full article
(This article belongs to the Special Issue Updates in Parkinson's Disease)
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13 pages, 648 KiB  
Review
Switching from Rasagiline to Safinamide as an Add-On Therapy Regimen in Patients with Levodopa: A Literature Review
by Pilar Sanchez Alonso, Beatriz De La Casa-Fages, Araceli Alonso-Cánovas and Juan Carlos Martínez-Castrillo
Brain Sci. 2023, 13(2), 276; https://doi.org/10.3390/brainsci13020276 - 7 Feb 2023
Cited by 5 | Viewed by 4163
Abstract
Parkinson’s disease (PD) is a complex disease, and the treatment is focused on the patient’s clinical symptoms. Levodopa continues to be the most effective drug for symptomatic PD treatment. However, chronic levodopa treatment is associated with the development of motor complications in most [...] Read more.
Parkinson’s disease (PD) is a complex disease, and the treatment is focused on the patient’s clinical symptoms. Levodopa continues to be the most effective drug for symptomatic PD treatment. However, chronic levodopa treatment is associated with the development of motor complications in most patients. Add-on therapeutic drugs, such as dopamine agonists and monoamine oxidase B (MAO-B) inhibitors, for example, safinamide and rasagiline, may be a desirable addition to continuously increase the levodopa dose for the optimization of motor control in PD. The scientific literature shows that safinamide significantly alleviated motor fluctuations with no increase in troublesome dyskinesia, thanks to its unique double mechanism, providing further benefits to fluctuating PD patients when compared to a placebo or other drugs. Switching from rasagiline to safinamide has been shown to improve the wearing-off phenomena, which is defined as the recurrent, predictable worsening of symptoms of parkinsonism at the end of the levodopa dose until the next dose reaches a clinical effect. In this situation, safinamide may be helpful for reducing the total daily dose of levodopa, improving the OFF time and ON time without troublesome dyskinesias, and being more effective than other MAO-B inhibitors. In this narrative review, we explore the switch from rasagiline to safinamide in patients with motor complications as a feasible and effective alternative to optimize antiparkinsonian treatment. Full article
(This article belongs to the Special Issue Updates in Parkinson's Disease)
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18 pages, 2876 KiB  
Review
Could Vitamins Have a Positive Impact on the Treatment of Parkinson’s Disease?
by Sandeep, Manas Ranjan Sahu, Linchi Rani, Arun S. Kharat and Amal Chandra Mondal
Brain Sci. 2023, 13(2), 272; https://doi.org/10.3390/brainsci13020272 - 6 Feb 2023
Cited by 16 | Viewed by 17496
Abstract
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer’s disease. Pathophysiologically, it is characterized by intracytoplasmic aggregates of α-synuclein protein in the Lewy body and loss of dopaminergic neurons from substantia nigra pars compacta and striatum regions of the [...] Read more.
Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder after Alzheimer’s disease. Pathophysiologically, it is characterized by intracytoplasmic aggregates of α-synuclein protein in the Lewy body and loss of dopaminergic neurons from substantia nigra pars compacta and striatum regions of the brain. Although the exact mechanism of neurodegeneration is not fully elucidated, it has been reported that environmental toxins such as MPTP, rotenone, paraquat, and MPP+ induce oxidative stress, which is one of the causative factors for it. To date, there is no complete cure. However, the indispensable role of oxidative stress in mediating PD indicates that antioxidant therapy could be a possible therapeutic strategy against the disease. The deficiency of vitamins has been extensively co-related to PD. Dietary supplementation of vitamins with antioxidant, anti-inflammatory, anti-apoptotic, and free radical scavenging properties could be the potential neuroprotective therapeutic strategy. This review summarizes the studies that evaluated the role of vitamins (A, B, C, D, E, and K) in PD. It will guide future studies in understanding the potential therapeutic role of vitamins in disease pathophysiology and may provide a framework for designing treatment strategies against the disease. Full article
(This article belongs to the Special Issue Updates in Parkinson's Disease)
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Other

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19 pages, 15633 KiB  
Systematic Review
Dual-Task vs. Single-Task Gait Training to Improve Spatiotemporal Gait Parameters in People with Parkinson’s Disease: A Systematic Review and Meta-Analysis
by Elisabetta Sarasso, Marco Pietro Parente, Federica Agosta, Massimo Filippi and Davide Corbetta
Brain Sci. 2024, 14(5), 517; https://doi.org/10.3390/brainsci14050517 - 20 May 2024
Viewed by 1944
Abstract
Background: People with Parkinson’s disease (pwPD) present alterations of spatiotemporal gait parameters that impact walking ability. While preliminary studies suggested that dual-task gait training improves spatiotemporal gait parameters, it remains unclear whether dual-task gait training specifically improves dual-task gait performance compared to single-task [...] Read more.
Background: People with Parkinson’s disease (pwPD) present alterations of spatiotemporal gait parameters that impact walking ability. While preliminary studies suggested that dual-task gait training improves spatiotemporal gait parameters, it remains unclear whether dual-task gait training specifically improves dual-task gait performance compared to single-task gait training. The aim of this review is to assess the effect of dual-task training relative to single-task gait training on specific gait parameters during dual-task tests in pwPD. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), searching three electronic databases. Two reviewers independently selected RCTs, extracted data, and applied the Cochrane risk-of-bias tool for randomized trials (Version 2) and the GRADE framework for assessing the certainty of evidence. The primary outcomes were dual-task gait speed, stride length, and cadence. Secondary outcomes included dual-task costs on gait speed, balance confidence, and quality of life. Results: We included 14 RCTs (548 patients). Meta-analyses showed effects favoring dual-task training over single-task training in improving dual-task gait speed (standardized mean difference [SMD] = 0.48, 95% confidence interval [CI] = 0.20–0.77; 11 studies; low certainty evidence), stride length (mean difference [MD] = 0.09 m, 95% CI = 0.04–0.14; 4 studies; very low certainty evidence), and cadence (MD = 5.45 steps/min, 95% CI = 3.59–7.31; 5 studies; very low certainty evidence). We also found a significant effect of dual-task training over single-task training on dual-task cost and quality of life, but not on balance confidence. Conclusions: Our findings support the use of dual-task training relative to single-task training to improve dual-task spatiotemporal gait parameters in pwPD. Further studies are encouraged to better define the features of dual-task training and the clinical characteristics of pwPD to identify better responders. Full article
(This article belongs to the Special Issue Updates in Parkinson's Disease)
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11 pages, 1249 KiB  
Brief Report
Altered Cerebral Vasoreactivity on Transcranial Color-Coded Sonography Related to Akinetic-Rigid Phenotype of Parkinson’s Disease: Interim Analysis of a Cross-Sectional Study
by Rodrigo Tavares Brisson, Rita de Cássia Leite Fernandes, Josevânia Fulgêncio de Lima Arruda, Thiffanny Cristini Cassiano da S. M. Rocha, Nathália de Góes Duarte Santos, Liene Duarte Silva, Marco Antônio Sales Dantas de Lima and Ana Lucia Zuma de Rosso
Brain Sci. 2023, 13(5), 709; https://doi.org/10.3390/brainsci13050709 - 24 Apr 2023
Cited by 1 | Viewed by 1504
Abstract
Background: A correlation between worse functional outcomes in Parkinson’s disease (PD) patients with cerebrovascular disease (CVD) or the Akinetic-rigid phenotype has been argued in recent studies. We aimed to evaluate the association of cerebral hemodynamics impairments, assessed by Transcranial Color-coded Doppler sonography (TCCS), [...] Read more.
Background: A correlation between worse functional outcomes in Parkinson’s disease (PD) patients with cerebrovascular disease (CVD) or the Akinetic-rigid phenotype has been argued in recent studies. We aimed to evaluate the association of cerebral hemodynamics impairments, assessed by Transcranial Color-coded Doppler sonography (TCCS), on PD patients with different phenotypes of the disease and with risk factors for CVD. Methodology: Idiopathic PD patients (n = 51) were divided into motor subtypes: Akinetic-rigid (AR) (n = 27) and Tremor-dominant (TD) (n = 24) and into two groups regarding vascular risk factors: when ≥2 were present (PDvasc) (n = 18) and <2 (PDnvasc) (n = 33). In a parallel analysis, the Fazekas scale on brain magnetic resonance imaging (MRI) was applied to a sample to assess the degree of leukoaraiosis. TCCS examinations were prospectively performed obtaining middle cerebral artery Mean Flow Velocities (Vm), Resistance Index (RI), and Pulsatility Index (PI). The Breath-Holding Index (BHI) was calculated to assess cerebrovascular reactivity (cVR). Standardized functional scales were administered (UPDRS III and Hoehn&Yahr). Results: The phenotype groups were similar in age, disease duration and demographic parameters, but there were significantly higher H&Y scores than TD group. cVR was impaired in 66.7% of AR vs. 37.5% of TD. AR group exhibited lower BHI (0.53 ± 0.31 vs. 0.91 ± 0.62; p = 0.000), lower Vm after apnea (44.3 ± 9.0 cm/s vs. 53.4 ± 11.4 cm/s; p = 0.003), higher PI (0.91 ± 0.26 vs. 0.76 ± 0.12; p = 0.000) and RI (0.58 ± 0.11 vs. 0.52 ± 0.06; p = 0.021). PDvasc group showed higher PI (0.98 vs. 0.76; p = 0.001) and higher frequency of altered cVR (72.2% vs. 42.2%; p = 0.004). There was a significant predominance of higher values on Fazekas scale in the PDvasc group. We found no difference between the Fazekas scale when comparing motor subtypes groups but there was a trend toward higher scores in the AR phenotype. Conclusions: TCCS, a cost-effective method, displayed impaired cVR in Parkinsonian patients with risk factors for CVD with higher degree of MRI leukoaraiosis. PD patients with the AR disease phenotype also presented impaired cVR on TCCS and greater functional impairment, although with just a trend to higher scores on MRI Fazekas. Full article
(This article belongs to the Special Issue Updates in Parkinson's Disease)
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