Hot Topics in Parkinson’s Disease: State of the Art and Future Perspectives

A topical collection in Brain Sciences (ISSN 2076-3425). This collection belongs to the section "Neuromuscular and Movement Disorders".

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Editor

Department of Clinical Neurosciences, Parkinson and Movement Disorders Unit, 20133 Milan, Italy
Interests: Parkinson's disease; movement disorders; tremor; neurodegenerative diseases; neu-roimaging; genetics; cognitive and behavioral disorders; dementia; neuropharma-cology; dyskinesias;

Topical Collection Information

Dear Colleagues,

In recent years, our knowledge about the pathophysiological mechanisms of Parkinson’s disease has grown substantially. On the one hand, the development of reliable clinical, biochemical, and imaging biomarkers has improved our diagnostic skills at the earliest stages of the disease, including prodromal stages. On the other hand, the advancements in the fields of basic science, genetics, and environmental factors have increased the chances of finding effective disease-modifying therapies. In the meanwhile, novel effective therapies are being developed and established symptomatic therapies are optimized worldwide.

The aim of the present topical collection is to provide a wide overview on preclinical and clinical research on the most recent ‘hot topics’ in Parkinson’s disease and other forms of parkinsonism. Accordingly, authors are invited to submit cutting-edge reviews and original research that include up-to-date background on the state of the art to be developed throughout the manuscript in order to provide clear take-home messages that will fuel future research on this common movement disorder.

Prof. Dr. Roberto Cilia
Section Editor-in-Chief

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Keywords

  • Parkinson’s disease
  • alpha-synuclein
  • genetics
  • neuroimaging
  • microbiota
  • focused ultrasound
  • gender
  • impulse control disorders
  • disease-modifying therapies
  • telemedicine

Published Papers (10 papers)

2024

Jump to: 2023, 2022

17 pages, 323 KiB  
Review
The Story behind the Mask: A Narrative Review on Hypomimia in Parkinson’s Disease
by Edoardo Bianchini, Domiziana Rinaldi, Marika Alborghetti, Marta Simonelli, Flavia D’Audino, Camilla Onelli, Elena Pegolo and Francesco E. Pontieri
Brain Sci. 2024, 14(1), 109; https://doi.org/10.3390/brainsci14010109 - 22 Jan 2024
Cited by 1 | Viewed by 1234
Abstract
Facial movements are crucial for social and emotional interaction and well-being. Reduced facial expressions (i.e., hypomimia) is a common feature in patients with Parkinson’s disease (PD) and previous studies linked this manifestation to both motor symptoms of the disease and altered emotion recognition [...] Read more.
Facial movements are crucial for social and emotional interaction and well-being. Reduced facial expressions (i.e., hypomimia) is a common feature in patients with Parkinson’s disease (PD) and previous studies linked this manifestation to both motor symptoms of the disease and altered emotion recognition and processing. Nevertheless, research on facial motor impairment in PD has been rather scarce and only a limited number of clinical evaluation tools are available, often suffering from poor validation processes and high inter- and intra-rater variability. In recent years, the availability of technology-enhanced quantification methods of facial movements, such as automated video analysis and machine learning application, led to increasing interest in studying hypomimia in PD. In this narrative review, we summarize the current knowledge on pathophysiological hypotheses at the basis of hypomimia in PD, with particular focus on the association between reduced facial expressions and emotional processing and analyze the current evaluation tools and management strategies for this symptom, as well as future research perspectives. Full article

2023

Jump to: 2024, 2022

7 pages, 773 KiB  
Brief Report
Association between Antiepileptic Drugs and Incident Parkinson’s Disease among Patients Followed in German Primary Care Practices
by Karel Kostev, Corinna Doege, Louis Jacob, Lee Smith, Ai Koyanagi, Celina Gollop and Anette Schrag
Brain Sci. 2023, 13(3), 450; https://doi.org/10.3390/brainsci13030450 - 06 Mar 2023
Cited by 2 | Viewed by 2204
Abstract
Background: The aim of this study was to analyze whether prescriptions of antiepileptic drugs (AEDs) are significantly associated with an increased incidence of Parkinson’s disease (PD) in the German population. Methods: This study used data from German primary care practices found in the [...] Read more.
Background: The aim of this study was to analyze whether prescriptions of antiepileptic drugs (AEDs) are significantly associated with an increased incidence of Parkinson’s disease (PD) in the German population. Methods: This study used data from German primary care practices found in the Disease Analyzer database (IQVIA) and included all patients aged ≥18 years who were diagnosed with PD between January 2010 and December 2021 (index date). The controls were patients without PD matched (1:1) by age, sex, and pre-diagnostic observation time in years. Associations between AED prescriptions (any AED as well as separate evaluations for carbamazepine, lamotrigine, levetiracetam, sodium valproate, gabapentin, and pregabalin) and subsequent diagnosis of PD were examined using a logistic regression model adjusted for epilepsy, restless legs syndrome, and neuropathy diagnoses. Results: We identified 24,950 cases that were matched with 24,950 controls (mean age 75.2 years, 47.3% women). Diagnoses of epilepsy, restless legs syndrome, and neuropathy as well as AED prescription were significantly associated with an increased incidence of PD. In the multivariate analysis, incidence of PD was significantly associated with epilepsy (OR: 1.91; 95% CI: 1.69–2.15), restless legs syndrome (OR: 3.02; 95% CI: 2.73–3.34), and neuropathy (OR: 1.53; 95% CI: 1.44–1.62)), as well as the prescription of any AED (OR: 1.43; 95% CI: 1.33–1.53), sodium valproate (OR: 2.39; 95% CI: 1.84–3.11), gabapentin (OR: 1.36; 95% CI: 1.22–1.52), and pregabalin (OR: 1.28; 95% CI: 1.15–1.41). Conclusion: Prescriptions of AEDs, including sodium valproate, gabapentin, and pregabalin, were associated with an increased risk of subsequent PD, even after adjustment for underlying diagnoses. Further studies are needed to confirm the present results. Full article
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2022

Jump to: 2024, 2023

10 pages, 1008 KiB  
Perspective
Telemedicine in the Management of Parkinson’s Disease: Achievements, Challenges, and Future Perspectives
by Esther Cubo and Pedro David Delgado-López
Brain Sci. 2022, 12(12), 1735; https://doi.org/10.3390/brainsci12121735 - 19 Dec 2022
Cited by 5 | Viewed by 1754
Abstract
Background: As the global population grows, there is an increasing demand for neurologic consultation that prompts new ways to reach more patients. Telemedicine can provide an accessible, cost-effective, and high-quality healthcare services. Objectives: In this article, we highlight recent developments, achievements, and challenges [...] Read more.
Background: As the global population grows, there is an increasing demand for neurologic consultation that prompts new ways to reach more patients. Telemedicine can provide an accessible, cost-effective, and high-quality healthcare services. Objectives: In this article, we highlight recent developments, achievements, and challenges regarding outcomes, clinical care, tele-education, teletreatment, teleresearch, and cybersecurity for telemedicine applied to Parkinson´s disease (PD) and other neurological conditions. Results: A growing body of evidence supports the feasibility and effectiveness of telemedicine tools for PD and other movement disorders. Outcome variables regarding satisfaction and efficacy in clinical care and specific issues about education, research, and treatment are reviewed. Additionally, a specific legal framework for teleconsultation has been developed in some centers worldwide. Yet, the implementation of telemedicine is conditioned by the limitations inherent to remote neurological examination, the variable computer usage literacy among patients, and the availability of a reliable internet connection. At present, telemedicine can be considered an additional tool in the clinical management of PD patients. Conclusions: There is an increasing use of remote clinical practice regarding the management of PD and other neurological conditions. Telemedicine is a new and promising tool aimed at special settings and subpopulations. Full article
18 pages, 708 KiB  
Review
Approaching the Gut and Nasal Microbiota in Parkinson’s Disease in the Era of the Seed Amplification Assays
by Alessandra Consonni, Martina Miglietti, Chiara Maria Giulia De Luca, Federico Angelo Cazzaniga, Arianna Ciullini, Ilaria Linda Dellarole, Giuseppe Bufano, Alessio Di Fonzo, Giorgio Giaccone, Fulvio Baggi and Fabio Moda
Brain Sci. 2022, 12(11), 1579; https://doi.org/10.3390/brainsci12111579 - 19 Nov 2022
Cited by 3 | Viewed by 1639
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder often associated with pre-motor symptoms involving both gastrointestinal and olfactory tissues. PD patients frequently suffer from hyposmia, hyposalivation, dysphagia and gastrointestinal dysfunctions. During the last few years it has been speculated that microbial agents could play [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disorder often associated with pre-motor symptoms involving both gastrointestinal and olfactory tissues. PD patients frequently suffer from hyposmia, hyposalivation, dysphagia and gastrointestinal dysfunctions. During the last few years it has been speculated that microbial agents could play a crucial role in PD. In particular, alterations of the microbiota composition (dysbiosis) might contribute to the formation of misfolded α-synuclein, which is believed to be the leading cause of PD. However, while several findings confirmed that there might be an important link between intestinal microbiota alterations and PD onset, little is known about the potential contribution of the nasal microbiota. Here, we describe the latest findings on this topic by considering that more than 80% of patients with PD develop remarkable olfactory deficits in their prodromal disease stage. Therefore, the nasal microbiota might contribute to PD, eventually boosting the gut microbiota in promoting disease onset. Finally, we present the applications of the seed amplification assays to the study of the gut and olfactory mucosa of PD patients, and how they could be exploited to investigate whether pathogenic bacteria present in the gut and the nose might promote α-synuclein misfolding and aggregation. Full article
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39 pages, 1218 KiB  
Review
Precision Medicine in Parkinson’s Disease: From Genetic Risk Signals to Personalized Therapy
by Giulia Straccia, Fabiana Colucci, Roberto Eleopra and Roberto Cilia
Brain Sci. 2022, 12(10), 1308; https://doi.org/10.3390/brainsci12101308 - 28 Sep 2022
Cited by 6 | Viewed by 2052
Abstract
Understanding the pathophysiology and genetic background of Parkinson’s disease (PD) increases the likelihood of developing effective disease-modifying therapeutic strategies. In particular, the discovery of genetic variants causing or increasing the risk for PD has contributed to refining the clinical, biological, and molecular classification [...] Read more.
Understanding the pathophysiology and genetic background of Parkinson’s disease (PD) increases the likelihood of developing effective disease-modifying therapeutic strategies. In particular, the discovery of genetic variants causing or increasing the risk for PD has contributed to refining the clinical, biological, and molecular classification of the disease and has offered new insights into sporadic forms. It is even more evident that specific genetic mutations can show different responses to pharmacological and device-aided therapies. To date, several agents acting on multiple PD-causing pathogenic pathways have been tested as disease-modifying strategies, with disappointing results. This may be caused by the recruitment of PD populations whose underlying molecular pathophysiology is heterogeneous. We believe that an effective model of personalized medicine must be prioritized in the near future. Here, we review the current therapeutic options under clinical and preclinical development for PD and discuss the key pending questions and challenges to face for successful clinical trials. Furthermore, we provide some insights into the role of genetics in guiding the decision-making process on symptomatic and device-aided therapies for PD in daily clinical practice. Full article
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30 pages, 1433 KiB  
Systematic Review
Imaging the Limbic System in Parkinson’s Disease—A Review of Limbic Pathology and Clinical Symptoms
by Magdalena Banwinkler, Hendrik Theis, Stéphane Prange and Thilo van Eimeren
Brain Sci. 2022, 12(9), 1248; https://doi.org/10.3390/brainsci12091248 - 15 Sep 2022
Cited by 11 | Viewed by 6051
Abstract
The limbic system describes a complex of brain structures central for memory, learning, as well as goal directed and emotional behavior. In addition to pathological studies, recent findings using in vivo structural and functional imaging of the brain pinpoint the vulnerability of limbic [...] Read more.
The limbic system describes a complex of brain structures central for memory, learning, as well as goal directed and emotional behavior. In addition to pathological studies, recent findings using in vivo structural and functional imaging of the brain pinpoint the vulnerability of limbic structures to neurodegeneration in Parkinson’s disease (PD) throughout the disease course. Accordingly, dysfunction of the limbic system is critically related to the symptom complex which characterizes PD, including neuropsychiatric, vegetative, and motor symptoms, and their heterogeneity in patients with PD. The aim of this systematic review was to put the spotlight on neuroimaging of the limbic system in PD and to give an overview of the most important structures affected by the disease, their function, disease related alterations, and corresponding clinical manifestations. PubMed was searched in order to identify the most recent studies that investigate the limbic system in PD with the help of neuroimaging methods. First, PD related neuropathological changes and corresponding clinical symptoms of each limbic system region are reviewed, and, finally, a network integration of the limbic system within the complex of PD pathology is discussed. Full article
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28 pages, 2167 KiB  
Review
Molecular Imaging in Parkinsonian Disorders—What’s New and Hot?
by Stéphane Prange, Hendrik Theis, Magdalena Banwinkler and Thilo van Eimeren
Brain Sci. 2022, 12(9), 1146; https://doi.org/10.3390/brainsci12091146 - 27 Aug 2022
Cited by 7 | Viewed by 3418
Abstract
Neurodegenerative parkinsonian disorders are characterized by a great diversity of clinical symptoms and underlying neuropathology, yet differential diagnosis during lifetime remains probabilistic. Molecular imaging is a powerful method to detect pathological changes in vivo on a cellular and molecular level with high specificity. [...] Read more.
Neurodegenerative parkinsonian disorders are characterized by a great diversity of clinical symptoms and underlying neuropathology, yet differential diagnosis during lifetime remains probabilistic. Molecular imaging is a powerful method to detect pathological changes in vivo on a cellular and molecular level with high specificity. Thereby, molecular imaging enables to investigate functional changes and pathological hallmarks in neurodegenerative disorders, thus allowing to better differentiate between different forms of degenerative parkinsonism, improve the accuracy of the clinical diagnosis and disentangle the pathophysiology of disease-related symptoms. The past decade led to significant progress in the field of molecular imaging, including the development of multiple new and promising radioactive tracers for single photon emission computed tomography (SPECT) and positron emission tomography (PET) as well as novel analytical methods. Here, we review the most recent advances in molecular imaging for the diagnosis, prognosis, and mechanistic understanding of parkinsonian disorders. First, advances in imaging of neurotransmission abnormalities, metabolism, synaptic density, inflammation, and pathological protein aggregation are reviewed, highlighting our renewed understanding regarding the multiplicity of neurodegenerative processes involved in parkinsonian disorders. Consequently, we review the role of molecular imaging in the context of disease-modifying interventions to follow neurodegeneration, ensure stratification, and target engagement in clinical trials. Full article
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16 pages, 2560 KiB  
Review
Magnetic Resonance Planimetry in the Differential Diagnosis between Parkinson’s Disease and Progressive Supranuclear Palsy
by Andrea Quattrone, Maurizio Morelli, Maria G. Bianco, Jolanda Buonocore, Alessia Sarica, Maria Eugenia Caligiuri, Federica Aracri, Camilla Calomino, Marida De Maria, Maria Grazia Vaccaro, Vera Gramigna, Antonio Augimeri, Basilio Vescio and Aldo Quattrone
Brain Sci. 2022, 12(7), 949; https://doi.org/10.3390/brainsci12070949 - 20 Jul 2022
Cited by 6 | Viewed by 4847
Abstract
The clinical differential diagnosis between Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) is often challenging. The description of milder PSP phenotypes strongly resembling PD, such as PSP-Parkinsonism, further increased the diagnostic challenge and the need for reliable neuroimaging biomarkers to enhance the [...] Read more.
The clinical differential diagnosis between Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) is often challenging. The description of milder PSP phenotypes strongly resembling PD, such as PSP-Parkinsonism, further increased the diagnostic challenge and the need for reliable neuroimaging biomarkers to enhance the diagnostic certainty. This review aims to summarize the contribution of a relatively simple and widely available imaging technique such as MR planimetry in the differential diagnosis between PD and PSP, focusing on the recent advancements in this field. The development of accurate MR planimetric biomarkers, together with the implementation of automated algorithms, led to robust and objective measures for the differential diagnosis of PSP and PD at the individual level. Evidence from longitudinal studies also suggests a role of MR planimetry in predicting the development of the PSP clinical signs, allowing to identify PSP patients before they meet diagnostic criteria when their clinical phenotype can be indistinguishable from PD. Finally, promising evidence exists on the possible association between MR planimetric measures and the underlying pathology, with important implications for trials with new disease-modifying target therapies. Full article
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32 pages, 365 KiB  
Commentary
Sex Differences in Parkinson’s Disease: From Bench to Bedside
by Maria Claudia Russillo, Valentina Andreozzi, Roberto Erro, Marina Picillo, Marianna Amboni, Sofia Cuoco, Paolo Barone and Maria Teresa Pellecchia
Brain Sci. 2022, 12(7), 917; https://doi.org/10.3390/brainsci12070917 - 13 Jul 2022
Cited by 14 | Viewed by 2830
Abstract
Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and gender differences have been described on several aspects of PD. In the present commentary, we aimed to collect and discuss the currently available evidence on gender differences in [...] Read more.
Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and gender differences have been described on several aspects of PD. In the present commentary, we aimed to collect and discuss the currently available evidence on gender differences in PD regarding biomarkers, genetic factors, motor and non-motor symptoms, therapeutic management (including pharmacological and surgical treatment) as well as preclinical studies. Methods: A systematic literature review was performed by searching the Pubmed and Scopus databases with the search strings “biomarkers”, “deep brain stimulation”, “female”, “gender”, “genetic”, “levodopa”, “men”, “male”, “motor symptoms”, “non-motor symptoms”, “Parkinson disease”, “sex”, “surgery”, and “women”. Results: The present review confirms the existence of differences between men and women in Parkinson Disease, pointing out new information regarding evidence from animal models, genetic factors, biomarkers, clinical features and pharmacological and surgical treatment. Conclusions: The overall goal is to acquire new informations about sex and gender differences in Parkinson Disease, in order to develop tailored intervetions. Full article
18 pages, 360 KiB  
Review
Vitamin D Status and Parkinson’s Disease
by Michela Barichella, Federica Garrì, Serena Caronni, Carlotta Bolliri, Luciano Zocchi, Maria Carmela Macchione, Valentina Ferri, Daniela Calandrella and Gianni Pezzoli
Brain Sci. 2022, 12(6), 790; https://doi.org/10.3390/brainsci12060790 - 16 Jun 2022
Cited by 16 | Viewed by 3239
Abstract
Parkinson’s disease (PD) is a complex and progressive neurodegenerative disease, characterized by resting tremor, rigidity, slowness of movement, and postural instability. Furthermore, PD is associated with a wide spectrum of non-motor symptoms that add to overall disability. In recent years, some investigations, from [...] Read more.
Parkinson’s disease (PD) is a complex and progressive neurodegenerative disease, characterized by resting tremor, rigidity, slowness of movement, and postural instability. Furthermore, PD is associated with a wide spectrum of non-motor symptoms that add to overall disability. In recent years, some investigations, from basic science to clinical applications, have focused on the role of vitamin D in PD, often with controversial findings. Vitamin D has widespread effects on several biological processes in the central nervous system, including neurotransmission in dopaminergic neural circuits. Various studies have recorded lower levels of vitamin D in PD patients than in healthy controls. Low vitamin D status has also been correlated with the risk for PD and motor severity, whereas less is known about the effects vitamin D has on cognitive function and other non-motor symptoms. This review aims to better characterize the correlation between vitamin D and PD, clarify the role of vitamin D in PD prevention and treatment, and discuss avenues for future research in this field. Full article
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