Journal of Parkinson's Disease - Volume 8, issue 2

Authors: Polinski, Nicole K. | Volpicelli-Daley, Laura A. | Sortwell, Caryl E. | Luk, Kelvin C. | Cremades, Nunilo | Gottler, Lindsey M. | Froula, Jessica | Duffy, Megan F. | Lee, Virginia M.Y. | Martinez, Terina N. | Dave, Kuldip D.

Article Type: Research Article

Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting approximately one-percent of the population over the age of sixty. Although many animal models have been developed to study this disease, each model presents its own advantages and caveats. A unique model has arisen to study the role of alpha-synuclein (aSyn) in the pathogenesis of PD. This model involves the conversion of recombinant monomeric aSyn protein to a fibrillar form—the aSyn pre-formed fibril (aSyn PFF)—which is then injected into the brain or introduced to the media in culture. Although many groups have successfully adopted and replicated the aSyn PFF …model, issues with generating consistent pathology have been reported by investigators. To improve the replicability of this model and diminish these issues, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has enlisted the help of field leaders who performed key experiments to establish the aSyn PFF model to provide the research community with guidelines and practical tips for improving the robustness and success of this model. Specifically, we identify key pitfalls and suggestions for avoiding these mistakes as they relate to generating the aSyn PFFs from monomeric protein, validating the formation of pathogenic aSyn PFFs, and using the aSyn PFFs in vivo or in vitro to model PD. With this additional information, adoption and use of the aSyn PFF model should present fewer challenges, resulting in a robust and widely available model of PD. Show more

Keywords: Alpha-synuclein, pre-formed fibril, Parkinson’s disease, preclinical model

DOI: 10.3233/JPD-171248

Citation: Journal of Parkinson's Disease, vol. 8, no. 2, pp. 303-322, 2018

Authors: Goubault, Etienne | Nguyen, Hung P. | Bogard, Sarah | Blanchet, Pierre J. | Bézard, Erwan | Vincent, Claude | Langlois, Mélanie | Duval, Christian

Article Type: Research Article

Abstract: Background: Clinical and anecdotal observations propose that patients with Parkinson’s disease (PD) may show drug-induced dyskinesia (DID) concomitantly with cardinal motor features. However, the extent of the concomitant presence of DID and cardinal features remains to be determined. Objectives: This cross-sectional study measured peak-dose choreic-type DID in a quantitative manner in patients diagnosed with PD, and determined whether symptoms such as tremor, bradykinesia, rigidity, postural instability or freezing of gait (FoG) were still detectable in these patients. Methods: 89 patients diagnosed with PD were recruited and assessed using a combination of quantitative measures using inertial measurement …units to capture DID, tremor, bradykinesia, and FoG. Clinical evaluations were also used to assess rigidity and postural instability. Motor symptoms of PD were assessed 3 times during the testing period, and a series of activities of daily living were repeated twice, in between clinical tests, during which the level of DID was quantified. Peak-dose was identified as the period during which patients had the highest levels of DID. Levels of tremor, rigidity, bradykinesia, postural instability, and FoG were used to determine the percentage of patients showing these motor symptoms simultaneously with DID. Results: 72.4% of patients tested presented with measurable DID during the experiment. Rest, postural and kinetic tremor (12.7% , 38.1% , and 15.9% respectively), bradykinesia (28.6% ), rigidity (55.6% ), postural instability (71.4% ) and FoG (9.5% ) were detected simultaneously with DID. Conclusions: PD symptomatology remains present in patients showing peak-dose choreic-type DID, illustrating the challenge facing physicians when trying to avoid dyskinesia while attempting to alleviate motor symptoms. Show more

Keywords: Chorea, drug-induced, dyskinesia, hypokinesia, movement disorders, Parkinson disease, tremor

DOI: 10.3233/JPD-181312

Citation: Journal of Parkinson's Disease, vol. 8, no. 2, pp. 323-331, 2018

Authors: Zhou, Hai-Yan | Huang, Pei | Sun, Qian | Du, Juan-Juan | Cui, Shi-Shuang | Tan, Yu-Yan | Hu, Yun-Yun | Zhan, Wei-Wei | Wang, Ying | Xiao, Qin | Liu, Jun | Chen, Sheng-Di

Article Type: Research Article

Abstract: Background: It is debatable whether transcranial sonography (TCS) could be a biomarker for monitoring disease progression. Various phenotypes of Parkinson’s disease (PD) may be a major reason contributing to the inconsistency. Objective: We classified PD patients into different subtypes and evaluated the correlation between SN echogenicity and disease progression. Methods: A total of 411 PD patients were included in this study. TCS evaluations of the substantia nigra (SN) were performed, and motor and non-motor symptoms were assessed by a series of rating scales in all PD patients. Results: Three hundred and thirteen patients had …appropriate temporal acoustic bone windows, and they were divided into three subgroups according to disease onset age. SN hyperechogenicity (SN+) was found to be associated with age, gender, disease duration, H-Y stage and UPDRS-II scores in 220 middle-age onset patients. Regression analysis identified both disease duration and gender as independent predictors for SN+. When this distinct group was separated into male and female subgroups, the correlation between larger SN echogenicity (SNL ) and disease duration was positive in males rather than females. When these middle-age onset male patients were classified as tremor dominant (TD) and non-TD subtypes, it turned out that correlation between disease duration and SNL only existed in male non-TD PD patients. Conclusions: Our study demonstrated correlation between the size of SN echogenicity and disease duration in Chinese patients with PD who were male non-TD subtypes with middle-age onset, suggesting the formation of SN echogenicity might be a dynamic process following disease progression in this distinct subtype. Show more

Keywords: Clinical subtype, disease severity, Parkinson’s disease, substantia nigra, transcranial sonography

DOI: 10.3233/JPD-171264

Citation: Journal of Parkinson's Disease, vol. 8, no. 2, pp. 333-340, 2018

Authors: Balconi, Michela | Siri, Chiara | Meucci, Nicoletta | Pezzoli, Gianni | Angioletti, Laura

Article Type: Research Article

Abstract: Background: Pathological gambling (PG) in Parkinson’s disease (PD) manifests as a persistent and uncontrollable gambling behavior, characterized by dysfunctional decision-making and emotional impairment related to high-risk decisions. Objective: The aim of this study was to explore the relationship between personality traits and prefrontal cortex activity in PD patients with or without PG. Methods: Thus, hemodynamic cortical activity measured by functional near-infrared spectroscopy (fNIRS) and Iowa Gambling Task (IGT) performance were recorded in forty-six PD patients, divided into three groups according to their gambling status: PD patients with active gambling behavior (PDG); PD patients who remitted from …PG (PDNG); and a control group (CG) composed by patients with PD only. Results: Results indicates that gambling behavior in PD patients is strongly predictive of dysfunctional cognitive strategy; affecting anomalous cortical response with a left hemispheric unbalance in dorsal areas; and it is related to more reward sensitivity than impulsivity personality components. Conclusions: PDG patients differed from PDNG and CG from both behavioral and brain response to decision-making. Overall, these effects confirm a pathological condition related to cognitive and emotional aspects which makes the patients with PGD victims of their dysfunctional behavior. Show more

Keywords: Gambling behavior, Parkinson’s disease, fNIRS, impulsivity, reward sensitivity, IGT

DOI: 10.3233/JPD-171290

Citation: Journal of Parkinson's Disease, vol. 8, no. 2, pp. 341-352, 2018

Authors: Keener, Adrienne M. | Paul, Kimberly C. | Folle, Aline | Bronstein, Jeff M. | Ritz, Beate

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is a heterogeneous disorder with variability in phenotype and progression. Objective: We describe characteristics of PD patients in the largest population-based cohort followed for progression to date, and evaluate clinical risk factors for cognitive impairment and mortality. Methods: We collected longitudinal data using the Unified Parkinson’s Disease Rating Scale (UPDRS), Mini-Mental State Exam (MMSE), and Geriatric Depression Scale (GDS) in 242 new-onset PD patients followed for progression. We compared those who developed cognitive impairment (MMSE≤24) with those who did not, using t -tests, chi-square tests, and Cox proportional hazards regression. Mortality risk …factors were assessed in all 360 patients enrolled at baseline. Results: Thirty-four patients developed cognitive impairment during follow-up. Baseline characteristics predictive of faster time to cognitive impairment were older age at diagnosis, fewer years of education, and longer average sleep duration reported. The 197 patients who died were older at diagnosis, reported longer average sleep duration, had lower baseline MMSE scores, higher UPDRS-III scores, and a higher proportion were of the postural instability gait difficulty (PIGD) subtype. Patients with the tremor dominant (TD) subtype at baseline were less likely to develop cognitive impairment or die during follow-up. Progression of cognitive, depressive, and motor symptoms occurred in parallel. Conclusions: Motor symptom severity and subtype influence the incidence of cognitive impairment and mortality in PD, with the TD motor subtype being relatively protective. In addition, we newly found that longer average sleep duration at baseline predicts faster progression to cognitive impairment and mortality. Show more

Keywords: Parkinson’s disease, disease progression, cognition, mortality, sleep

DOI: 10.3233/JPD-171257

Citation: Journal of Parkinson's Disease, vol. 8, no. 2, pp. 353-362, 2018

Authors: van Dijsseldonk, Karlijn | Wang, Ying | van Wezel, Richard | Bloem, Bastiaan R. | Nonnekes, Jorik

Article Type: Letter

Keywords: Freezing of gait, Parkinson’s disease, gait, clinical assessment

DOI: 10.3233/JPD-181332

Citation: Journal of Parkinson's Disease, vol. 8, no. 2, pp. 363-365, 2018