Journal of Parkinson's Disease - Volume 10, issue 4

Authors: Huang, Xuemei | Lewis, Mechelle M. | Van Scoy, Lauren Jodi | De Jesus, Sol | Eslinger, Paul J. | Arnold, Amy C. | Miller, Amanda J. | Fernandez-Mendoza, Julio | Snyder, Bethany | Harrington, William | Kong, Lan | Wang, Xi | Sun, Dongxiao | Delnomdedieu, Marielle | Duvvuri, Sridhar | Mahoney, Susan E. | Gray, David L. | Mailman, Richard B.

Article Type: Research Article

Abstract: Background: Current drug treatments have little efficacy in advanced-to-end-stage Parkinson’s disease (advPD), yet there are no reports of interventional trials in advPD. D1 dopamine agonists have the potential to provide benefit. Objective: To determine the feasibility and safety of the selective D1 /D5 dopamine partial agonist PF 06412562 in advPD. Methods: A two-week, randomized, double blind, crossover phase Ib study in advPD patients compared standard-of-care (SoC) carbidopa/levodopa with PF 06412562. Each week, there was a Day 1 baseline evaluation with overnight levodopa washout, then treatment on Days 2 and 3 with either SoC or …PF-06412562 (split dose 25 + 20 mg), followed by discharge on Day 4. Primary endpoints were safety and tolerability. Secondary endpoints were global clinical impression of change (GCI-C) rated by clinicians and caregivers. Results: Eight advPD patients and their caregivers consented to participate and six were randomized (average disease duration: 22 y). None withdrew voluntarily. One participant with baseline Day 1 dehydration, pre-renal kidney injury, and autonomic dysfunction experienced symptomatic and serious hypotension after receiving PF-06412562 in Week 1 and was discontinued from the study. All other adverse events were rated mild (PF-06412562: n  = 1, SoC: n  = 0), moderate (PF-06412562: n  = 1, SoC: n  = 1), or severe but non-serious (PF-06412562: n  = 3, SoC: n  = 2). No clinically meaningful laboratory changes were observed. Among the five participants who completed the study, GCI-C favored PF-06412562 in two per clinicians’ and four participants per caregivers’ rating. Conclusion: PF-06412562 was tolerated in advPD patients. This study provides the feasibility for future safety and efficacy studies in this population with unmet needs. Show more

Keywords: D1 dopamine receptor, dopamine D1 agonists, advanced Parkinson’s disease, levodopa, safety, feasibilityTrial Registration#: ClinicalTrials.gov:NCT03665454

DOI: 10.3233/JPD-202188

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1515-1527, 2020

Authors: Nyholm, Dag | Adnan, Malak | Senek, Marina

Article Type: Research Article

Abstract: Background: Levodopa/carbidopa intestinal gel (LCIG) infusion is an efficacious treatment of motor and non-motor fluctuations in people with Parkinson’s disease (PD). Real-life use of the treatment is not previously studied. Objective: The aims of the study were to explore the use of LCIG and to determine how extra doses of LCIG are used in daily life. Methods: Twenty-five PD patients with ongoing LCIG therapy were consecutively included. Pump data was retrieved from 30 days on average, by means of software, extracting the most recent pump events. Results: The daily duration of infusion was 15 …hours on average, in 18 patients, whereas the remaining 7 patients used 24-hour infusion. Morning doses ranged from 38–190 mg levodopa, for patients who utilized this function. Median number of daily extra doses was 2.5 (range: 0–10.6) and median size of the extra dose was 24 mg (0–80 mg) levodopa. Median total daily levodopa intake with LCIG was 1201 mg (range: 417–2322 mg). Conclusion: Retrieving pump data is possible and may be important for evaluating the at-home use of LCIG, to optimize the therapy. Adherence to treatment should be monitored, which is not technically difficult, at least in device-aided treatments for PD. Show more

Keywords: Levodopa, carbidopa intestinal gel, infusion pump, Parkinson’s disease, medication adherence

DOI: 10.3233/JPD-202114

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1529-1534, 2020

Authors: Leta, Valentina | van Wamelen, Daniel J. | Sauerbier, Anna | Jones, Shelley | Parry, Miriam | Rizos, Alexandra | Chaudhuri, K. Ray

Article Type: Short Communication

Abstract: Combined catechol-O -methyl-transferase-inhibition and Levodopa-Carbidopa intestinal gel (LCIG) infusion has the potential to reduce LCIG daily dose and the costs of this therapy. In this retrospective analysis, we report on Parkinson’s disease (PD) patients on LCIG with concomitant Opicapone. In 11 patients, the introduction of Opicapone led to LCIG daily dose being reduced by 24.8% (p  = 0.05) without any significant worsening of dyskinesia. Three patients withdrew from Opicapone due to side effects or inefficacy. LCIG daily dose reduction could lead to cost savings of £142,820.63/year in the United Kingdom while maintaining clinical care.

Keywords: Levodopa-Carbidopa intestinal gel, intrajejunal Levodopa infusion, Catechol-O-methyl-transferase-inhibitor, Opicapone, cost savings

DOI: 10.3233/JPD-202022

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1535-1539, 2020

Authors: Chung, Seok Jong | Lee, Sangwon | Yoo, Han Soo | Lee, Yang Hyun | Lee, Hye Sun | Choi, Yonghoon | Lee, Phil Hyu | Yun, Mijin | Sohn, Young H.

Article Type: Research Article

Abstract: Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18 F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n  = 91) and severe NMS burden groups …(PDNMS-severe) (NMSQuest score >9; n  = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD. Show more

Keywords: Dopamine transporter, non-motor, Parkinson’s disease, subtype

DOI: 10.3233/JPD-202127

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1541-1549, 2020

Authors: Nance, Martha A. | Boettcher, Lesa | Edinger, Germaine | Gardner, Joan | Kitzmann, Ron | Erickson, Lauren O. | Wichmann, Rose | Wielinski, Catherine L.

Article Type: Research Article

Abstract: Background: Patients hospitalized with Parkinson’s disease (PD) require timely delivery of carbidopa-levodopa (C/L) medication. Ill-timed administration of C/L doses is associated with greater morbidity and longer lengths of stay. Objective: To understand the barriers to timely C/L administration, and implement strategies to improve the administration of the drug to hospitalized PD patients. Methods: Several key strategies were employed in 2015 to improve the timely delivery of C/L doses: 1. three kinds of nursing alert in the electronic medical record (EMR); 2. staff in-service education; 3. stocking immediate-release C/L into automated medication dispensing machines on key hospital …units; 4. reports to nurse unit managers on timeliness of C/L administration; and 5. reconciliation of inpatient and outpatient levodopa orders by the hospital pharmacist upon admission. The primary outcome was the percent of C/L doses administered within 60, 30, and 15 minutes of scheduled time. Results: Our urban hospital, affiliated with a Parkinson’s Foundation Center of Excellence, had 5,939 C/L administrations in 2018. There was sustained improvement in timely delivery of doses, from 89.3% in 2012 to 96.5% in 2018 (within 60 minutes of the scheduled time), 65.5% to 86.4% (30 minutes), and 42.3% to 71.1% (15 minutes) (all p  < 0.001). Conclusions: With multifaceted but relatively simple measures, we were able to “change the culture” so that hospitalized patients with Parkinson’s disease receive levodopa on time. Show more

Keywords: Parkinson’s disease, levodopa, quality improvement, nursing care, hospital

DOI: 10.3233/JPD-202024

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1551-1559, 2020

Authors: Suwijn, Sven R. | Samim, Hamdia | Eggers, Carsten | Espay, Alberto J. | Fox, Susan | Lang, Anthony E. | Samuel, Mike | Silverdale, Monty | Verschuur, Constant V.M. | Dijk, Joke M. | Verberne, Hein J. | Booij, Jan | de Bie, Rob M. A.

Article Type: Research Article

Abstract: Background: In clinical trials that recruited patients with early Parkinson’s disease (PD), 4–15% of the participants with a clinical diagnosis of PD had normal dopamine transporter single photon emission computed tomography (DAT SPECT) scans, also called “scans without evidence of dopaminergic deficit” (SWEDD). Objective: To investigate in patients with a clinical diagnosis of PD, if specific clinical features are useful to distinguish patients with nigrostriatal degeneration from those that have no nigrostriatal degeneration. Methods: We performed a diagnostic test accuracy study. Patients that participated in the Levodopa in Early Parkinson’s disease trial, a clinical trial in …patients with early PD, were asked to participate if they had not undergone DAT SPECT imaging earlier. The index tests were specific clinical features that were videotaped. A panel of six neurologists in training (NT), six general neurologists (GN), and six movement disorders experts (MDE) received a batch of ten videos consisting of all SWEDD subjects and a random sample of patients with abnormal DAT SPECT scans. The raters analyzed the videos for presence of specific signs and if they suspected the patient to have SWEDD. The reference test was visually assessed DAT SPECT imaging. Results: Of a total of 87 participants, three subjects were SWEDDs (3.4%). The overall intraclass correlation coefficient (ICC) of the Parkinsonian signs was poor to moderate with ICCs ranging from 0.14 to 0.67. NT correctly identified 50.0% of the SWEDD subjects, GN 33.3%, and MDE 66.7%. Conclusion: Our study suggests that the selected videotaped clinical features cannot reliably distinguish patients with a clinical diagnosis of PD and an abnormal DAT SPECT from patients with clinical PD and a SWEDD. Show more

Keywords: DAT SPECT, diagnostic accuracy, clinical features, Parkinson’s disease, SWEDD, neurodegeneration, inter-rater agreement

DOI: 10.3233/JPD-202090

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1561-1569, 2020

Authors: Hasimoglu, Yasemin G. | Chen, Xiqun | Bakshi, Rachit | Schwarzschild, Michael A. | Macklin, Eric A.

Article Type: Short Communication

Abstract: Higher serum urate concentration is associated with decreased risk of Parkinson’s disease (PD) as well as slower disease progression, but its relationship with severity of PD remains unclear. This study investigated whether changes in serum urate concentration over 5 years were associated with disease progression assessed by MDS-UPDRS Part III score, Hoehn and Yahr stage, or DaTscan imaging. Average serum urate concentration was stable over time and change in serum urate concentration did not correlate with worsening of measures of PD progression. These results suggest that serum urate concentration is not a monitoring biomarker of PD progression in early stages.

Keywords: Parkinson’s disease, urate, disease progression, longitudinal study

DOI: 10.3233/JPD-202064

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1571-1576, 2020

Authors: Fullard, Michelle | Thibault, Dylan | Zisling, Hanan | Crispo, James A. | Willis, Allison

Article Type: Research Article

Abstract: Background: Advances in the treatment of Parkinson’s disease (PD) have allowed for improvements in mortality and quality survival, making the management of comorbid conditions of aging, such as osteoarthritis, crucial. Objective: To determine the extent to which PD impacts hospitalization outcomes after an elective orthopedic procedure. Methods: This retrospective cohort study used data from the National Readmissions Database and included adults ages 40 and above with and without PD. Primary outcomes included length of stay of the index admission, discharge disposition and 30-day readmission. Logistic regression was used to compare the odds of readmission for PD …patients compared to non-PD. Clinical conditions associated with readmission were compared between the two groups. Results: A total of 4,781 subjects with PD and 947,475 subjects without PD met inclusion criteria. Length of stay (LOS) during the index admission was longer for PD patients. PD patients were much more likely to be discharged to inpatient post-acute care (49.3% vs 26.2%) while non-PD subjects were more likely to be discharged home with (31.9% [PD] vs 44.8% [non-PD]) or without home health (18.7% [PD] vs 28.9% [non-PD]). A total of 271 PD patients (5.66%) and 28,079 non-PD patients (2.96%) were readmitted within 30 days following surgery. After adjusting for age, sex, socioeconomic status, expected payer, comorbidities, index admission LOS, year and discharge disposition, PD subjects were 31% more likely to be readmitted than non-PD subjects (AOR 1.31, 1.07–1.62). Conclusions: Parkinson’s disease patients were readmitted more often than non-PD patients, although the rate of readmission was still low. Show more

Keywords: Parkinson’s disease, cohort studies, arthroplasty, knee replacement, hip replacement

DOI: 10.3233/JPD-201992

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1577-1586, 2020

Authors: Tremblay, Cécilia | Iravani, Behzad | Aubry Lafontaine, Émilie | Steffener, Jason | Fischmeister, Florian Ph.S | Lundström, Johan N. | Frasnelli, Johannes

Article Type: Research Article

Abstract: Background: Olfactory dysfunction (OD) is a frequent symptom of Parkinson’s disease (PD) that appears years prior to diagnosis. Previous studies suggest that PD-related OD is different from non-parkinsonian forms of olfactory dysfunction (NPOD) as PD patients maintain trigeminal sensitivity as opposed to patients with NPOD who typically exhibit reduced trigeminal sensitivity. We hypothesize the presence of a specific alteration of functional connectivity between trigeminal and olfactory processing areas in PD. Objective: We aimed to assess potential differences in functional connectivity within the chemosensory network in 15 PD patients and compared them to 15 NPOD patients, and to 15 …controls. Methods: Functional MRI scanning session included resting-state and task-related scans where participants carried out an olfactory and a trigeminal task. We compared functional connectivity, using a seed-based correlation approach, and brain network modularity of the chemosensory network. Results: PD patients had impaired functional connectivity within the chemosensory network while no such changes were observed for NPOD patients. No group differences we found in modularity of the identified networks. Both patient groups exhibited impaired connectivity when executing an olfactory task, while network modularity was significantly weaker for PD patients than both other groups. When performing a trigeminal task, no changes were found for PD patients, but NPOD patients exhibited impaired connectivity. Conversely, PD patients exhibited a significantly higher network modularity than both other groups. Conclusion: In summary, the specific pattern of functional connectivity and chemosensory network recruitment in PD-related OD may explain distinct behavioral chemosensory features in PD when compared to NPOD patients and healthy controls. Show more

Keywords: Parkinson’s disease, olfactory dysfunction, trigeminal system, functional connectivity, fMRI, resting-state

DOI: 10.3233/JPD-202062

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1587-1600, 2020

Authors: Roper, Jaimie A. | Schmitt, Abigail C. | Gao, Hanzhi | He, Ying | Wu, Samuel | Schmidt, Peter | Okun, Michael S. | Hass, Chris J. | Cubillos, Fernando | on behalf of the Parkinson’s Foundation Quality Improvement Initiative Investigators

Article Type: Research Article

Abstract: Background: The impact of concurrent osteoarthritis on mobility and mortality in individuals with Parkinson’s disease is unknown. Objective: We sought to understand to what extent osteoarthritis severity influenced mobility across time and how osteoarthritis severity could affect mortality in individuals with Parkinson’s disease. Methods: In a retrospective observational longitudinal study, data from the Parkinson’s Foundation Quality Improvement Initiative was analyzed. We included 2,274 persons with Parkinson’s disease. The main outcomes were the effects of osteoarthritis severity on functional mobility and mortality. The Timed Up and Go test measured functional mobility performance. Mortality was measured as the …osteoarthritis group effect on survival time in years. Results: More individuals with symptomatic osteoarthritis reported at least monthly falls compared to the other groups (14.5% vs. 7.2% without reported osteoarthritis and 8.4% asymptomatic/minimal osteoarthritis, p  = 0.0004). The symptomatic group contained significantly more individuals with low functional mobility (TUG≥12 seconds) at baseline (51.5% vs. 29.0% and 36.1%, p  < 0.0001). The odds of having low functional mobility for individuals with symptomatic osteoarthritis was 1.63 times compared to those without reported osteoarthritis (p  < 0.0004); and was 1.57 times compared to those with asymptomatic/minimal osteoarthritis (p  = 0.0026) after controlling pre-specified covariates. Similar results hold at the time of follow-up while changes in functional mobility were not significant across groups, suggesting that osteoarthritis likely does not accelerate the changes in functional mobility across time. Coexisting symptomatic osteoarthritis and Parkinson’s disease seem to additively increase the risk of mortality (p  = 0.007). Conclusion: Our results highlight the impact and potential additive effects of symptomatic osteoarthritis in persons with Parkinson’s disease. Show more

Keywords: Comorbidity, Parkinson’s disease, arthritis, mobility, mortality

DOI: 10.3233/JPD-202170

Citation: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1601-1610, 2020