Journal of Parkinson's Disease - Volume 13, issue 4

Authors: Breit, Sorin | Milosevic, Luka | Naros, Georgios | Cebi, Idil | Weiss, Daniel | Gharabaghi, Alireza

Article Type: Research Article

Abstract: Background: Axial symptoms of Parkinson’s disease (PD) can be debilitating and are often refractory to conventional therapies such as dopamine replacement therapy and deep brain stimulation (DBS) of the subthalamic nuclei (STN). Objective: Evaluate the efficacy of bilateral DBS of the pedunculopontine nucleus area (PPNa) and investigate structural and physiological correlates of clinical response. Methods: A randomized, double-blind, cross-over clinical trial was employed to evaluate the efficacy of bilateral PPNa-DBS on axial symptoms. Lead positions and neuronal activity were evaluated with respect to clinical response. Connectomic cortical activation profiles were generated based on the volumes of …tissue activated. Results: PPNa-DBS modestly improved (p  = 0.057) axial symptoms in the medication-off condition, with greatest positive effects on gait symptoms (p  = 0.027). Electrode placements towards the anterior commissure (ρ= 0.912; p  = 0.011) or foramen caecum (ρ= 0.853; p  = 0.031), near the 50% mark of the ponto-mesencephalic junction, yielded better therapeutic responses. Recording trajectories of patients with better therapeutic responses (i.e., more anterior electrode placements) had neurons with lower firing-rates (p  = 0.003) and higher burst indexes (p  = 0.007). Structural connectomic profiles implicated activation of fibers of the posterior parietal lobule which is involved in orienting behavior and locomotion. Conclusion: Bilateral PPNa-DBS influenced gait symptoms in patients with PD. Anatomical and physiological information may aid in localization of a favorable stimulation target. Show more

Keywords: Deep brain stimulation, Parkinson’s disease, pedunculopontine nucleus

DOI: 10.3233/JPD-225031

Citation: Journal of Parkinson's Disease, vol. 13, no. 4, pp. 563-573, 2023

Authors: Geraedts, Victor J. | van Vugt, Jeroen P.P. | Marinus, Johan | Kuiper, Roy | Middelkoop, Huub A.M. | Zutt, Rodi | van der Gaag, Niels A. | Hoffmann, Carel F.E. | Dorresteijn, Lucille D.A. | van Hilten, Jacobus J. | Contarino, Maria Fiorella

Article Type: Research Article

Abstract: Background: Standardized screening for subthalamic deep brain stimulation (STN DBS) in Parkinson’s disease (PD) patients is crucial to determine eligibility, but its utility to predict postoperative outcomes in eligible patients is inconclusive. It is unknown whether wearable data can contribute to this aim. Objective: To evaluate the utility of universal components incorporated in the DBS screening, complemented by a wearable sensor, to predict motor outcomes and Quality of life (QoL) one year after STN DBS surgery. Methods: Consecutive patients were included in the OPTIMIST cohort study from two DBS centers. Standardized assessments included a preoperative Levodopa …Challenge Test (LCT), and questionnaires on QoL and non-motor symptoms including cognition, psychiatric symptoms, impulsiveness, autonomic symptoms, and sleeping problems. Moreover, an ambulatory wearable sensor (Parkinson Kinetigraph (PKG)) was used. Postoperative assessments were similar and also included a Stimulation Challenge Test to determine DBS effects on motor function. Results: Eighty-three patients were included (median (interquartile range) age 63 (56–68) years, 36% female). Med-OFF (Stim-OFF) motor severity deteriorated indicating disease progression, but patients significantly improved in terms of Med-ON (Stim-ON) motor function, motor fluctuations, QoL, and most non-motor domains. Motor outcomes were not predicted by preoperative tests, including covariates of either LCT or PKG. Postoperative QoL was predicted by better preoperative QoL, lower age, and more preoperative impulsiveness scores in multivariate models. Conclusion: Data from the DBS screening including wearable data do not predict postoperative motor outcome at one year. Post-DBS QoL appears primarily driven by non-motor symptoms, rather than by motor improvement. Show more

Keywords: Deep brain stimulation, subthalamic nucleus, Parkinson’s disease, motor function, quality of life, screening

DOI: 10.3233/JPD-225101

Citation: Journal of Parkinson's Disease, vol. 13, no. 4, pp. 575-588, 2023

Authors: Mammen, Jennifer R. | Speck, Rebecca M. | Stebbins, Glenn M. | Müller, Martijn L.T.M. | Yang, Phillip T. | Campbell, Michelle | Cosman, Josh | Crawford, John E. | Dam, Tien | Hellsten, Johan | Jensen-Roberts, Stella | Kostrzebski, Melissa | Simuni, Tanya | Barowicz, Kimberly Ward | Cedarbaum, Jesse M. | Dorsey, E. Ray | Stephenson, Diane | Adams, Jamie L.

Article Type: Research Article

Abstract: Background: Adoption of new digital measures for clinical trials and practice has been hindered by lack of actionable qualitative data demonstrating relevance of these metrics to people with Parkinson’s disease. Objective: This study evaluated of relevance of WATCH-PD digital measures to monitoring meaningful symptoms and impacts of early Parkinson’s disease from the patient perspective. Methods: Participants with early Parkinson’s disease (N = 40) completed surveys and 1:1 online-interviews. Interviews combined: 1) symptom mapping to delineate meaningful symptoms/impacts of disease, 2) cognitive interviewing to assess content validity of digital measures, and 3) mapping of digital measures back to personal …symptoms to assess relevance from the patient perspective. Content analysis and descriptive techniques were used to analyze data. Results: Participants perceived mapping as deeply engaging, with 39/40 reporting improved ability to communicate important symptoms and relevance of measures. Most measures (9/10) were rated relevant by both cognitive interviewing (70–92.5%) and mapping (80–100%). Two measures related to actively bothersome symptoms for more than 80% of participants (Tremor, Shape rotation). Tasks were generally deemed relevant if they met three participant context criteria: 1) understanding what the task measured, 2) believing it targeted an important symptom of PD (past, present, or future), and 3) believing the task was a good test of that important symptom. Participants did not require that a task relate to active symptoms or “real” life to be relevant. Conclusion: Digital measures of tremor and hand dexterity were rated most relevant in early PD. Use of mapping enabled precise quantification of qualitative data for more rigorous evaluation of new measures. Show more

Keywords: Parkinson’s disease, digital health technology, qualitative, meaningfulness, patient experience data

DOI: 10.3233/JPD-225122

Citation: Journal of Parkinson's Disease, vol. 13, no. 4, pp. 589-607, 2023

Authors: Sung, Chee Boon | Danoudis, Mary | Paul, Eldho | Iansek, Robert

Article Type: Review Article

Abstract: Background: Tablet formulations of Parkinson’s disease (PD) medications may become ineffective at managing motor fluctuations in advanced PD. The liquid formulation, levodopa carbidopa ascorbic acid solution, or LCAS, is an effective and inexpensive treatment for motor fluctuations however it remains underutilized. Objective: We compared the efficacy of LCAS with tablet formulations and Duodopa jejunal infusion through routine inpatient management using hourly functional status measures, the Timed Up and Go Test (TUG). The TUG differentiates between ‘off’ and ‘on’ states and quantifies motor fluctuations. Methods: Experienced nurses used the TUG times and functional observations recorded hourly throughout …the waking day to optimize the LCAS hourly dose and the Duodopa flow rate over several days. When patients were stabilized on each of the interventions, the TUG measures were then recorded to compare the outcomes of the interventions. Results: Twenty-six participants had TUG times recorded while on one or more of the formulations: 19 had TUG times recorded on tablets, 23 on LCAS and 10 on Duodopa. TUG times on LCAS and Duodopa were significantly faster compared to tablets (p  < 0.0001, p  = 0.001 respectively). Severity of dyskinesia was not significantly different between formulations (p  = 0.35). Daily dose for the three formulations and the hourly doses for LCAS and Duodopa did not differ significantly (p  = 0.37, p  = 0.19 respectively). Conclusion: This report demonstrated the efficacy of LCAS for improving motor complications and its equivalency with Duodopa jejunal infusion. Show more

Keywords: Advanced Parkinson’s disease, Duodopa, inpatient management, liquid sinemet, motor fluctuations, Timed Up and Go test

DOI: 10.3233/JPD-225117

Citation: Journal of Parkinson's Disease, vol. 13, no. 4, pp. 609-617, 2023

Authors: Mammen, Jennifer R. | Speck, Rebecca M. | Stebbins, Glenn T. | Müller, Martijn L.T.M. | Yang, Phillip T. | Campbell, Michelle | Cosman, Josh | Crawford, John E. | Dam, Tien | Hellsten, Johan | Jensen-Roberts, Stella | Kostrzebski, Melissa | Simuni, Tanya | Barowicz, Kimberly Ward | Cedarbaum, Jesse M. | Dorsey, E. Ray | Stephenson, Diane | Adams, Jamie L.

Article Type: Research Article

Abstract: Background: Patient perspectives on meaningful symptoms and impacts in early Parkinson’s disease (PD) are lacking and are urgently needed to clarify priority areas for monitoring, management, and new therapies. Objective: To examine experiences of people with early-stage PD, systematically describe meaningful symptoms and impacts, and determine which are most bothersome or important. Methods: Forty adults with early PD who participated in a study evaluating smartwatch and smartphone digital measures (WATCH-PD study) completed online interviews with symptom mapping to hierarchically delineate symptoms and impacts of disease from “Most bothersome” to “Not present,” and to identify which of …these were viewed as most important and why. Individual symptom maps were coded for types, frequencies, and bothersomeness of symptoms and their impacts, with thematic analysis of narratives to explore perceptions. Results: The three most bothersome and important symptoms were tremor, fine motor difficulties, and slow movements. Symptoms had the greatest impact on sleep, job functioning, exercise, communication, relationships, and self-concept— commonly expressed as a sense of being limited by PD. Thematically, most bothersome symptoms were those that were personally limiting with broadest negative impact on well-being and activities. However, symptoms could be important to patients even when not present or limiting (e.g., speech, cognition). Conclusion: Meaningful symptoms of early PD can include symptoms that are present or anticipated future symptoms that are important to the individual. Systematic assessment of meaningful symptoms should aim to assess the extent to which symptoms are personally important , present , bothersome, and limiting Show more

Keywords: Parkinson’s disease, digital health technology, qualitative, meaningfulness

DOI: 10.3233/JPD-225068

Citation: Journal of Parkinson's Disease, vol. 13, no. 4, pp. 619-632, 2023

Authors: Domingos, Josefa | Teixeira Bastos, Maria do Carmo | Couto, Rui | Cameira, Ana Rita | Cardoso, Ana Leal | Reffóios, Alexandre | Magalhães, Susana | Massano, João | Outeiro, Tiago Fleming

Article Type: Article Commentary

Abstract: Patient organizations play an ever-growing role in modern societies by providing organized resources for patients and care partners. Importantly, patient organizations enable patients to define and share their needs and views. In Parkinson’s disease (PD), patient organizations play significant roles in different countries. However, there is limited support and resources tailored for people with early onset Parkinson’s disease (EOPD). These individuals face unique social, professional, and personal challenges that are often not accounted for by general PD organizations, which play very important roles for a significant proportion of individuals with PD. In Portugal, this was the situation until 2022, when …Young Parkies Portugal (YPP) was founded to allow people with EOPD and various stakeholders to join forces to cover their specific needs. In this manuscript, we aim to share our experience in building an association for people with EOPD, reflecting on the reasons for this need, the activities developed thus far, challenges in implementation, and future directions. In summary, we believe that nonprofit organizations like YPP play an essential role in shaping the care and support of people with PD care and should be considered key partners of care alongside the larger multidisciplinary team. We are confident that sharing our experience can inspire and guide the implementation of similar initiatives in other countries. Show more

Keywords: Parkinson’s disease, early-onset, neurodegeneration, parkinsonism, patient association

DOI: 10.3233/JPD-230039

Citation: Journal of Parkinson's Disease, vol. 13, no. 4, pp. 633-636, 2023

Authors: Meinders, Marjan J. | Marks Jr. , William J. | van Zundert, Sabine B.M. | Kapur, Ritu | Bloem, Bastiaan R.

Article Type: Letter

DOI: 10.3233/JPD-225015

Citation: Journal of Parkinson's Disease, vol. 13, no. 4, pp. 637-640, 2023