Clinical Parkinsonism Related Disorders最新文献

Obesity and the development of Parkinson’s disease within the Framingham Heart study cohort 弗雷明汉心脏研究队列中的肥胖和帕金森病的发展。

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2024.100291

Sarah O’Shea , Yuilin Liu , Chunyu Liu , Samuel A. Frank , Ludy C. Shih , Rhoda Au

Objective

To determine the role of obesity in the development of Parkinson’s disease (PD).

Background

Obesity has been reported to be both a risk factor for PD, as well as potentially protective. The Framingham Heart Study (FHS) is a multigenerational longitudinal cohort study that was started in 1948, which is well-known for its cardiovascular health studies. In this study, we utilized the extensive cardiovascular and neurological data to determine if obesity contributes to the risk of the development of PD.

Methods

Participants in the FHS Original and Offspring cohorts were included in this study. Controls were selected based on sex and age at baseline examination, 1:10. Cox proportional hazard regression models were used, adjusting for age and sex. PD case status was determined utilizing prior medical and neurological examination data, Framingham Heart Study examinations, and self-report data by a panel of movement disorders neurologists using the UK Brain Bank Criteria (UKBB) and other supporting clinical details after being flagged for review by FHS neurologists. We used p < 0.05 for significance.

Results

Accounting for missing covariate data, this study included 117 participants with PD, with 1170 controls. We found that higher BMI was associated with lower PD risk, with participants with BMI 25 kg/m2 to 30 kg/m2 having HR of 0.66 (CI 0.44–0.98; p = 0.04) and BMI >= 30 kg/m2 having HR 0.47 (CI 0.27–0.84; p = 0.01). When the overweight and obese BMI groups were combined, we noted a more robust association, with combined HR of 0.67 (0.41–0.86; p = 0.01).

Conclusions

Obesity during mid-life potentially reduces the risk of developing PD; however, additional studies are needed to further explore this association.

目的：探讨肥胖在帕金森病（PD）发展中的作用。背景：据报道，肥胖既是帕金森病的危险因素，也是潜在的保护因素。弗雷明汉心脏研究（FHS）是一项多代纵向队列研究，始于1948年，以其心血管健康研究而闻名。在这项研究中，我们利用广泛的心血管和神经学数据来确定肥胖是否会增加PD的发病风险。方法：本研究纳入了FHS原始和后代队列的参与者。对照根据基线检查时的性别和年龄选择，1:10。采用Cox比例风险回归模型，对年龄和性别进行调整。PD病例的状态是根据先前的医学和神经学检查数据、弗雷明汉心脏研究检查和运动障碍神经科医生使用英国脑库标准（UKBB）和其他支持性临床细节的自我报告数据确定的，这些数据由FHS神经科医生进行标记审查。考虑到协变量数据的缺失，本研究包括117名PD患者和1170名对照。我们发现较高的BMI与较低的PD风险相关，BMI为25 kg/m2至30 kg/m2的参与者的风险比为0.66 (CI 0.44-0.98；p = 0.04), BMI >= 30 kg/m2的危险度为0.47 (CI 0.27-0.84；p = 0.01)。当超重和肥胖BMI组合并时，我们注意到一个更强的关联，合并HR为0.67 (0.41-0.86；p = 0.01)。结论：中年肥胖可降低患帕金森病的风险；然而，需要进一步的研究来进一步探讨这种联系。

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引用次数: 0

The role of intraoperative monitoring in target selection in deep brain stimulation: A single centre study

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100299

Sandro Ibrulj , Dejan Georgiev , Žiga Samsa , Polona Mušič , Mitja Benedičič , Maja Trošt

Introduction

Intraoperative microelectrode recording (MER) and intraoperative test stimulation may provide vital information for optimal electrode placement and clinical outcome in movement disorders patients treated with deep brain stimulation (DBS). The aims of this retrospective study were to determine (i) how often the planned (imaging based) placements of electrodes were changed due to MER and intraoperative test stimulation in Parkinson’s disease (PD), dystonia and essential tremor (ET) patients; (ii) whether the frequency of repositioning changed over time; (iii) whether patients’ age or disease duration (in PD) influenced the frequency of repositioning.

Methods

Data on the planned and the final placement of 141 electrodes in 72 consecutive DBS treated patients (52 PD, 11 dystonia, 9 ET) was collected over the first 8 years of DBS implementation in a single center. An association between the rate of electrode repositioning and the patients’ age, disease duration and the time/year of implementation was explored.

Results

Analysis of all targets showed a change in final electrode placement in 39.7 % (56/141); 39.8 % (41/103) in PD, 40.9 % (9/22) in dystonia and 37.5 % (6/16) in ET. Annual analysis showed a decrease in rate of repositioning between the centre’s first and eighth year (p = 0.013) of implementation. No correlation was found between electrode repositioning rate and patient age (p = 0.42) nor disease duration (p = 0.09) in PD.

Conclusion

This retrospective analysis confirms the benefit of MER and intraoperative test stimulation during DBS surgery in determining the final electrode position during the early / initial period of implementing the procedure. Our findings show a learning curve in successful preoperative planning in our centre achieved through experience.

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引用次数: 0

Minimal important changes of HFS-30 and HFS-7 questionnaires for patients with hemifacial spasm

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2024.100295

Weerawat Saengphatrachai, Nutchara Inthapong, Yuvadee Pitakpatapee, Natthapon Rattanathamsakul, Prachaya Srivanitchapoom

Introduction

Hemifacial spasm (HFS) significantly reduces health-related quality of life (HRQoL). Currently, the HFS-30 and HFS-7 questionnaires are used to evaluate the HRQoL in HFS patients; however, their minimal important changes (MICs) have not yet to be established. This study aimed to determine the MICs for HFS-30 and HFS-7 and patients’ characteristics associated with them.

Methods

Data were prospectively collected from HFS patients aged ≥18 years at a botulinum toxin clinic in a single tertiary university hospital between April 2022 and April 2023. We assessed HFS-30 and HFS-7 scores, Samsung Medical Center (SMC) grades, Patient Health Questionnaire-9 (PHQ-9) scores, and patient-reported HRQoL global rating of change scores at baseline, followed by assessments every two days for two weeks and at the one-month follow-up. MICs were determined based on the first follow-up visit when patients reported minimal improvement.

Results

The 112 enrolled patients had a median age of 62.8 years (IQR: 56.6–69.3) and a median disease duration of 10 years (IQR: 4–17). The MICs of the HFS-30 and HFS-7 questionnaires were −4.55 points (95 % CI: −5.49 to −3.62) and −0.96 points (95 % CI: −1.28 to −0.64), respectively. Patients with moderate-to-severe depression reported significantly greater MICs than those with milder depression (p < 0.001). Patients aged less than 60 had significantly greater MICs than older patients (p = 0.045).

Conclusions

The MICs of the HFS-30 and HFS-7 questionnaires were −4.55 and −0.96, respectively. The MIC is substantially greater in HFS patients with moderate-to-severe depression and younger age.

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引用次数: 0

Assessment of social isolation and changes in Parkinson’s disease symptoms during the COVID-19 pandemic: A longitudinal study COVID-19大流行期间社会隔离和帕金森病症状变化的评估：一项纵向研究

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2024.100293

Anish Mehta , Samuel Y.E. Ng , Shermyn X.M. Neo , Nicole S.Y. Chia , Ehsan S. Saffari , Thyagarajan Shivashanmugam , Xinyi Choi , Dede L. Heng , Z.Y. Xu , K.Y. Tay , W.L. Au , E.K. Tan , Louis C.S. Tan

Background

COVID-19-related social restrictions provided an opportunity to evaluate the impact of social isolation on Parkinson’s disease.

Objective

This study aimed to explore changes in social isolation and their associations with PD symptoms using the Lubben Social Network Scale-Revised (LSNS-R).

Methods

Data from 80 participants of the Early Parkinson’s Disease Longitudinal Singapore cohort were collected from April 2019 to April 2023, covering the periods before and after the imposition of COVID-19 restrictions. Individuals with LSNS-R scores ≤ 24 were considered socially isolated. Data were stratified into strata 1 (improved LSNS-R scores) and strata 2 (worsened/unchanged scores). Linear regression was used to identify predictors of LSNS-R change, and MANCOVA was used to examine associations between LSNS-R change and motor/ non-motor symptoms.

Results

Mean LSNS-R scores decreased (p = 0.014), and proportions of social isolation increased (p < 0. 001) during COVID-19 restrictions. However, 35 % showed improved LSNS-R scores, while 65 % had worsened/unchanged scores. The regression model was significant in strata 1 (R2 = 0.806, p = 0.001), with age, marital status, and social isolation status being significantly associated with change in LSNS-R scores. LSNS-R. Results of MANCOVA indicated that LSNS-R improvements in LSNS-R were significantly associated with outcomes (Roy’s Largest Root statistic = 126.638, p < 0.001), particularly for changes in PDQ8, HADS-Anxiety, and HADS-Depression scores. The regression model was not significant in strata 2 (R2 = 0. 279, p = 0.206), wherein motor and non-motor symptoms worsened.

Conclusion

While worsening LSNS-R scores were associated with poorer outcomes, improvements in social networks were associated with improved non-motor symptoms and quality of life. These findings underscore the complexity of social isolation in PD and the need for targeted interventions.

背景：与covid -19相关的社会限制为评估社会隔离对帕金森病的影响提供了机会。目的：本研究旨在利用Lubben社会网络量表（LSNS-R）探讨社会隔离的变化及其与PD症状的关系。方法：从2019年4月至2023年4月收集了80名早期帕金森病新加坡纵向队列参与者的数据，涵盖了COVID-19限制实施前后的时期。LSNS-R评分≤24的个体被认为是社会孤立的。将数据分为第1层（改善的LSNS-R评分）和第2层（恶化/不变的评分）。使用线性回归来确定LSNS-R变化的预测因子，并使用MANCOVA来检查LSNS-R变化与运动/非运动症状之间的关联。结果：平均LSNS-R评分下降（p = 0.014），社会隔离比例增加(p)。结论：LSNS-R评分恶化与预后较差相关，而社会网络的改善与非运动症状和生活质量的改善相关。这些发现强调了PD中社会隔离的复杂性和有针对性干预的必要性。

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引用次数: 0

Hospital utilization and telemedicine preferences in patients with late-stage Parkinson’s disease and caregivers

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2024.100296

Seo Hyun Hong , Seoyeon Kim , Seungmin Lee , Bora Jin , Jung Hwan Shin , Kyung Ah Woo , Han-Joon Kim

Background

There remains a significant gap in systematic research on healthcare utilization behaviors and the influencing factors for patients with Parkinson’s disease (PD), particularly those in late stages.

Methods

PD patients in late stage (Hoehn and Yahr (HY) stages 4 and 5) and their caregivers from Seoul National University Hospital Movement Disorders Clinic participated. A total of 103 respondents completed a questionnaire covering medical utilization behaviors, perceptions of face-to-face and telemedicine consultations, and additional medical service needs. Descriptive analysis was conducted based on HY stage, age, and travel time to the hospital.

Results

82.1% of patients in HY4 make more than 50% of in-person visits by themselves or with caregivers, compared with only 38.9% of patients in HY5. Despite proxy visits by caregivers were common, audiovisual or written materials about the patient’s condition were underused (63% answered ‘never’). Over three-quarters of patients did not receive rehabilitation therapy, mainly due to mobility issues and the lack of nearby facilities. One third of respondents were open to telemedicine, with differing preferences between age groups. 22% of HY5 patients or their caregivers were willing to pay more for telemedicine than in-person visit.

Conclusion

This study seeks to understand hospital use patterns and needs in late-stage PD patients and their caregivers. Current treatment framework for PD has areas that, if improved, could significantly enhance the quality of care. Telemedicine offers an opportunity to enhance PD education and assessment, introducing new methods for remotely measuring symptoms.

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引用次数: 0

Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesions

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100297

Nicola Rifino , Silvia Baratta , Esteban Zacarias , Isabella Canavero , Benedetta Storti , Mario Stanziano , Emanuela Maderna , Gianluca Marucci , Franco Taroni , Anna Bersano

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary small vessel disease caused by mutations in the NOTCH3 gene, characterized by recurrent strokes, cognitive decline, and psychiatric symptoms. This report presents a novel NOTCH3 c.1564 T > A (p.Cys522Ser) mutation associated with early-onset parkinsonism and significant white matter lesions. We describe a patient who presented with early-onset parkinsonism, characterized by bradykinesia and rigidity, alongside extensive white matter lesions observed through neuroimaging. Genetic testing revealed a novel c.1564 T > A (p.Cys522Ser) mutation in the NOTCH3 gene, contributing to the clinical diagnosis of CADASIL. This case underscores the phenotypic variability of CADASIL and the potential for atypical presentations, including parkinsonism. Early identification of genetic mutations can facilitate appropriate management and counseling for affected individuals and their families. Further research is warranted to explore the mechanisms underlying the association between NOTCH3 mutations and parkinsonism. Our findings contribute to the understanding of CADASIL, suggesting that clinicians should consider CADASIL in differential diagnoses of early-onset parkinsonism, especially in patients with concurrent white matter lesions.

{"title":"Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesions","authors":"Nicola Rifino , Silvia Baratta , Esteban Zacarias , Isabella Canavero , Benedetta Storti , Mario Stanziano , Emanuela Maderna , Gianluca Marucci , Franco Taroni , Anna Bersano","doi":"10.1016/j.prdoa.2025.100297","DOIUrl":"10.1016/j.prdoa.2025.100297","url":null,"abstract":"<div><div>CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary small vessel disease caused by mutations in the NOTCH3 gene, characterized by recurrent strokes, cognitive decline, and psychiatric symptoms. This report presents a novel NOTCH3 c.1564 T > A (p.Cys522Ser) mutation associated with early-onset parkinsonism and significant white matter lesions. We describe a patient who presented with early-onset parkinsonism, characterized by bradykinesia and rigidity, alongside extensive white matter lesions observed through neuroimaging. Genetic testing revealed a novel c.1564 T > A (p.Cys522Ser) mutation in the NOTCH3 gene, contributing to the clinical diagnosis of CADASIL. This case underscores the phenotypic variability of CADASIL and the potential for atypical presentations, including parkinsonism. Early identification of genetic mutations can facilitate appropriate management and counseling for affected individuals and their families. Further research is warranted to explore the mechanisms underlying the association between NOTCH3 mutations and parkinsonism. Our findings contribute to the understanding of CADASIL, suggesting that clinicians should consider CADASIL in differential diagnoses of early-onset parkinsonism, especially in patients with concurrent white matter lesions.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"12 ","pages":"Article 100297"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A four-year trajectory of Alexithymia in Parkinson’s disease patients

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100298

Lea Krey, Annika Heike Ritzrau, Theresa Schnur, Stephan Greten, Florian Wegner, Martin Klietz

The aim of this study was to assess the presence of Alexithymia in Parkinson’s disease (PD) patients compared to their caregivers (CG) and to investigate whether Alexithymia progressed over a 4-year observational period. Alexithymia in PD is a cognitive affective disturbance resulting in difficulty to identify, distinguish and describe feelings and it is known to be strongly associated with health-related quality of life and other cognitive/ neuropsychiatric symptoms. So far, there have been no longitudinal investigations of Alexithymia in PD. We recruited 34 moderately progressed PD patients (mean disease duration of 8.9 ± 5.3 years) and their caregivers in our neurological department and did a baseline and follow-up assessment using the validated Toronto Alexithymia Scale-26 (TAS-26). Our data show that Alexithymia is more abundant in the PD cohort compared to their caregivers (p = 0.007, PD 21 %, CG 6 % at follow-up). In the 4-year observational period, Alexithymia did not increase significantly in PD patients or caregivers. However, there was a high variance in Alexithymia scores in both groups. It remains unclear when Alexithymia appears during the disease course and whether there is a dynamic in Alexithymia scores later in PD progression. This should be the objective for future studies of Alexithymia in advanced PD patients.

{"title":"A four-year trajectory of Alexithymia in Parkinson’s disease patients","authors":"Lea Krey, Annika Heike Ritzrau, Theresa Schnur, Stephan Greten, Florian Wegner, Martin Klietz","doi":"10.1016/j.prdoa.2025.100298","DOIUrl":"10.1016/j.prdoa.2025.100298","url":null,"abstract":"<div><div>The aim of this study was to assess the presence of Alexithymia in Parkinson’s disease (PD) patients compared to their caregivers (CG) and to investigate whether Alexithymia progressed over a 4-year observational period. Alexithymia in PD is a cognitive affective disturbance resulting in difficulty to identify, distinguish and describe feelings and it is known to be strongly associated with health-related quality of life and other cognitive/ neuropsychiatric symptoms. So far, there have been no longitudinal investigations of Alexithymia in PD. We recruited 34 moderately progressed PD patients (mean disease duration of 8.9 ± 5.3 years) and their caregivers in our neurological department and did a baseline and follow-up assessment using the validated Toronto Alexithymia Scale-26 (TAS-26). Our data show that Alexithymia is more abundant in the PD cohort compared to their caregivers (p = 0.007, PD 21 %, CG 6 % at follow-up). In the 4-year observational period, Alexithymia did not increase significantly in PD patients or caregivers. However, there was a high variance in Alexithymia scores in both groups. It remains unclear when Alexithymia appears during the disease course and whether there is a dynamic in Alexithymia scores later in PD progression. This should be the objective for future studies of Alexithymia in advanced PD patients.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"12 ","pages":"Article 100298"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retrospective database analysis on the demographics and resource utilization of patients with Parkinson’s disease in Quebec, Canada

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100300

Véronique Baribeau , Shawn Mohammed , Amnah Awan , Diana Parison , Jean Lachaine

Introduction

Parkinson’s disease (PD) is the most prevalent neurodegenerative movement disorder. Despite its recognized significance, there remains a paucity of recent studies reporting treatment utilization and the economic impact of PD in a real-world setting, especially in Canada. This study aimed to analyze real-world treatment patterns and health care resource utilization (HCRU) of patients with PD in Quebec, Canada.

Methods

This was a retrospective observational study using data between 2010–2019 from the Régie de l’assurance maladie du Québec (RAMQ) databases. Patients with PD were compared to age- and sex-matched controls. Treatment adherence and persistence were measured over 24 months. All-cause and PD-related HCRU and costs were characterized on an annual basis.

Results

Overall, 303 PD patients and 909 age- and sex-matched controls were selected. Adherence rates were high (≥85 %) among all drug classes, but lower with dopamine agonists. Persistence to PD treatment declined over time, with nearly 50 % discontinuation rates at 24 months in all PD drug classes, except the levodopa class (discontinuation rate: 20.4 %). PD patients had a significantly higher total costs per year than the matched control group ($17,405 vs. $6,431), mainly driven by higher inpatient costs.

Conclusion

Many pharmacological options exist for PD patients and, though patients are adherent while on therapy, treatment discontinuation rates are high. This suggests potential long-term challenges in PD management, especially since PD continues to place a substantial burden on the health care system. This study underscores the need for enhanced therapeutic strategies, particularly for patients inadequately controlled with standard therapies.

{"title":"Retrospective database analysis on the demographics and resource utilization of patients with Parkinson’s disease in Quebec, Canada","authors":"Véronique Baribeau , Shawn Mohammed , Amnah Awan , Diana Parison , Jean Lachaine","doi":"10.1016/j.prdoa.2025.100300","DOIUrl":"10.1016/j.prdoa.2025.100300","url":null,"abstract":"<div><h3>Introduction</h3><div>Parkinson’s disease (PD) is the most prevalent neurodegenerative movement disorder. Despite its recognized significance, there remains a paucity of recent studies reporting treatment utilization and the economic impact of PD in a real-world setting, especially in Canada. This study aimed to analyze real-world treatment patterns and health care resource utilization (HCRU) of patients with PD in Quebec, Canada.</div></div><div><h3>Methods</h3><div>This was a retrospective observational study using data between 2010–2019 from the Régie de l’assurance maladie du Québec (RAMQ) databases. Patients with PD were compared to age- and sex-matched controls. Treatment adherence and persistence were measured over 24 months. All-cause and PD-related HCRU and costs were characterized on an annual basis.</div></div><div><h3>Results</h3><div>Overall, 303 PD patients and 909 age- and sex-matched controls were selected. Adherence rates were high (≥85 %) among all drug classes, but lower with dopamine agonists. Persistence to PD treatment declined over time, with nearly 50 % discontinuation rates at 24 months in all PD drug classes, except the levodopa class (discontinuation rate: 20.4 %). PD patients had a significantly higher total costs per year than the matched control group ($17,405 vs. $6,431), mainly driven by higher inpatient costs.</div></div><div><h3>Conclusion</h3><div>Many pharmacological options exist for PD patients and, though patients are adherent while on therapy, treatment discontinuation rates are high. This suggests potential long-term challenges in PD management, especially since PD continues to place a substantial burden on the health care system. This study underscores the need for enhanced therapeutic strategies, particularly for patients inadequately controlled with standard therapies.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"12 ","pages":"Article 100300"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143176206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Moving to a non-dopaminergic approach for the treatment of OFF fluctuations in Parkinson’s disease

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100303

Stuart H. Isaacson , Peter Jenner

In levodopa treated patients with Parkinson’s disease (PD), the standard approach to managing motor fluctuations is to adjust dopaminergic therapy. However, despite the availability of a wide armamentarium of dopaminergic medications, most patients treated with levodopa will still experience significant OFF time, and it is increasingly clear that motor fluctuations have a significant non-dopaminergic component. In this narrative review, we compare and contrast the therapeutic profiles of the only two non-dopaminergic medications approved in the US for the management of OFF time, namely amantadine and istradefylline. When compared against each other the two agents exemplify two different pharmacological approaches to treatment. Whereas amantadine has a multimodal pharmacology, istradefylline has highly specific actions at A_2A receptors which are highly expressed in the indirect pathway of the basal ganglia. We discuss how both offer an important alternative approach to treatment, without increasing total dopaminergic load. Clinicians can also consider that amantadine and istradefylline each have overlapping indications with classic dopaminergic medications, but with distinct mechanisms of action that can complement each other to reduce motor complications in patients already being treated with other dopaminergic agents.

{"title":"Moving to a non-dopaminergic approach for the treatment of OFF fluctuations in Parkinson’s disease","authors":"Stuart H. Isaacson , Peter Jenner","doi":"10.1016/j.prdoa.2025.100303","DOIUrl":"10.1016/j.prdoa.2025.100303","url":null,"abstract":"<div><div>In levodopa treated patients with Parkinson’s disease (PD), the standard approach to managing motor fluctuations is to adjust dopaminergic therapy. However, despite the availability of a wide armamentarium of dopaminergic medications, most patients treated with levodopa will still experience significant OFF time, and it is increasingly clear that motor fluctuations have a significant non-dopaminergic component. In this narrative review, we compare and contrast the therapeutic profiles of the only two non-dopaminergic medications approved in the US for the management of OFF time, namely amantadine and istradefylline. When compared against each other the two agents exemplify two different pharmacological approaches to treatment. Whereas amantadine has a multimodal pharmacology, istradefylline has highly specific actions at A<sub>2A</sub> receptors which are highly expressed in the indirect pathway of the basal ganglia. We discuss how both offer an important alternative approach to treatment, without increasing total dopaminergic load. Clinicians can also consider that amantadine and istradefylline each have overlapping indications with classic dopaminergic medications, but with distinct mechanisms of action that can complement each other to reduce motor complications in patients already being treated with other dopaminergic agents.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"12 ","pages":"Article 100303"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143176205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Limb-Kinetic apraxia of legs in Parkinson’s disease: Prospective clinical investigation

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100302

Yacov Balash , Evelin D. Mate , Riyad Idries , Anda Eilam , Amos D. Korczyn

Background

The study of dynamic organization of motor acts is important for investigation of motor impairment, and a possible sign of a disorder of fronto-parietal areas of the brain in Parkinson’s disease (PD). We aimed to prospectively investigate whether limb-kinetic apraxia in legs (LKA-L) is a heretofore unrecognized manifestation of PD independent of bradykinesia and rigidity.

Methods

Patients with PD and healthy controls (HC) performed bipedal reciprocal coordination (BRC) and monopedal reciprocal coordination (MRC) tests as a foot modification of the Oseretzky exam (originally alternate antiphase clenching and unclenching of the fists of the right and left hands). While MRC allowed for alternating movements of one leg per unit of time, BRC required synchronous movements of both legs in antiphase. Leg movement rates and their quality were measured by video recording and compared statistically between the groups of PD and HC.

Results

The cohort consisted of 31 PD patients (mean age 69.3 ± 7.1 years,16 males) and 12 HC (mean age 69 ± 6.2 years, 6 males). No differences between PD and HC groups were identified in MRC rate of performance, which were used as a measure of legs movement speed, although the quality of MRC movements was poorer in PD patients (p = 0.022). BRC rate and its performance quality were significantly flawed in PD compared to controls (P = 0.002 and P = 0.003, respectively).

Conclusions

Testing for dynamic organization of LKA-L revealed disorder in individuals with PD. LKA-L analyses should be considered in the diagnosis of leg movements and gait disorders in PD.

{"title":"Limb-Kinetic apraxia of legs in Parkinson’s disease: Prospective clinical investigation","authors":"Yacov Balash , Evelin D. Mate , Riyad Idries , Anda Eilam , Amos D. Korczyn","doi":"10.1016/j.prdoa.2025.100302","DOIUrl":"10.1016/j.prdoa.2025.100302","url":null,"abstract":"<div><h3>Background</h3><div>The study of dynamic organization of motor acts is important for investigation of motor impairment, and a possible sign of a disorder of fronto-parietal areas of the brain in Parkinson’s disease (PD). We aimed to prospectively investigate whether limb-kinetic apraxia in legs (LKA-L) is a heretofore unrecognized manifestation of PD independent of bradykinesia and rigidity.</div></div><div><h3>Methods</h3><div>Patients with PD and healthy controls (HC) performed bipedal reciprocal coordination (BRC) and monopedal reciprocal coordination (MRC) tests as a foot modification of the Oseretzky exam (originally alternate antiphase clenching and unclenching of the fists of the right and left hands). While MRC allowed for alternating movements of one leg per unit of time, BRC required synchronous movements of both legs in antiphase. Leg movement rates and their quality were measured by video recording and compared statistically between the groups of PD and HC.</div></div><div><h3>Results</h3><div>The cohort consisted of 31 PD patients (mean age 69.3 ± 7.1 years,16 males) and 12 HC (mean age 69 ± 6.2 years, 6 males). No differences between PD and HC groups were identified in MRC rate of performance, which were used as a measure of legs movement speed, although the quality of MRC movements was poorer in PD patients (<em>p</em> = 0.022). BRC rate and its performance quality were significantly flawed in PD compared to controls (<em>P</em> = 0.002 and <em>P</em> = 0.003, respectively).</div></div><div><h3>Conclusions</h3><div>Testing for dynamic organization of LKA-L revealed disorder in individuals with PD. LKA-L analyses should be considered in the diagnosis of leg movements and gait disorders in PD.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"12 ","pages":"Article 100302"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143176199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0