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Mujahid BIM, Holla VV, Kamble N, Yadav R, Pal PK, Mahale RR. Non-motor fluctuations in Parkinson's disease: frequency and clinical correlate. J Neural Transm (Vienna) 2025:10.1007/s00702-025-02908-0. [PMID: 40082320 DOI: 10.1007/s00702-025-02908-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Accepted: 03/02/2025] [Indexed: 03/16/2025]
Abstract
Non-motor symptoms (NMS) occur in 60-97% of Parkinson's disease (PD) patients. NMS show fluctuations over the course of the day referred to as non-motor fluctuations (NMF). To assess the frequency, severity, predictors and effect of the NMF on the quality of life in PD patients. This was a cross-sectional, hospital based, single-centre study. A total of 150 patients with PD were recruited. NMF was assessed using the MDS-Non-motor rating scale (MDS-NMS) and the Non-motor fluctuation assessment questionnaire (NoMoFA). The mean age at presentation and age at onset was 51.3 ± 10.8 years and 44.6 ± 11.1 years respectively and male predominance (75.3%). The mean duration of parkinsonism was 5.3 ± 3.7 years. Motor fluctuations (MF) were seen in 97 patients. A total of 143 patients (95.3%) had at least single NMS. Depression, cognition and pain was the most common NMS domain. NMF was seen in 57 patients (39.8%). NMF occurred in 50.5% in PD patients with MF. Pain was the most frequent NMS which showed NMF followed by fatigue, anxiety and depression. Pain had greater degree of change from ON to OFF period as compared to other NMS domains. NMF was associated with longer disease duration, higher levodopa dose and longer levodopa intake, greater motor severity, MF, higher NMS burden and poor quality of life. NMF is seen in association with MF. Pain, anxiety, depression and fatigue was the common NMS showing NMF. Pain had a large degree of fluctuation in the severity.
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Affiliation(s)
- Baig Ilyas Mirza Mujahid
- Department of Neurology, First Floor, Neurosciences Faculty Block, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, Karnataka, 560029, India
| | - Vikram V Holla
- Department of Neurology, First Floor, Neurosciences Faculty Block, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, Karnataka, 560029, India
| | - Nitish Kamble
- Department of Neurology, First Floor, Neurosciences Faculty Block, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, Karnataka, 560029, India
| | - Ravi Yadav
- Department of Neurology, First Floor, Neurosciences Faculty Block, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, Karnataka, 560029, India
| | - Pramod Kumar Pal
- Department of Neurology, First Floor, Neurosciences Faculty Block, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, Karnataka, 560029, India
| | - Rohan R Mahale
- Department of Neurology, First Floor, Neurosciences Faculty Block, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, Karnataka, 560029, India.
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Reese R, Koeglsperger T, Schrader C, Tönges L, Deuschl G, Kühn AA, Krack P, Schnitzler A, Storch A, Trenkwalder C, Höglinger GU. Invasive therapies for Parkinson's disease: an adapted excerpt from the guidelines of the German Society of Neurology. J Neurol 2025; 272:219. [PMID: 39985674 PMCID: PMC11846738 DOI: 10.1007/s00415-025-12915-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 01/07/2025] [Accepted: 01/12/2025] [Indexed: 02/24/2025]
Abstract
BACKGROUND Parkinson's disease (PD) is characterized by hypokinetic motor symptoms, tremor, and various non-motor symptoms with frequent fluctuations of symptoms in advanced disease stages. Invasive therapies, such as deep brain stimulation (DBS), ablative therapies, and continuous subcutaneous or intrajejunal delivery of dopaminergic drugs via pump therapies are available for the management of this complex motor symptomatology and may also impact non-motor symptoms. The recent update of the clinical guideline on PD by the German Neurological Society (Deutsche Gesellschaft für Neurologie e.V.; DGN) offers clear guidance on the indications and applications of these treatment options. METHODS The guideline committee formulated diagnostic questions for invasive therapies and structured them according to the PICOS framework (Population-Intervention-Comparisons-Outcome-Studies). A systematic literature review was conducted. Questions were addressed using the findings from the literature review and consented by the guideline committee. RESULTS Specific recommendations are given regarding (i) the optimal timing for starting invasive therapies, (ii) the application of DBS, (iii) the use of pump therapies in advanced PD, (iv) the indications for ablative procedures, and (iv) selecting the most appropriate therapy according to individual patient characteristics. CONCLUSION This review is an adapted excerpt of the chapters on the use of invasive therapies in PD of the novel German guideline on PD. Clear recommendations on the use of treatment options for advanced PD are provided.
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Affiliation(s)
- René Reese
- Department of Neurology, Rostock University Medical Center, Rostock, Germany.
- Klinik und Poliklinik für Neurologie, Universitätsmedizin Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany.
| | - Thomas Koeglsperger
- Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany
- German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Rostock, Germany
| | | | - Lars Tönges
- Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany
- Neurodegeneration Research, Protein Research Unit Ruhr (PURE), Ruhr University Bochum, Bochum, Germany
| | - Günther Deuschl
- Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Andrea A Kühn
- Movement Disorder and Neuromodulation Unit, Department of Neurology, Charité, University Medicine Berlin, Berlin, Germany
| | - Paul Krack
- Movement Disorders Center, Department of Neurology, University Hospital (Inselspital) and University of Bern, Bern, Switzerland
| | - Alfons Schnitzler
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
- Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
| | - Alexander Storch
- Department of Neurology, Rostock University Medical Center, Rostock, Germany
- Center for Transdisciplinary Neurosciences Rostock (CTNR), Rostock University Medical Center, Rostock, Germany
- German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Rostock, Germany
| | - Claudia Trenkwalder
- Paracelsus-Elena-Klinik, Kassel, Germany
- Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany
| | - Günter U Höglinger
- Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany
- German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
- Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
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Boura I, Poplawska-Domaszewicz K, Spanaki C, Chen R, Urso D, van Coller R, Storch A, Chaudhuri KR. Non-Motor Fluctuations in Parkinson's Disease: Underdiagnosed Yet Important. J Mov Disord 2025; 18:1-16. [PMID: 39703981 PMCID: PMC11824532 DOI: 10.14802/jmd.24227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 12/12/2024] [Accepted: 12/20/2024] [Indexed: 12/21/2024] Open
Abstract
Non-motor fluctuations (NMFs) in Parkinson's disease (PD) significantly affect patients' well-being. Despite being identified over two decades ago, NMFs remain largely underrecognized, undertreated, and poorly understood. While they are often temporally associated with motor fluctuations (MFs) and can share common risk factors and pathophysiologic mechanisms, NMFs and MFs are currently considered distinct entities. The prevalence and severity of NMFs, often categorized into neuropsychiatric, sensory, and autonomic subtypes, vary significantly across studies due to the heterogeneous PD populations screened and the diverse evaluation tools applied. The consistent negative impact of NMFs on PD patients' quality of life underscores the importance of further investigations via focused and controlled studies, validated assessment instruments and novel digital technologies. High-quality research is essential to illuminate the complex pathophysiology and clinical nuances of NMFs, ultimately enhancing clinicians' diagnostic and treatment options in routine clinical practice.
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Affiliation(s)
- Iro Boura
- School of Medicine, University of Crete, Heraklion, Greece
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
| | - Karolina Poplawska-Domaszewicz
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
- Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
| | - Cleanthe Spanaki
- School of Medicine, University of Crete, Heraklion, Greece
- Neurology Department, University General Hospital of Heraklion, Crete, Greece
| | - Rosabel Chen
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
| | - Daniele Urso
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
- Center for Neurodegenerative Diseases and the Aging Brain, Department of Clinical Research in Neurology, University of Bari ‘Aldo Moro’, “Pia Fondazione Cardinale G. Panico”, Tricase, Lecce, Italy
| | - Riaan van Coller
- Department of Neurology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Alexander Storch
- Department of Neurology, University of Rostock, Rostock, Germany
- German Center for Neurodegenerative Diseases (DZNE) Rostock-Greifswald, Rostock, Germany
| | - Kallol Ray Chaudhuri
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
- Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK
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Storch A, Bremer A, Gandor F, Odin P, Ebersbach G, Löhle M. Pain Fluctuations in Parkinson's Disease and Their Association with Motor and Non-Motor Fluctuations. JOURNAL OF PARKINSON'S DISEASE 2024; 14:1451-1468. [PMID: 39302380 PMCID: PMC11492001 DOI: 10.3233/jpd-240026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/09/2024] [Indexed: 09/22/2024]
Abstract
Background Pain fluctuations are a characteristic phenomenon in advanced Parkinson's disease (PD), but their temporal association with motor and non-motor symptom (NMS) fluctuations remains largely enigmatic. Moreover, data on their importance for disease severity perception and health-related quality-of-life (hr-QoL) is limited. Objective To dissect pain fluctuations with respect to pain type and frequency patterns, and their association with motor and non-motor fluctuations. Methods Prospective observational cohort study in advanced PD assessing symptom fluctuations by simultaneous hourly ratings using the PD Home diary (Off, On, Dyskinetic state), a pain diary (assessing 9 pain types) and a non-motor diary (10 key NMS) based on validated instruments. Results Forty-seven out of 55 eligible participants with fluctuating PD (51% men, median age 65, median disease duration 10 years) had sufficient datasets (>95% of hours) from 2 consecutive days. Pain was reported in 35% of waking hours with clear circadian rhythm peaking in early morning Off periods and clustering during motor Off state (49% of Off state hours with pain). Main NMS co-fluctuating with pain were "Fatigue" and "Inner Restlessness". Simultaneous assessment of global disease severity by participants revealed that pain was associated with worse disease severity only in motor On and Dyskinetic state but not in Off state, which translated into significant correlations of daily pain times with hr-QoL only during motor On and Dyskinetic state. Conclusions Aside from treating motor Off periods, specific recognition of pain particularly during motor On and Dyskinetic state comprises an important aspect for disease management in advanced PD.
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Affiliation(s)
- Alexander Storch
- Department of Neurology, University of Rostock, Rostock, Germany
- German Center for Neurodegenerative Diseases (DZNE) Rostock-Greifswald, Rostock, Germany
| | - Alexander Bremer
- Department of Neurology, University of Rostock, Rostock, Germany
| | - Florin Gandor
- Movement Disorder Clinic, Beelitz-Heilstätten, Beelitz, Germany
- Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany
| | - Per Odin
- Division of Neurology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
- Department of Neurology, Rehabilitation Medicine, Memory and Geriatrics, Skåne University Hospital, Lund, Sweden
| | - Georg Ebersbach
- Movement Disorder Clinic, Beelitz-Heilstätten, Beelitz, Germany
| | - Matthias Löhle
- Department of Neurology, University of Rostock, Rostock, Germany
- German Center for Neurodegenerative Diseases (DZNE) Rostock-Greifswald, Rostock, Germany
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Donzuso G, Cicero CE, Vinciguerra E, Sergi R, Luca A, Mostile G, Terravecchia C, Zappia M, Nicoletti A. Gender differences in non-motor fluctuations in Parkinson's disease. J Neural Transm (Vienna) 2023; 130:1249-1257. [PMID: 37526768 PMCID: PMC10480257 DOI: 10.1007/s00702-023-02679-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 07/23/2023] [Indexed: 08/02/2023]
Abstract
Non-motor symptoms (NMS) and Non-motor fluctuations (NMF) in Parkinson's Disease (PD) are common, involving several domains and affecting quality of life. Aim of the study is to estimate the burden of NMF in PD patients and to evaluate the possible gender effect. PD patients fulfilling the MDS-PD diagnostic criteria attending the "Parkinson's Disease and Movement Disorders Centre" of the University of Catania were evaluated using the Non-Motor Fluctuations Assessment (NoMoFA) Questionnaire. NoMoFA items were also grouped into the following domains: cognitive, mood, sleep/fatigue, dysautonomia, hallucination/perception and miscellaneous domains were identified. One-hundred and twenty-one patients with PD (67 men, 55.4%; mean age 70.2 ± 8.9 years, disease duration 8.3 ± 4.6 years) were evaluated. All PD patients reported at least one NMS, whereas 87 (71.9%) also reported NMF. "Feel sluggish or had low energy levels" (47.2%) along with "Feel excessively sleepy during the day" (40.0%) were the most common NMF reported in the whole sample. The majority of PD patients reported the presence of NMF during the OFF state (79, 65.3%). At multivariate analysis, NMF were positively associated with the female gender (adjusted OR 3.13; 95%CI 1.21-8.11 p-value 0.01). Women with PD had higher NMF scores especially in depression/anxiety, sleep/fatigue and dysautonomia domains. Our study reported the presence of a gender-related pattern in the frequency of NMS and NMF in PD patients, with female gender associated with a higher risk of developing NMF, highlighting the need for personalized treatment strategies when addressing NMF.
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Affiliation(s)
- Giulia Donzuso
- Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Calogero Edoardo Cicero
- Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Erica Vinciguerra
- Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Rosy Sergi
- Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Antonina Luca
- Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Giovanni Mostile
- Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Claudio Terravecchia
- Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Mario Zappia
- Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Alessandra Nicoletti
- Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy.
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Schmitt E, Debu B, Castrioto A, Kistner A, Fraix V, Bouvard M, Moro E. Fluctuations in Parkinson's disease and personalized medicine: bridging the gap with the neuropsychiatric fluctuation scale. Front Neurol 2023; 14:1242484. [PMID: 37662035 PMCID: PMC10469620 DOI: 10.3389/fneur.2023.1242484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 08/02/2023] [Indexed: 09/05/2023] Open
Abstract
Background Neuropsychiatric fluctuations (NpsyF) are frequent and disabling in people with Parkinson's disease (PD). In OFF-medication, NpsyF entail minus neuropsychiatric symptoms (NPS) like anxiety, apathy, sadness, and fatigue. In ON-medication, NpsyF consist in plus NPS, such as high mood, hypomania, and hyperactivity. Accurate identification of these NpsyF is essential to optimize the overall PD management. Due to lack of punctual scales, the neuropsychiatric fluctuation scale (NFS) has been recently designed to assess NpsyF in real time. The NFS comprises 20 items with two subscores for plus and minus NPS, and a total score. Objective To evaluate the psychometric properties of the NFS in PD. Methods PD patients with motor fluctuations and healthy controls (HC) were assessed. In PD patients, the NFS was administrated in both the ON-and OFF-medication conditions, together with the movement disorders society-unified Parkinson disease rating scale parts I-IV. Depression (Beck depression scale II), apathy (Starkstein apathy scale) and non-motor fluctuations items of the Ardouin scale of behaviour in PD (ASBPD OFF and ON items) were also assessed. NFS internal structure was evaluated with principal component analysis consistency (PCA) in both medication conditions in PD patients and before emotional induction in HC. NFS internal consistency was assessed using Cronbach's alpha coefficient. NFS convergent and divergent validity was measured through correlations with BDI-II, Starktein, and ASBPD OFF and ON non motor items. Specificity was assessed comparing NFS global score between the HC and PD populations. Sensitivity was evaluated with t-student test comparing the ON-and the OFF-medication conditions for NFS global score and for minus and plus subscores. Results In total, 101 consecutive PD patients and 181 HC were included. In PD patients and HC, PCA highlighted one component that explained 32-35 and 42% of the variance, respectively. Internal consistency was good for both the NFS-plus (alpha =0.88) and NFS-minus items (alpha =0.8). The NFS showed a good specifity for PD (p < 0.0001) and a good sensitivity to the medication condition (p < 0.0001). Conclusion The satisfactory properties of the NFS support its use to assess acute neuropsychiatric fluctuations in PD patients, adding to available tools.
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Affiliation(s)
- Emmanuelle Schmitt
- Division of Neurology, CHU Grenoble Alpes, Grenoble Institute of Neuroscience, INSERM U1216, Grenoble Alpes University, Grenoble, France
| | - Bettina Debu
- Division of Neurology, CHU Grenoble Alpes, Grenoble Institute of Neuroscience, INSERM U1216, Grenoble Alpes University, Grenoble, France
| | - Anna Castrioto
- Division of Neurology, CHU Grenoble Alpes, Grenoble Institute of Neuroscience, INSERM U1216, Grenoble Alpes University, Grenoble, France
| | - Andrea Kistner
- Division of Neurology, CHU Grenoble Alpes, Grenoble Institute of Neuroscience, INSERM U1216, Grenoble Alpes University, Grenoble, France
| | - Valerie Fraix
- Division of Neurology, CHU Grenoble Alpes, Grenoble Institute of Neuroscience, INSERM U1216, Grenoble Alpes University, Grenoble, France
| | - Martine Bouvard
- Psychology and Neurocognition Laboratory, Grenoble Alpes University, Université Savoie Mont Blanc, CNRS, LPNC, Grenoble, France
| | - Elena Moro
- Division of Neurology, CHU Grenoble Alpes, Grenoble Institute of Neuroscience, INSERM U1216, Grenoble Alpes University, Grenoble, France
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Nilashi M, Abumalloh RA, Alyami S, Alghamdi A, Alrizq M. Parkinson’s Disease Diagnosis Using Laplacian Score, Gaussian Process Regression and Self-Organizing Maps. Brain Sci 2023; 13:brainsci13040543. [PMID: 37190508 DOI: 10.3390/brainsci13040543] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 03/10/2023] [Accepted: 03/18/2023] [Indexed: 03/29/2023] Open
Abstract
Parkinson’s disease (PD) is a complex degenerative brain disease that affects nerve cells in the brain responsible for body movement. Machine learning is widely used to track the progression of PD in its early stages by predicting unified Parkinson’s disease rating scale (UPDRS) scores. In this paper, we aim to develop a new method for PD diagnosis with the aid of supervised and unsupervised learning techniques. Our method is developed using the Laplacian score, Gaussian process regression (GPR) and self-organizing maps (SOM). SOM is used to segment the data to handle large PD datasets. The models are then constructed using GPR for the prediction of the UPDRS scores. To select the important features in the PD dataset, we use the Laplacian score in the method. We evaluate the developed approach on a PD dataset including a set of speech signals. The method was evaluated through root-mean-square error (RMSE) and adjusted R-squared (adjusted R²). Our findings reveal that the proposed method is efficient in the prediction of UPDRS scores through a set of speech signals (dysphonia measures). The method evaluation showed that SOM combined with the Laplacian score and Gaussian process regression with the exponential kernel provides the best results for R-squared (Motor-UPDRS = 0.9489; Total-UPDRS = 0.9516) and RMSE (Motor-UPDRS = 0.5144; Total-UPDRS = 0.5105) in predicting UPDRS compared with the other kernels in Gaussian process regression.
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Both Motor and Non-Motor Fluctuations Matter in the Clinical Management of Patients with Parkinson's Disease: An Exploratory Study. J Pers Med 2023; 13:jpm13020242. [PMID: 36836476 PMCID: PMC9964567 DOI: 10.3390/jpm13020242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/27/2023] [Accepted: 01/28/2023] [Indexed: 01/31/2023] Open
Abstract
Non-motor symptoms (NMS) characterize the Parkinson's disease (PD) clinical picture, and as well as motor fluctuations, PD patients can also experience NMS fluctuations (NMF). The aim of this observational study was to investigate the presence of NMS and NMF in patients with PD using the recently validated Non-Motor Fluctuation Assessment questionnaire (NoMoFa) and to evaluate their associations with disease characteristics and motor impairment. Patients with PD were consecutively recruited, and NMS, NMF, motor impairment, motor fluctuations, levodopa-equivalent daily dose, and motor performance were evaluated. One-third of the 25 patients included in the study (10 females, 15 males, mean age: 69.9 ± 10.3) showed NMF, and patients with NMF presented a higher number of NMS (p < 0.01). Static NMS and NoMoFa total score were positively associated with motor performance assessed with the Global Mobility Task (p < 0.01 and p < 0.001), and the latter was also correlated with motor impairment (p < 0.05) but not with motor fluctuations. Overall, this study shows evidence that NMF are frequently reported by mild-to-moderate PD patients and associated with an increased number of NMS. The relationship between NoMoFa total score and motor functioning highlights the importance of understanding the clinical role of NMS and NMF in the management of PD patients.
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Seki M, Kurihara K, Konno T, Fujioka S, Tsuboi Y. [Characteristics and treatment of pain in Parkinson's disease]. Rinsho Shinkeigaku 2022; 62:763-772. [PMID: 36184418 DOI: 10.5692/clinicalneurol.cn-001733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Pain is a representative non-motor symptom in patients with Parkinson's disease (PD). Pain is one of the most common symptoms that plague patients with PD regardless of the stage of the disease, also it can exacerbate other symptoms, such as depression, anxiety or sleep disturbance, and lead to impaired quality of life. However, pain is often not adequately evaluated and treated. PD patients complain of a wide variety of pain, including both PD-related pain which caused by PD-specific symptoms, for example, rigidity, bradykinesia or motor fluctuation, and PD-unrelated pain, and it can be divided into central and peripheral depending on the site of the disorder. In the medical care of the pain, it is important to evaluate the type and severity of the pain using PD-specific assessment scales such as King's PD pain scale and to consider the evidence-based treatment methods according to the pathophysiology of the pain.
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Affiliation(s)
- Morinobu Seki
- Department of Neurology, Keio University School of Medicine, Japan
| | - Kanako Kurihara
- Department of Neurology, Faculty of Medicine, Fukuoka University, Japan
| | - Takuya Konno
- Department of Neurology, Brain Research Institute, Niigata University, Japan
| | - Shinsuke Fujioka
- Department of Neurology, Faculty of Medicine, Fukuoka University, Japan
| | - Yoshio Tsuboi
- Department of Neurology, Faculty of Medicine, Fukuoka University, Japan
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Do neuropsychiatric fluctuations temporally match motor fluctuations in Parkinson’s disease? Neurol Sci 2022; 43:3641-3647. [DOI: 10.1007/s10072-021-05833-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 12/13/2021] [Indexed: 11/25/2022]
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Barreto KS, Oliveira J, Reis LD, Ribeiro TG, Kauark RBG. Non-motor symptoms fluctuations in patients with Parkinson's disease at the Clinical Hospital of Salvador, Bahia. Dement Neuropsychol 2022; 16:213-219. [PMID: 35720653 PMCID: PMC9173797 DOI: 10.1590/1980-5764-dn-2021-0056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 10/23/2021] [Accepted: 11/12/2021] [Indexed: 11/22/2022] Open
Abstract
Motor fluctuations in Parkinson's disease (PD) are a frequent long-term complication. Knowledge is limited on the prevalence and incidence of non-motor symptoms (NMS) fluctuations, especially in Brazil.
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Affiliation(s)
| | - Jamary Oliveira
- Complexo Hospitalar Universitário Professor Edgard Santos, Salvador BA, Brazil
| | - Luana Dias Reis
- Universidade Federal da Bahia, Faculdade de Medicina da Bahia, Salvador BA, Brazil
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Could New Generations of Sensors Reshape the Management of Parkinson’s Disease? CLINICAL AND TRANSLATIONAL NEUROSCIENCE 2021. [DOI: 10.3390/ctn5020018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Parkinson's disease (PD) is a chronic neurologic disease that has a great impact on the patient’s quality of life. The natural course of the disease is characterized by an insidious onset of symptoms, such as rest tremor, shuffling gait, bradykinesia, followed by improvement with the initiation of dopaminergic therapy. However, this “honeymoon period” gradually comes to an end with the emergence of motor fluctuations and dyskinesia. PD patients need long-term treatments and monitoring throughout the day; however, clinical examinations in hospitals are often not sufficient for optimal management of the disease. Technology-based devices are a new comprehensive assessment method of PD patient’s symptoms that are easy to use and give unbiased measurements. This review article provides an exhaustive overview of motor complications of advanced PD and new approaches to the management of the disease using sensors.
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Rastgardani T, Armstrong MJ, Gagliardi AR, Grabovsky A, Marras C. Experience and Impact of OFF Periods in Parkinson's Disease: A Survey of Physicians, Patients, and Carepartners. JOURNAL OF PARKINSONS DISEASE 2021; 10:315-324. [PMID: 31815702 DOI: 10.3233/jpd-191785] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND OFF periods impair quality of life in Parkinson's disease but the nature and degree of this impact is largely unquantified. Optimal treatment relies on assessing the experience and impact of these periods on patients and their carepartners. OBJECTIVES To understand the experience and impact of OFF periods on their lives. METHODS Informed by qualitative interviews we designed questionnaires and surveyed neurologists, people with Parkinson's disease and carepartners. RESULTS 50 general neurologists, 50 movement disorder neurologists, 442 patients (median disease duration 5 years) and 97 carepartners were included. The most common OFF symptoms reported by patients and carepartners were stiffness, slowness of movement and changes in gait. Non-motor symptoms were less common. A higher proportion of carepartners reported each symptom. A minority of neurologists recognized pain, sweating and anxiety as possible symptoms of OFF periods. The three OFF symptoms most frequently designated as having great impact by people with Parkinson's disease were changes in gait, slowness and stiffness. In contrast, cognitive impairment was most frequently rated as having great impact on carepartners. OFF periods were reported to impact many aspects of the lives of both patients and carepartners. CONCLUSIONS In people with Parkinson's disease of under 10 years duration, motor symptoms of OFF periods predominate in impact, however cognitive impairment has great impact on carepartners. Education is needed for neurologists regarding the non-motor aspects of OFF. The importance of involving carepartners in the assessment regarding OFF periods is supported by the higher frequency of symptom reporting by carepartners, and the significant impact on their lives.
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Affiliation(s)
- Tara Rastgardani
- The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Research, Toronto Western Hospital, Toronto, ON, Canada
| | - Melissa J Armstrong
- Department of Neurology, University of Florida College of Medicine, Gainesville, FL, USA
| | - Anna R Gagliardi
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | | | - Connie Marras
- The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's Research, Toronto Western Hospital, Toronto, ON, Canada
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Mantese CE, Medeiros M, Schumacher-Schuh A, Rieder CRDM. Validation of 19-items wearing-off (WOQ-19) questionnaire to Portuguese. ARQUIVOS DE NEURO-PSIQUIATRIA 2020; 78:624-628. [PMID: 32935734 DOI: 10.1590/0004-282x20200045] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 04/06/2020] [Indexed: 11/21/2022]
Abstract
BACKGROUND The treatment of Parkinson disease with dopaminergic therapy improves functionality and quality of life. However, as the disease progresses, the wearing-off phenomenon develops. To improve the recognition of this phenomenon, the 19-item wearing-off questionnaire (WOQ-19) was developed. OBJECTIVE To translate and validate the WOQ-19 into Portuguese. METHODS The questionnaire was translated into Portuguese and, subsequently, back-translated into English and analyzed. The final version was tested in Parkinson disease patients for reliability through the test-retest paradigm and internal consistency. Also, sensitivity and specificity were obtained in different cut-off positive items. RESULTS The WOQ-19 showed good test stability, with an intraclass correlation coefficient of 0.877 (95%CI 0.690-0.951; p<0.001), and good internal consistency, with Cronbach alpha of 0.815. Two items of positive cut-off showed the best accuracy: 0.873 (95%CI 0.791-0.954). Sensitivity was 0.975 (95%CI 0.892-1) and specificity was 0.714 (95%CI 0.565-0.863). CONCLUSION The Portuguese version of the WOQ-19 showed excellent diagnostic properties and can be used to diagnose wearing-off phenomena.
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Affiliation(s)
- Carlos Eduardo Mantese
- Universidade Federal do Rio Grande do Sul, Programa de Pós-graduação em Ciências Médicas, Porto Alegre RS, Brazil.,Hospital Mãe de Deus, Porto Alegre RS, Brazil
| | - Marcio Medeiros
- Universidade Federal do Rio Grande do Sul, Programa de Pós-graduação em Ciências Médicas, Porto Alegre RS, Brazil
| | - Artur Schumacher-Schuh
- Universidade Federal do Rio Grande do Sul, Programa de Pós-graduação em Ciências Médicas, Porto Alegre RS, Brazil.,Hospital de Clínicas de Porto Alegre, Porto Alegre RS, Brazil
| | - Carlos Roberto de Melo Rieder
- Universidade Federal do Rio Grande do Sul, Programa de Pós-graduação em Ciências Médicas, Porto Alegre RS, Brazil.,Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre RS, Brazil
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Löhle M, Hermann W, Hausbrand D, Wolz M, Mende J, Beuthien-Baumann B, Oehme L, van den Hoff J, Kotzerke J, Reichmann H, Hermann A, Storch A. Putaminal Dopamine Turnover in de novo Parkinson's Disease Predicts Later Neuropsychiatric Fluctuations but Not Other Major Health Outcomes. JOURNAL OF PARKINSONS DISEASE 2020; 9:693-704. [PMID: 31381528 DOI: 10.3233/jpd-191672] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVE To investigate the predictive value of striatal dopamine turnover in patients with de novo Parkinson's disease (PD) for later occurrence of major non-motor health outcomes. METHODS This retrospective, observer-blinded cohort study followed up 29 patients with de novo PD for a median of 10.7 years, who completed 18Fluorodopa PET imaging to measure striatal effective distribution volume ratio (EDVR, inverse of dopamine turnover) prior to antiparkinsonian treatment. Outcomes were assessed with a battery of non-motor, health-related quality-of-life and non-motor fluctuation (WOQ-19) measures and survival. RESULTS During follow-up, 52% of patients developed wearing-off, 43% neuropsychiatric fluctuations, 35% sensory fluctuations, 32% dementia, 46% depression, 30% psychosis, and PD-related mortality was 26%. Patients with wearing-off and neuropsychiatric fluctuations showed significantly lower baseline EDVR (higher dopamine turnover) in the putamen but not in the caudate nucleus than those without these fluctuations. Consistently, baseline EDVR in the putamen predicted development of wearing-off and neuropsychiatric fluctuations with a lower risk with higher EDVR (lower dopamine turnover), whereas EDVR in caudate nucleus did not correlate with these fluctuations. No relationships were observed between baseline PET measures and the presence of other major health outcomes including survival. CONCLUSIONS Lower putaminal dopamine turnover in de novo PD is associated with reduced risk for later neuropsychiatric fluctuations comprising a disease-intrinsic predisposing factor for their development, similar as reported for levodopa-induced motor complications. Striatal (putaminal/caudate) dopamine turnover is not predictive for other long-term major health outcomes. These results should be treated as hypothesis generating and require confirmation.
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Affiliation(s)
- Matthias Löhle
- Department of Neurology, University of Rostock, Rostock, Germany.,German Centre for Neurodegenerative Diseases (DZNE) Rostock, Rostock, Germany
| | - Wiebke Hermann
- Department of Neurology, University of Rostock, Rostock, Germany.,German Centre for Neurodegenerative Diseases (DZNE) Rostock, Rostock, Germany.,Department of Neurology, Technische Universität Dresden, Dresden, Germany
| | - Denise Hausbrand
- Department of Neurology, Technische Universität Dresden, Dresden, Germany
| | - Martin Wolz
- Department of Neurology, Elblandklinikum Meißen, Meissen, Germany
| | - Julia Mende
- Department of Neurology, Technische Universität Dresden, Dresden, Germany
| | - Bettina Beuthien-Baumann
- Department of Nuclear Medicine, Technische Universität Dresden, Dresden, Germany.,Positron Emission Tomography Division, Helmholtz-Zentrum Dresden-Rossendorf; Dresden, Germany.,German Cancer Research Centre (DKFZ), Radiology, Heidelberg, Germany
| | - Liane Oehme
- Department of Nuclear Medicine, Technische Universität Dresden, Dresden, Germany
| | - Jörg van den Hoff
- Positron Emission Tomography Division, Helmholtz-Zentrum Dresden-Rossendorf; Dresden, Germany
| | - Jörg Kotzerke
- Department of Nuclear Medicine, Technische Universität Dresden, Dresden, Germany
| | - Heinz Reichmann
- Department of Neurology, Technische Universität Dresden, Dresden, Germany
| | - Andreas Hermann
- Department of Neurology, University of Rostock, Rostock, Germany.,German Centre for Neurodegenerative Diseases (DZNE) Rostock, Rostock, Germany.,Department of Neurology, Technische Universität Dresden, Dresden, Germany
| | - Alexander Storch
- Department of Neurology, University of Rostock, Rostock, Germany.,German Centre for Neurodegenerative Diseases (DZNE) Rostock, Rostock, Germany
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Rastgardani T, Armstrong MJ, Gagliardi AR, Grabovsky A, Marras C. Communication About OFF Periods in Parkinson's Disease: A Survey of Physicians, Patients, and Carepartners. Front Neurol 2019; 10:892. [PMID: 31481924 PMCID: PMC6709650 DOI: 10.3389/fneur.2019.00892] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 08/01/2019] [Indexed: 12/16/2022] Open
Abstract
Background: OFF periods impair quality of life in Parkinson's disease and are often amenable to treatment. Optimal treatment decisions rely on effective communication between physicians, patients and carepartners regarding this highly variable and complex phenomenon. Little is published in the literature about communication about OFF periods. Methods: Informed by interviews with physicians, patients and carepartners we designed questionnaires for each group. We surveyed these parties using an online platform to investigate the frequency, content and ease of communication about OFF periods and barriers and facilitators of communication with physicians. Results: Fifty movement disorder neurologists, 50 general neurologists, 442 patients and 97 carepartners participated. A free-flowing dialogue is the mainstay of communication according to all parties. Motor aspects of OFF periods are discussed more frequently than non-motor aspects (90 vs. <50% according to both general neurologists and movement disorder neurologists). The most common physician-reported barriers to communication are patient cognitive impairment, patient difficulty recognizing OFF periods and poor patient understanding of OFF periods' relationship to medication timing. The barriers most commonly cited as major by patients were that they perceived OFF periods to be part of the disease (i.e., not a clinical aspect that could be improved by a physician), variability of symptoms, and difficulty in describing symptoms. The most commonly described facilitator (by physicians) was the input of a caregiver. Positively viewed but less commonly used facilitators included pre-visit questionnaires or diaries, digital apps and wearable devices to monitor fluctuations. The majority of patients and carepartners identified a free-flowing dialogue with their physicians and having an agenda as helpful facilitators of communication about OFF periods which they already use. The majority of both groups felt that keeping a diary and pre-visit questionnaires were potentially helpful facilitators that were not currently in use. Conclusions: Perceived barriers and facilitators to communication about OFF periods are different between health care providers and receivers of health care. Modifiable barriers and facilitators that could be implemented were identified by both groups. Future research should develop and test strategies based on this input to optimize communication and thus clinical care for this common and debilitating problem.
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Affiliation(s)
- Tara Rastgardani
- The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Research, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada
| | - Melissa J Armstrong
- Department of Neurology, University of Florida College of Medicine, Gainesville, FL, United States
| | - Anna R Gagliardi
- Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada
| | | | - Connie Marras
- The Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Research, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada
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Ha ULN, Tran TN, Le M, Dang THT, Vũ NA, Truong D. Validating the Vietnamese version of wearing - Off 19 questionnaire for patients with Parkinson's disease. Clin Park Relat Disord 2019; 1:37-40. [PMID: 34316597 PMCID: PMC8288827 DOI: 10.1016/j.prdoa.2019.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 07/17/2019] [Accepted: 07/31/2019] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND One of the most common complication of the progression of Parkinson's disease (PD) is the wearing off phenomenon. A validated Vietnamese version of Wearing off 19 (WO19) questionnaire is necessary to optimize the Vietnamese PD treatment. OBJECTIVES This study was undertaken to determine the quality attribute of the questionnaire as a tool for early detection of wearing off (WO) in Vietnamese population with PD. We also sought the relationship between the WO phenomenon and factors concerning the clinical condition and course of the disease. SUBJECTS AND METHODS This is an observational, cross-sectional study. Patients diagnosed with PD under dopaminergic treatment came to University Medical Center Ho Chi Minh city for a regular appointment were sequentially asked to complete the Vietnamese WO19 questionnaire. A neurologist specialized in movement disorders assessed the patient and determined whether he had experienced wearing off or not. The questionnaire results were then compared to the clinical opinion of the expert which is considered the gold standard for diagnosing wearing off. The reliability of the questionnaire is evaluated by Cronbach'α and Cohen's kappa coefficient. The validity is measured by the sensitivity and the specificity of the instrument compared to the gold standard. The multivariate logistic regression analysis is used to learn the relations of associated factors and wearing off phenomenon. RESULTS 98 patients with the mean age 59.12 ± 10.99 have joined our study; 58.2% are male; and the mean disease duration is 6.32 years. The Vietnamese version of the WO19 questionnaire has a good reliability (Cronbach'α = 0.778) and the agreement with the expert assessment (the diagnostic accuracy) is at a substantial level (Kappa value = 0.618). The sensitivity and specificity of the questionnaire resulted 89.28% and 71.43% respectively. The multivariate logistic regression analysis revealed a long disease duration (≥6 years) (OR: 16.96; 95% CI: 2.17-132.57; p = 0.007), a high daily levodopa dosage (≥400 mg/day) (OR: 6.31; 95% CI: 1.36-29.23; p = 0.019) and high score of MDS-UPDRS part IV (≥4) (OR: 15.36; 95% CI: 2.13-110.58; p = 0.007) were independent predictive factors for wearing off in Vietnamese PD patients. CONCLUSIONS Vietnamese - WO19 is a reliable and effective tool which should be used in clinical practice for early detecting PD patients with wearing off.
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Affiliation(s)
- Uyen Le Ngoc Ha
- Neurology department, University Medical Center, Ho Chi Minh City, Vietnam
| | - Tai Ngoc Tran
- Neurology department, University Medical Center, Ho Chi Minh City, Vietnam
| | - Minh Le
- Neurology department, University Medical Center, Ho Chi Minh City, Vietnam
| | | | - Nhi Anh Vũ
- Neurology department, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
| | - Daniel Truong
- The Truong Neuroscience Institute, Orange Coast Memorial Medical Center, Fountain Valley, CA 92708, USA
- Department of Psychiatry and Neuroscience, UC Riverside, Riverside, CA, USA
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Storch A, Rosqvist K, Ebersbach G, Odin P. Disease stage dependency of motor and non-motor fluctuations in Parkinson’s disease. J Neural Transm (Vienna) 2019; 126:841-851. [DOI: 10.1007/s00702-019-02033-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 06/14/2019] [Indexed: 12/18/2022]
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Rodríguez-Violante M, Ospina-García N, Dávila-Avila NM, Cruz-Fino D, Cruz-Landero ADL, Cervantes-Arriaga A. Motor and non-motor wearing-off and its impact in the quality of life of patients with Parkinson's disease. ARQUIVOS DE NEURO-PSIQUIATRIA 2019; 76:517-521. [PMID: 30231124 DOI: 10.1590/0004-282x20180074] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 04/24/2018] [Indexed: 11/21/2022]
Abstract
OBJECTIVES The wearing-off phenomenon is common in patients with Parkinson's disease. Motor and non-motor symptoms can fluctuate in relation to the "on/off" periods. To assess the impact of motor and non-motor wearing-off on activities of daily living and quality of life of patients with PD. METHODS A cross-sectional study was carried out. All patients were evaluated using the Movement Disorders Society Unified Parkinson's Disease Rating Scale. Wearing-off was assessed using the Wearing-Off Questionnaire-19, and quality of life was assessed using the Parkinson's Disease Questionnaire-8. RESULTS A total of 271 patients were included; 73.4% had wearing-off; 46.8% had both motor and non-motor fluctuations. Patients with both motor and non-motor wearing-off had a worst quality of life compared with those with only motor fluctuations (p = 0.047). CONCLUSIONS Motor and non-motor fluctuations have an impact on activities of daily living and quality of life. Non-motor wearing-off may have a higher impact.
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Affiliation(s)
- Mayela Rodríguez-Violante
- Instituto Nacional de Neurología y Neurociurgía, Laboratorio Clínico de Enfermedades Neurodegenerativas, Mexico City, Mexico.,Instituto Nacional de Neurología y Neurociurgía, Clínica de Trastornos del Movimiento, Mexico City, Mexico
| | - Natalia Ospina-García
- Instituto Nacional de Neurología y Neurociurgía, Laboratorio Clínico de Enfermedades Neurodegenerativas, Mexico City, Mexico
| | - Ned Merari Dávila-Avila
- Instituto Nacional de Neurología y Neurociurgía, Laboratorio Clínico de Enfermedades Neurodegenerativas, Mexico City, Mexico
| | - Diego Cruz-Fino
- Instituto Nacional de Neurología y Neurociurgía, Laboratorio Clínico de Enfermedades Neurodegenerativas, Mexico City, Mexico
| | - Alejandra de la Cruz-Landero
- Instituto Nacional de Neurología y Neurociurgía, Laboratorio Clínico de Enfermedades Neurodegenerativas, Mexico City, Mexico
| | - Amin Cervantes-Arriaga
- Instituto Nacional de Neurología y Neurociurgía, Laboratorio Clínico de Enfermedades Neurodegenerativas, Mexico City, Mexico
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Schmitt E, Krack P, Castrioto A, Klinger H, Bichon A, Lhommée E, Pelissier P, Fraix V, Thobois S, Moro E, Martinez-Martin P. The Neuropsychiatric Fluctuations Scale for Parkinson's Disease: A Pilot Study. Mov Disord Clin Pract 2018; 5:265-272. [PMID: 30363450 DOI: 10.1002/mdc3.12607] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 01/11/2018] [Accepted: 02/02/2018] [Indexed: 12/19/2022] Open
Abstract
Background Non-motor fluctuations represent a main source of disability in Parkinson's disease (PD). Among them, neuropsychiatric fluctuations are the most frequent and are often under-recognized by patients and physicians, partly because specific tools for assessment of neuropsychiatric fluctuations are lacking. Objective To develop a scale for detecting and evaluating the presence and the severity of neuropsychological symptoms during the ON and OFF phases of non-motor fluctuations. Methods Neuropsychiatric symptoms reported by PD patients in the OFF- and the ON-medication conditions were collected using different neuropsychiatric scales (BDI-II, BAI, Young, VAS, etc.). Subsequently, tree phases of a pilot study was performed for cognitive pretesting, identification of ambiguous or redundant items (item reduction), and to obtain preliminary data of acceptability of the new scale. In all the three phases, the scale was applied in both the OFF and ON condition during a levodopa challenge. Results Twenty items were selected for the final version of the neuropsychiatric fluctuation scale (NFS): ten items measured the ON neuropsychological symptoms and ten items the OFF neuropsychological manifestations. Each item rated from 0-3, providing respective subscores from 0 to 30. Conclusions Once validated, our NFS can be used to identify and quantify neuropsychiatric fluctuations during motor fluctuations. The main novelty is that it could be used in acute settings. As such, the NFS can assess the neuropsychiatric state of the patient at the time of examination. The next step will be to validate the NFS to be used in current practice.
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Affiliation(s)
- Emmanuelle Schmitt
- Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation CHU Grenoble Grenoble France.,Grenoble Institut des Neurosciences Grenoble Alpes University France.,Inserm U1216 Grenoble France
| | - Paul Krack
- Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation CHU Grenoble Grenoble France.,Grenoble Institut des Neurosciences Grenoble Alpes University France.,Inserm U1216 Grenoble France.,Department of Clinical Neuroscience, Hôpitaux Universitaires de Genève University of Geneva Switzerland
| | - Anna Castrioto
- Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation CHU Grenoble Grenoble France.,Grenoble Institut des Neurosciences Grenoble Alpes University France.,Inserm U1216 Grenoble France
| | - Helene Klinger
- Hospices Civils de Lyon, Hôpital Neurologique Neurologie C Lyon France.,Faculté de Médecine et de Maïeutique Lyon Sud Charles Mérieux, Université de Lyon 1 Université de Lyon Lyon France.,CNRS, UMR 5229 Centre de Neurosciences Cognitives Bron France
| | - Amelie Bichon
- Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation CHU Grenoble Grenoble France.,Grenoble Institut des Neurosciences Grenoble Alpes University France.,Inserm U1216 Grenoble France
| | - Eugénie Lhommée
- Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation CHU Grenoble Grenoble France.,Grenoble Institut des Neurosciences Grenoble Alpes University France.,Inserm U1216 Grenoble France
| | - Pierre Pelissier
- Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation CHU Grenoble Grenoble France.,Grenoble Institut des Neurosciences Grenoble Alpes University France.,Inserm U1216 Grenoble France
| | - Valerie Fraix
- Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation CHU Grenoble Grenoble France.,Grenoble Institut des Neurosciences Grenoble Alpes University France.,Inserm U1216 Grenoble France
| | - Stephane Thobois
- Hospices Civils de Lyon, Hôpital Neurologique Neurologie C Lyon France.,Faculté de Médecine et de Maïeutique Lyon Sud Charles Mérieux, Université de Lyon 1 Université de Lyon Lyon France.,CNRS, UMR 5229 Centre de Neurosciences Cognitives Bron France
| | - Elena Moro
- Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation CHU Grenoble Grenoble France.,Grenoble Institut des Neurosciences Grenoble Alpes University France.,Inserm U1216 Grenoble France
| | - Pablo Martinez-Martin
- National Center of Epidemiology Carlos III Institute of Health Madrid Spain.,CIBERNED Carlos III Institute of Health Madrid Spain
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Clinimetrics of the 9- and 19-Item Wearing-Off Questionnaire: A Systematic Review. PARKINSONS DISEASE 2018; 2018:5308491. [PMID: 29808113 PMCID: PMC5902048 DOI: 10.1155/2018/5308491] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Revised: 01/17/2018] [Accepted: 02/19/2018] [Indexed: 11/17/2022]
Abstract
The treatment of Parkinson's disease (PD) with dopaminergic therapy improves functionality and quality of life. However, as the disease progresses, the wearing-off phenomenon develops, which necessitates complex posology adjustment or adjuvant therapy. This phenomenon may not be well recognized, especially if it is mild or involves nonmotor symptoms. Questionnaires were developed to improve the recognition of the wearing-off phenomenon. The questionnaires consist of a list of symptoms that patients must check if they have and if the symptoms improve with medication. A recent review by the Movement Disorder Society suggested the 19-item (WOQ-19) and 9-item (WOQ-9) questionnaires as screening tools for the wearing-off phenomenon. However, there has not been a systematic review to assess the questionnaires' clinimetric properties, such as sensitivity, specificity, test-retest reliability, and responsiveness. We conducted an extensive search for studies using these two tools. We identified 3 studies using WOQ-19 and 5 studies using WOQ-9. Both questionnaires seem to have good sensitivity (0.81–1). WOQ-19 has variable specificity (0.39–0.8), depending on the number of positive items, while WOQ-9 lacks specificity (0.1–0.69). Only one study using WOQ-19 reported test-retest, and only two studies reported responsiveness. Thus, this report describes the first independent systematic review to exam quantitatively the clinimetric properties of these two questionnaires.
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Kim A, Kim HJ, Shin CW, Kim A, Kim Y, Jang M, Jung YJ, Lee WW, Park H, Jeon B. Emergence of non-motor fluctuations with reference to motor fluctuations in Parkinson's disease. Parkinsonism Relat Disord 2018; 54:79-83. [PMID: 29724602 DOI: 10.1016/j.parkreldis.2018.04.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Revised: 03/27/2018] [Accepted: 04/17/2018] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Non-motor fluctuations (NMF) and motor fluctuations (MF) are frequent in patients with Parkinson's disease (PD) with long-term medical treatment. We aimed to examine the timing of the emergence of NMF with reference to MF in a prospective cohort of patients with PD without symptom fluctuations. METHODS A total of 334 patients with PD who had neither MF nor NMF were recruited. The exclusion criteria included a Mini-Mental State Examination score of less than 26 points at baseline and an alternative diagnosis or significant comorbidity during follow-up. The "SNUH-Fluctuation Questionnaire" consisting of 29 items (9 on MF and 20 on NMF) was administered on a semi-annually basis for 3 years. RESULTS Three hundred seven out of 334 patients were analyzed for symptom fluctuations with the Kaplan-Meier survival analysis. MF were observed in more patients and developed earlier than NMF (cumulative survival of 0.572 for MF and 0.619 for NMF at 36 months of follow-up). In 212 patients who finished the follow-up for 36 months, MF and NMF developed simultaneously in 58 (27.4%), MF developed first in 45 (21.2%), and NMF developed first in only 3 (1.4%). The remaining 106 patients (50.0%) did not develop either MF or NMF. CONCLUSION NMF developed simultaneously with or later than MF. From these data, we hypothesize that NMF develop in the disease state where the pathology in the brain has been severe enough to develop MF. Hence, pharmacologic management should consider targeting both dopaminergic and non-dopaminergic systems to treat NMF.
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Affiliation(s)
- Aryun Kim
- Department of Neurology, Movement Disorder Center, Seoul National University Hospital, Parkinson Study Group, Seoul National University College of Medicine, Seoul, South Korea
| | - Han-Joon Kim
- Department of Neurology, Movement Disorder Center, Seoul National University Hospital, Parkinson Study Group, Seoul National University College of Medicine, Seoul, South Korea
| | - Chae Won Shin
- Department of Neurology, Kyung Hee University Medical Center, Seoul, South Korea
| | - Ahro Kim
- Department of Neurology, Catholic University of Korea, Seoul, South Korea
| | - Yoon Kim
- Department of Neurology, Movement Disorder Center, Seoul National University Hospital, Parkinson Study Group, Seoul National University College of Medicine, Seoul, South Korea
| | - Mihee Jang
- Department of Neurology, Movement Disorder Center, Seoul National University Hospital, Parkinson Study Group, Seoul National University College of Medicine, Seoul, South Korea
| | - Yu Jin Jung
- Department of Neurology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, South Korea
| | - Woong-Woo Lee
- Department of Neurology, Nowon Eulji Medical Center, Eulji University, Seoul, South Korea
| | - Hyeyoung Park
- Department of Neurology, Hallym Hospital, Incheon, South Korea
| | - Beomseok Jeon
- Department of Neurology, Movement Disorder Center, Seoul National University Hospital, Parkinson Study Group, Seoul National University College of Medicine, Seoul, South Korea.
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Chou KL, Stacy M, Simuni T, Miyasaki J, Oertel WH, Sethi K, Fernandez HH, Stocchi F. The spectrum of "off" in Parkinson's disease: What have we learned over 40 years? Parkinsonism Relat Disord 2018; 51:9-16. [PMID: 29456046 DOI: 10.1016/j.parkreldis.2018.02.001] [Citation(s) in RCA: 105] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Revised: 12/18/2017] [Accepted: 02/01/2018] [Indexed: 02/07/2023]
Abstract
The terms "on" and "off" were used by Marsden and his contemporaries over 40 years ago to describe times when Parkinson's disease patients experienced good motor function ("on") and immobility ("off"). Yet there remains no published consensus definition of "off", leading clinicians and patients to develop individualized impressions of "off" determinations. In this paper, we first discuss the evolution of the terminology and understanding of "off" states since Marsden's time, which now include non-motor as well as motor symptoms. We then review pathophysiology and risk factors for the development of "off" states as well as tools to detect the "off" state, before proposing a practical definition of "off" for consideration. A common, practical definition of the "off" state could improve clinical recognition of "off" symptoms and lead to significant benefit for patients.
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Affiliation(s)
- Kelvin L Chou
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
| | - Mark Stacy
- Department of Neurology, Duke University Medical Center, Durham, NC, USA
| | - Tanya Simuni
- Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Janis Miyasaki
- Division of Neurology, Department of Medicine, University of Alberta, Kaye Edmonton Clinic, Canada
| | - Wolfgang H Oertel
- Department of Neurology, University Clinic, Philipps Universität Marburg, Marburg, Germany; Institute for Neurogenomics, Helmholtz Center for Health and Environment, Munich, Germany
| | - Kapil Sethi
- Department of Neurology, Medical College of Georgia at Augusta University, Augusta, GA, USA
| | - Hubert H Fernandez
- Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA
| | - Fabrizio Stocchi
- Department of Neurology, Institute for Research and Medical Care, IRCCS San Raffaele Roma, Roma, Italy
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24
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Objective Measurement and Monitoring of Nonmotor Symptoms in Parkinson's Disease. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2017. [PMID: 28802925 DOI: 10.1016/bs.irn.2017.04.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/25/2024]
Abstract
The comprehensive evaluation of nonmotor symptoms (NMS) in Parkinson's disease (PD) starts with the awareness of physicians, patients, and caregivers on their nature, clinical presentation, and effect on patient's daily activities and quality of life. This awareness can be better achieved if the symptoms can be visualized, measured, and monitored. As NMS are largely subjective in nature, a majority of them cannot be visualized (unlike tremor, which is easily seen), making their identification and quantification difficult. While symptoms are nonmotor, it does not mean that they are not measurable, as many NMS are integral to motor symptoms of Parkinson's, yet often neglected. In this review, we attempt to provide the most up-to-date and comprehensive literature review on the objective measurement and monitoring of NMS in PD. The aim is to make it clinically relevant by approaching NMS by domains as identified in the NMS Questionnaire. A section on the assessment of nonmotor fluctuations is also included, providing prospects for future objective monitoring. With the advances of technology, it is likely that many NMS will have objective outcomes, thus making these symptoms easily measurable and hopefully lead to future clinical trials that incorporate nonmotor outcomes. Nevertheless, it still requires a physician's judgment to determine which method, scales, objective measures, or monitoring devices or a combination of these is most appropriate to the individual patient in order to answer a particular clinical question.
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25
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Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues. J Neural Transm (Vienna) 2017; 124:1029-1036. [PMID: 28702850 DOI: 10.1007/s00702-017-1757-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 07/06/2017] [Indexed: 02/07/2023]
Abstract
Parkinson's disease (PD) is a neurodegenerative multisystem disorder characterized by progressive motor symptoms such as bradykinesia, tremor and muscle rigidity. Over the course of the disease, numerous non-motor symptoms, sometimes preceding the onset of motor symptoms, significantly impair patients' quality of life. The significance of non-motor symptoms may outweigh the burden through progressive motor incapacity, especially in later stages of the disease. The advanced stage of the disease is characterized by motor complications such as fluctuations and dyskinesias induced by the long-term application of levodopa therapy. In recent years, it became evident that various non-motor symptoms such as psychiatric symptoms, fatigue and pain also show fluctuations after chronic levodopa therapy (named non-motor fluctuations or NMFs). Although NMFs have moved into the focus of interest, current national guidelines on the treatment of PD may refer to non-motor symptoms and their management, but do not mention NMF, and do not contain recommendations on their management. The present article summarizes major issues related to NMF including clinical phenomenology and pathophysiology, and outlines a number of open issues and topics for future research.
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Abstract
Apart from the typical motor symptoms, Parkinson's disease is characterized by a wide range of different non-motor symptoms, which are highly prevalent in all stages of the disease and have an incisive influence on quality of life. Moreover, their treatment continues to be challenging. In this review, we critically summarize the evidence for the impact of dopaminergic therapies on non-motor symptoms in Parkinson's disease. We performed a PubMed search to identify relevant clinical studies that investigated the response of non-motor symptoms to dopaminergic therapy. In the domain of neuropsychiatric disturbances, there is increasing evidence that dopamine agonists can ameliorate depression or anxiety. Other neuropsychiatric symptoms such as psychosis or impulse control disorders can also be worsened or even be induced by dopaminergic agents. For the treatment of sleep disturbances, it is essential to identify different subtypes of sleep pathologies. While there is for example profound evidence for the effectiveness of dopaminergic medication for the treatment of restless legs syndrome and sleep fragmentation, evidence for an improvement of rapid eye movement sleep behavior disorder is lacking. With regard to the broad spectrum of autonomic disturbances, response to dopaminergic treatment seems to differ largely, with on the one hand, some evidence for an improvement of sexual function or sweating with dopaminergic treatment, while on the other hand, constipation can be worsened. Finally, the analysis of sensory deficits reveals that some forms of pain, in particular fluctuation-dependent dystonic pain, can be well addressed by adapting the dopaminergic therapy, while no effect has been seen so far for hyposmia or visual deficits. Moreover, the occurrence of non-motor fluctuations is gaining increased attention, as they can be specifically addressed by a more continuous dopaminergic intake. Taken together, there is evidence of a good response of some (but not all) non-motor symptoms to dopaminergic therapy, which must be individually adapted to the special spectrum of symptoms.
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Affiliation(s)
- Eva Schaeffer
- Department of Neurology, Christians-Albrechts University, Arnold-Heller-Str. 3, Haus 41, Kiel, 24105, Germany.
| | - Daniela Berg
- Department of Neurology, Christians-Albrechts University, Arnold-Heller-Str. 3, Haus 41, Kiel, 24105, Germany
- Department of Neurodegeneration, Hertie-Institute of Clinical Brain Research, Tuebingen, Germany
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Martinez-Martin P, Rodriguez-Blazquez C, Forjaz MJ, Kurtis MM, Skorvanek M. Measurement of Nonmotor Symptoms in Clinical Practice. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2017; 133:291-345. [PMID: 28802923 DOI: 10.1016/bs.irn.2017.04.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nonmotor symptoms constitute a prominent part of Parkinson's disease manifestations. They are present since the first phases of the disease, increase their number and severity with disease progression, and importantly impact on patients' health and quality of life, caregivers' burden, and social resources. Research on Parkinson's disease has traditionally focused on the motor aspects of the disease, but an increasing interest in the nonmotor manifestations has risen in the past decade. The availability of assessment instruments for detecting and measuring these symptoms has allowed understanding of their importance and course over time, as well as estimation of therapeutic effects on them. In this chapter, a review of the basic characteristics of nonmotor symptom assessments used in clinical practice and research are presented.
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Affiliation(s)
- Pablo Martinez-Martin
- National Center of Epidemiology and CIBERNED, Institute of Health Carlos III, Madrid, Spain.
| | | | - Maria João Forjaz
- National School of Public Health and REDISSEC, Institute of Health Carlos III, Madrid, Spain
| | - Monica M Kurtis
- Movement Disorders Unit, Hospital Ruber Internacional, Madrid, Spain
| | - Matej Skorvanek
- P.J. Safarik University, Kosice, Slovakia; University Hospital of L. Pasteur, Kosice, Slovakia
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28
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Nonmotor Fluctuations in Parkinson's Disease. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2017; 134:947-971. [DOI: 10.1016/bs.irn.2017.05.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Ouma S, Fukae J, Fujioka S, Yamamoto S, Hatano T, Yoritaka A, Okuma Y, Kashihara KI, Hattori N, Tsuboi Y. The Risk Factors for the Wearing-off Phenomenon in Parkinson's Disease in Japan: A Cross-sectional, Multicenter Study. Intern Med 2017; 56:1961-1966. [PMID: 28768964 PMCID: PMC5577070 DOI: 10.2169/internalmedicine.56.7667] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Objective Parkinson's disease (PD) is a common, progressive, neurodegenerative disorder. With progression of PD, the wearing-off phenomenon occurs more frequently as a motor complication, decreasing the patient's quality of life. The aim of this study was to investigate the risk factors for the wearing-off phenomenon in Japanese PD patients. Methods All of the study participants were clinically diagnosed as having PD. Each patient was assessed for the wearing-off phenomenon based on the findings of clinical assessments and interviews that were conducted during a single visit. The risk factors for wearing-off were analyzed by univariate and multivariate logistic regression analyses. Results Wearing-off was observed in 101 of the 180 (56.1%) patients who were enrolled in this study. The multivariate logistic regression analysis revealed that the onset of PD at ≥69 years of age (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.05-0.88; p=0.032), female sex (OR, 6.49; 95% CI, 2.34-17.99; p<0.001), catechol-O-methyltransferase (COMT) inhibitor treatment (OR, 19.59; 95% CI, 3.55-108.11; p<0.001) and a high daily levodopa dosage (≥600 mg/day) (OR, 7.69; 95% CI, 1.41-41.84; p=0.018) were independent predictive factors for wearing-off in Japanese PD patients. Conclusion Age at the symptomatic disease onset, female sex, COMT inhibitor treatment, and a high daily levodopa dose were associated with the occurrence of wearing-off in Japanese PD patients. Physicians need to consider the risk factors and carefully choose medications for PD patients to postpone the occurrence of this phenomenon for as long as possible.
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Affiliation(s)
- Shinji Ouma
- Department of Neurology, Fukuoka University School of Medicine, Japan
| | - Jiro Fukae
- Department of Neurology, Fukuoka University School of Medicine, Japan
| | - Shinsuke Fujioka
- Department of Neurology, Fukuoka University School of Medicine, Japan
| | | | - Taku Hatano
- Department of Neurology, Juntendo University School of Medicine, Japan
| | - Asako Yoritaka
- Department of Neurology, Juntendo Koshigaya Hospital, Japan
| | - Yasuyuki Okuma
- Department of Neurology, Juntendo Shizuoka Hospital, Japan
| | | | - Nobutaka Hattori
- Department of Neurology, Juntendo University School of Medicine, Japan
| | - Yoshio Tsuboi
- Department of Neurology, Fukuoka University School of Medicine, Japan
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30
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Nonmotor Symptoms in Parkinson's Disease: Gender and Ethnic Differences. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2017; 133:417-446. [DOI: 10.1016/bs.irn.2017.05.032] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
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Murata M, Mihara M, Hasegawa K, Jeon B, Tsai CH, Nishikawa N, Oeda T, Yokoyama M, Robieson WZ, Ryman D, Eaton S, Chatamra K, Benesh J. Efficacy and safety of levodopa-carbidopa intestinal gel from a study in Japanese, Taiwanese, and Korean advanced Parkinson's disease patients. NPJ PARKINSONS DISEASE 2016; 2:16020. [PMID: 28725701 PMCID: PMC5516619 DOI: 10.1038/npjparkd.2016.20] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 07/01/2016] [Accepted: 08/23/2016] [Indexed: 01/12/2023]
Abstract
In a previous multinational, randomized, double-blind, double-dummy study, levodopa–carbidopa intestinal gel (LCIG) was tolerable and significantly improved ‘off’ time in advanced Parkinson’s disease (PD) patients. However, efficacy and safety in the Asian population has not yet been demonstrated. In this open-label study, efficacy and safety of LCIG were assessed in Japanese, Korean, and Taiwanese advanced PD patients with motor complications not adequately controlled by available PD medication. The patients were treated with LCIG monotherapy for 12 weeks. The primary end point was the mean change from baseline to week 12 in ‘off’ time, as reported in the PD Symptom Diary, normalized to a 16 h waking day and analyzed by a mixed-model repeated-measures analysis. Adverse events (AEs) were recorded. Thirty-one patients were enrolled (23 Japanese, 4 Taiwanese, 4 Korean) and 28 (90%) completed the study. For those who completed the study, the mean (s.d.) total daily levodopa dose from LCIG was 1,206.3 (493.6) mg/day at final visit (n=28); last observation carried forward (n=30) was 1,227.6 (482.8) mg/day. There was a significant mean change (s.d.) of −4.6 (3.0) hours of ‘off’ time from baseline (mean (s.d.)=7.4 (2.3)) to week 12 (n=29), P<0.001. All the patients had an AE, with the most frequently reported being incision site pain (42%); 1 (3.2%) discontinued treatment because of an AE and later died because of sepsis, which the investigator considered unrelated to LCIG treatment. These results suggest that LCIG is efficacious and tolerable in Japanese, Taiwanese, and Korean advanced PD patients.
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Affiliation(s)
- Miho Murata
- National Center of Neurology and Psychiatry, Tokyo, Japan
| | | | - Kazuko Hasegawa
- National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan
| | | | - Chon-Haw Tsai
- Department of Neurology, China Medical University Hospital and Medical College, China Medical University, Taichung, Taiwan
| | | | - Tomoko Oeda
- National Hospital Organization Utano Hospital, Kyoto, Japan
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Young Blood MR, Ferro MM, Munhoz RP, Teive HAG, Camargo CHF. Classification and Characteristics of Pain Associated with Parkinson's Disease. PARKINSON'S DISEASE 2016; 2016:6067132. [PMID: 27800210 PMCID: PMC5069361 DOI: 10.1155/2016/6067132] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 09/18/2016] [Indexed: 12/25/2022]
Abstract
Neuropsychiatric symptoms and pain are among the most common nonmotor symptoms of Parkinson's disease (PD). The correlation between pain and PD has been recognized since its classic descriptions. Pain occurs in about 60% of PD patients, two to three times more frequent in this population than in age matched healthy individuals. It is an early and potentially disabling symptom that can precede motor symptoms by several years. The lower back and lower extremities are the most commonly affected areas. The most used classification for pain in PD defines musculoskeletal, dystonic, central, or neuropathic/radicular forms. Its different clinical characteristics, variable relationship with motor symptoms, and inconsistent response to dopaminergic drugs suggest that the mechanism underlying pain in PD is complex and multifaceted, involving the peripheral nervous system, generation and amplification of pain by motor symptoms, and neurodegeneration of areas related to pain modulation. Although pain in DP is common and a significant source of disability, its clinical characteristics, pathophysiology, classification, and management remain to be defined.
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Affiliation(s)
| | - Marcelo Machado Ferro
- Neuropsychopharmacology Laboratory, State University of Ponta Grossa, Ponta Grossa, PR, Brazil
| | - Renato Puppi Munhoz
- Movement Disorders Centre, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada
| | - Hélio Afonso Ghizoni Teive
- Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, PR, Brazil
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Martínez-Fernández R, Schmitt E, Martinez-Martin P, Krack P. The hidden sister of motor fluctuations in Parkinson's disease: A review on nonmotor fluctuations. Mov Disord 2016; 31:1080-94. [PMID: 27431515 DOI: 10.1002/mds.26731] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 06/13/2016] [Accepted: 06/19/2016] [Indexed: 12/29/2022] Open
Abstract
Only a few years after the introduction of levodopa, the first descriptions of motor fluctuations and dyskinesia related to dopaminergic therapy appeared. In PD, attention turned to their management, that had dampened the euphoria of the "levodopa miracle." It soon became clear that neuropsychiatric, autonomic, and sensory features also tend to develop fluctuations after chronic exposure to l-dopa. The diversity of fluctuating nonmotor symptoms, their largely subjective nature, coupled with a frequent lack of insight led to difficulties in identification and quantification. This may explain why, despite the high impact of nonmotor symptoms on patient autonomy and quality of life, evaluation of nonmotor fluctuations is not part of clinical routine. In view of the lack of specific validated assessment tools, detailed anamnesis should ideally be coupled with an evaluation in both ON and OFF drug conditions. The mechanisms of nonmotor fluctuations are not well understood. It is thought that they share dopaminergic presynaptic pharmacokinetic and postsynaptic pharmacodynamic mechanisms with the classical motor complications, but involve different neural pathways. Although symptoms fluctuate with dopaminergic treatment, serotonine and norepinephrine denervation, as well as interactions between neurotransmitter systems, probably contribute to their diversity. The lack of validated tools for assessment of these phenomena explains the almost complete absence of treatment studies. Management, largely resulting from expert opinion, includes psychiatric follow-up, nondopaminergic drugs, and advanced dopaminergic treatment, including drug delivery pumps and DBS. This review aims to provide a starting point for the understanding, diagnosis, and management of nonmotor fluctuations. © 2016 International Parkinson and Movement Disorder Society.
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Affiliation(s)
| | - Emmanuelle Schmitt
- Movement Disorders Unit, Department of Psychiatry and Neurology, CHU de Grenoble, Université de Grenoble Alpes and Grenoble Institut des Neurosciences, INSERM U386, Grenoble, France
| | - Pablo Martinez-Martin
- National Center of Epidemiology, Carlos III Institute of Health and CIBERNED, Madrid, Spain
| | - Paul Krack
- Neurology Division, Department of Clinical Neurosciences, University Hospital of Geneva, Geneva, Switzerland
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Nonmotor Features in Parkinson's Disease: What Are the Most Important Associated Factors? PARKINSONS DISEASE 2016; 2016:4370674. [PMID: 27195172 PMCID: PMC4853954 DOI: 10.1155/2016/4370674] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Accepted: 03/30/2016] [Indexed: 11/24/2022]
Abstract
Introduction. The purpose of this study was to demonstrate the frequency and severity of nonmotor symptoms and their correlations with a wide range of demographic and clinical factors in a large cohort of patients with Parkinson's disease (PD). Methods. 268 PD patients were assessed using the validated Movement Disorders Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Beck Depression Inventory (BDI), Parkinson's Disease Questionnaire (PDQ-39), the Hoehn and Yahr scale (HY), the Schwab and England Activities of Daily Living (SE-ADL) Scale, and the Minimental State Examination (MMSE). Results. Nonmotor symptoms had a strong positive relationship with depression and lower quality of life. Also, age, duration and severity of PD, cognitive impairment, daily dose, and duration of levodopa treatment correlated with the burden of nonmotor symptoms. Patients with postural instability and gait disorder (PIGD) dominance or with the presence of motor complications had higher MDS-UPDRS Part I scores expressing the load of nonmotor features, compared to participants with other disease subtypes or without motor complications. Conclusions. Though the severity of individual nonmotor symptoms was generally rated by PD patients as “mild” or less, we found a significant cumulative effect of nonmotor symptoms on patients' mood, daily activities, and quality of life.
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Fauser M, Löhle M, Ebersbach G, Odin P, Fuchs G, Jost WH, Chaudhuri KR, Koch R, Storch A. Intraindividual Variability of Nonmotor Fluctuations in Advanced Parkinson’s Disease. JOURNAL OF PARKINSONS DISEASE 2015; 5:737-41. [DOI: 10.3233/jpd-150656] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Mareike Fauser
- Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, Dresden, Germany
| | - Matthias Löhle
- Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, Dresden, Germany
- Department of Neurology, University of Rostock, Rostock, Germany
| | | | - Per Odin
- Department of Neurology, Klinikum Bremerhaven, Bremerhaven, Germany
- Department of Neurology, University Hospital, Lund, Sweden
| | - Gerd Fuchs
- Parkinson Clinic Wolfach, Wolfach, Germany
| | | | - K. Ray Chaudhuri
- National Parkinson Foundation Centre of Excellence, Kings College Hospital and Kings College London and Biomedical Research Centre, Kings College London, UK
| | - Rainer Koch
- Department of Medical Informatics and Biometry, Technische Universität Dresden, Dresden, Germany
| | - Alexander Storch
- Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden, Dresden, Germany
- Department of Neurology, University of Rostock, Rostock, Germany
- German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany
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Bhidayasiri R, Hattori N, Jeon B, Chen RS, Lee MK, Bajwa JA, Mok VCT, Zhang B, Syamsudin T, Tan LCS, Jamora RDG, Pisarnpong A, Poewe W. Asian perspectives on the recognition and management of levodopa ‘wearing-off’ in Parkinson’s disease. Expert Rev Neurother 2015; 15:1285-97. [DOI: 10.1586/14737175.2015.1088783] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Baquero M, Martín N. Depressive symptoms in neurodegenerative diseases. World J Clin Cases 2015; 3:682-693. [PMID: 26301229 PMCID: PMC4539408 DOI: 10.12998/wjcc.v3.i8.682] [Citation(s) in RCA: 114] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Revised: 02/12/2015] [Accepted: 05/27/2015] [Indexed: 02/05/2023] Open
Abstract
Depressive symptoms are very common in chronic conditions. This is true so for neurodegenerative diseases. A number of patients with cognitive decline and dementia due to Alzheimer’s disease and related conditions like Parkinson’s disease, Lewy body disease, vascular dementia, frontotemporal degeneration amongst other entities, experience depressive symptoms in greater or lesser grade at some point during the course of the illness. Depressive symptoms have a particular significance in neurological disorders, specially in neurodegenerative diseases, because brain, mind, behavior and mood relationship. A number of patients may develop depressive symptoms in early stages of the neurologic disease, occurring without clear presence of cognitive decline with only mild cognitive deterioration. Classically, depression constitutes a reliable diagnostic challenge in this setting. However, actually we can recognize and evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in order to establish their clinical significance and to plan some therapeutic strategies. Depressive symptoms can appear also lately, when the neurodegenerative disease is fully developed. The presence of depression and other neuropsychiatric symptoms have a negative impact on the quality-of-life of patients and caregivers. Besides, patients with depressive symptoms also tend to further decrease function and reduce cognitive abilities and also uses to present more affected clinical status, compared with patients without depression. Depressive symptoms are treatable. Early detection of depressive symptoms is very important in patients with neurodegenerative disorders, in order to initiate the most adequate treatment. We review in this paper the main neurodegenerative diseases, focusing in depressive symptoms of each other entities and current recommendations of management and treatment.
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Chattha PK, Greene PE, Ramdhani RA. Pseudobulbar laughter as a levodopa off phenomenon exacerbated by subthalamic deep brain stimulation. JOURNAL OF CLINICAL MOVEMENT DISORDERS 2015; 2:13. [PMID: 26788349 PMCID: PMC4711012 DOI: 10.1186/s40734-015-0023-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 07/27/2015] [Indexed: 11/10/2022]
Abstract
Pseudobulbar affect is a common symptom in neurodegenerative diseases and can also result from lesions in cortical, subcortical and brainstem regions. In Parkinson’s disease (PD), pseudobulbar affect (PBA) can occur as a wearing off phenomenon, manifested usually as crying without emotionality. In addition, subthalamic (STN) deep brain stimulation (DBS) has been reported to induce PBA in PD patients with no prior history of such episodes. We present a case of inappropriate laughter lacking mirth as a levodopa OFF phenomenon in a patient with PD, whose laughter also worsened with STN-DBS in his non-medicated state. Levodopa ameliorated his PBA both with and without stimulation. The case demonstrates pseudobulbar laughter as a levodopa OFF phenomenon that is also exacerbated by STN-DBS.
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Affiliation(s)
- P K Chattha
- Medical University of Lublin, Lublin, Poland
| | - P E Greene
- Department of Neurology Division of Movement Disorders, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA
| | - Ritesh A Ramdhani
- Department of Neurology Division of Movement Disorders, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA ; Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, 5 East 98th St. First Floor, New York, NY 10029 USA
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39
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Storch A, Schneider CB, Klingelhöfer L, Odin P, Fuchs G, Jost WH, Martinez-Martin P, Koch R, Reichmann H, Chaudhuri KR, Ebersbach G. Quantitative assessment of non-motor fluctuations in Parkinson’s disease using the Non-Motor Symptoms Scale (NMSS). J Neural Transm (Vienna) 2015; 122:1673-84. [DOI: 10.1007/s00702-015-1437-x] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Accepted: 07/29/2015] [Indexed: 01/09/2023]
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40
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Utility of the Japanese version of the 9-item Wearing-off Questionnaire. Clin Neurol Neurosurg 2015; 134:110-5. [DOI: 10.1016/j.clineuro.2015.04.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2014] [Revised: 04/21/2015] [Accepted: 04/26/2015] [Indexed: 11/21/2022]
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Altavista M, Cassetta E, Brusa L, Viselli F, Denaro A, Ventriglia M, Pasqualetti P, Peppe A. Wearing-off detection in clinical practice: The wearing off real practice key (WORK-PD) study in Parkinson's disease. Parkinsonism Relat Disord 2015; 21:95-100. [DOI: 10.1016/j.parkreldis.2014.11.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Revised: 10/03/2014] [Accepted: 11/03/2014] [Indexed: 11/27/2022]
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Brun L, Lefaucheur R, Fetter D, Derrey S, Borden A, Wallon D, Bourre B, Maltête D. Non-motor fluctuations in Parkinson's disease: Prevalence, characteristics and management in a large cohort of parkinsonian outpatients. Clin Neurol Neurosurg 2014; 127:93-6. [DOI: 10.1016/j.clineuro.2014.10.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2014] [Revised: 08/20/2014] [Accepted: 10/04/2014] [Indexed: 01/27/2023]
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Abstract
Non-motor symptoms are a key component of Parkinson's disease, possibly representing a clinical biomarker of its premotor phase. The burden of non-motor symptoms can define a patient's health-related quality of life. Non-motor symptoms substantially increase the cost of care-requiring increased hospitalisation and treatment-and pose a major challenge to healthcare professionals. However, clinicians often regard non-motor symptoms and their management as peripheral to that of the motor symptoms. Here, we address the clinical issues and unmet needs of non-motor symptoms in Parkinson's disease.
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Affiliation(s)
- Antoniya Todorova
- Department of Neurology, National Parkinson Foundation Centre of Excellence, King's College Hospital, and Kings College, London, UK
| | - Peter Jenner
- Institute of Pharmaceutical Science, King's College London, London, UK
| | - K Ray Chaudhuri
- Department of Neurology, National Parkinson Foundation Centre of Excellence, King's College Hospital, and Kings College, London, UK
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