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The 5-2-1 criteria was developed to facilitate the identification and referral of patients with Parkinson's Disease (PD) inadequately controlled by oral medications. The criterion was not developed to screen patients with PD for device-aided therapy eligibility. The robust design and validation of the 5-2-1 criteria minimizes over or inappropriate referrals, and supports physicians in the timely identification of patients with PD who may warrant further evaluation for treatment optimization. This response letter clarifies concerns raised by Moes et al.
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Enfermedad de Parkinson , Enfermedad de Parkinson/diagnóstico , Humanos , Antiparkinsonianos/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: Sleep disturbances are amongst most frequent non-motor symptoms of Parkinson's Disease (PD), and they are similarly frequently reported in other alpha-syncleinopathies, such as Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). More recently, the orexin system has been implicated in control of arousal based on salient environmental set points, and its dysregulation in sleep issues in alpha-synucleinopathies suggested by the findings from the translational animal models. However, its role in the patients with alpha-synucleinopathies remains unclear. We thus set to systematically review, and to critically assess, contemporary evidence on the association of the orexinergic system and sleep disturbances in alpha-synucleinopathies. In this systematic review, studies investigating orexin and sleep in alpha-synucleinopathies (Rapid Eye Movement (REM) Behaviour Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) were identified using electronic database searches of PubMed, Web of Science and PsychINFO using MeSH terms, keywords, and title words such as "Alpha-synucleinopathies" AND "Orexin" AND "Sleep Disturbances". RECENT FINDINGS: 17 studies were included in this systemic review, of which 2 studies on RBD, 10 on PD, 4 on DLB, and 1 on MSA patients. Taken together, RBD and PD studies suggest a potential adaptive increase in orexin levels in early stages of the neurodegenerative process, with reduced levels more often reported for later, more advanced stages of illness. To date, no differences in orexin levels were demonstrated between MSA patients and healthy controls. There is a dearth of studies on the role of orexin levels in alpha-synucleinopathies. Moreover, significant methodologic limitations in the current body of work, including use of non-standardised research protocols and lack of prospective, multi-centre studies, disallow for any finite conclusion in regards to underlying pathomechanisms. Nonetheless, a picture of a complex, multifaceted relationship between the dysregulation of the orexinergic pathway and sleep disturbances in alpha-synucleinopathies is emerging. Hence, future studies disentangling orexinergic pathomechanisms of alpha-syncleinopathies are urgently needed to obtain a more comprehensive account of the role of orexinergic pathway in alpha-synucleinopathies. Pharmacological manipulations of orexins may have multiple therapeutic applications in treatment strategies, disease diagnosis, and might be effective for treating both motor and non-motor symptoms.
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The management of Parkinson's disease (PD) continues to evolve with advancements in non-oral levodopa-based therapies aiming to provide continuous drug delivery (CDD). Such therapies address the challenges posed by the emergence of motor fluctuations, dyskinesias, and non-motor fluctuations (NMF) associated with oral levodopa administration and contributing to define the advanced stage of PD. The key focus of this review is placed on subcutaneous foslevodopa/foscarbidopa (Foslevodopa/foscarbidopa) infusion, showcasing its recent clinical availability and efficacy in providing continuous levodopa delivery. While providing an overview of the other non-oral levodopa-based CDD systems, such as intrajejunal levodopa-carbidopa infusion and levodopa-entacapone-carbidopa infusion, we highlight the current promising evidence for Foslevodopa/foscarbidopa to improve, for example, "on time" without troublesome dyskinesia and reducing "off time" in people with advanced PD. Additionally, Foslevodopa/foscarbidopa demonstrates potential in managing early morning off periods, sleep quality and other motor and non-motor symptoms. Moreover, other non-oral CDD options such as ND0612 and DIZ102/DIZ101 are discussed, with focus on their pharmacokinetics/pharmacodynamics, efficacy, and safety profiles. While these advancements present new therapeutic avenues, long-term observational studies are warranted to elucidate their impact on existing PD therapies. Overall, this review provides insights into the evolving landscape of non-oral CDD therapies and offers a pragmatic approach for their integration into clinical practice.
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Objective: Pain is one of the most common non-motor symptoms in Parkinson's disease (PD), with variable characteristics among populations. This multicenter Egyptian study aimed to translate and validate the King's Parkinson's Disease Pain Scale (KPPS) and questionnaire (KPPQ) into Arabic versions and to investigate the pain characteristics in Egyptian people with PD (PWP). Methods: 192 PWP and 100 sex and age-matched controls were evaluated by KPPS-Arabic and KPPQ-Arabic. Both tools were assessed for test-retest reliability, floor or ceiling effects, construct validity and convert validity. PWP were assessed also by MDS-UPDRS, Hoehn and Yahr, NMSS, PD Questionnaire-39, and the Non-Motor Fluctuation Assessment (NoMoFA). Results: KPPS-Arabic and KPPQ-Arabic showed inter and intra-rater consistency and high validity, with an acceptable ceiling effect. 188 PWP (97.9%) reported at least 1 type of pain, (p<0.001). The severity and prevalence of KPPS-Arabic domains were significantly higher in all pain domains among PWP compared to controls (p < 0.001). Fluctuation-related and musculoskeletal pains were the most common (81.3% and 80.7%, respectively). In the PD group, the total and domains of KPPS-Arabic were significantly correlated to the MDS-UPDRS total, parts I, II, III, PIGD, axial, and H &Y scores, but not age or age of onset. Predictors of KPPS-Arabic included the total MDS-UPDRS, part III-Off, disease duration, total NMSS, and NoMoFA. Conclusion: The current multicentre study provided a validated Arabic versions of KPPS and KPPQ, with high reliability and validity, and demonstrated a high prevalence and severity of pain within Egyptian PWP and characterized its determinants.
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Fatigue is a common non-motor symptom in Parkinson's disease (PD), but even so, it may still be underdiagnosed or misdiagnosed in current practice due to its non-specific manifestations. The aims of this study were to investigate the prevalence of fatigue in PD patients compared to healthy controls and to identify the main characteristics and associations of fatigue with other non-motor symptoms and the impact of fatigue on sleep disturbances in Parkinson's disease. MATERIALS AND METHODS: case-control study in which 131 PD patients and 131 age- and sex-matched controls were enrolled. Main characteristics of fatigue, sleep, and other non-motor symptoms were assessed using specific validated questionnaires. RESULTS: According to the Chalder fatigue scale, fatigue is more prevalent in PD patients (38.16%) compared to healthy controls (26.71%). Fatigue was identified in 46.54% of the PD patients using the Parkinson's Fatigue Scale (PFS-16). PD patients with fatigue presented a worse motor status, more sleep disturbances (insomnia, daytime sleepiness), a broader spectrum of non-motor symptoms (pain, anxiety, urinary disturbances), worse cognitive performances, a lower level of happiness, and worse quality of life compared to PD patients without fatigue. CONCLUSION: Fatigue is a common symptom of PD and needs to be assessed, considering its consequences on quality of life. Sleep disturbances have a great influence over fatigue in PD patients.
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OBJECTIVE: To evaluate the effects of transcranial direct current stimulation (tDCS) on Parkinson's disease (PD)-related pain. METHODS: This triple-blind randomized controlled trial included twenty-two patients (age range 38-85, 10 male) with PD-related pain. Eleven subjects received ten sessions of 20 minutes tDCS over the primary motor cortex contralateral to pain at 2 mA intensity. Eleven subjects received sham stimulation. Outcome measures included changes in the Kinǵs Parkinsons Pain Scale (KPPS), Brief Pain Inventory (BPI), widespread mechanical hyperalgesia (WMH), temporal summation of pain (TS), and conditioned pain modulation (CPM). RESULTS: Significant differences were found in KPPS between groups favoring the active-tDCS group compared to the sham-tDCS group at 15-days follow-up (p = 0.014) but not at 2 days post-intervention (p = 0.059). The active-group showed significant improvements over the sham-group after 15 days (p = 0.017). Significant changes were found in CPM between groups in favor of active-tDCS group at 2 days post-intervention (p = 0.002) and at 15 days (p = 0.017). No meaningful differences were observed in BPI or TS. CONCLUSIONS: tDCS of the primary motor cortex alleviates perceived PD-related pain, reduces pain sensitization, and enhances descending pain inhibition. SIGNIFICANCE: This is the first study to test and demonstrate the use of tDCS for improving PD-related pain.
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Enfermedad de Parkinson , Estimulación Transcraneal de Corriente Directa , Humanos , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/complicaciones , Masculino , Estimulación Transcraneal de Corriente Directa/métodos , Anciano , Persona de Mediana Edad , Femenino , Adulto , Anciano de 80 o más Años , Corteza Motora/fisiopatología , Manejo del Dolor/métodos , Dolor/etiología , Dolor/fisiopatología , Dimensión del DolorRESUMEN
BACKGROUND: Apomorphine sublingual film (SL-APO) is an on-demand treatment for OFF episodes in patients with Parkinson's disease (PD). OBJECTIVE: To assess the long-term (≥ 3 years) safety/tolerability and efficacy of SL-APO. METHODS: Study CTH-301 ( http://www. CLINICALTRIALS: gov NCT02542696; registered 2015-09-03) was a phase 3, multicentre, open-label study of SL-APO in PD patients with motor fluctuations, comprised of a dose-titration and long-term safety phase. All participants received SL-APO. The primary endpoint was safety/tolerability (treatment-emergent adverse events [TEAEs]) during the long-term safety phase. Efficacy assessments included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (motor examination), assessed at weeks 24, 36 and 48 during the first year of the long-term safety phase. RESULTS: 496 patients were included and 120 (24.2%) completed the long-term safety phase. Mean duration of SL-APO exposure was 294.3 days. TEAEs related to study drug were experienced by 65.3% of patients (most common: nausea [6.0%], stomatitis [1.8%], lip swelling [1.8%], dizziness [1.6%], oral mucosal erythema [1.6%], mouth ulceration [1.6%]). TEAEs leading to study drug withdrawal were experienced by 34.0% of patients (most common: nausea [5.4%], lip swelling [4.5%], mouth ulceration [2.6%], stomatitis [2.3%]). A clinically meaningful reduction in MDS-UPDRS part III score was observed as soon as 15 min following administration of SL-APO, with peak effects observed approximately 30 min post-dose and sustained up to 90 min post-dose; results were consistent over 48 weeks. CONCLUSIONS: SL-APO was generally well tolerated and efficacious over the long term as an on-demand treatment for OFF episodes in patients with PD.
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Antiparkinsonianos , Apomorfina , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , Apomorfina/administración & dosificación , Apomorfina/efectos adversos , Apomorfina/farmacología , Administración Sublingual , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Foslevodopa/foscarbidopa is a subcutaneous infusion of levodopa/carbidopa prodrugs. OBJECTIVES: Assess correlations between sleep and efficacy from interim data of a phase 3 trial of foslevodopa/foscarbidopa (NCT03781167). METHODS: Pearson correlations between sleep (Parkinson's Disease Sleep Scale-2 [PDSS-2]) and quality of life (QoL; Parkinson's Disease Questionnaire-39), motor experiences of daily living (m-EDL; Movement Disorder Society-Unified Parkinson's Disease Scale Part II), and "Off"/"On" times were calculated for baseline and week 26 improvements. Regression analyses were adjusted for baseline PDSS-2 score. RESULTS: Baseline sleep correlated moderately with QoL (r = 0.44, P < 0.001) and weakly with m-EDL (r = 0.28; P < 0.001). Sleep improvement weakly correlated with improved "Off" time (r = 0.37; P < 0.001) and QoL (r = 0.36; P < 0.001). Regression analyses demonstrated significant positive associations for improved sleep, "Off" time, QoL, and m-EDL. CONCLUSIONS: Improved sleep with foslevodopa/foscarbidopa was associated with improved QoL and "Off" time.
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Antiparkinsonianos , Carbidopa , Combinación de Medicamentos , Levodopa , Enfermedad de Parkinson , Calidad de Vida , Sueño , Humanos , Carbidopa/administración & dosificación , Carbidopa/uso terapéutico , Levodopa/administración & dosificación , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Masculino , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/uso terapéutico , Femenino , Persona de Mediana Edad , Sueño/efectos de los fármacos , Anciano , Resultado del Tratamiento , Método Doble Ciego , Actividades CotidianasRESUMEN
INTRODUCTION: Although the reported frequency of diplopia is between 10 to 40% of patients with Parkinson's disease (PD) and other movement disorders, it remains one of the most undiagnosed non-motor symptoms. Furthermore, it has a major impact on the quality of life of these patients. The aim of this study is to systematically review the literature regarding the frequency, causes, and implications of diplopia in movement disorders. METHODOLOGY: An electronic search was conducted in March and June 2023 using the PubMed database in order to identify appropriate studies. Studies that were written in English, that represented observational, analytical studies, and case reports, and that provided information regarding diplopia in movement disorders were included in the systematic review. RESULTS: A total of 686 articles were identified out of which 43 met the inclusion criteria. The studies included in the systematic review ranged from descriptive studies (case reports and case series) to analytical-observational studies (cross-sectional studies, prospective and retrospective cohort studies, and case-control studies). In Parkinson's disease, the incidence of diplopia ranged from 10 to 38%. In these patients, diplopia was linked to the presence of visual hallucinations and cognitive decline but also to convergence insufficiency and the presence of motor fluctuations. Cases of diplopia secondary to deep brain stimulation were also reported. Diplopia was associated with longer disease duration and worse motor and non-motor scores. Diplopia was also reported in other movement disorders such as multiple system atrophy (frequency as high as 18%) and progressive supranuclear palsy (frequency as high as 39%) and was associated with increased mortality and shorter duration in life span. CONCLUSIONS: Diplopia occurs in up to 38% of patients with movement disorders and has a negative impact on their health-related quality of life. Treating physicians should actively ask about diplopia and other ophthalmological symptoms, as many patients do not spontaneously report them. The pathophysiology of diplopia is complex, and it involves heterogeneous peripheral and central mechanisms. The management of these patients should involve a multidisciplinary team of health professionals in order to provide appropriate, tailored management.
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Background: Speech graph analysis (SGA) of dreams has recently shown promise as an objective and language-invariant diagnostic tool that can aid neuropsychiatric diagnosis. Whilst the notion that dreaming mentations reflect distinct physiologic processes is not new, such studies in patients with sleep disorders remain exceptionally scarce. Here, using SGA and other dream content analyses, we set to investigate structural and thematic differences in morning dream recalls of patients diagnosed with Non-Rapid Eye Movement Parasomnia (NREMP) and Idiopathic REM Sleep Behavior Disorder (iRBD). Methods: A retrospective cross-sectional study of morning dream recalls of iRBD and NREMP patients was undertaken. Traditional dream content analyses, such as Orlinsky and Hall and Van de Castle analyses, were initially conducted. Subsequently, SGA was performed in order to objectively quantify structural speech differences between the dream recalls of the two patient groups. Results: Comparable rate of morning recall of dreams in the sleep laboratory was recorded; 25% of iRBD and 18.35% of NREMP patients. Aggression in dreams was recorded by 28.57% iRBD versus 20.00% in NREMP group. iRBD patients were more likely to recall dreams (iRBD vs NREMP; P = 0.007), but they also had more white dreams, ie having a feeling of having dreamt, but with no memory of it. Visual and quantitative graph speech analyses of iRBD dreams suggested stable sequential structure, reflecting the linearity of the chronological narrative. Conversely, NREMP dream reports displayed more recursive, less stable systems, with significantly higher scores of graph connectivity measures. Conclusion: The findings of our exploratory study suggest that iRBD and NREMP patients may not only differ on what is recalled in their dreams but also, perhaps more strikingly, on how dreams are recalled. It is hoped that future SGA-led dream investigations of larger groups of patients will help discern distinct mechanistic underpinnings and any associated clinical implications.
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Non-motor symptoms (NMS) of Parkinson's disease (PD) are well described in both clinical practice and the literature, enabling their management and enhancing our understanding of PD. NMS can dominate the clinical pictures and NMS subtypes have recently been proposed, initially based on clinical observations, and later confirmed in data driven analyses of large datasets and in biomarker-based studies. In this chapter, we provide an update on what is known about three common subtypes of NMS in PD. The pain (Park-pain), sleep dysfunction (Park-sleep), and autonomic dysfunction (Park-autonomic), providing an overview of their individual classification, clinical manifestation, pathophysiology, diagnosis, and potential treatments.
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Enfermedades del Sistema Nervioso Autónomo , Enfermedad de Parkinson , Trastornos del Sueño-Vigilia , Humanos , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/etiología , Dolor/diagnóstico , Dolor/etiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Sueño , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/etiología , Trastornos del Sueño-Vigilia/terapiaRESUMEN
The heterogeneity of non-motor features observed in people with Parkinson's disease (PD) is often dominated by one or more symptoms belonging to the neuropsychiatric spectrum, such as cognitive impairment, psychosis, depression, anxiety, and apathy. Due to their high prevalence in people with PD (PwP) and their occurrence in every stage of the disease, from the prodromal to the advanced stage, it is not surprising that PD can be conceptualised as a complex neuropsychiatric disorder. Despite progress in understanding the pathophysiological mechanisms underlying the neuropsychiatric signs and symptoms in PD, and better identification and diagnosis of these symptoms, effective treatments are still a major unmet need. The impact of these symptoms on the quality of life of PwP and caregivers, as well as their contribution to the overall non-motor symptom burden can be greater than that of motor symptoms and require a personalised, holistic approach. In this chapter, we provide a general clinical overview of the major neuropsychiatric symptoms of PD.
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Disfunción Cognitiva , Enfermedad de Parkinson , Trastornos Psicóticos , Humanos , Ansiedad , Disfunción Cognitiva/diagnóstico , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Trastornos Psicóticos/etiología , Calidad de VidaRESUMEN
INTRODUCTION: The King's Parkinson's Disease Pain Scale (KPPS)/King's Parkinson's Disease Pain Questionnaire (KPPQ) was developed as a tool to quantitatively assess pain in patients with Parkinson's disease (PwPD). Here, we conducted a Japanese multicenter validation study to verify the reliability of KPPS/KPPQ in Japanese PwPD. METHODS: PwPD, ≥20 years, with unexplained pain were included; those with a definitive primary cause of pain other than PD were excluded. A total of 151 patients who fulfilled the criteria were analyzed, and test-retest reliability was investigated in 25 individuals. RESULTS: The 151 patients included 101 women (66.9 %); mean age 68.3 ± 9.9 years, mean disease duration 9.2 ± 5.2 years. The most frequent pain type in the KPPS classification was musculoskeletal pain (82.8 %). There was a positive correlation between KPPS total score and the Non-Motor Symptoms Scale (NMSS) total score, NMSS item 27, the Parkinson's disease sleep scale-version 2 (PDSS-2) total score, PDSS-2 item 10, the Parkinson's Disease Questionnaire-8 (PDQ-8) summary index and PDQ-8 item 7. Cronbach's alpha of KPPS was 0.626 (0.562-0.658) and the intraclass correlation coefficient of test-retest reliability was 0.740. Cronbach's alpha of KPPQ was 0.660 (0.617-0.705) and a test-retest reliability of kappa coefficient was 0.593 (0.0-1.0). CONCLUSIONS: KPPS correlated well with other scales for assessing pain. KPPS correlated well with patients' quality of life, non-motor symptoms, and sleep disturbances. The reproducibility of KPPS/KPPQ makes it suitable for continuous evaluation of the same patient. On the other hand, the internal consistency of KPPS/KPPQ is rather low.
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Dolor Musculoesquelético , Enfermedad de Parkinson , Anciano , Femenino , Humanos , Persona de Mediana Edad , Japón , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Calidad de Vida , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Masculino , Adulto Joven , AdultoRESUMEN
BACKGROUND: Parkinson's disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of the disease leads to a gradual deterioration in patients' quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers. OBJECTIVE: We aimed to quantify the incremental economic burden of Parkinson's disease by disease severity in a real-world setting across differing geographic regions. METHODS: Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson's Disease Specific Program™, conducted in the USA, five European countries, and Japan. RESULTS: A total of 563 neurologists provided data for 5299 individuals with Parkinson's disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs. CONCLUSIONS: People with Parkinson's disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson's disease and their caregivers, whilst also substantially impacting societal costs.
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Importance: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life (QOL) in patients with advanced Parkinson disease (PD). However, controlled studies with more than 3 years of follow-up are lacking. Objective: To investigate the long-term effects of STN-DBS on QOL compared with standard-of-care medication (MED). Design, Setting, and Participants: In this prospective, observational, quasi-experimental, longitudinal nonrandomized controlled trial, 183 patients were screened for eligibility and 167 were enrolled from March 1, 2011, to May 31, 2017, at 3 European university centers. Propensity score matching for demographic and clinical characteristics was applied to 108 patients with PD (62 in the STN-DBS group and 46 in the MED group), resulting in a well-balanced, matched subcohort of 25 patients per group. Data analysis was performed from September 2022 to January 2023. Exposure: Treatment for PD of STN-DBS or MED. Main Outcomes and Measures: Assessments included Parkinson's Disease Questionnaire 8 (PDQ-8), Unified PD Rating Scale-motor examination, Scales for Outcomes in PD-activities of daily living (ADL) and motor complications, and levodopa-equivalent daily dose. Within-group longitudinal outcome changes, between-group differences, and correlations of change scores were analyzed. Results: The study population in the analysis included 108 patients (mean [SD] age, 63.7 [8.3] years; 66 [61.1%] male). At 5-year follow-up, PDQ-8 and ADL worsened only in the MED group (PDQ-8 change, -10.9; 95% CI, -19.0 to -2.7; P = .01; ADL change: -2.0; 95% CI, -3.1 to -0.8; P = .002), whereas both outcomes remained stable in the STN-DBS group (PDQ-8 change, -4.3; 95% CI, -13.2 to 4.7; P = .34; ADL change, -0.8; 95% CI, -2.5 to 1.0; P = .38). Changes in PDQ-8 and ADL correlated moderately (rs = .40, P = .008). Furthermore, STN-DBS outcomes were favorable for motor complications (median difference in change scores between STN-DBS and MED, -2.0; 95% CI, -4.0 to -1.0; P = .003), mobility (-1.0; 95% CI, -2.0 to 0; P = .03), and levodopa-equivalent daily dose reduction (-821.4; 95% CI, -1111.9 to -530.8; P < .001). Conclusions and Relevance: This study provides evidence of differences in QOL outcomes at 5-year follow-up between STN-DBS (stable) and MED (worsened), mainly driven by the favorable effect of STN-DBS on mobility (class IIb evidence). The association between changes in QOL and ADL, but not motor impairment or complications, highlights the relative importance of ADL outcomes for long-term DBS assessments. Trial Registration: German ClinicalTrials Registry: DRKS00006735.
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Enfermedad de Parkinson , Calidad de Vida , Femenino , Humanos , Masculino , Persona de Mediana Edad , Actividades Cotidianas , Levodopa , Enfermedad de Parkinson/terapia , Estudios Prospectivos , AncianoRESUMEN
Parkinson's disease (PD) is the second most common neurodegenerative disorder, and the condition is complicated by the emergence of wearing off/motor fluctuations with levodopa treatment after a variable period. COMT inhibitors when used as adjunct therapy to levodopa tend to smoothen out these wearing off fluctuations by enhancing delivery of levodopa and increasing its bioavailability to the brain. The study was conducted to investigate the motor and nonmotor effect, safety and tolerability of the third generation once-daily COMT inhibitor (opicapone), as add-on, adjuvant therapy to levodopa and at 6 and 12 months follow-up in a real-life cohort of consecutive Emirati and non-White PD patients. A real-life observational analysis using tolerability parameters as used previously by Rizos et al. and Shulman et al. based on clinical database of cases rat Kings College Hospital Dubai Parkinson care database. This was a prospective, single-arm follow-up clinical evaluation study that evaluated the effectiveness of opicapone 50 mg once-daily regime in 50 patients diagnosed with idiopathic neurodegenerative disorder. All patients were assessed with scales used in clinical pathway and include motor Unified Parkinson's Disease Rating Scale (UPDRS), nonmotor symptom scale (NMSS), quality of life (PDQ8) Parkinson's fatigue scale (PFS16) and King's Parkinson's Pain Scale (KIPS). Out of 50 patients treated with opicapone (72% male, mean age 66.9 years (SD 9.9, range 41-82 years) and mean duration of disease 5.7 years (SD 2.5 range (2-11), there was significant statistical improvements shown in motor function-UPDRS part 3: baseline 40.64 ± 2.7, at 6 months 32.12 ± 3.14 and after 12 months 33.72 ± 3.76. Nonmotor burden NMSS: 107.00 ± 21.86, at 6 months 100.78 ± 17.28 and 12 months 96.88 ± 16.11. Reduction in dyskinesias (UPDRS part 4): baseline 8.78 ± 1.07, at 6 months 7.4 ± 0.81 and 12 months 6.82 ± 0.75. Opicapone provides beneficial motor and nonmotor effects in Emirati and other non-White Parkinson's patients, resident in UAE, proving its efficacy across different racial groups as COMT activity may vary between races.
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Enfermedad de Parkinson , Humanos , Masculino , Animales , Ratas , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Enfermedad de Parkinson/tratamiento farmacológico , Levodopa/efectos adversos , Antiparkinsonianos/efectos adversos , Emiratos Árabes Unidos , Estudios Prospectivos , Calidad de Vida , Inhibidores de Catecol O-Metiltransferasa/farmacología , Inhibidores de Catecol O-Metiltransferasa/uso terapéuticoRESUMEN
BACKGROUND: Musculoskeletal (MSK) pain affects over 80% of People with Parkinson's (PD, PwP) and may, in part, be dopaminergic in origin, as dopaminergic medication often leads to its relief. METHODS: PwP who underwent striatal dopamine transporter visualization with a radiopharmaceutical DaTscan™ (123 I-Ioflupane Injection) using a single-photon emission computed tomography (SPECT) as a part of their clinical-diagnostic work up were enrolled in the "Non-motor International Longitudinal Study" (NILS; UK National Institute for Health Research Clinical Research Network Number 10084) and included in this cross-sectional analysis. The association between specific DaTscan binding ratios for each striatum, the caudate nucleus and putamen and clinical ratings for MSK pain (assessed using the King's Parkinson's Disease Pain Scale (KPPS)) were analysed. RESULTS: 53 PwP (30.2% female; age: 63.79 ± 11.31 years; disease duration (DD): 3.32 (0.31-14.41) years; Hoehn & Yahr stage (H&Y): 2 (1-4); Levodopa Equivalent Daily Dose (LEDD): 543.08 ± 308.94 mg) were assessed and included in this analysis. MSK pain was highly prevalent (71.7% of all participants, mean KPPS Item 1 score 5.34 ± 4.76) and did not correlate with the motor symptoms burden (SCOPA-Motor total score; p = 0.783) but showed a significant correlation with quality of life (PDQ-8, rs = 0.290, p = 0.035). z-scores for the caudate nucleus (Exp (B) = 0.367, 95% CI for Exp (B) 0.148-0.910, p = 0.031) and striatum (Exp (B) = 0.338, 95% CI for Exp (B) 0.123-0.931, p = 0.036), adjusted for DD, H&Y and LEDD, were significant determinants of MSK pain. CONCLUSIONS: Our findings suggest an association between MSK pain in PwP and the severity of dopaminergic deficiency in the caudate nucleus. SIGNIFICANCE: In People with Parkinson's, musculoskeletal pain does not arise simply as a direct sequel to motor symptoms-instead, it is linked to the severity of dopaminergic depletion in the caudate nucleus.