RESUMO
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.
Assuntos
Doença de Parkinson , Humanos , Masculino , Animais , Ratos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Doença de Parkinson/tratamento farmacológico , Levodopa/efeitos adversos , Antiparkinsonianos/efeitos adversos , Emirados Árabes Unidos , Estudos Prospectivos , Qualidade de Vida , Inibidores de Catecol O-Metiltransferase/farmacologia , Inibidores de Catecol O-Metiltransferase/uso terapêuticoRESUMO
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.
Assuntos
Doença de Parkinson , Doença de Parkinson/diagnóstico , Humanos , Antiparkinsonianos/uso terapêuticoRESUMO
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.
Assuntos
Orexinas , Transtornos do Sono-Vigília , Sinucleinopatias , Humanos , Orexinas/metabolismo , Transtornos do Sono-Vigília/metabolismo , Sinucleinopatias/metabolismo , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/metabolismo , Animais , Doença de Parkinson/metabolismo , Doença de Parkinson/complicações , Doença por Corpos de Lewy/metabolismo , Doença por Corpos de Lewy/complicaçõesRESUMO
BACKGROUND AND OBJECTIVES: It has been recently suggested that LRRK2 mutations are associated with a more benign clinical phenotype and a potentially more preserved cholinergic function in Parkinson's disease (PD). However, to our knowledge, no studies have tested whether the better clinical progression observed in LRRK2-PD patients is associated with more preserved volumes of a cholinergic brain area, the basal forebrain (BF). To address this hypothesis, here we compared BF volumes in LRRK2 carriers with and without PD with respect to idiopathic PD (iPD) patients and controls, and assessed whether they are associated with better clinical progression observed in LRRK2-PD compared to iPD. METHODS: Thirty-one symptomatic LRRK2-PD patients and 13 asymptomatic LRRK2 individuals were included from the Parkinson's Progression Markers Initiative. In addition, 31 patients with iPD and 13 healthy controls matched to the previous groups were also included. BF volumes were automatically extracted from baseline T1-weighted MRI scans using a stereotactic atlas of cholinergic nuclei. These volumes were then compared between groups and their relationship with longitudinal cognitive changes was evaluated using linear mixed effects models. Mediation analyses assessed whether BF volumes mediated differences in cognitive trajectories between groups. RESULTS: LRRK2-PD patients showed significantly higher BF volumes compared to iPD (P = 0.019) as did asymptomatic LRRK2 subjects compared to controls (P = 0.008). There were no other significant differences in cortical regions or subcortical volumes between these groups. BF volumes predicted longitudinal decline in several cognitive functions in iPD patients but not in LRRK2-PD, who did not show cognitive changes over a 4-year follow-up period. BF volumes were a significant mediator of the different cognitive trajectories between iPD and LRRK2-PD patients (95% CI 0.056-2.955). DISCUSSION: Our findings suggest that mutations in LRRK2 are associated with increased BF volumes, potentially reflecting a compensatory hypercholinergic state that could prevent cognitive decline in LRRK2-PD patients.
Assuntos
Prosencéfalo Basal , Disfunção Cognitiva , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , Doença de Parkinson/complicações , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Mutação/genética , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Disfunção Cognitiva/complicações , Colinérgicos , Progressão da DoençaRESUMO
OBJECTIVE: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). METHODS: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. RESULTS: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. CONCLUSIONS: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.
Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Proteínas do Tecido Nervoso , Doença de Parkinson , Mapas de Interação de Proteínas , Vesículas Sinápticas , Autopsia , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Vesículas Sinápticas/genética , Vesículas Sinápticas/metabolismoRESUMO
BACKGROUND: A better understanding of pain in adult-onset idiopathic dystonia (AOID) is needed to implement effective therapeutic strategies. OBJECTIVE: To develop a new rating instrument for pain in AOID and validate it in cervical dystonia (CD). METHODS: Development and validation of the Pain in Dystonia Scale (PIDS) comprised three phases. In phase 1, international experts and participants with AOID generated and evaluated the preliminary items for content validity. In phase 2, the PIDS was drafted and revised by the experts, followed by cognitive interviews to ensure self-administration suitability. In phase 3, the PIDS psychometric properties were assessed in 85 participants with CD and retested in 40 participants. RESULTS: The final version of PIDS evaluates pain severity (by body-part), functional impact, and external modulating factors. Test-retest reliability showed a high-correlation coefficient for the total score (0.9, P < 0.001), and intraclass correlation coefficients were 0.7 or higher for all items in all body-parts subscores. The overall PIDS severity score showed high internal consistency (Cronbach's α, 0.9). Convergent validity analysis revealed a strong correlation between the PIDS severity score and the Toronto Western Spasmodic Torticollis Rating Scale pain subscale (0.8, P < 0.001) and the Brief Pain Inventory-short form items related to pain at time of the assessment (0.7, P < 0.001) and impact of pain on daily functioning (0.7, P < 0.001). CONCLUSION: The PIDS is the first specific questionnaire developed to evaluate pain in all patients with AOID, here, demonstrating high-level psychometric properties in people with CD. Future work will validate PIDS in other forms of AOID. © 2023 International Parkinson and Movement Disorder Society.
Assuntos
Distúrbios Distônicos , Torcicolo , Adulto , Humanos , Torcicolo/complicações , Medição da Dor , Reprodutibilidade dos Testes , Dor , Psicometria , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors. METHOD: Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change. RESULTS: Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status. CONCLUSIONS: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , Feminino , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , COVID-19/epidemiologia , Pandemias , Depressão/psicologia , Estudos Retrospectivos , Estudos Prospectivos , SARS-CoV-2 , Ansiedade/psicologia , Reino Unido/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: Motor fluctuations are a significant driver of healthcare resource utilization (HCRU) in people with Parkinson's disease (pwPD). A common management strategy is to include catechol-O-methyltransferase (COMT) inhibition with either opicapone or entacapone in the levodopa regimen. However, to date, there has been a lack of head-to-head data comparing the two COMT inhibitors in real-world settings. The aim of this study was to evaluate changes in HCRU and effect on sleep medications when opicapone was initiated as first COMT inhibitor versus entacapone. METHODS: In this retrospective cohort study, we assessed HCRU outcomes in pwPD naïve to COMT inhibition via UK electronic healthcare records (Clinical Practice Research Datalink and Hospital Episodes Statistics databases, June 2016 to December 2019). HCRU outcomes were assessed before (baseline) and after COMT inhibitor prescription at 0-6 months, 7-12 months and 13-18 months. Opicapone-treated pwPD were algorithm-matched (1:4) to entacapone-treated pwPD. RESULTS: By 6 months, treatment with opicapone resulted in 18.5% fewer neurology outpatient visits compared to entacapone treatment; this effect was maintained until the last follow-up (18 months). In the opicapone group, the mean levodopa equivalent daily dose decreased over the first year and then stabilized, whereas the entacapone-treated group showed an initial decrease in the first 6 months followed by a dose increase between 7 and 18 months. Neither COMT inhibitor had a significant impact on sleep medication use. CONCLUSIONS: This head-to-head study is the first to demonstrate, using 'real-world' data, that initiating COMT inhibition with opicapone is likely to decrease the need for post-treatment HCRU versus initiation of COMT inhibition with entacapone.
Assuntos
Doença de Parkinson , Humanos , Antiparkinsonianos/uso terapêutico , Catecol O-Metiltransferase , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Inibidores de Catecol O-Metiltransferase/farmacologia , Levodopa/uso terapêutico , Oxidiazóis/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde , Estudos RetrospectivosRESUMO
PURPOSE OF REVIEW: The purpose of this review is to outline the impact of the COVID-19 pandemic on movement disorder holistic care, particularly in the care of people with Parkinson disease (PWP). RECENT FINDINGS: As the pandemic unfolds, a flurry of literature was published regarding the impact of COVID-19 on people with Parkinson disease including the direct impact of infection, availability of ambulatory care, loss of community-based team care, and acceptability of telemedicine. SUMMARY: COVID-19 has impacted the care of PWP in numerous ways. Recognizing infection in PWP poses challenges. Specific long-term complications, including emerging reports of long COVID syndrome is a growing concern. Caregivers and PWP have also been impacted by COVID-19 social isolation restrictions, with radical changes to the structure of social networks and support systems globally. In a matter of weeks, the global community saw an incredible uptake in telemedicine, which brought benefits and pitfalls. As PWP adapted to virtual platforms and the changing architecture of care delivery, the pandemic amplified many preexisting inequities amongst populations and countries, exposing a new 'digital divide'.
Assuntos
COVID-19 , Transtornos dos Movimentos , Doença de Parkinson , Telemedicina , COVID-19/complicações , COVID-19/epidemiologia , Humanos , Transtornos dos Movimentos/epidemiologia , Transtornos dos Movimentos/terapia , Pandemias , Doença de Parkinson/epidemiologia , Doença de Parkinson/terapia , SARS-CoV-2 , Síndrome de COVID-19 Pós-AgudaRESUMO
Many of the motor symptoms of Parkinson disease (PD) can be preceded, sometimes for several years, by non-motor symptoms that include hyposmia, sleep disorders, depression and constipation. These non-motor features appear across the spectrum of patients with PD, including individuals with genetic causes of PD. The neuroanatomical and neuropharmacological bases of non-motor abnormalities in PD remain largely undefined. Here, we discuss recent advances that have helped to establish the presence, severity and effect on the quality of life of non-motor symptoms in PD, and the neuroanatomical and neuropharmacological mechanisms involved. We also discuss the potential for the non-motor features to define a prodrome that may enable the early diagnosis of PD.
Assuntos
Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Sintomas Prodrômicos , Encéfalo/patologia , Constipação Intestinal/complicações , Depressão/complicações , Diagnóstico Precoce , Humanos , Neurotransmissores/fisiologia , Transtornos do Olfato/complicações , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Qualidade de Vida , Transtornos do Sono-Vigília/complicaçõesRESUMO
This corrects the article DOI: 10.1038/nrn.2017.62.
RESUMO
BACKGROUND: Neuropalliative care is an emerging field for those with neurodegenerative illnesses, but access to neuropalliative care remains limited. OBJECTIVE: We sought to determine Movement Disorder Society (MDS) members' attitudes and access to palliative care. METHODS: A quantitative and qualitative survey instrument was developed by the MDS Palliative Care Task Force and e-mailed to all members for completion. Descriptive statistics and qualitative analysis were triangulated. RESULTS: Of 6442 members contacted, 652 completed the survey. Completed surveys indicating country of the respondent overwhelmingly represented middle- and high-income countries. Government-funded homecare was available to 54% of respondents based on patient need, 25% limited access, and 21% during hospitalization or an acute defined event. Eighty-nine percent worked in multidisciplinary teams. The majority endorsed trigger-based referrals to palliative care (75.5%), while 24.5% indicated any time after diagnosis was appropriate. Although 66% referred patients to palliative care, 34% did not refer patients. Barriers were identified by 68% of respondents, the most significant being available workforce, financial support for palliative care, and perceived knowledge of palliative care physicians specific to movement disorders. Of 499 respondents indicating their training in palliative care or desire to learn these skills, 55% indicated a desire to gain more skills. CONCLUSIONS: The majority of MDS member respondents endorsed a role for palliative care in movement disorders. Many members have palliative training or collaborate with palliative care physicians. Although significant barriers exist to access palliative care, the desire to gain more skills and education on palliative care is an opportunity for professional development within the MDS. © 2021 International Parkinson and Movement Disorder Society.
Assuntos
Transtornos dos Movimentos , Cuidados Paliativos , Atitude , Humanos , Transtornos dos Movimentos/terapia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Twenty-four-hour treatment options could provide a continuous drug delivery strategy in advanced Parkinson's disease and can ameliorate motor and non-motor complications. Use of levodopa infusion is often limited to 12-16 h/day due to its cost. Adjunctive overnight rotigotine transdermal patch is a continuous drug delivery option successfully used in clinical practice coupled with apomorphine infusion. However, real-life data addressing the tolerability of transdermal dopamine agonist therapy with concomitant use of intrajejunal levodopa infusion in advanced Parkinson's disease are not available. OBJECTIVE: To evaluate the tolerability and beneficial effects of combined therapy with overnight rotigotine transdermal patch and intrajejunal levodopa infusion over a follow-up period of 12 months in advanced Parkinson's disease. METHOD: In this retrospective data analysis, data before and after the initiation of the continuous drug delivery combined therapy using overnight rotigotine transdermal patch and intrajejunal levodopa infusion were collected from the ongoing non-motor-international-longitudinal study (NILS) and local clinical practice at King's College Hospital (London, United Kingdom). 12 advanced Parkinson's disease patients on intrajejunal levodopa therapy who were additionally treated with overnight rotigotine transdermal patch (mean dose 5.67 ± 4.19 mg) are included. Tolerability over a 12-month period was assessed. In addition, changes in motor symptoms (SCales for Outcomes in Parkinson's disease, SCOPA-Motor), non-motor symptoms (Non-Motor Symptoms Scale, NMSS) and quality of life (Parkinson's disease Questionnaire-8, PDQ-8) before and 12-month after continuous drug delivery combined therapy initiation are evaluated. RESULTS: Tolerability was 100% irrespective of age, disease duration, stages of disease. (Treatment with overnight rotigotine transdermal patch that was maintained for a minimum of 6 months was considered "tolerated", primary tolerability). In addition, we noted a significant reduction of the NMSS total score (p = 0.009) and the NMSS domain 3 score (mood and apathy domain) (p = 0.028), although the latter did not remain statistically significant after correction for multiple testing (p2 = 0.252) at 12 months. CONCLUSION: Combination of intrajejunal levodopa infusion with overnight rotigotine transdermal patch is well tolerated and extend the beneficial effects of infusion with excellent tolerability; and also improved aspects of mood and apathy sustained at 12 months in advanced Parkinson's disease.
Assuntos
Levodopa , Doença de Parkinson , Administração Cutânea , Agonistas de Dopamina/farmacologia , Humanos , Levodopa/efeitos adversos , Estudos Longitudinais , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Tetra-Hidronaftalenos , Tiofenos , Adesivo TransdérmicoRESUMO
BACKGROUND: Optimisation of dopaminergic therapy may alleviate fluctuation-related pain in Parkinson's disease (PD). Opicapone (OPC) is a third-generation, once-daily catechol-O-methyltransferase inhibitor shown to be generally well tolerated and efficacious in reducing OFF-time in two pivotal trials in patients with PD and end-of-dose motor fluctuations. The OpiCapone Effect on motor fluctuations and pAiN (OCEAN) trial aims to investigate the efficacy of OPC 50 mg in PD patients with end-of-dose motor fluctuations and associated pain, when administered as adjunctive therapy to existing treatment with levodopa/dopa decarboxylase inhibitor (DDCi). METHODS: OCEAN is a Phase IV, international, multicentre, randomised, double-blind, placebo-controlled, parallel-group, interventional trial in PD patients with end-of-dose motor fluctuations and associated pain. It consists of a 1-week screening period, 24-week double-blind treatment period and 2-week follow-up period. Eligible patients will be randomised 1:1 to OPC 50 mg or placebo once daily while continuing current treatment with levodopa/DDCi and other chronic, stable anti-PD and/or analgesic treatments. The primary efficacy endpoint is change from baseline in Domain 3 (fluctuation-related pain) of the King's Parkinson's disease Pain Scale (KPPS). The key secondary efficacy endpoint is change from baseline in Domain B (anxiety) of the Movement Disorder Society-sponsored Non-Motor rating Scale (MDS-NMS). Additional secondary efficacy assessments include other domains and total scores of the KPPS and MDS-NMS, the Parkinson's Disease Questionnaire (PDQ-8), the MDS-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts III and IV, Clinical and Patient's Global Impressions of Change, and change in functional status via Hauser's diary. Safety assessments include the incidence of treatment-emergent adverse events. The study will be conducted in approximately 140 patients from 50 clinical sites in Germany, Italy, Portugal, Spain and the United Kingdom. Recruitment started in February 2021 and the last patient is expected to complete the study by late 2022. DISCUSSION: The OCEAN trial will help determine whether the use of adjunctive OPC 50 mg treatment can improve fluctuation-associated pain in PD patients with end-of-dose motor fluctuations. The robust design of OCEAN will address the current lack of reliable evidence for dopaminergic-based therapy in the treatment of PD-associated pain. TRIAL REGISTRATION: EudraCT number 2020-001175-32 ; registered on 2020-08-07.
Assuntos
Doença de Parkinson , Antiparkinsonianos , Catecol O-Metiltransferase/uso terapêutico , Humanos , Oxidiazóis , Dor/tratamento farmacológico , Dor/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológicoRESUMO
BACKGROUND: The burden of Parkinson's disease (PD) worsens with disease progression. However, the lack of objective and uniform disease classification challenges our understanding of the incremental burden in patients with advanced Parkinson's disease (APD) and suboptimal medication control. The 5-2-1 criteria was proposed by clinical consensus to identify patients with advancing PD. Our objective was to evaluate the screening accuracy and incremental clinical burden, healthcare resource utilization (HCRU), and humanistic burden in PD patients meeting the 5-2-1 screening criteria. METHODS: Data were drawn from the Adelphi Parkinson's Disease Specific Program (DSP™), a multi-country point-in-time survey (2017-2020). People with PD who were naive to device-aided therapy and on oral PD therapy were included. Patients meeting the 5-2-1 screening criteria had one or more of the three clinical indicators of APD: (i) ≥5 doses of oral levodopa/day, OR (ii) "off" symptoms for ≥2 h of waking day, OR (iii) ≥1 h of troublesome dyskinesia. Clinician assessment of PD stage was used as the reference in this study. Clinical screening accuracy of the 5-2-1 criteria was assessed using area under the curve and multivariable logistic regression models. Incremental clinical, HCRU, and humanistic burden were assessed by known-group comparisons between 5 and 2-1-positive and negative patients. RESULTS: From the analytic sample (n = 4714), 33% of patients met the 5-2-1 screening criteria. Among physician-classified APD patients, 78.6% were 5-2-1 positive. Concordance between clinician judgment and 5-2-1 screening criteria was > 75%. 5-2-1-positive patients were nearly 7-times more likely to be classified as APD by physician judgment. Compared with the 5-2-1-negative group, 5-2-1-positive patients had significantly higher clinical, HCRU, and humanistic burden across all measures. In particular, 5-2-1-positive patients had 3.8-times more falls, 3.6-times higher annual hospitalization rate, and 3.4-times greater dissatisfaction with PD treatment. 5-2-1-positive patients also had significantly lower quality of life and worse caregiver burden. CONCLUSIONS: 5-2-1 criteria demonstrated potential as a screening tool for identifying people with APD with considerable clinical, humanistic, and HCRU burden. The 5-2-1 screening criteria is an objective and reliable tool that may aid the timely identification and treatment optimization of patients inadequately controlled on oral PD medications.
Assuntos
Doença de Parkinson , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Aceitação pelo Paciente de Cuidados de Saúde , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
Non-motor symptoms (NMS) occur in patients with cervical dystonia (CD) but with variable frequencies and impact on health-related quality of life (HRQoL). To define non-motor and motor profiles and their respective impact on HRQoL in CD patients using the newly validated Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest). In an observational prospective multicentre case-control study, we enrolled 61 patients with CD and 61 age- and sex-matched healthy controls (HC) comparing demographic data, motor and non-motor symptoms and HRQoL measurements. 95% CD patients reported at least one NMS. Mean total NMS score was significantly higher in CD patients (5.62 ± 3.33) than in HC (1.74 ± 1.52; p < 0.001). Pain, insomnia and stigma were the most prevalent NMS and HRQoL was significantly impaired in CD patients compared to HC. There was strong correlation of NMS burden with HRQoL (CDQ-24: r = 0.72, EQ-5D: r = - 0.59; p < 0.001) in CD patients. Regression analysis between HRQoL and NMS suggested that emotional well-being (standardized beta = - 0.352) and pain (standardized beta = - 0.291) had a major impact on HRQoL while, in contrast motor severity had no significant impact in this model. Most NMS with the exception of pain, stigma and ADL did not correlate with motor severity. NMS are highly prevalent in CD patients and occur independent of age, sex, disease duration, duration of botulinum neurotoxin therapy and socio-economic status. Specific NMS such as emotional well-being and pain have a major impact on HRQoL and are more relevant than motor severity.
Assuntos
Qualidade de Vida , Torcicolo , Estudos de Casos e Controles , Humanos , Dor , Estudos ProspectivosRESUMO
Parkinson's disease-related pain has increasingly been investigated in research studies. Still, only a few studies have addressed the prevalence and clinical characteristics of pain in neurodegenerative disorders with atypical parkinsonism. The existing evidence, although scarce, suggests that, similarly as in Parkinson's disease, individuals with neurodegenerative diseases with atypical parkinsonism might be predisposed to the development of persistent pain. Today, as the global population is aging and we face an epidemic of neurodegenerative disorders, under-treated pain is taking a great toll on an ever-rising number of people. Here, we provide an up-to-date review of the current knowledge on the prevalence of pain, its clinical features, and findings from experimental studies that might signpost altered pain processing in the most prevalent neurodegenerative disorders with atypical parkinsonism: multiple system atrophy, progressive supranuclear palsy, corticobasal syndrome, frontotemporal dementia, and dementia with Lewy bodies. Finally, we point out the current gaps and unmet needs that future research studies should focus on. Large-scale, high-quality clinical trials, coupled with pre-clinical research, are urgently needed to reveal the exact pathophysiological mechanisms underpinning heightened pain and pave the path for mechanistically-driven analgesic interventions to be developed, ultimately leading to an improvement in the quality of life of individuals with neurodegenerative disorders.
Assuntos
Degeneração Corticobasal , Demência Frontotemporal , Doença por Corpos de Lewy , Atrofia de Múltiplos Sistemas , Dor Musculoesquelética , Neuralgia , Paralisia Supranuclear Progressiva , Degeneração Corticobasal/complicações , Degeneração Corticobasal/epidemiologia , Degeneração Corticobasal/fisiopatologia , Demência Frontotemporal/complicações , Demência Frontotemporal/epidemiologia , Demência Frontotemporal/fisiopatologia , Humanos , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/epidemiologia , Doença por Corpos de Lewy/fisiopatologia , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/epidemiologia , Atrofia de Múltiplos Sistemas/fisiopatologia , Dor Musculoesquelética/epidemiologia , Dor Musculoesquelética/etiologia , Dor Musculoesquelética/fisiopatologia , Neuralgia/epidemiologia , Neuralgia/etiologia , Neuralgia/fisiopatologia , Prevalência , Paralisia Supranuclear Progressiva/complicações , Paralisia Supranuclear Progressiva/epidemiologia , Paralisia Supranuclear Progressiva/fisiopatologiaRESUMO
BACKGROUND: The Movement Disorder Society-sponsored Nonmotor Rating Scale is an update of the existing Parkinson's disease Nonmotor Symptoms Scale modified to address some limitations in Nonmotor Symptoms Scale scoring, structure, and symptom coverage. METHODS: PD patients were recruited from movement disorder centers in an international, multicenter study. The Movement Disorder Society Nonmotor Rating Scale, consisting of 13 domains plus a subscale for nonmotor fluctuations, was rater administered, along with the Nonmotor Symptoms Scale and other clinical assessments. Standard reliability and validity testing were conducted. RESULTS: Four hundred and two PD patients were recruited (mean age ± standard deviation, 67.42 ± 9.96 years; mean age at PD onset ± standard deviation, 59.27 ± 10.67 years; median Hoehn and Yahr stage 2 (interquartile range 2-3). Data quality was satisfactory for all Movement Disorder Society Nonmotor Rating Scale domains except sexual (6.7% missing data). There were no floor or ceiling effects for the Movement Disorder Society Nonmotor Rating Scale and nonmotor fluctuations total score; domains had no ceiling effects, but some floor effects (13.5%-83.5%). The Movement Disorder Society Nonmotor Rating Scale and nonmotor fluctuations total score internal consistency were acceptable (average Cronbach's alpha, 0.66 and 0.84, respectively); interrater reliability was excellent (intraclass correlation coefficient, >0.95); for test-retest reliability, the intraclass correlation coefficient was 0.84 for the Movement Disorder Society Nonmotor Rating Scale and 0.70 for Movement Disorder Society nonmotor fluctuations total score, and precision was excellent for the Movement Disorder Society Nonmotor Rating Scale (standard error of measurement, 25.30) and fair for nonmotor fluctuations (standard error of measurement, 7.06). Correlations between Movement Disorder Society Nonmotor Rating Scale score and the corresponding Nonmotor Symptoms Scale and Movement Disorder Society UPDRS scores were high. There were no significant sex or age effects. The Movement Disorder Society Nonmotor Rating Scale score increased with increasing PD duration, disease severity, and PD medication dose (all P < 0.001). CONCLUSIONS: The Movement Disorder Society Nonmotor Rating Scale is a valid measure for measuring the burden of a wide range of Nonmotor Rating Scale scores, including nonmotor fluctuations, in PD patients. © 2019 International Parkinson and Movement Disorder Society.
Assuntos
Atividades Cotidianas/psicologia , Avaliação da Deficiência , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
Sialorrhoea in Parkinson's disease (PD) is an often neglected yet key non-motor symptom with impact on patient quality of life. However, previous studies have shown a broad range of prevalence figures. To assess prevalence of drooling in PD and its relationship to quality of life, we performed a retrospective analysis of 728 consecutive PD patients who had a baseline and follow-up assessment as part of the Non-motor International Longitudinal Study (NILS), and for whom drooling presence and severity were available, assessed through the Non-Motor Symptoms Scale (NMSS). In addition, we analysed the prevalence of associated dysphagia through self-reported outcomes. Quality of life was assessed through the PDQ-8 scale. Baseline (disease duration 5.6 years) prevalence of drooling was 37.2% (score ≥ 1 NMSS question 19), and after 3.27 ± 1.74 years follow-up, this was 40.1% (p = 0.17). The prevalence of drooling increased with age (p < 0.001). The severity of drooling, however, did not change (p = 0.12). While in 456 patients without drooling at baseline, only 16% (n = 73) had dysphagia (question 20 of the NMSS), in those with drooling this was 34.3% (p < 0.001). At follow-up, the number of patients with dysphagia had increased, 20.4% with no drooling had dysphagia, and 43.6% with drooling had dysphagia. Both at baseline and follow-up, drooling severity was significantly positively associated with quality of life (PDQ-8; r = 0.199; p < 0.001). In moderately advanced PD patients, subjective drooling occurs in over one-third of patients and was significantly associated with decreased quality of life. Dysphagia occurred significantly more often in patients with drooling.
Assuntos
Doença de Parkinson , Sialorreia , Humanos , Estudos Longitudinais , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Prevalência , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença , Sialorreia/epidemiologia , Sialorreia/etiologia , Inquéritos e QuestionáriosRESUMO
Most patients with Parkinson disease (PD) have non-motor symptoms (NMS), and on average these can range from four to 19 different symptoms. NMS dominate the prodromal phase of PD and some may serve as clinical biomarkers of PD. NMS can be dopaminergic, non-dopaminergic, of genetic origin or drug induced. Clinical assessment of NMS should include the NMS Questionnaire (completed by patients) for screening, as recommended by the International Parkinson and Movement Disorders Society and other international societies. The total number of NMS in a patient with PD constitutes the NMS burden, which can be graded using validated cut-off scores on the NMS Questionnaire and Scale and can be used as an outcome measure in clinical trials. Despite NMS burden having a major effect on the quality of life of patients and carers, a large European study showed that NMS are often ignored in the clinic. The syndromic nature of PD is underpinned by non-motor subtypes which are likely to be related to specific dysfunction of cholinergic, noradrenergic, serotonergic pathways in the brain, not just the dopaminergic pathways. NMS can be treated by dopaminergic and non-dopaminergic strategies, but further robust studies supported by evidence from animal models are required. The future of modern treatment of PD needs to be supported by the delivery of personalised medicine.