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OBJECTIVE: The role of inflammation and neuroimmune mechanisms, which have been documented in various neuropsychiatric disorders including the seizure subtype of functional neurological disorder, remains unclear in functional movement disorders (FMD). To explore these mechanisms, we analyzed selected inflammatory markers in cerebrospinal fluid (CSF) in patients with FMD. METHODS: We compared CSF markers in 26 patients with clinically established FMD (20 females; mean [SD] age = 43.3 [10.9], disease duration = 3.9 [3], range = 0.1-11 years; mean follow-up after lumbar puncture = 4.3 [2] years, range = 0.5-7 years) and 26 sex- and age-matched clinical controls with noninflammatory nonneurodegenerative neurological disorders, mostly sleep disorders. RESULTS: Sixty-five percent of FMD patients versus 15% of controls showed cytological abnormalities (i.e., increased white blood cells [WBC] count, signs of WBC activation, or both; odds ratio [OR] = 9.85, 95% confidence interval = 2.37-52.00, p < .01, corrected), with a significantly higher frequency of an isolated lymphocytic activation, 35% versus 0% (OR = ∞, 95% confidence interval = 2.53-∞, p < .05, corrected). There were no differences in CSF protein and albumin levels, quotient albumin, IgG index, and oligoclonal bands. CSF abnormalities were not associated with more severe motor symptoms or a higher frequency of depression in FMD. CONCLUSIONS: Our results suggest a possible involvement of immune mechanisms in the pathophysiology of (at least a subtype of) FMD that deserves further investigation.
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Transtornos dos Movimentos , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Transtornos dos Movimentos/líquido cefalorraquidiano , Transtornos dos Movimentos/fisiopatologia , Transtorno Conversivo/líquido cefalorraquidiano , Transtorno Conversivo/fisiopatologia , Contagem de Leucócitos , Biomarcadores/líquido cefalorraquidiano , CitologiaRESUMO
The term "catatonia" was introduced by German psychiatrist Karl Kahlbaum in 1874. Although historically tied to schizophrenia, catatonia exhibits a diverse range of phenotypes and has been observed in various medical and neuropsychiatric conditions. Its intrinsic movement characteristics and association with hypokinetic and hyperkinetic phenomenologies place catatonia within the purview of movement disorders. Despite the presence of catatonia in psychiatry literature for over 150 years, many gaps and controversies persist regarding its etiopathogenesis, phenomenology, diagnostic criteria, and treatment. The current versions of the International Classification of Diseases (ICD-11) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) require clinicians to identify any three signs of 15 (ICD-11) or 12 (DSM-5) for the diagnosis of catatonia. Catalepsy and waxy flexibility are the only motor features with high specificity for the diagnosis. We highlight the gaps and controversies in catatonia as a movement disorder, emphasize the lack of a clear definition, and discuss the inconsistencies in the description of various catatonic signs. We propose the exploration of a bi-axial classification framework similar to that used for dystonia and tremor to encourage the evaluation of underlying etiologies and to guide therapeutic decisions to improve the outcome of these patients. © 2024 International Parkinson and Movement Disorder Society.
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BACKGROUND: IPX203 is a novel oral extended-release formulation of carbidopa/levodopa (CD/LD) developed to address the short half-life of immediate-release CD/LD. In the phase 3 RISE-PD trial, IPX203 significantly improved "Good On" time in patients with Parkinson's disease compared with immediate-release CD/LD. OBJECTIVES: To evaluate the safety and efficacy of IPX203 in an open-label extension of the pivotal phase 3 study. METHODS: This 9-month extension enrolled patients who completed the randomized, double-blind trial. Key efficacy endpoints included Movement Disorder Society-Unified Parkinson's Disease Rating Scale and Patient and Clinical Global Impression scores. Adverse events (AEs) were recorded. RESULTS: Improvements in efficacy were maintained and dosing frequency and total daily dose remained stable through the trial. A total of 52.7% of patients experienced ≥1 treatment-emergent AE, mostly mild or moderate and occurred within the first 90 days of treatment. CONCLUSIONS: In this phase 3 open-label extension, IPX203 exhibited a favorable safety and tolerability profile and sustained efficacy of comparable magnitude to the end of the double-blind study. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Levodopa/efeitos adversos , Carbidopa/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Pesquisa , Combinação de Medicamentos , Método Duplo-CegoRESUMO
The International Parkinson and Movement Disorder Society (MDS) created a task force (TF) to provide a critical overview of the Parkinson's disease (PD) subtyping field and develop a guidance on future research in PD subtypes. Based on a literature review, we previously concluded that PD subtyping requires an ultimate alignment with principles of precision medicine, and consequently novel approaches were needed to describe heterogeneity at the individual patient level. In this manuscript, we present a novel purpose-driven framework for subtype research as a guidance to clinicians and researchers when proposing to develop, evaluate, or use PD subtypes. Using a formal consensus methodology, we determined that the key purposes of PD subtyping are: (1) to predict disease progression, for both the development of therapies (use in clinical trials) and prognosis counseling, (2) to predict response to treatments, and (3) to identify therapeutic targets for disease modification. For each purpose, we describe the desired product and the research required for its development. Given the current state of knowledge and data resources, we see purpose-driven subtyping as a pragmatic and necessary step on the way to precision medicine. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Medicina de Precisão , Progressão da Doença , Comitês ConsultivosRESUMO
We describe a novel superoxide dismutase (SOD1) mutation-associated clinical phenotype of cerebellar ataxia and motor neuron disease with a variant in the ceruloplasmin (Cp) gene, which may have possibly contributed to a multi-factorial phenotype, supported by genetic and protein structure analyses.
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Esclerose Lateral Amiotrófica , Ataxia Cerebelar , Doença dos Neurônios Motores , Humanos , Esclerose Lateral Amiotrófica/genética , Ataxia Cerebelar/genética , Ceruloplasmina/genética , Ceruloplasmina/metabolismo , Doença dos Neurônios Motores/genética , Mutação/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismoRESUMO
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.
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Terapia Cognitivo-Comportamental , Síndrome de Fadiga Crônica , Humanos , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/terapia , Inquéritos e Questionários , Terapia por ExercícioRESUMO
BACKGROUND: Bradykinesia is a cardinal feature in parkinsonisms. No study has assessed the differential features of bradykinesia in patients with pathology-proven synucleinopathies and tauopathies. OBJECTIVE: We examined whether bradykinesia features (speed, amplitude, rhythm, and sequence effect) may differ between pathology-proven synucleinopathies and tauopathies. METHODS: Forty-two cases who underwent autopsy were included and divided into synucleinopathies (Parkinson's disease and dementia with Lewy bodies) and tauopathies (progressive supranuclear palsy). Two raters blinded to the diagnosis retrospectively scored the Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III and Modified Bradykinesia Rating Scale on standardized videotaped neurological examinations. Bradykinesia scores were compared using the Mann-Whitney test and logistic regression models to adjust for disease duration. RESULTS: Demographic and clinical parameters were similar between synucleinopathies and tauopathies. There were no differences between speed, amplitude, rhythm, and sequence effect in synucleinopathies and tauopathies in unadjusted comparisons and adjusted models (all P > 0.05). CONCLUSIONS: Clinical bradykinesia features do not distinguish the underlying neuropathology in neurodegenerative parkinsonisms. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Hipocinesia , Doença de Parkinson , Sinucleinopatias , Tauopatias , Gravação em Vídeo , Humanos , Hipocinesia/complicações , Hipocinesia/fisiopatologia , Modelos Logísticos , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Estudos Retrospectivos , Estatísticas não Paramétricas , Paralisia Supranuclear Progressiva/complicações , Paralisia Supranuclear Progressiva/patologia , Paralisia Supranuclear Progressiva/fisiopatologia , Sinucleinopatias/complicações , Sinucleinopatias/patologia , Sinucleinopatias/fisiopatologia , Tauopatias/complicações , Tauopatias/patologia , Tauopatias/fisiopatologia , Autopsia , Masculino , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: Psychosis is a common manifestation of Parkinson's disease (PD), and a major source of caregiver burden, nursing home placement, and mortality. Psychosis symptoms are often not volunteered during the clinic visit because of embarrassment or lack of insight, and there is no validated screening scale. We compare a new self-administered psychosis screening questionnaire against the Parkinson's Disease Psychosis Scale (PDPS) and physician interview as the gold standard assessments. OBJECTIVE: To create and validate the Self-Administered Screening Questionnaire for PD-Associated Psychosis (SASPAP). METHODS: The questionnaire was developed through a modified Delphi method by a committee of two neurologists, a psychiatrist, a patient, and patient advocate and underwent several rounds of revisions, including patient ß-testing. It was provided by staff at intake to 250 consecutive patients diagnosed with PD, at the Methodist Hospital Movement Disorders Clinic, and separately to their caregivers when available. Later, the PDPS and a general psychosis interview were administered by PD specialists without knowledge of the screening questionnaire responses. RESULTS: Two hundred and fifty consecutive patients with PD (mean age, 68.6 ± 7.0; mean age of PD onset, 62.7 ± 10.5 years; 35.2% female) were included. The screening questionnaire was positive for psychosis (any of the four questions positive) in 33.6% of patients. Compared to the gold standard, the SASPAP sensitivity was 87.8% and the specificity 92.3%. CONCLUSION: This four-question self-administered screening questionnaire for PD psychosis demonstrated high diagnostic accuracy compared with the gold standard assessments and can be self-completed at visit intake. © 2023 International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Transtornos Psicóticos , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/etiologia , Inquéritos e Questionários , Casas de Saúde , CuidadoresRESUMO
BACKGROUND: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. OBJECTIVES: To update LED conversion formulae based on a systematic review. METHODS: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. RESULTS: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. CONCLUSIONS: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Levodopa , Doença de Parkinson , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/uso terapêutico , Resultado do TratamentoRESUMO
Essential tremor (ET) may present with head tremor (HT), of presumed cerebellar nature. Deep brain stimulation (DBS) targeting the ventral intermediate (Vim) nucleus of the thalamus is a highly effective therapy for medication-refractory ET. However, stimulation-related side effects may include cerebellar abnormalities, such as postural instability. This retrospective cohort study evaluated the risk of post-Vim DBS postural instability (primary outcome measure) in patients with versus without head tremor (HT vs. nHT). The primary outcome measure, namely post-DBS postural instability, was assessed in both groups using a Wilcoxon rank sum t-test. The time to postural instability was determined using Cox proportional hazards regression analysis adjusted for age and sex. Out of 30 patients analyzed during the follow up period, there was similar postural instability detected in HT (9/14, 64%) and nHT patients (11/16, 69%) at 24 months post-Vim DBS (p=0.82), adjusted hazard ratio[aHR]=0.82, p=0.69). These data suggest that the presence or absence of HT does not have an impact on postural instability after bilateral Vim DBS in patients with ET.
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Estimulação Encefálica Profunda , Tremor Essencial , Humanos , Tremor/etiologia , Tremor Essencial/terapia , Estudos Retrospectivos , Estimulação Encefálica Profunda/efeitos adversos , Tálamo , Núcleos Ventrais do Tálamo , Resultado do TratamentoRESUMO
OBJECTIVE: Advanced Parkinson's Disease (PD) is associated with Parkinson's Disease gait impairment (PDg), which increases the risk for falls and is often treatment-refractory. Subthalamic nucleus (STN) and globus pallidus pars interna (GPi) deep brain stimulation (DBS) often fails to improve axial symptoms like PDg. Spinal cord stimulation (SCS) has been suggested to improve PDg. SCS may benefit PDg by disrupting pathologic beta-oscillations and hypersynchrony in cortico-striatal-thalamic circuits to override excessive inhibition of brainstem locomotor regions. SCS may potentially improve locomotion by acting at any of these levels, either alone or in combination. METHODS: We conducted a comprehensive literature search and scoping review, identifying 106 patients in whom SCS was evaluated for PDg. RESULTS: Among the identified patients, 63% carried a pain diagnosis. Overall, the most common stimulation location was thoracic (78%), most commonly T9-T10. Burst (sub-perception) was the most common stimulation modality (59%). Prior treatment with DBS was used in 25%. Motor outcomes were assessed by the Unified Parkinson Disease Rating Scale (UPDRS) III-motor, UPDRS, the Timed Up and Go (TUG), and/or 10-/20-meter walking tests.Among these patients, 95 (90%) had PDg amelioration and improved motor outcomes. CONCLUSIONS: Despite small sample sizes, patient heterogeneity, and unblinded evaluations complicating interpretations of efficacy and safety, SCS may be beneficial for at least a subset of PDg. Further research is required to clarify the role of SCS for PDg and the patients most suitable to benefit from this intervention.
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Estimulação Encefálica Profunda , Doença de Parkinson , Estimulação da Medula Espinal , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Resultado do Tratamento , MarchaRESUMO
OBJECTIVE: The purpose of this study was to evaluate if the cognitive benefit of rivastigmine is affected by the presence of orthostatic hypotension (OH) in patients with Parkinson's disease dementia (PDD). METHODS: We conducted a post hoc analysis on 1,047 patients with PDD from 2 randomized controlled trials comparing rivastigmine versus placebo at week 24 (n = 501) and rivastigmine patch versus capsule at week 76 (n = 546). A drop ≥ 20 mm Hg in systolic blood pressure (SBP) or ≥ 10 in diastolic blood pressure (DBP) upon standing classified subjects as OH positive (OH+); otherwise, OH negative (OH-). The primary end point was the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) at week 24 and the Mattis Dementia Rating Scale (MDRS) at week 76, using intention-to-treat with retrieved dropout at week 24 and observed cases at week 76, consistent with the original analyses. RESULTS: Overall safety was comparable between OH+ (n = 288, 27.5%) and OH- (n = 730, 69.7%), except for higher frequency of syncope (9.2%) in the OH+ placebo arm. The placebo-adjusted effect of rivastigmine on ADAS-Cog at week 24 was 5.6 ± 1.2 for OH+ and 1.9 ± 0.9 in OH- (p = 0.0165). Among subjects with OH, the MDRS change from baseline at week 76 was higher for rivastigmine capsules versus patch (10.6 ± 2.9 vs -1.5 ± 3.0, p = 0.031). The overall prevalence of OH was lower for rivastigmine than placebo at week 24 (28.3% vs 44.6%, p = 0.0476). INTERPRETATION: The cognitive benefit from rivastigmine is larger in patients with PDD with OH, possibly mediated by a direct antihypotensive effect. ANN NEUROL 2021;89:91-98.
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Doença de Alzheimer/tratamento farmacológico , Hipotensão/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Rivastigmina/uso terapêutico , Idoso , Inibidores da Colinesterase/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/uso terapêutico , Testes NeuropsicológicosRESUMO
Poststroke movement disorders (PSMDs) are a common cause of secondary movement disorders. Although prior studies have highlighted the clinical spectrum and phenomenology of PSMDs, there are many knowledge gaps worth addressing. Some of the most important include lack of clinical definitions, variable stroke symptom latencies, and lack of biomarkers for vulnerability for or resilience against developing PSMDs. Collectively, the association between stroke localization and phenomenology is less than 30%, and the long-term clinical prognosis and treatment responses are highly variable. After summarizing the accumulated evidence regarding the phenomenology, pathophysiology, neuroimaging, and treatment of PSMDs, highlighting the many gaps and controversies including diagnostic challenges, we propose a roadmap for future research to fill these gaps and resolve the related controversies. More research is warranted concerning the phenomenology, classification, diagnostic criteria, and pathophysiology of PSMDs. Further, there is an urgent need for treatment guidelines for the management of PSMDs. © 2022 International Parkinson and Movement Disorder Society.
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Transtornos dos Movimentos , Acidente Vascular Cerebral , Humanos , Transtornos dos Movimentos/complicações , Transtornos dos Movimentos/terapia , Neuroimagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapiaRESUMO
Movement disorders comprise a heterogeneous and complex group of neurological disorders that increase (hyperkinetic) or decrease (hypokinetic) the speed or amplitude of movements, or disrupt their coordinated sequencing. In this article, we describe three instructive cases, exemplifying classic movement disorders, namely dystonia, chorea, and ataxia. We highlight the diagnostic approach based on clinical clues, syndromic reasoning, evaluation, and management recommendations. Each case ends with key messages for the clinicians.
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Coreia , Distonia , Distúrbios Distônicos , Transtornos dos Movimentos , Humanos , Coreia/diagnóstico , Coreia/terapia , Distonia/diagnóstico , Distonia/terapia , Transtornos dos Movimentos/diagnóstico , Ataxia/diagnóstico , Ataxia/terapiaRESUMO
OBJECTIVE: To evaluate the relationship between health-related quality of life (HR-QoL) and both physical and psychiatric factors in a large, international, multicentre cohort of patients with isolated dystonia, the Dystonia Coalition. METHODS: Natural history data from 603 patients with isolated dystonia (median age 57 years (IQR: 48 to 64 years), 67.0% women) were prospectively acquired and analysed. HR-QoL (RAND 36-Item Health Survey), severity of depressive symptoms, generalised anxiety (Hospital Anxiety and Depression Scale) and social anxiety (Liebowitz Social Anxiety Scale) were assessed. Dystonia severity (Burke-Fahn-Marsden Dystonia Rating Scale) and dystonic tremor were examined. Statistical predictors of HR-QoL were calculated using saturated path analysis. RESULTS: Reduced HR-QoL was strongly associated with the degree of depressive symptoms and generalised and social anxiety (8/8 RAND 36 subscales, p≤0.001). Increased dystonia severity was associated with worse physical functioning, physical and emotional role functioning and social functioning (all p≤0.001). The presence of tremor correlated with worse physical functioning and pain (all p≤0.006). Younger age was associated with reduced emotional well-being and vitality (all p≤0.006). There were no HR-QoL differences between sexes. CONCLUSION: HR-QoL in isolated dystonia is strongly associated with psychiatric and physical features. While current standard of care focus on motor aspects of dystonia, comprehensive care should address both physical and mental aspects of health.
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Many disease symptoms restrict the quality of life of the affected. This usually occurs indirectly, at least in most neurological diseases. Here, impaired daily function is interposed between the symptoms and the reduced quality of life. This is reflected in the International Classification of Function, Disability and Health model published by the World Health Organization in 2001. This correlation between symptom, daily function, and quality of life makes it clear that to evaluate the success of a therapy and develop new therapies, daily function must also be evaluated as accurately as possible. However, daily function is a complex construct and therefore difficult to quantify. To date, daily function has been measured primarily by capacity (clinical assessments) and perception (surveys and patient-reported outcomes) assessment approaches. Now, daily function can be captured in a new dimension, that is, performance, through new digital technologies that can be used in the home environment of patients. This viewpoint discusses the differences and interdependencies of capacity, perception, and performance assessment types using the example of Parkinson's disease. Options regarding how future study protocols should be designed to get the most comprehensive and validated picture of daily function in patients are presented. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Pessoas com Deficiência , Doença de Parkinson , Atividades Cotidianas , Humanos , Percepção , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Continuous, subcutaneous (SC) levodopa/carbidopa infusion with ND0612 is under development as a treatment for patients with Parkinson's disease (PD) and motor fluctuations. OBJECTIVE: Evaluate 1-year safety data. METHODS: BeyoND is an open-label study evaluating the long-term safety of two ND0612 dosing regimens. RESULTS: Of the 214 enrolled patients (24-hour SC infusion: n = 90; 16-hour SC infusion: n = 124), 120 (56%) completed 12 months of treatment. Leading causes for study discontinuation were consent withdrawal (19.6%) and adverse events (17.3%). Rates of discontinuation were reduced from 49% to 29% after a protocol revision and retraining. Systemic safety was typical for PD patients treated with levodopa/carbidopa. Most patients experienced infusion site reactions, particularly nodules (30.8%) and hematoma (25.2%), which were judged mostly mild to moderate and led to discontinuation in only 10.3% of the participants. CONCLUSIONS: Subcutaneous levodopa/carbidopa continuous infusion with ND0612 is generally safe, with typical infusion site reactions for SC delivery as the main adverse event. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Levodopa , Doença de Parkinson , Antiparkinsonianos/efeitos adversos , Carbidopa/efeitos adversos , Combinação de Medicamentos , Géis , Humanos , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológicoRESUMO
BACKGROUND: Patients with bipolar spectrum disorders (BSDs) exhibit an increased risk of Parkinson's disease (PD). OBJECTIVE: The aim is to investigate whether a previous diagnosis of BSDs influences the phenotype of PD. METHODS: Of 2660 PD patients followed for at least 6 years (6-27), 250 (BSD-PD) had BSDs, 6-20 years before PD diagnosis; 48%-43% had a PD or BSD family history, and 34 carried glucocerebrosidase (GBA) and Parkin (PRKN) mutations. The cohort was split into a subset of 213 BSD-PD patients, compared with 426 matched PD patients without BSDs, and a subset of 34 BSD-PD and 79 PD patients carrying GBA or PRKN mutations. Carriers of mutations absent in BSD-PD patients and of synuclein triplication were excluded. Structured clinical interviews and mood disorder questionnaires assessed BSDs. Linear mixed models evaluated the assessment scales over time. Thirteen BSD-PD patients underwent subthalamic nucleus deep brain stimulation (STN-DBS) and were compared with 27 matched STN-DBS-treated PD patients. RESULTS: Compared to PD patients, BSD-PD showed (1) higher frequency of family history of PD (odds ratio [OR] 3.31; 2.32-4.71) and BSDs (OR 6.20; 4.11-9.35) 5); (2) higher incidence of impulse control disorders (hazard ratio [HR] 5.95, 3.89-9.09); (3) higher frequency of functional disorders occurring before PD therapy (HR, 5.67, 3.95-8.15); (4) earlier occurrence of delusions or mild dementia (HR, 7.70, 5.55-10.69; HR, 1.43, 1.16-1.75); and (5) earlier mortality (1.48; 1.11-1.97). Genetic BSD-PD subjects exhibited clinical features indistinguishable from nongenetic BSD-PD subjects. STN-DBS-treated BSD-PD patients showed no improvements in quality of life compared to the control group. CONCLUSIONS: BSDs as a prodrome to PD unfavorably shape their course and are associated with detrimental neuropsychiatric features and treatment outcomes. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Transtorno Bipolar , Estimulação Encefálica Profunda , Doença de Parkinson , Transtorno Bipolar/complicações , Transtorno Bipolar/genética , Estimulação Encefálica Profunda/efeitos adversos , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/genética , Fenótipo , Qualidade de VidaRESUMO
BACKGROUND: In patients with Parkinson's disease (PD), sleep, mood, cognitive, autonomic, and other non-motor symptoms may fluctuate in a manner similar to motor symptoms. OBJECTIVES: To validate a final version of a patient-rated questionnaire that captures the presence and severity of non-motor fluctuations in levodopa-treated PD patients (NoMoFA). METHODS: We recruited PD subjects from five movement disorders centers across the US and Canada. We assessed the internal consistency, floor and ceiling effects, test-retest reliability, and concurrent validity of NoMoFA. Classical test theory and item response theory methods informed item reduction and Delphi process yielded a final questionnaire. RESULTS: Two hundred subjects and their care-partners participated in the study (age: 66.4 ± 9.6 years; disease duration: 9 ± 5.5 years; median Hoehn and Yahr [H&Y] OFF: 3 [range 1-5]; mean Unified Parkinson's Disease Rating Scale (UPDRS) III ON score: 27.4 ± 14.9). Acceptability of the scale was adequate. There were floor effects in 8/28 items. Cronbach's alpha was 0.894. While eight items had "item-to-total" correlations below the cutoff of 0.4, removing these items did not improve Cronbach's alpha. Test-retest reliability was acceptable (intraclass correlation coefficient [ICC] 0.73; 95% confidence interval, 0.64-0.80). Concurrent validity was adequate with all Spearman's rho values comparing NoMoFA score to other measures of parkinsonian severity showing significance and in the expected direction. A final Delphi panel eliminated one item to avoid redundancy. CONCLUSIONS: The final 27-item self-administered NoMoFA is a valid and reliable questionnaire, capturing both static and fluctuating non-motor symptoms in PD. © 2021 International Parkinson and Movement Disorder Society.
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Doença de Parkinson , Idoso , Canadá , Humanos , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Biallelic PRKN mutation carriers with Parkinson's disease (PD) typically have an earlier disease onset, slow disease progression, and, often, different neuropathology compared to sporadic PD patients. However, the role of heterozygous PRKN variants in the risk of PD is controversial. OBJECTIVES: Our aim was to examine the association between heterozygous PRKN variants, including single-nucleotide variants and copy-number variations (CNVs), and PD. METHODS: We fully sequenced PRKN in 2809 PD patients and 3629 healthy controls, including 1965 late-onset (63.97 ± 7.79 years, 63% men) and 553 early-onset PD patients (43.33 ± 6.59 years, 68% men). PRKN was sequenced using targeted next-generation sequencing with molecular inversion probes. CNVs were identified using a combination of multiplex ligation-dependent probe amplification and ExomeDepth. To examine whether rare heterozygous single-nucleotide variants and CNVs in PRKN are associated with PD risk and onset, we used optimized sequence kernel association tests and regression models. RESULTS: We did not find any associations between all types of PRKN variants and risk of PD. Pathogenic and likely-pathogenic heterozygous single-nucleotide variants and CNVs were less common among PD patients (1.52%) than among controls (1.8%, false discovery rate-corrected P = 0.55). No associations with age at onset and in stratified analyses were found. CONCLUSIONS: Heterozygous single-nucleotide variants and CNVs in PRKN are not associated with PD. Molecular inversion probes allow for rapid and cost-effective detection of all types of PRKN variants, which may be useful for pretrial screening and for clinical and basic science studies targeting specifically PRKN patients. © 2020 International Parkinson and Movement Disorder Society.