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1.
Brain Nerve ; 73(3): 273-281, 2021 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-33678619

RESUMO

The current therapeutic approach for Parkinson's disease (PD) is mainly dopamine replacement with levodopa and other anti-parkinsonian drugs. As PD progresses, the number of these drugs used steadily increases. Using prescription-based database for 10 or more years up to October 2019, we investigated actual prescribing patterns for anti-parkinsonian drugs in Japan. The main analyses included data from patients continuously prescribed levodopa for 1 or more years (n=16,270), and of these, those continuously prescribed adjuvants to levodopa for 1 or more years (n=3,675). The results showed that the number of anti-parkinsonian drugs, their daily dose frequencies, and the number of tablets increased over time. These trends were observed not only for levodopa but also for adjuvants to levodopa; the number of adjuvants, their daily dose frequencies and number of tablets also increased. As the daily number of tablets increased, the proportion of dopamine agonists increased. Moreover, as the daily dosage of levodopa increased, the daily number of tablets increased for both overall anti-parkinsonian drugs and adjuvants to levodopa. This study revealed the process of polypharmacy in PD treatment objectively. Our results are valuable for maintaining and improving therapeutic adherence in PD. (Received 25 August, 2020; Accepted 23 October, 2020; Published 1 March, 2021).


Assuntos
Antiparkinsonianos , Preparações Farmacêuticas , Antiparkinsonianos/uso terapêutico , Humanos , Japão , Levodopa/uso terapêutico , Prescrições
2.
BMC Neurol ; 21(1): 46, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33516182

RESUMO

BACKGROUND: Many patients with Parkinson's disease (PD) who receive carbidopa/levodopa experience symptom reemergence or worsening, or "OFF" episodes. This study assessed the association of "OFF" episodes with health-related quality of life (HRQoL). METHODS: US-specific data from the 2017 and 2019 Adelphi Real World Disease Specific Programme for PD, a real-world cross-sectional survey, were used. Neurologists provided data for 10-12 consecutive patients with PD who completed the 39-item Parkinson's Disease Questionnaire (PDQ-39) and the EuroQol 5-Dimension (EQ-5D). Data were grouped by patients who experienced "OFF" episodes versus those who did not and by average hours of daily "OFF" time. Differences between patient groups were assessed for demographics and clinical characteristics; regression analyses were used to model the relationship between HRQoL and "OFF" episodes with age, sex, body mass index, current PD stage on the Hoehn and Yahr scale, and number of concomitant conditions related and unrelated to mobility as covariates. RESULTS: Data from 722 patients were analyzed. Overall, 321 patients (44%) had "OFF" episodes (mean of 2.9 h of daily "OFF" time). Patients who experienced "OFF" episodes were less likely to work full-time and more likely to live with family members other than their spouse/partner or reside in a long-term care facility than those without "OFF" episodes. The presence of "OFF" episodes, regardless of the average hours of daily "OFF" time, was significantly associated with high scores (reflecting poor HRQoL) on most PDQ-39 dimensions and the summary index and low scores (reflecting poor health status) on the EQ-5D health utility index, visual analog scale (VAS), and all dimensions. Furthermore, increased average hours of daily "OFF" time was significantly correlated with higher scores for all PDQ-39 dimensions and the summary index, as well as with the EQ-5D health utility index and VAS scores. Patients with "OFF" episodes experienced reduced HRQoL even after correcting for potentially confounding variables. CONCLUSIONS: This study demonstrated that the occurrence of "OFF" episodes in patients with PD is associated with reduced HRQoL and that the impact on HRQoL increased incrementally with increasing average hours of daily "OFF" time.


Assuntos
Doença de Parkinson/complicações , Qualidade de Vida , Exacerbação dos Sintomas , Idoso , Carbidopa/uso terapêutico , Estudos Transversais , Combinação de Medicamentos , Feminino , Nível de Saúde , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Análise de Regressão , Inquéritos e Questionários , Estados Unidos
3.
Rev. neurol. (Ed. impr.) ; 71(11): 407-420, 1 dic., 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-198940

RESUMO

INTRODUCCIÓN: Las fluctuaciones motoras son una de las complicaciones más frecuentes en la enfermedad de Parkinson y su tratamiento sigue siendo complejo. Por ello, desde el Grupo de Trastornos del Movimiento de la Asociación Madrileña de Neurología presentamos nuestra experiencia clínica en el tratamiento de estas complicaciones, con la intención de que sea de utilidad en la toma de decisiones en la práctica clínica diaria. DESARROLLO: Se elaboraron 19 preguntas a partir de una revisión bibliográfica y una encuesta abierta respondida por los miembros de dicho grupo. Dichas cuestiones se debatieron en dos fases, utilizando la metodología Delphi. Considerando los resultados de la encuesta, el ajuste de la dosis de levodopa y los agonistas dopaminérgicos son la opción con mejor relación eficacia/tolerabilidad en el tratamiento de las fluctuaciones motoras. La rotigotina es útil en las fluctuaciones motoras asociadas a gastroparesia, y la apomorfina subcutánea intermitente, en pacientes con off impredecible. El efecto adverso más relevante asociado a los agonistas dopaminérgicos es el trastorno del control de impulsos. Los inhibidores de la catecol-O-metiltransferasa son útiles en las fluctuaciones motoras de inicio, especialmente en el wearing off. Los inhibidores de la monoaminooxidasa son fármacos, en general, bien tolerados y útiles en las fluctuaciones motoras. En caso de que estas medidas no resulten eficaces, se deben indicar terapias de segunda línea de manera individualizada. CONCLUSIÓN: El perfil clínico del paciente con enfermedad de Parkinson es primordial para decidir la terapia más adecuada en el tratamiento de las fluctuaciones motora


INTRODUCTION. Motor fluctuations are one of the most common complications of Parkinsons disease and their treatment is still a complex matter. Therefore, from the Neurology Movement Disorders Group we present our clinical experience in the treatment of these complications, with the intention of it being useful in decision-making in daily clinical practice. DEVELOPMENT. Nineteen questions were developed based on a literature review and an open survey answered by members of this group. These issues were discussed in two phases, using the Delphi methodology. Considering the results of the survey, levodopa dose adjustment and dopamine agonists are the option with the best efficacy/tolerability ratio in the treatment of motor fluctuations. Rotigotine is useful in the motor fluctuations associated with gastroparesis, and intermittent subcutaneous apomorphine has positive effects in patients with unpredictable off periods. The most relevant adverse effect associated with dopamine agonists is impulse control disorder. Catechol-O-methyltransferase inhibitors are useful in the initial stages of motor fluctuations, especially in wearing off. Monoamine oxidase inhibitors are generally drugs that are well-tolerated and useful in motor fluctuations. If these measures are not effective, second-line treatments should be indicated on a case-by-case basis. CONCLUSION. The clinical profile of patients with Parkinson's disease is paramount in deciding the most appropriate therapy for the treatment of motor fluctuations


Assuntos
Humanos , Consenso , Técnica Delfos , Doença de Parkinson/tratamento farmacológico , Transtornos Motores/tratamento farmacológico , Transtornos Motores/fisiopatologia , Doença de Parkinson/fisiopatologia , Levodopa/uso terapêutico , Dopaminérgicos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Estimulação Encefálica Profunda
4.
Medicine (Baltimore) ; 99(46): e23249, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181715

RESUMO

Levodopa-carbidopa intestinal gel (LCIG) is a method of continuous administration of levodopa - the standard treatment in Parkinson disease (PD, a neurodegenerative disorder characterized by resting tremor, rigidity, gait impairment, and bradykinesia), thought to reduce the short-life and pulsatile problems of oral administration. We aimed to study the effects of Levodopa-Carbidopa therapy in 2 separate groups: one with intrajejunal administration of Levodopa-Carbidopa gel and the second with oral therapy.We performed an observational retrospective Romanian cohort study on 61 patients diagnosed with PD patients, with Hoehn and Jahr 3 and 4 stages, recruited from a single regional tertiary center in Cluj-Napoca, Romania, between 2009 and 2019.The mean adjusted UPDRS III (and similarly for UPDRS II) improved in the LCIG compared to the oral therapy group with 15.6 (95% CI 12.0-19.2, P < .001), and with 18.4 (95% CI 13.8-22.9, P < .001), stratified for the Hoehn and Jahr stages 3 and 4. There was a 41.7% (10) reduction in dyskinesia, and 29.2% reduction in wearing off/on-off at 1 year in the LCIG group compared to 0% (0) dyskinesia reduction, and 2.7% reduction in wearing off/on-off in the oral therapy group.Continuous intrajejunal infusion of LCIG ensures a significant and clinical reduction in motor fluctuations compared to oral therapy in advanced PD, even after adjustment for important confounders.


Assuntos
Carbidopa/administração & dosagem , Jejuno/efeitos dos fármacos , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Carbidopa/uso terapêutico , Estudos de Coortes , Combinação de Medicamentos , Feminino , Humanos , Injeções/métodos , Injeções/normas , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Romênia
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3666-3669, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018796

RESUMO

This study has investigated the efficiency of voice features in estimating the motor Unified Parkinson's Disease Rating Scale (UPDRS) score in Parkinson's disease (PD) patients. A total of 26 PD patients (mean age = 72) and 22 control subjects (mean age = 66.91) were recruited for the study. The sustained phonation /a/, /u/ and /m/ were collected in both off-state and on-state of Levodopa medication. The average motor UPDRS for PD off-state patients was 27.31, on-state was 20.42 and that of controls was 2.63. Voice features were extracted from the phonation tasks and were reduced to the most relevant 6 features for each phonation task using the Least Absolute Shrinkage and Selection Operator (LASSO) feature ranking method. The correlation between the reduced features and motor UPDRS was tested using the Spearman correlation coefficient test. AdaBoost regression learner was trained and used for automatically estimating the motor UPDRS score using the voice features. The results show that the vocal features for /m/ performed best by estimating the motor UPDRS score for PD off-state with the mean absolute error (MAE) of 3.52 and 5.90 for PD on-state. This study shows that assessment of voice can be used for day to day remote monitoring of PD patients.


Assuntos
Doença de Parkinson , Voz , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Fonação
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5406-5409, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019203

RESUMO

More than one million people currently live with Parkinson's Disease (PD) in the U.S. alone. Medications, such as levodopa, can help manage PD symptoms. However, medication treatment planning is generally based on patient history and limited interaction between physicians and patients during office visits. This limits the extent of benefit that may be derived from the treatment as disease/patient characteristics are generally non-stationary. Wearable sensors that provide continuous monitoring of various symptoms, such as bradykinesia and dyskinesia, can enhance symptom management. However, using such data to overhaul the current static medication treatment planning approach and prescribe personalized medication timing and dosage that accounts for patient/care-giver/physician feedback/preferences remains an open question. We develop a model to prescribe timing and dosage of medications, given the motor fluctuation data collected using wearable sensors in real-time. We solve the resulting model using deep reinforcement learning (DRL). The prescribed policy determines the optimal treatment plan that minimizes patient's symptoms. Our results show that the model-prescribed policy outperforms the static a priori treatment plan in improving patients' symptoms, providing a proof-of-concept that DRL can augment medical decision making for treatment planning of chronic disease patients.


Assuntos
Discinesias , Doença de Parkinson , Tomada de Decisão Clínica , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico
8.
Medicine (Baltimore) ; 99(33): e21753, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872068

RESUMO

RATIONAL: Tyrosine hydroxylase deficiency (THD) is a rare cause of dopa-responsive dystonia (DRD). Although the symptoms of DRD may be improved by treatment with L-dopa, the low morbidity of THD can lead to its misdiagnosis. Thus, it is important for physicians to be aware of THD as a cause of DRD. PATIENT CONCERNS: We report 3 cases of THD. A 5-year-old boy with DRD was diagnosed with THD and found to have compound heterozygous mutations of the TH gene, including TH:c.647G>C from his mother and TH:c.646G>A from his father. Two female siblings also were found to have TH:c.698G>A from their mother and TH:c.710T>C from their father. The younger daughter, at age 3.5 years, was diagnosed with DRD caused by THD, and then the diagnosis of the older daughter, at age 11 years, was changed from cerebral palsy to DRD caused by THD. DIAGNOSIS: The diagnosis of dopa-responsive dystonia caused by tyrosine hydroxylase deficiency was determined by whole exome sequencing. INTERVENTION: They all treated with low dose levodopa and benserazide tablets. OUTCOMES: The boy had a very good therapeutic effect, and he could walk very well by the second day of treatment. The younger sister of the siblings had a partial therapeutic effect, but her elder sister was only little effective with a milder improvement of dystonia and improvement of myodynamia. CONCLUSION: The characteristics of THD are heterogeneous, and its phenotypes are classified as type A or type B according to increasing severity. Generally, L-dopa has a good therapeutic effect in cases with type A phenotypes. We reviewed 87 cases of reported in the literature and found that c.698G>A and c.707T>C are hot spot mutations. Changes on cerebral magnetic resonance imaging were nonspecific. Analysis of neurotransmitter levels in cerebrospinal fluid is an invasive means of achieving a biochemical diagnosis.


Assuntos
Distúrbios Distônicos/congênito , Tirosina 3-Mono-Oxigenase/genética , Benserazida/uso terapêutico , Criança , Pré-Escolar , Dopaminérgicos/uso terapêutico , Distúrbios Distônicos/complicações , Distúrbios Distônicos/tratamento farmacológico , Distúrbios Distônicos/genética , Humanos , Levodopa/uso terapêutico , Masculino
9.
PLoS One ; 15(8): e0237498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822437

RESUMO

The EARLYSTIM Study compared deep brain stimulation (DBS) with best medical treatment (BMT) over 2-years, showing a between-group difference of 8.0 from baseline in favor of DBS in health-related quality of life (HRQoL), measured with the PDQ-39 SI (summary index). This study obtained complementary information about the importance of the change in HRQoL as measured by the PDQ-39, using anchor-based (Patient Global Impression of Change, PGIC) and distribution-based techniques (magnitude of change, effect size, thresholds, distribution of benefit) applied to the EARLYSTIM study data. Anchor-based techniques showed a difference follow-up-baseline for patients who reported "minimal improvement" of -5.8 [-9.9, -1.6] (mean [95%CI]) in the DBS group vs -2.9 [-9.0, 3.1] in the BMT group. As the vast majority (80.8%) of DBS patients reported "much or very much improvement", this difference was explored for the latter group and amounted to -8.7 for the DBS group and -6.5 in the BMT group. Distribution-based techniques that analyzed the relative change and treatment effect size showed a moderate benefit of the DBS on the HRQoL, whereas a slight worsening was observed in the BMT group. The change in the DBS group (-7.8) was higher than the MIC (Minimally Important Change) estimated value (-5.8 by the anchor; -6.3 by triangulation of thresholds), but not in the BMT (0.2 vs. -3.0 to -5.4, respectively). Almost 90% of the patients in the DBS group declared some improvement (58.3% and 56.7% beyond the estimated MIC), which was significantly different from the BMT group whose proportions were 32.0% and 30.3%, respectively. The number needed to treat to improve ≥1 MIC by DBS vs BMT was 3.8. Change in depression, disability and pain influenced the improvement of the DBS group. DBS improved HRQoL in a high proportion of patients to a significant and moderate degree, at 2 years follow-up.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson/terapia , Qualidade de Vida , Atividades Cotidianas , Estudos de Coortes , Humanos , Levodopa/uso terapêutico , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Doença de Parkinson/psicologia , Índice de Gravidade de Doença , Resultado do Tratamento
10.
PLoS One ; 15(8): e0237472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817705

RESUMO

A higher levodopa dose is a strong risk factor for levodopa-induced dyskinesia (LID) in patients with Parkinson's disease (PD). However, levodopa dose can change during long-term medication. We explored the relationship between levodopa dose and time to onset of LID using longitudinal multicenter data. Medical records of 150 patients who were diagnosed with de novo PD and treated with levodopa until onset of LID were collected. Levodopa dose were assessed as the dose at 6 months from levodopa initiation and rate of dose increase between 6 months and onset of LID. The groups with earlier LID onset had higher levodopa and levodopa-equivalent dose at the first 6 months of treatment and rapid increase in both levodopa and levodopa-equivalent dose. Multivariable linear regression models revealed that female sex, severe motor symptom at levodopa initiation, and higher rate of increase in both levodopa and levodopa-equivalent dose were significantly associated with early onset of LID. The present results demonstrated that rapid increase in levodopa dose or levodopa-equivalent dose is associated with early onset of LID.


Assuntos
Antiparkinsonianos/uso terapêutico , Discinesia Induzida por Medicamentos/diagnóstico , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Idoso , Antiparkinsonianos/efeitos adversos , Relação Dose-Resposta a Droga , Discinesia Induzida por Medicamentos/etiologia , Feminino , Humanos , Levodopa/uso terapêutico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
11.
Expert Opin Pharmacother ; 21(14): 1659-1665, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32640853

RESUMO

INTRODUCTION: Heterogeneity of symptoms and individual variability of progression characterizes Parkinson's disease. Unmet therapeutic needs include a cure, disease modification, and improvement of available marketed dopamine-substituting compounds. Personalized treatment, tailored to the patients' needs and symptoms, aims to ameliorate impaired motor behavior and non-motor features. Injection or infusion of apomorphine is a therapeutic option for more advanced patients with severe levodopa associated motor complications. AREAS COVERED: This narrative review summarizes the subcutaneous administration, efficacy, and side effects of the non-ergot derivative dopamine agonist apomorphine following a non-systematic literature research. EXPERT OPINION: Subcutaneous apomorphine hydrochloride application rapidly terminates intervals with severe motor impairment with bolus injections. Oscillation of motor behavior well responds to continuous apomorphine infusions. Long-term application of the commercially available apomorphine hydrochloride solution sooner or later affects skin and oral mucosa. Onset of skin nodules associated with subcutaneous tissue inflammation probably results from the antioxidant preservative sodium metabisulfite in the apomorphine solution. Addition of another better tolerated and safer antioxidant instead of sodium metabisulphite or use of an already available concentrated apomorphine-free base formulation will enhance its future use, its tolerability, safety, and acceptance of subcutaneous and sublingual application.


Assuntos
Antiparkinsonianos/administração & dosagem , Apomorfina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Apomorfina/efeitos adversos , Apomorfina/uso terapêutico , Progressão da Doença , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Humanos , Reação no Local da Injeção , Injeções Subcutâneas , Levodopa/administração & dosagem , Levodopa/efeitos adversos , Levodopa/uso terapêutico , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/imunologia
12.
Neurology ; 95(11): e1461-e1470, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32651292

RESUMO

OBJECTIVE: We tested the hypothesis that there are 2 distinct phenotypes of Parkinson tremor, based on interindividual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor by comparing interindividual differences in the dopamine response of tremor to that of bradykinesia. METHODS: In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson tremor. Clinical scores (Movement Disorders Society-sponsored version of the Unified Parkinson's Disease Rating Scale part III) were collected "off" and "on" a standardized dopaminergic challenge (200/50 mg dispersible levodopa-benserazide). In both sessions, resting tremor intensity was quantified using accelerometry, both during rest and during cognitive coactivation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for resting tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately 6 months. RESULTS: The dopamine response of resting tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster analysis on 3 clinical and electrophysiologic markers of tremor dopamine-responsiveness revealed 3 clusters: dopamine-responsive, intermediate, and dopamine-resistant tremor. A repeated levodopa challenge after 6 months confirmed this classification. Patients with dopamine-responsive tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. CONCLUSION: Parkinson resting tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine response. These tremor phenotypes may be associated with different underlying pathophysiologic mechanisms, requiring a different therapeutic approach.


Assuntos
Antiparkinsonianos/uso terapêutico , Dopaminérgicos/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Tremor/tratamento farmacológico , Acelerometria , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Resistência a Medicamentos/fisiologia , Feminino , Seguimentos , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/tratamento farmacológico , Hipocinesia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Resultado do Tratamento , Tremor/diagnóstico por imagem , Tremor/fisiopatologia
13.
Fortschr Neurol Psychiatr ; 88(9): 620-633, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32588409

RESUMO

Inhibitors of COMT and MAO-B are well established in the pharmacotherapy of Parkinson's disease (PD). MAO-B inhibitors are used as monotherapy as well as in combination with levodopa, whereas COMT inhibitors exert their effects only in conjungtion with levodopa. Both classes of compounds prolong the response duration of levodopa and optimise its clinical benefit. As a result, the ON-times are prolonged significantly. In the past, MAO-B inhibitors were also adminstered for neuroprotection; however, despite convincing scientific reasoning in support of neuroprotective effects, these could not be substantiated in clinical studies performed so far.


Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Catecol O-Metiltransferase/metabolismo , Humanos , Levodopa/uso terapêutico , Monoaminoxidase/metabolismo
14.
Acta Neurol Scand ; 142(3): 248-254, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32383152

RESUMO

OBJECTIVES: Parkinson's disease (PD) features both motor and non-motor symptoms that substantially impact quality of life (QoL). Levodopa-carbidopa intestinal gel (LCIG) reduces motor complications and improves some non-motor symptoms in advanced PD (APD). Change in patients' health-related quality of life (hrQoL) is a common endpoint in PD trials and has become an important factor in judging overall effect of LCIG. However, hrQoL is considered to be only one dimension of QoL. The primary aim of this prospective observational study was to observe the effects of LCIG on individual quality of life (iQoL) in PD and caregivers. The secondary aim was to investigate its effects on patients' motor and non-motor symptoms as well as effects on caregiver burden. MATERIALS & METHODS: Utilizing the Schedule for the Evaluation of Individual Quality of Life-Questionnaire (SEIQoL-Q) and the Personal Wellbeing Index-Adult (PWI-A), twelve patients with advanced PD and their caregivers were followed for six months after initiation of LCIG treatment. RESULTS: At the final follow-up, improvements of iQoL for patients (median SEIQoL index improvement 0.16, P < .05) and caregivers (median SEIQoL index improvement 0.20, P < .05) were seen together with improvements of motor and non-motor symptoms. There were no significant improvements of hrQoL. CONCLUSIONS: The study results indicate that LCIG improves iQoL in PD in addition to the improvement of motor and non-motor symptoms. Furthermore, this study signals that LCIG may also contribute to improvement of iQoL in caregivers.


Assuntos
Antiparkinsonianos/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Carbidopa , Cuidadores/psicologia , Efeitos Psicossociais da Doença , Combinação de Medicamentos , Feminino , Humanos , Infusões Parenterais , Jejuno , Levodopa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Movimento , Estudos Prospectivos , Desempenho Psicomotor , Qualidade de Vida , Resultado do Tratamento
15.
Medicine (Baltimore) ; 99(19): e20154, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384503

RESUMO

To investigate the effect of multi-disciplinary teamwork on balance performance of Parkinson's disease (PD).Sixteen primary Parkinson's disease patients (8 male, 8 female) treated with bilateral subthalamic nucleus deep brain stimulation (STN-DBS) were included in the study. The median age of patients was 60.5 years; all patients were in the Hoehn&Yahr (H&Y) 3 stage; the median PD duration of the disease was 9 years. For each patient, multi-disciplinary teamwork treatment including DBS, medication, physical therapy and psychotherapy proceeded. levodopa equivalent daily dose (LEDD, mg/day), life quality (PDQ-39), Motor disability (MDS-UPDRSIII) and balance performance (MDS-UPDRS 3.12, Berg Balance Scale BBS, Limits of Stability LoS) were assessed in different time and status respectively: preoperation (Med-off, Med-on), postoperation (Stim-Off/Med-Off, Stim-On/Med-Off, Stim-On/Med-On), 6 months postoperation (Stim-On/ Med-Off, Stim-On/Med-On) and 12 months postoperation (Stim-On/Med-Off, Stim-On/Med-On).The LEDD, life quality (PDQ-39) continued to improve during the follow-up, statistical difference were found in both 6 months postoperation and 12 months postoperation compared with preoperation. The Motor disability (MDS-UPDRSIII), balance performance (MDS-UPDRS 3.12, BBS) and the LoS (target acquisition percentage, trunk swing angle standard deviation, time) showed significant improvement in Stim-On/med-Off 6 months postoperation and 12 months postoperation separately compared with Med-Off preoperation.Multi-disciplinary teamwork for PD patients with STN-DBS could improve balance performance.


Assuntos
Estimulação Encefálica Profunda/métodos , Doença de Parkinson/terapia , Modalidades de Fisioterapia , Equilíbrio Postural/fisiologia , Idoso , Antiparkinsonianos/uso terapêutico , Terapia Combinada , Avaliação da Deficiência , Pessoas com Deficiência , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Equipe de Assistência ao Paciente , Psicoterapia/métodos , Qualidade de Vida , Núcleo Subtalâmico/patologia
16.
Nat Commun ; 11(1): 2388, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404907

RESUMO

Deep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson's disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics, behavioral tasks and mathematical modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A computational model highlights that a decrease in pyramidal neuron activity induced by DBS or by a stimulation of cortical somatostatin interneurons can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation.


Assuntos
Estimulação Encefálica Profunda/métodos , Levodopa/uso terapêutico , Transtornos Parkinsonianos/terapia , Somatostatina/metabolismo , Algoritmos , Animais , Antiparkinsonianos/uso terapêutico , Modelos Animais de Doenças , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Córtex Motor/efeitos dos fármacos , Córtex Motor/metabolismo , Córtex Motor/fisiopatologia , Optogenética/métodos , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/fisiopatologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Células Piramidais/fisiologia , Núcleo Subtalâmico/efeitos dos fármacos , Núcleo Subtalâmico/metabolismo , Núcleo Subtalâmico/fisiopatologia
17.
Am J Trop Med Hyg ; 103(2): 851-854, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32372748

RESUMO

Dengue fever continues to be an important cause of morbidity and mortality in tropical and subtropical countries. A wide range of neurological manifestations including dengue encephalopathy, Guillain-Barre syndrome, acute disseminated encephalomyelitis, transverse myelitis, cranial nerve palsies, and myositis have been reported following dengue infection. But parkinsonism secondary to dengue virus infection is uncommon, with only three published case reports in adults and one in children. We describe a 13-year-old pre-morbidly normal boy, who presented with bradykinesia, bradyphonia, mask-like facies, and cogwheel rigidity while recovering from uncomplicated DF. He responded favorably to levodopa/carbidopa supplementation and had resolution of symptoms over the next 2 weeks. We also did a comparative review of all published cases of dengue-induced parkinsonism. Post-dengue, parkinsonism is uncommon, and treating clinicians should be aware of this uncommon but treatable neurological complication of a common arboviral infection.


Assuntos
Dengue/complicações , Doença de Parkinson Secundária/etiologia , Adolescente , Antiparkinsonianos/uso terapêutico , Encéfalo/diagnóstico por imagem , Carbidopa/uso terapêutico , Imagem de Difusão por Ressonância Magnética , Combinação de Medicamentos , Eletroencefalografia , Humanos , Índia , Levodopa/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Doença de Parkinson Secundária/diagnóstico por imagem , Doença de Parkinson Secundária/tratamento farmacológico , Doença de Parkinson Secundária/fisiopatologia , Resultado do Tratamento
18.
J Neurol Neurosurg Psychiatry ; 91(7): 687-694, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32371534

RESUMO

OBJECTIVE: To examine 36-month effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on non-motor symptoms (NMS) compared with standard-of-care medical treatment (MED) in Parkinson's disease (PD). METHODS: Here we report the 36-month follow-up of a prospective, observational, controlled, international multicentre study of the NILS cohort. Assessments included NMSScale (NMSS), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). Propensity score matching resulted in a pseudo-randomised sub-cohort balancing baseline demographic and clinical characteristics between the STN-DBS and MED groups. Within-group longitudinal outcome changes were analysed using Wilcoxon signed-rank and between-group differences of change scores with Mann-Whitney U test. Strength of clinical responses was quantified with Cohen's effect size. In addition, bivariate correlations of change scores were explored. RESULTS: Propensity score matching applied on the cohort of 151 patients (STN-DBS n=67, MED n=84) resulted in a well-balanced sub-cohort including 38 patients per group. After 36 months, STN-DBS significantly improved NMSS, PDQ-8, SCOPA-motor examination and -complications and reduced LEDD. Significant between-group differences, all favouring STN-DBS, were found for NMSS, SCOPA-motor complications, LEDD (large effects), motor examination and PDQ-8 (moderate effects). Furthermore, significant differences were found for the sleep/fatigue, urinary (large effects) and miscellaneous NMSS domains (moderate effects). NMSS total and PDQ-8 change scores correlated significantly. CONCLUSIONS: This study provides Class IIb evidence for beneficial effects of STN-DBS on NMS at 36-month follow-up which also correlated with quality of life improvements. This highlights the importance of NMS for DBS outcomes assessments.


Assuntos
Estimulação Encefálica Profunda/métodos , Fadiga/fisiopatologia , Doença de Parkinson/terapia , Sono/fisiologia , Núcleo Subtalâmico/fisiopatologia , Atividades Cotidianas , Idoso , Antiparkinsonianos/uso terapêutico , Terapia Combinada , Feminino , Seguimentos , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Estudos Prospectivos , Resultado do Tratamento
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