Levodopa-Induced Dyskinesias are Frequent and Impact Quality of Life in Parkinson's Disease: A 5-Year Follow-Up Study.

BACKGROUND: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD). OBJECTIVE: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL). PATIENTS AND METHODS: PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL. RESULTS: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (ß = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (ß = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ-39SI. CONCLUSION: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL.

Clinical and structural brain correlates of hypomimia in early-stage Parkinson's disease.

BACKGROUND AND PURPOSE: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. METHODS: The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross-sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used. RESULTS: After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS-III speech and bradykinesia items and was significantly related to the severity of apathy (ß = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto-temporo-parietal regions involved in the decoding, recognition and production of facial expression of emotions. CONCLUSION: Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non-motor aspects converge.

Increased homocysteine levels correlate with cortical structural damage in Parkinson's disease.

BACKGROUND: Blood homocysteine appears to be increased in Parkinson's disease (PD) and may play a role in the development and progression of this disorder. However, the specific contribution of abnormal homocysteine levels to cortical degeneration in PD remains elusive. OBJECTIVE: To characterize the cortical structural correlates of homocysteine levels in PD. METHODS: From the COPPADIS cohort, we identified a subset of PD patients and healthy controls (HC) with available homocysteine and imaging data. Surface-based vertex-wise multiple regression analyses were performed to investigate the cortical macrostructural (cortical thinning) and microstructural (increased intracortical diffusivity) correlates of homocysteine levels in this sample. RESULTS: A total of 137 PD patients and 43 HC were included. Homocysteine levels were increased in the PD group (t = -2.2, p = 0.03), correlating in turn with cognitive performance (r = -0.2, p = 0.03). Homocysteine in PD was also associated with frontal cortical thinning and, in a subset of patients with available DTI data, with microstructural damage in frontal and posterior-cortical regions (p < 0.05 Monte-Carlo corrected). CONCLUSIONS: Homocysteine in PD appears to be associated with cognitive performance and structural damage in the cerebral cortex. These findings not only reinforce the presence and importance of cortical degeneration in PD, but also suggest that homocysteine plays a role among the multiple pathological processes thought to be involved in its development.

Estudio DISCREPA: tratamiento de la enfermedad de Parkinson avanzada y utilización de terapias de segunda línea en Cataluña / DISCREPA study: treatment of advanced Parkinson's disease and use of second-line treatments in Catalonia

INTRODUCCIÓN: El tratamiento de la enfermedad de Parkinson (EP) es complejo y la instauración de terapias de segunda línea en la EP avanzada sigue siendo controvertida. OBJETIVO: Analizar la asistencia de pacientes con EP en Cataluña, con especial atención a la utilización de las terapias de segunda línea en la EP avanzada. Sujetos y métodos: Encuesta en línea autoadministrada a través de la Societat Catalana de Neurología a neurólogos de Cataluña que atendían a pacientes con EP. RESULTADOS: Participaron 72 neurólogos que visitaban una media mensual de 38 pacientes con EP (el 37,3% con complicaciones motoras). El 86% preguntaba rutinariamente por complicaciones motoras. Los principales motivos para indicar terapias de segunda línea fueron la discapacidad en off (83,1%), el impacto de las discinesias (76,9%), el impacto del tiempo en off (75,4%) y el tiempo en off (73,8%). El 70% de los neurólogos declaró limitaciones para instaurar terapias de segunda línea: escasez de recursos en su hospital, falta de tiempo para visitar al paciente o para realizar tareas administrativas y falta de soporte de enfermería (33,3%). No se utilizan terapias de segunda línea en el 72% de los pacientes que podrían ser potencialmente candidatos, sobre todo por rechazo del paciente (37,9%). CONCLUSIONES: La mayoría de los neurólogos en Cataluña que visitan pacientes con EP pregunta rutinariamente por complicaciones motoras sin utilizar herramientas específicas. Aunque los neurólogos conocen bien las indicaciones de instauración de terapias de segunda línea, la negativa del paciente, la falta de tiempo y la falta de protocolos asistenciales definidos para derivar a pacientes pueden contribuir a una menor utilización de terapias de segunda línea en la EP avanzada

INTRODUCTION: The treatment of Parkinson's disease (PD) is complex, and the establishment of second-line therapies in advanced PD remains controversial. AIM: To analyze the assistance of patients with PD in Catalonia, with special attention to the use of second-line therapies in advanced PD. SUBJECTS AND METHODS: Online self-administered survey to neurologists in Catalonia who treated patients with PD, through the Catalan Society of Neurology. RESULTS: 72 neurologists who visited a monthly average of 38 PD patients (37.3% motor complications) participated. 86% routinely asked about motor. The main reasons for indicating second-line therapies were disability in off (83.1%), impact of dyskinesias (76.9%), impact of time in off (75.4%) and time in off (73.8%). 70% of neurologists declared limitations to establish second-line therapies: lack of resources in their hospital, lack of time to visit the patient or to perform administrative tasks and lack nursing support. Second-line therapies is not used in 72% of patients who could potentially be candidates, especially due to patient rejection (37.9%). CONCLUSIONS: The majority of neurologists in Catalonia who visit patients with PD routinely ask about motor complications without using specific tools. Although neurologists are well aware of the indications for the establishment of second-line therapies, the refusal of the patient, the lack of time and the lack of defined care protocols to refer patients, they can contribute to a lower use of second-line therapies in advanced PD

Active bilingualism delays the onset of mild cognitive impairment.

Lifelong bilingualism may contribute to cognitive reserve (CR) in neurodegenerative diseases as shown by a delay of the age at symptom onset in bilinguals with Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). However, some studies have failed to show this bilingual advantage, suggesting that it might depend on the type and degree of bilingualism. In the present study, we tested the hypothesis that active bilingualism, defined as the continuous use of the two languages as opposed to second language exposition only, may protect against cognitive decline. Moreover, we investigated whether bilingualism as a CR factor may be explained by an advantage within the executive control (EC) system. To do so, we collected clinical measures (age at onset of cognitive symptoms, age at the first medical visit for cognitive impairments, and age at diagnosis) in patients with MCI and patients with AD with different degrees of language experience and usage of Catalan and Spanish. Additionally, all participants were tested on four EC tasks and one long-term memory recognition task. First, results from multiple regression analyses showed that active bilingualism was a significant predictor of delay in the age at onset for all the clinical measures in MCI, but not AD patients. Second, the effect of active bilingualism was independent of occupation, educational level and job attainment across the individuals' lifespan. Finally, although we did not find an effect of active bilingualism across all EC tasks, we did find an effect for conflict resolution. These results are discussed in the context of CR hypotheses, suggesting that compensatory mechanisms may play a role in protecting against cognitive decline.

Rasagiline and safinamide as a dopamine-sparing therapy for Parkinson's disease.

OBJECTIVES: To evaluate whether the prescription of monoamine oxidase B inhibitors (MAOB-I), rasagiline and safinamide, contributes to the reduction of levodopa and/or dopamine agonists (DA) dose in order to minimize adverse effects. MATERIALS AND METHODS: A total of 724 patients with Parkinson's disease (PD) have been prospectively included in our database since the year 2000, representing a total of 5124 visits. For each patient and visit, antiparkinsonian treatment was recorded. In the presence of rasagiline and safinamide, we analysed the evolution of levodopa equivalent dose (LED) and LED for DA (LED-DA). RESULTS: The data obtained from the 1664 visits between 2006 and 2010 (321 patients) and the 1709 visits between 2014 and 2018 (403 patients) were analysed in order to assess the impact of the introduction of rasagiline and safinamide, respectively. The annual mean LED remained stable without statistically significant differences. In the first period (impact of rasagiline), the annual mean LED-DA in 2010 was significantly higher than in 2006 (P = 0.001). In the second period (impact of safinamide), the annual mean LED-DA in 2018 was significantly lower than in 2014 (P = 0.002). A repeated-measure analyses of LED-DA including only patients who had taken safinamide showed a statistically significant decrease in LED-DA (P = 0.027). CONCLUSIONS: The introduction of MAOB-I in the overall treatment of PD as part of routine clinical practice has not helped to reduce annual mean LED. However, safinamide reduces annual mean LED-DA and may be linked to a reduction in dose-dependent adverse effects in the long term.

Agomelatine for Depression in Parkinson Disease: Additional Effect on Sleep and Motor Dysfunction.

Depression and sleep disorders are among the most prevalent nonmotor symptoms of Parkinson disease (PD). Because agomelatine acts as a MT1 and MT2 agonist and as a 5HT2c antagonist, this study was designed to assess the efficacy of agomelatine in treating depressive symptoms in PD patients, and the potential changes both in sleep quality and motor symptoms. Depressed patients with PD were treated with agomelatine for 6 months, and they were evaluated with an array of scales. Completed nocturnal video-polysomnography was performed at baseline and week 12. The efficacy analysis population included 24 patients (12 men). The mean (SD) age was 75.2 (8.3) years. The mean (SD) daily dose of agomelatine was 25.00 (10.43) mg at 24 weeks. No changes in dopamine replacement therapy were made. There was a significant decrease in the 17-item Hamilton Depression Scale score over the course of the study (P < 0.0005). The Scales for Outcomes in Parkinson disease Sleep Questionnaire showed a statistically significant improvement over time in each of its subscales: nighttime sleep (P < 0.005), last month nighttime sleep (P < 0.0005), and daytime sleepiness (P < 0.0005). Surprisingly, changes over time in the motor subscale of Unified Parkinson Disease Rating Scale were statistically significant (P < 0.0005). Periodic limb movements and awakenings measured by polysomnography improved significantly (P < 0.005 and P < 0.05, respectively). We concluded that the use of agomelatine in PD depressed patients may have a considerable therapeutic potential because of its dual action for treating both symptoms of depression and disturbed sleep given its secondary beneficial effects regarding the reduction of extrapyramidal symptoms.

Impulsive and compulsive behaviors in Parkinson's disease: a one-year follow-up study.

Impulsive and compulsive behaviors (ICBs) have been reported to occur frequently in Parkinson's disease (PD) and include impulse control disorders (ICDs), punding and dopamine dysregulation syndrome (SSD). We report on the outcomes of 25 PD patients who developed ICBs. Information was collected on changes in parkinsonian and psychiatric medication follow-up (median=12.1 months). At time 1, only 18 patients (72%) were taking dopamine agonists (DA). At time 2, fifteen patients (83.33%) either discontinued or decreased their DA treatment. Of these patients, thirteen (86.67%) reported experiencing full or partial remission of their ICBs symptoms. When analyzing separately the 11 patients with punding, these symptoms remained unchanged in 9 patients (81.82%) independently of changes in dopaminergic drugs. In conclusion, the current study suggests that there are clear similarities, but also important differences, between punding and ICDs over time. Pathological gambling, binge or compulsive eating, pathological hypersexuality and compulsive shopping in PD were robustly associated with the use of DA but the relationship between dopaminergic medications and punding is less clear. It is important to determine if other treatment strategies may be effective for punding in PD.

Blood pressure in the initial phase of acute ischaemic stroke: evolution and its role as an independent prognosis factor at discharge and after 3 months of follow-up.

BACKGROUND: A prospective observational study was aimed at assessing the role of blood pressure (BP) during the first 24 h from stroke onset on the outcome of acute ischaemic stroke. METHODS: Subjects admitted within the first 3 h from stroke onset were included. Stroke severity was evaluated with the Canadian Stroke Scale (CSS). Functional recovery was defined as a modified Rankin Scale score < or =2. RESULTS: One hundred subjects were included. In a logistic regression model, the independent predictors of poor functional recovery at discharge were: age (OR = 1.12; 95% CI 1.04-1.21; p = 0.0033), non-lacunar stroke subtype (OR = 4.31; 95% CI 1.07-17.31; p = 0.0395), diabetes mellitus (OR = 8.38; 95% CI 1.67-41.95; p = 0.0097), a CSS score at admission < or =8 (OR = 28.64; 95% CI 5.59-146.68; p<0.0001), an average systolic BP during the first 6 h > or =180 mmHg (OR = 13.34; 95% CI 1.34-133.10; p = 0.0272) and a lower diastolic BP average from 6 to 24 h (OR for 5 mmHg increase: 0.57; CI 95% 0.36-0.88; p = 0.0115). Similar results were observed after 3 months of follow-up. CONCLUSION: In ischaemic stroke patients, systolic BP over 180 mmHg in the first 6 h and a decrease of diastolic BP during the 6-24 h from stroke onset were independent predictors of a poor functional recovery.

Does nefazodone improve both depression and Parkinson disease? A pilot randomized trial.

Some of the selective serotonin reuptake inhibitors (SSRI)-induced motor side effects are mediated by stimulating 5-HT2 receptors in the basal ganglia, probably because serotonin inhibits the subsequent neuronal dopamine release. We hypothesized that nefazodone, a serotonin 2 antagonist/reuptake inhibitor (SARI) that selectively blocks 5-HT2 receptors, could disrupt the aforementioned inhibitory pathway. Therefore, increased dopamine levels in the postsynaptic milieu and an improvement in the motor symptoms in depressed patients with Parkinson disease (PD) should be observed. This study was designed to determine whether nefazodone has a dual activity as an antidepressant and as an agent capable of reducing the extrapyramidal symptoms in depressed parkinsonian patients. Depressed patients with PD were randomly assigned to 2 therapeutic groups: nefazodone or fluoxetine. Patients were evaluated by a psychiatrist and were blindly assessed by a neurologist with an array of scales. Patients on nefazodone (n = 9) showed a significant improvement over time in the total Unified Parkinson Disease Rating Scale score (UPDRS) (part II + part III) (P = 0.004) and in the UPDRS subscore part III (P = 0.003). None of these scores changed over time in the fluoxetine group (n = 7). Both, nefazodone and fluoxetine were equally effective as antidepressants: Beck Depression Inventory scores significantly improved (P < 0.001), with no significant differences between treatment groups (P = 0.97). If our results can be confirmed in a larger clinical trial, nefazodone ought to be considered over fluoxetine given its secondary beneficial effects regarding the reduction of extrapyramidal symptoms in depressed PD patients.