Search

RESUMEN: Introducción: La enfermedad de Parkinson es el segundo trastorno neurodegenerativo más frecuente, cuya principal característica es la afectación de la marcha. Entre los diferentes abordajes terapéuticos se encuentran el tapiz rodante o la estimulación rítmica auditiva, así como el uso conjunto de estas dos técnicas. Objetivo: Estudiar los efectos que tiene la estimulación rítmica auditiva asistida en el entrenamiento en tapiz rodante en comparación con el entrenamiento en tapiz rodante. Material y métodos: 34 pacientes diagnosticados de enfermedad de Parkinson se dividirán en dos grupos de 17. El grupo 1 entrenará en tapiz rodante, y el grupo 2 en tapiz rodante asistido con estimulación rítmica auditiva. En total, 12 sesiones de 45 minutos repartidas en 4 semanas. Los datos se recogerán por medio de Timed Up and Go, 6 Minute Walk Test, Freezing Of Gait Questionnaire y satisfacción mediante escala visual analógica. Plan de análisis de los resultados: Clasificando a la muestra según los estadios de Hoehn y Yahr, se compararán las variables obtenidas entre grupos y entre las diferentes mediciones tomadas en el tiempo. Fortalezas y debilidades: Aunque con una muestra relativamente pequeña, es el primer estudio que observa el uso de la estimulación rítmica auditiva en el entrenamiento de la marcha en tapiz rodante según los estadios de Hoehn y Yahr. Discusión/Conclusión: Se esperan obtener resultados favorables para el grupo 2. La estimulación rítmica auditiva implementada en el entrenamiento de la marcha en tapiz rodante es un tipo de abordaje a tener en cuenta a la hora de rehabilitar la marcha en enfermos de Parkinson. ABSTRACT: Introduction: Parkinson´s disease is the second most common neurodegenerative disorder, whose main characteristic is the gait impairment. Among the different therapeutic approaches are, treadmill training or rhythmic auditory stimulation as well as the use of these two techniques simultaneously. Objective: Study the effects of rhythmic auditory stimulation assisted on treadmill training compared with the treadmill training. Material and Methods: 34 patients diagnosed of PD will be divided into two groups of 17. The group 1 will train on treadmill training, and the group 2 on treadmill training assisted with rhythmic auditory stimulation. In total, 12 sessions of 45 minutes divided into 4 weeks. Measurements shall be taken through Timed Up and Go test, 6 Minute Walk Test, Freezing Of Gait Questionnaire and satisfaction of the session through visual analogical scale. Results analysis plan: Classifying the sample according to the Hoehn and Yahr stages, the variables obtained between groups and between the different measurements taken over the time will be compared. Strong and weak points: Although with a relatively small sample size, it is the first study to look at the use of the rhythmic auditory stimulation in treadmill training according to the Hoehn and Yahr stages. Discussion/Conclusion: Favorable results are expected for group 2. The rhythmic auditory stimulation implemented in treadmill training is a type of approach to take into account when rehabilitating gait in Parkinson´s disease. Grado en Fisioterapia

Uvod: Parkinsonova bolezen je progresivna nevrodegenerativna bolezen, ki privede do postopnega upada motoričnih funkcij. Napredovanje bolezni privede do slabšega ravnotežja, hoje in posledično do padcev. Z vadbo funkcijskih nalog za ravnotežje naj bi pripomogli k izboljšanju motoričnih simptomov, ravnotežja in hoje pacientov s Parkinsonovo boleznijo. Namen: Na podlagi pregleda literature ugotoviti učinkovitost vadbe funkcijskih nalog za ravnotežje pri pacientih s Parkinsonovo boleznijo. Metode dela: Literaturo smo iskali v podatkovnih zbirkah Pubmed in PEDro. Iskanje je zajelo raziskave, objavljene do vključno septembra 2020. Vključeni so bili le randomizirani kontrolirani poskusi. Izključene so bile raziskave, ki so vključevale vadbo za ravnotežje z uporabo naprav ali vadbo, pridruženo drugim oblikam vadbe, in raziskave, ocenjene po lestvici PEDro z manj kot 4. Rezultati: V pregled je bilo vključenih sedem raziskav. Skupno je v njih sodelovalo 499 pacientov s Parkinsonovo boleznijo. Vadbeni programi so vključevali funkcijske vaje za ravnotežje. Trajali so od pet do deset tednov, vadba je bila izvedena dvakrat do trikrat na teden po 45−60 minut. Ugotovili smo, da je pri pacientih s Parkinsonovo boleznijo vadba funkcijskih nalog za ravnotežje učinkovitejša za izboljšanje ravnotežja kot splošna vadba za gibljivost in koordinacijo, poučevanje pacientov ali odsotnost kakršnekoli obravnave. V primerjavi z vadbo proti uporu so si ugotovitve raziskav nasprotujoče. Z vadbo funkcijskih nalog za ravnotežje lahko izboljšamo tudi premičnost in funkcionalno neodvisnost, zaupanje v ravnotežje in zmanjšamo pogostost padcev. Ugotovili smo tudi, da so pacienti bolj motivirani, če vadba poteka pod nadzorom fizioterapevta. Razprava in zaključek: Vadba funkcijskih nalog za ravnotežje je ustrezen in učinkovit fizioterapevtski postopek za izboljšanje ravnotežja in premičnosti pacientov s Parkinsonovo boleznijo. Njeni učinki se prenesejo tudi na dejavnosti vsakodnevnega življenja. Potrebne so nadaljnje raziskave, ki bi vključile paciente s kognitivnimi okvarami in višjo stopnjo Parkinsonove bolezni. Introduction: Parkinson's disease is a progressive neurodegenerative disease that leads to a gradual decline in motor functions. Progression of the disease can lead to a decline in balance, walking and consequently to falls. Functional balance training may improve motor simptoms, balance and walking in patients with Parkinson´s disease. Purpose: The purpose of this review was to determine the effectiveness of functional balance training in patients with Parkinson´s disease. Methods: The literature was searched in the Pubmed and PEDro databases. The search included randomized controlled trials published until September 2020. We did not include studies with the use of devices, or any other forms of exercises, except functional balance training. Also all randomized controlled trials, which were assessed with a PEDro scale 3 or less, were excluded. Results: Seven studies were included in the review. A total of 499 patients with Parkinson´s disease were included in the studies. Functional balance training programmes lasted from five to ten weeks, with two to three sessions per week. Individual sessions lasted 45−60 minutes. Functional balance training program was found to be more effective than programs of exercise for mobility and coordination or placebo. Compared to resistance training, the findings of the studies were contradictory. Functional balance training improved balance, mobility, and functional independence, confidence in balance and reduced the frequency of falls in patients with Parkinson’s disease. We also found that patients were more motivated if the physiotherapist was present during functional balance training. Discussion and conclusion: Functional balance training without the use of devices is an appropriate and effective physiotherapy procedure that improves balance and mobility of patients with Parkinson’s disease. The effects of functional balance training are transferred to the activities of daily living. Further studies including patients with cognitive impairment and a higher rate of Parkinson´s disease are necessary.

Some studies observed a benefit of Parkinson´s disease (PD) patients after treatment with safinamide in some non-motor symptoms (NMSs). The aim of this study was to analyze the effectiveness of safinamide on NMS burden in PD. SAFINONMOTOR (an open-label study of the effectiveness of safinamide on non-motor symptoms in Parkinson´s disease patients) is a prospective open-label single-arm study conducted in five centers from Spain. The primary efficacy outcome was the change from baseline (V1) to the end of the observational period (6 months) (V4) in the non-motor symptoms scale (NMSS) total score. Between May/2019 and February/2020 50 patients were included (age 68.5 ± 9.12 years, 58% females, 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The NMSS total score was reduced by 38.5% (from 97.5 ± 43.7 in V1 to 59.9 ± 35.5 in V4, p &lt, 0.0001). By domains, improvement was observed in sleep/fatigue (−35.8%, p = 0.002), mood/apathy (−57.9%, 0.0001), attention/memory (−23.9%, p = 0.026), gastrointestinal symptoms (−33%, p = 0.010), urinary symptoms (-28.3%, p = 0.003), and pain/miscellaneous (−43%, 0.0001). Quality of life (QoL) also improved with a 29.4% reduction in the PDQ-39SI (from 30.1 ± 17.6 in V1 to 21.2 ± 13.5 in V4, 0.0001). A total of 21 adverse events in 16 patients (32%) were reported, 5 of which were severe (not related to safinamide). Dyskinesias and nausea were the most frequent (6%). Safinamide is well tolerated and improves NMS burden and QoL in PD patients with severe or very severe NMS burden at 6 months.

Background: Consecutive adult neurogenesis is a well-known phenomenon in the ventricular–subventricular zone of the lateral wall of the lateral ventricles (V–SVZ) and has been controversially discussed in so-called “non-neurogenic” brain areas such as the periventricular regions (PVRs) of the aqueduct and the fourth ventricle. Dopamine is a known modulator of adult neural stem cell (aNSC) proliferation and dopaminergic neurogenesis in the olfactory bulb, though a possible interplay between local dopaminergic neurodegeneration and induction of aNSC proliferation in mid/hindbrain PVRs is currently enigmatic. Objective/Hypothesis: To analyze the influence of chronic–progressive dopaminergic neurodegeneration on both consecutive adult neurogenesis in the PVRs of the V–SVZ and mid/hindbrain aNSCs in two mechanistically different transgenic animal models of Parkinson´s disease (PD). Methods: We used Thy1-m[A30P]h α synuclein mice and Leu9′Ser hypersensitive α4* nAChR mice to assess the influence of midbrain dopaminergic neuronal loss on neurogenic activity in the PVRs of the V–SVZ, the aqueduct and the fourth ventricle. Results: In both animal models, overall proliferative activity in the V–SVZ was not altered, though the proportion of B2/activated B1 cells on all proliferating cells was reduced in the V–SVZ in Leu9′Ser hypersensitive α4* nAChR mice. Putative aNSCs in the mid/hindbrain PVRs are known to be quiescent in vivo in healthy controls, and dopaminergic deficiency did not induce proliferative activity in these regions in both disease models. Conclusions: Our data do not support an activation of endogenous aNSCs in mid/hindbrain PVRs after local dopaminergic neurodegeneration. Spontaneous endogenous regeneration of dopaminergic cell loss through resident aNSCs is therefore unlikely.

The symptoms of dysautonomia are frequent non-motor complaints in Parkinson’s disease (PD). They are present even in the early stages of disease and cause a negative impacto in quality of life. The aim of study was: to chacaterize the dysautonomy profile of individuals with PD treated at University Hospital Lauro Wanderley; to make comparisions between groups of patients, which were segregated by the modified Hoen-Yarh score, time of disease and total daily levodopa dose. Twenty subjects participated in the research, who underwent a neurological clinical evaluation, application of a socio-demographic questionnaire, modified Hoen-Yarh and SCOPA-AUT. Data were evaluated through SPSS, using the Mann-Whitney test, considering the level of significancfe p < 0.05. The most frequent symptom of dysautonomy was nocturia (90%). The most affected domains were: urinary and gastrointestinal, with 100% of participants reporting at least one symptom of each, with the majority having 04 affected domains (45%). The average amount of symptoms presente was 11.05 (4-17, standard deviation 0.94). The average SCOPA-AUT score was 21.85 (6-40, standard deviation of 9.06). The comparison between groups, according to the modified Hoen-Yarh score, showed a significant difference between groups with scores up to 2,0 and from 2,5 only for the daily total levodopa (U = 22.5, z = -2.06, p = 0.047). There was no statistical significant difference for the variables: age, time of disease and SCOPA-AUT score. There were significant diferences between groups (levodopa dose ≤ 400mg and > 400 mg) for orthostatic symptoms (U = 21, z = -2.189, p = 0.039); gastrointestinal (U = 13.5, z = -2.731, p = 0.012). Autonomic dysfunction is a clinically relevant and widespread problem in PD, wich it can be presente even in early stages, and don´t have a defined pattern of involvement. And so, it’s necessary to research and properly treat these non-dopaminergic symptoms throughot the course of the disease, providing improvement in quality of life. Nenhuma Os sintomas de disautonomia são queixas não-motoras frequentes na Doença de Parkinson (DP), mesmo nas fases precoces, com impacto negativo na qualidade de vida. Objetiva-se com o presente estudo: caracterizar o perfil de disautonomia dos indivíduos com DP atendidos no HULW; tecer comparações entre grupos de pacientes, os quais foram segregados pelo escore do Hoen-Yarh modificado, tempo de doença, e dose total de levodopa diária. Participaram da pesquisa 20 participantes, os quais foram submetidos à uma avaliação clínica neurológica, aplicação de questionário sócio-demográfico, Hoen-Yarh modificado e SCOPA-AUT. Os dados foram avaliados através do SPSS, utilizando o teste de Mann-Whitney, considerando o nível de significância p < 0,05. O sintoma de disautonomia mais frequente foi noctúria (90%). Os domínios mais acometidos foram: urinário e gastrintestinal, com 100% dos indivíduos relatando pelo menos um sintoma de cada, sendo que a maioria teve 04 domínios acometidos (45%). A quantidade média de sintomas presentes entre os entrevistados foi de 11,05 (4-17, desvio-padrão 0,94). A pontuação média do SCOPA-AUT foi de 21,85 (6-40, desvio-padrão de 9,06). A comparação entre grupos, de acordo com o escore do Hoen-Yarh modificado, mostrou diferença significativa entre os grupos com pontuação até 2 e a partir de 2,5 apenas para a dose diária total de levodopa (U = 22,50, z = -2,06, p = ,047). Não houve diferença estatística significativa para as variáveis: idade, tempo de doença e pontuação no SCOPA AUT. Houve diferenças significativas entre os grupos (dose de levodopa ≤ 400 mg e > 400 mg) em relação à quantidade de sintomas de Disautonomia para os sintomas ortostáticos (U = 21, z = -2,189, p = 0,039); gastrintestinais (U = 13,5, z = -0,2731, p = 0,005); e sexuais (U = 0,5, z = -2,438, p = 0,012). A disfunção autonômica é um problema clinicamente relevante e generalizado na DP, podendo ocorrer mesmo em fases precoces, e sem um padrão definido de acometimento, o que reforça a necessidade de pesquisar e tratar adequadamente esses sintomas não dopaminérgicos durante todo o curso da doença, proporcionando melhoria na qualidade de vida.

Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed in food, several synthetic but also non-synthetic methylxanthines are used as pharmaceuticals, in particular in treating airway constrictions. Besides the well-established bronchoprotective effects, methylxanthines are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid homeostasis and have neuroprotective effects. Known molecular mechanisms include adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation and gene regulation. By affecting several pathways associated with neurodegenerative diseases via different pleiotropic mechanisms and due to its moderate side effects, intake of methylxanthines have been suggested to be an interesting approach in dealing with neurodegeneration. Especially in the past years, the impact of methylxanthines in neurodegenerative diseases has been extensively studied and several new aspects have been elucidated. In this review we summarize the findings of methylxanthines linked to Alzheimer´s disease, Parkinson’s disease and Multiple Sclerosis since 2017, focusing on epidemiological and clinical studies and addressing the underlying molecular mechanisms in cell culture experiments and animal studies in order to assess the neuroprotective potential of methylxanthines in these diseases.

Nonadherence is a growing issue in the treatment of Parkinson’s disease (PD). Many factors are known to influence nonadherence, but little is known about the influence of quality of life (QoL). Detailed clinical data were obtained from 164 patients with PD using the Parkinson’s Disease Questionnaire-39 (PDQ-39) and the German Stendal Adherence with Medication Score (SAMS). Descriptive statistics were used to identify reasons for nonadherence, and multivariable linear models were used to study associations between QoL and clinical parameters as well as nonadherence. Multivariate analysis of variance (MANOVA) and multivariate analysis of covariance (MANCOVA) were used to study the effect of the SAMS on PDQ domains and other medical covariates. The results showed that 10.4% (n = 17) of patients were fully adherent, 66.4% (n = 109) were moderately nonadherent, and 23.2% (n = 38) were nonadherent. Nonadherence was associated with male gender, lower Montreal Cognitive Assessment (MoCA) score, higher non-motor symptoms questionnaire (NMS-Quest) score, greater number of medications per day (an indicator of comorbidity), and higher Beck Depression Inventory (BDI) score. QoL was correlated with male gender, lower MoCA score, higher NMS-Quest score, more comorbidities, and higher BDI score, but was not correlated with nonadherence.

Background Parkinson´s disease (PD) has a large phenotypic variability, which may, at least partly, be genetically driven including alterations of gene products. Candidates might not only be proteins associated with disease risk but also pathways that play a role in aging. Objective To evaluate phenotype-modifying effects of genetic variants in Klotho, a longevity gene. Methods We analyzed two longitudinal cohorts: one local cohort comprising 459 PD patients who underwent genotyping for the KL-VS haplotype in Klotho including a subgroup of 125 PD patients and 50 healthy controls who underwent biochemical cerebrospinal fluid (CSF) analyses of Klotho and fibroblast growth factor 23 as well as vitamin D metabolites. The second cohort comprised 297 patients from the Parkinson's Progression Markers Initiative (PPMI) for validation of genetic-clinical findings. Results PD patients carrying the KL-VS haplotype demonstrated a shorter interval between PD onset and onset of cognitive impairment (both cohorts) and higher Unified Parkinson´s Disease Rating Scale part III (UPDRS III) scores (PPMI). CSF protein levels of Klotho and fibroblast growth factor 23 were lower in PD patients irrespective of gender compared to controls. Moreover, low CSF levels of Klotho were associated with higher scores in the UPDRS III and Hoehn and Yahr Scale. Conclusions Our results indicate that genetic variants in Klotho together with its corresponding CSF protein profiles are associated with aspects of disease severity in PD. These findings suggest that pathways associated with aging might be targets for future biomarker research in PD.

Introduction Bradyphrenia is a key cognitive feature in Parkinson's disease (PD). There is no consensus on whether information processing speed is impaired or not beyond motor performance. Objective This study aims to explore which perceptual, motor, or cognitive components of information processing are involved in the slowdown affecting cognitive performance. Methods The study included 48 patients with PD (age: 63, 3 ± 8, 18; HY I‐III; UPDRS 15,46 ± 7,76) and 53 healthy controls (age: 60,09 ± 12,83). Five reaction time (RT) tasks were administered to all participants. The average RT in each of the tasks and the percentage of correct answers were measured. Patients with PD were in "ON state" at the time of the evaluation. Perceptual, motor, and cognitive components were isolated by means of a series of ANCOVAs. Results As expected, the motor component was slowed down in patients with PD. Moreover, while patients with PD showed slower RT than controls in all tasks, differences between groups did not exponentially increase with the increasing task complexity. ANCOVA analyses also revealed that the perceptual and sustained alert component resulted to be slowed down, with no differences being found in any of the remaining isolated cognitive components (i.e., response strategy‐inhibition, decisional, visual search, or interference control). Conclusions The results revealed that slowness of information processing in PD was mainly associated with an impaired processing speed of the motor and perceptual‐alertness components analyzed. The results may help designing new neurorehabilitation strategies, focusing on the improvement of perceptual and alertness mechanisms., The level of cognitive deceleration in PD is determined by a deterioration focused on perceptual and motor components and independently of the task complexity. Alterations in the brain networks involved in alertness to react to stimuli could justify the slowness of information processing in Parkinson´s disease

COPPADIS Study Group., [Introduction] The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients., [Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson’s disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems., [Results] The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015–1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009–1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments., [Conclusion] Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.

When presented with short, rhythmical, musical excerpts, containing omitted beats which vary in saliency in terms of rhythmical patterns (contextual omission), and position (salience omissions), fMRI studies have shown a small effect depending on position of omission. Furthermore, when presented with auditory stimuli, a pupillary dilation response (PDR) is evoked, resulting in a pupillary peak dilation (PPD) sometime after stimulus onset. By utilizing and adapting an auditory beat-omission fMRI paradigm, to allow measurement of PDR and PPD, we used pupillometry data to investigate the effect of contextual omission (Simple vs Complex rhythm) and salience omission (O1 vs O2). We report data from a total of 25 participants, based on 45 datasets. The data were analyzed using four separate direct t-tests. We found that the omission has an effect on PPD, in that the most metrical salient omission (O1) results in a higher activation level compared to a less salient omission (O2), i.e., PPD was significantly higher in O1 simple rhythm omissions, and in O1 complex rhythm omissions, at an uncorrected threshold level. Masteroppgave i psykologi MAPSYK360 INTL-HF INTL-PSYK INTL-SV INTL-MN INTL-MED INTL-KMD MAPS-PSYK INTL-JUS

Sudden and Unexpected Death in Parkinson's Disease (SUDPAR) is a sudden and unexpected death without correlated findings at autopsy or in the history of patients with Parkinson's Disease (PD). Our objective was to evaluate the knowledge regarding SUDPAR among Speech-Language pathologists (SLPs) and audiologists in the state of Alagoas, Northeastern Brazil, and to analyze the opinions of these professionals about whether to discuss about the SUDPAR phenomenon with their patients and families. SPLs and audiologists from Alagoas were recruited through an active search on social media, then answered a structured questionnaire with questions about frequency of care for patients with PD; epidemiology and mortality in PD, in addition to questions about SUDPAR. Most SPLs and audiologists (87.2%) did not know about the SUDPAR phenomenon. Among the 26 SPLs and audiologists who knew about SUDPAR, 15 stated that they discuss about the phenomenon with patients and their families/caregivers when asked about the risks related to the possibility of SUDPAR. In conclusion SPLs and audiologists in the state of Alagoas do not know about SUDPAR. La muerte súbita e inesperada en la enfermedad de Parkinson (SUDPAR) es una muerte súbita e inesperada sin hallazgos correlacionados en la autopsia o en la historia pasada de pacientes con enfermedad de Parkinson (EP). Nuestro objetivo era Evaluar el conocimiento sobre SUDPAR entre fonoaudiólogos en el estado de Alagoas, Nordeste de Brasil, y analizar la opinión de estos profesionales acerca de discutir o no el fenómeno SUDPAR con sus pacientes y familiares. Los logopedas y adiólogos de Alagoas fueron reclutados através de una búsqueda activa en las redes sociales, luego respondieron un cuestionario estructurado con preguntas sobre la frecuencia de atención a pacientes con EP; epidemiología y mortalidad en la EP, así como preguntas sobre SUDPAR. La gran mayoría de logopedas y audiólogos (87,2%) no conocían el fenómeno SUDPAR. Entre los 26 logopedas y audiólogos que conocían la SUDPAR, 15 afirmaron que discutían el fenómeno con los pacientes y sus familiares/cuidadores cuando se les preguntaba sobre los riesgos relacionados con la posibilidad de la SUDPAR. In conclusión, los logopedas y audiólogos del estado de Alagoas no conocen la SUDPAR. A Morte Súbita e Inesperada na Doença de Parkinson (SUDPAR) é uma morte súbita e inesperada sem achados correlacionados na autópsia ou na história pregressa de pacientes com Doença de Parkinson (DP). Nosso objetivo foi avaliar o conhecimento sobre SUDPAR entre fonoaudiólogos do estado de Alagoas, Nordeste do Brasil, e analisar a opinião desses profissionais sobre discutir ou não sobre o fenômeno SUDPAR com seus pacientes e familiares. Os fonoaudiólogos de Alagoas foram recrutados por meio de busca ativa nas redes sociais, em seguida responderam a um questionário estruturado com perguntas sobre frequência de atendimento ao paciente com DP; epidemiologia e mortalidade na DP, além de perguntas sobre a SUDPAR. A grande maioria dos fonoaudiólogos (87,2%) não conhecia o fenômeno SUDPAR. Entre os 26 fonoaudiólogos que conheciam a SUDPAR, 15 afirmaram discutir sobre o fenômeno com os pacientes e seus familiares/cuidadores quando questionados sobre os riscos relacionados à possibilidade de SUDPAR. Em conclusão, os fonoaudiólogos do estado de Alagoas não conhecem a SUDPAR.

Cerebral deposition of abnormally aggregated α-synuclein (αSyn) is a neuropathological hallmark of Parkinson’s disease (PD). PD-associated αSyn (αSynPD) aggregates can act as proteinaceous nuclei (“seeds”) able of self-templated propagation. Since this is strikingly reminiscent to properties of proteinaceous infectious particles (prions), lessons learned from prion diseases suggest to test whether transferred αSynPD can propagate and induce neurological impairments or disease in a new host. Two studies that addressed this question provided divergent results. Intracerebral (i.c.) injection of Lewy body extracts from PD patients caused cerebral αSyn pathology, as well as nigrostriatal neurodegeneration, of wild-type mice and macaques, with the mice also showing motor impairments (Recasens et al. 2014, Ann Neurol 75:351–362). In contrast, i.c. transmission of homogenates from PD brains did not stimulate, after “> 360” days post-injection (dpi), pathological αSyn conversion or clinical symptoms in transgenic TgM83+/− mice hemizygously expressing mutated (A53T) human αSyn (Prusiner et al. 2015, PNAS 112:E5308–E5317). To advance the assessment of possible αSynPD hazards by providing further data, we examined neuropathological and clinical effects upon i.c. transmission of brain, stomach wall and muscle tissue as well as blood from PD patients in TgM83+/− mice up to 612 dpi. This revealed a subtle, yet distinctive stimulation of localized αSyn aggregation in the somatodendritic compartment and dystrophic neurites of individual or focally clustered cerebral neurons after challenge with brain and stomach wall homogenates. No such effect was observed with transmitted blood or homogenized muscle tissue. The detected stimulation of αSyn aggregation was not accompanied by apparent motor impairments or overt neurological disease in TgM83+/− mice. Our study substantiated that transmitted αSynPD seeds, including those from the stomach wall, are able to propagate in new mammalian hosts. The consequences of such propagation and potential safeguards need to be further investigated.

Voice Onset Time (VOT) has been used as an acoustic measure for a better understanding of the impact of different motor speech disorders in speech production. The purpose of our paper is to present a methodology for the manual measuring of VOT in voiceless plosive sounds and to analyze its suitability to detect specific articulation problems in Parkinson’s disease (PD) patients. The experiments are performed with recordings of the diadochokinetic evaluation which consists in the rapid repetition of the syllables /pa-ta-ka/. A total of 50 PD patients and 50 healthy speakers (HC) participated in this study. Manual measurements include VOT values and also duration of the closure phase, duration of the consonant, and the maximum spectral energy during the burst phase. Results indicate that the methodology is consistent and allows the automatic classification between PD patients and healthy speakers with accuracies of upto 77%.

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia RESUMO REFERENTE À MONOGRAFIA INTITULADA "DOENÇA DE PARKINSON: MECANISMOS DE NEURODEGENERAÇÃO E A INFLUÊNCIA DO GÉNERO"A Doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum. Trata-se de uma doença extremamente incapacitante devido, principalmente, ao grave comprometimento motor, tendo um tremendo impacto negativo não só na qualidade de vida dos doentes, mas também dos seus familiares e cuidadores. Apesar da intensiva investigação que tem sido realizada no âmbito da DP, a sua etiologia permanece essencialmente desconhecida. No entanto, atualmente, é amplamente aceite que a maior parte dos casos se deve a um complexo interplay envolvendo o envelhecimento, fatores genéticos e ambientais. Além do mais, a disfunção mitocondrial, o stresse nitroxidativo e a neuroinflamação têm sido apontados como mecanismos centrais na neurodegeneração. Não existe ainda uma cura para a DP, sendo que as estratégias terapêuticas atualmente utilizadas visam apenas controlar a sintomatologia e proporcionar uma melhor adaptação do doente à condição patológica em que se encontra. Atualmente, é sabido que o género influencia de forma crítica a incidência e o fenótipo da DP, bem como a resposta à terapêutica. O principal objetivo desta monografia é elucidar não só o papel de alguns mecanismos moleculares na degeneração e morte dos neurónios dopaminérgicos, como também, a influência do género no desenvolvimento e decurso da DP.BREVE APRECIAÇÃO DO ESTÁGIO CURRICULAR EM FARMÁCIA COMUNITÁRIAO presente relatório foi elaborado seguindo o modelo de uma análise SWOT. Esta análise visa avaliar de forma crítica (Strengths, Weaknesses, Opportunities,Threats) o Estágio Curricular realizado em Farmácia Comunitária, Farmácia Moura. SUMMARY REGARDING THE MONOGRAPH TITLE "PARKINSON'S DISEASE: NEURODEGENERATION MECHANISMS AND THE INFLUENCE OF GENDER"Parkinson’s Disease (PD) is the second most common neurodegenerative disease. It is an extremely disabling disease due to the severe motor impairment, which negatively impact not only in the patients’ life quality, but also of their relatives and caregivers. Despite the research that has been developed in the PD field, its aetiology remains essentially unknown. However, currently, it is widely accepted that the majority of the cases are due to a complex interplay envolving ageing, genetic and environmental factors. Moreover, mitochondrial dysfunction, nitroxidative stress and neuroinflammation are considered central mechanisms in neurodegeneration. PD has no cure yet and the current therapeutic strategies only intent to control the symptomatology and to provide a better adaptation of the patient to his/her pathological condition. Currently, it is known that the gender critically influences the incidence and the phenotype of the PD, as well as the treatment response. The main goal of this monography is to highlight not only the role of some molecular mechanisms in the degeneration and death of the dopaminergic neurons, but also the importance of gender in the progression of the PD.BRIEF ASSESSMENT OF CURRICULAR INTERNSHIP IN PHARMACY This report was prepared following the model of a SWOT analysis. This analysis aims to critically evaluate (Strengths, Weaknesses, Opportunities, Threats) the Curricular Internship held in Pharmacy, Pharmacy Moura.

Tese de Doutoramento em Ciências da Saúde, A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum mundialmente, caracterizada principalmente pela perda de neurónios dopaminérgicos na substancia nigra pars compacta (SNc), levando a uma desnervação do sistema nigroestriatal. A neurodegeneração na SNc e noutras áreas dopaminérgicas e não dopaminérgicas são clinicamente traduzidas em lentidão dos movimentos, rigidez e tremor em repouso, bem como manifestações não-motoras, como a depressão. Devido à sua complexidade e causa desconhecida, terapias modificadoras da doença, capazes de abrandar, interromper ou reverter a neurodegeneração inerente à DP, constituem uma necessidade não atendida na área. As células estaminais mesenquimatosas (MSCs) são uma população adulta de células estaminais que tem sido sugerida como uma abordagem terapêutica promissora para a DP, particularmente devido à libertação de fatores solúveis e vesículas, coletivamente designados como secretoma. Apesar da crescente evidência do potencial neuroprotetor do secretoma das MSCs, MSCs derivadas de tecidos, tais como a comumente utilizada medula óssea (BM-MSCs), têm uma capacidade proliferativa limitada e estão sujeitas a variabilidade do dador, dificultando assim a recolha de volumes de secretoma significativos para uma aplicação clínica abrangente. O principal objetivo desta tese é avaliar o potencial terapêutico do secretoma recolhido de uma fonte MSCs emergente e clinicamente adequada – as células estaminais pluripotentes induzidas (iPSCs). Para isso, gerámos iPSCs de sujeitos saudáveis e de pacientes com DP, através da reprogramação de fibroblastos e células mononucleares do sangue periférico. Posteriormente, as iPSCs obtidas de sujeitos saudáveis foram diferenciadas em MSCs (iMSCs) e o seu secretoma foi recolhido e comparado com o secretoma das BM-MSCs. Tanto o secretoma das BM-MSCs como o das iMSCs atenuaram os défices motores e a degeneração nigrostriatal num modelo de DP de rato baseado na exposição a 6-OHDA, apesar de não protegerem de maneira significativa neurónios dopaminergicos derivados de células estaminais embrionárias de murganho do mesmo insulto tóxico in vitro. A semelhança entre as duas fontes foi também revelada numa análise proteómica direcionada do secretoma das duas fontes, mostrando um perfil de secreção comparável de citocinas e fatores de crescimento, que podem mediar os seus efeitos neuroprotetores in vivo. Deste modo, o nosso estudo demonstra o potencial terapêutico do secretoma das iMSCs no contexto da DP, abrindo caminho para o uso desta fonte de MSCs emergente em testes clínicos subsequentes., Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, mainly characterized by the loss of dopaminergic neurons from the substantia nigra pars compacta (SNc) leading to the denervation of the nigrostriatal tract. Neurodegeneration at the SNc and other dopaminergic and non-dopaminergic areas are clinically translated into slowness of movement, rigidity and tremor at rest, as well as nonmotor manifestations, such as depression. Due to its complexity and unknown etiology, disease-modifying therapies, able to slow, halt or reverse PD underlying neurodegeneration, are a large unmet need in the field. Mesenchymal stem cells (MSCs) are a population of adult of stem cells that has been put forward as a promising therapeutic approach for PD, particularly due to the release of soluble factors and vesicles, collectively known as secretome. Despite the growing evidence of the neuroprotective potential of MSCs secretome, tissue-derived MSCs, such as the commonly used bone marrow-derived MSCs (BM-MSCs), have limited proliferative capacity and are subjected to donor variability, thereby hindering the collection of significant volumes of secretome for a widespread clinical application. The main goal of this thesis was to address the therapeutic potential of the secretome collected from an emerging and clinically appropriate source of MSCs – induced pluripotent stem cells (iPSCs). For that, we have firstly generated iPSCs from heathy subjects and PD patients, through the reprograming of fibroblasts and peripheral blood mononuclear cells. Subsequently, iPSCs obtained from healthy subjects were differentiated into MSCs (iMSCs) and their secretome was collected and compared to BM-MSCs secretome. Both BM-MSCs and iMSCs secretome were able to attenuate motor deficits and nigrostriatal degeneration in a rat model of PD based on 6-OHDA exposure, although they did not significantly protect mouse embryonic stem cells (mESCs)-derived dopaminergic neurons from the same toxic insult in vitro. The similarity between both sources was further revealed in a targeted proteomic analysis of the secretome from both sources, showing a comparable secretion profile of neuroregulatory cytokines and growth factors, which might mediate their neuroprotective effects in vivo. Therefore, our study demonstrates the therapeutic potential of iMSCs secretome in the context of PD, paving the way for the use of this emerging MSC source in subsequent clinical testing., The work presented in this thesis was performed at the Life and Health Sciences Research Institute (ICVS) and at the Bn’ML – Behavioral & Molecular Lab, at the School of Medicine, University of Minho. Financial support was provided by Portuguese Foundation for Science and Technology (FCT): Doctoral fellowship (PDE/BDE/113598/2015) to A. Marote; IF Development Grants to A. J. Salgado (IF/00111/2013) and L. Pinto (IF/01079/2014). This work was also funded by FEDER, through the Competitiveness Internationalization Operational Programme (POCI), and by National funds, through the FTC, under the scope of the projects POCI-01-0145-FEDER-007038; POCI-01-0145-FEDER-029751 and POCI-01-0145-FEDER-032619. This project has also been developed under the scope of the project NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Part of the work was also developed at Department of Experimental Medical Science at Lund University and financially supported by the Strategic Research Environment MultiPark—multidisciplinary research on Parkinson's disease and Crafoord Foundation Sweden.