Diffusion tensor metrics, motor and non-motor symptoms in de novo Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. METHODS: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. RESULTS: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. CONCLUSION: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD.

Posterior insula repetitive transcranial magnetic stimulation for chronic pain in patients with Parkinson disease - pain type matters: A double-blinded randomized sham-controlled trial.

OBJECTIVES: Altered somatosensory processing in the posterior insula may play a role in chronic pain development and contribute to Parkinson disease (PD)-related pain. Posterior-superior insula (PSI) repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to have analgesic effects among patients with some chronic pain conditions. This study aimed at assessing the efficacy of PSI-rTMS for treating PD-related pain. METHODS: This was a double-blinded, randomized, sham-controlled, parallel-arm trial (NCT03504748). People with PD (PwP)-related chronic pain underwent five daily PSI-rTMS sessions for a week, followed by once weekly maintenance stimulations for seven weeks. rTMS was delivered at 10 Hz and 80% of the resting motor threshold. The primary outcome was a ≥ 30% pain intensity reduction at 8 weeks compared to baseline. Functionality, mood, cognitive, motor status, and somatosensory thresholds were also assessed. RESULTS: Twenty-five patients were enrolled. Mean age was 55.2 ± 9.5 years-old, and 56% were female. Nociceptive pain accounted for 60%, and neuropathic and nociplastic for 20% each. No significant difference was found for 30% pain reduction response rates between active (42.7%) and sham groups (14.6%, p = 0.26). Secondary clinical outcomes and sensory thresholds also did not differ significantly. In a post hoc analysis, PwP with nociceptive pain sub-type experienced more pain relief after active (85.7%) compared to sham PSI-rTMS (25%, p = 0.032). CONCLUSION: Our preliminary results suggest that different types of PD-related pain may respond differently to treatment, and therefore people with PD may benefit from having PD-related pain well characterized in research trials and in clinical practice.

Association between fatigue and MDS-UPDRS in individuals with Parkinson's disease: cross-sectional study.

BACKGROUND: Fatigue is significant in the context of Parkinson's disease (PD), considering that one-third of patients classify it as the most restricting symptom in their daily life activities (DLAs). The objective was to verify the relationship (association) between fatigue and non-motor and motor symptoms of PD. METHODS: A cross-sectional study which included 100 individuals with PD. Initially, demographic and clinical data (modified Hoehn and Yahr scale-HY, anxiety, and depression) were collected. To assess the non-motor and motor symptoms of PD, the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was applied. Fatigue was evaluated using the Parkinson Fatigue Scale. RESULTS: A higher HY score, greater severity of non-motor aspects of DLAs and motor aspects of DLAs, more motor complications, and higher levels of anxiety as well as depression were observed in the "fatigue" group. Fatigue was associated with a lower daily equivalent levodopa dose (LEDD), a higher body mass index (BMI), anxiety, depression, and the presence of non-motor symptoms. CONCLUSION: Non-motor symptoms are more determining factors for fatigue than the motor condition itself, with an association between fatigue and higher BMI scores, increased anxiety and depression, lower LEDD, and greater severity of non-motor aspects of DLAs. Individuals in the "fatigue" group had higher HY scores, anxiety, and depression, worse non-motor and motor symptoms related to experiences of daily life, as well as motor complications.

Follow-up of pre-motor symptoms of Parkinson's disease in adult patients with Gaucher disease type 1 and analysis of their lysosomal enzyme profiles in the CSF.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Its classic motor symptoms may be preceded by non-motor symptoms (NMS). Population studies have identified GBA variants as risk factors for idiopathic PD. The increased risk of PD has also been suggested in other Lysosomal Storage Disorders (LSDs). OBJECTIVE: To assess the evolution of the prevalence of NMS compatible with PD in a cohort of South Brazilian adult patients with Gaucher Disease (GD) type 1, already evaluated 3 years ago (2018). Cerebrospinal Fluid (CSF) was collected to assess the levels of LSD enzymes (beta-hexosaminidases, beta-glucuronidase) and biomarker of macrophage activation (chitotriosidase, ChT), compared to controls (metachromatic leukodystrophy, MLD). Cognition was evaluated by the Montreal Cognitive Assessment (MoCA) questionnaire, daytime sleepiness by the Epworth Sleepiness Scale (ESS), depression by Beck´s Inventory, constipation by the Unified Multiple System Atrophy Rating Scale (UMSARS) scale, and REM sleep behavior disorder by the single-question screen. Hyposmia was assessed with Sniffin' Sticks (SST). RESULTS: Nineteen patients completed the follow-up (mean age of the sample was 44 years; range, 26-71). The patient with the highest number of NMS at the baseline (4 including the lowest SST score) was diagnosed with PD four years later. Apart from an improvement in the ESS score, no other statistical significance was found between the number of NMS between the first and second evaluation, nor between patients with one L444P variant (n = 5) and the rest of the cohort. CSF was collected in five patients (mean age of the sample was 40 years, range 30-53. A significant difference was found in the mean CSF activity levels of beta-hexosaminidases and beta-glucuronidase between GD1 and MLD patients. Mean ChT (CSF) was 62 nmol/h/mL in GD patients and 142 in MLD (n = 6) patients. CONCLUSIONS: The patient with the highest number of NMS in our 2018 cohort was the one that developed PD, corroborating with the importance of this longitudinal follow-up. CSF and plasma analysis might allow a better understanding of the neurodegenerative processes connecting PD and the lysosomal environment. Further analysis is needed to understand this relationship.

Remote Assessment of Parkinson's Disease Patients Amidst the COVID-19 Lockdown in Mexico.

The COVID-19 pandemic introduced unprecedented challenges in managing patients with Parkinson's disease (PD) due to disruptions in healthcare services and the need for social distancing. Understanding the effects of COVID-19 on PD symptoms is crucial for optimizing patient care. We conducted a comprehensive analysis of the data obtained during the period of COVID-19 lockdown, comparing it with analogous timeframes in 2018 and 2019. Our objective was to examine the influence of this unique circumstance on both motor and non-motor symptoms in patients with PD. Telemedicine was employed to assess symptoms using the Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Our findings revealed a notable worsening of symptoms, evidenced by a significant increase in the total MDS-UPDRS score. Specifically, there was an increase in Part III scores, reflecting changes in motor function. However, no differences were observed in Parts I or II, which pertain to non-motor symptoms. Additionally, patient satisfaction and the feasibility of telemedicine consultations were high, highlighting the efficacy of this alternative approach during the pandemic. The COVID-19 pandemic had a discernible impact on PD symptoms, with a significant worsening of motor symptoms observed during the lockdown period. Telemedicine was a valuable tool for remote assessment and follow-up, ensuring continuity of care for individuals with PD in the face of pandemic-related challenges.

Rotenone-Induced Model of Parkinson's Disease: Beyond Mitochondrial Complex I Inhibition.

Parkinson's disease (PD) is usually diagnosed through motor symptoms that make the patient incapable of carrying out daily activities; however, numerous non-motor symptoms include olfactory disturbances, constipation, depression, excessive daytime sleepiness, and rapid eye movement at sleep; they begin years before motor symptoms. Therefore, several experimental models have been studied to reproduce several PD functional and neurochemical characteristics; however, no model mimics all the PD motor and non-motor symptoms to date, which becomes a limitation for PD study. It has become increasingly relevant to find ways to study the disease from its slowly progressive nature. The experimental models most frequently used to reproduce PD are based on administering toxic chemical compounds, which aim to imitate dopamine deficiency. The most used toxic compounds to model PD have been 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), which inhibit the complex I of the electron transport chain but have some limitations. Another toxic compound that has drawn attention recently is rotenone, the classical inhibitor of mitochondrial complex I. Rotenone triggers the progressive death of dopaminergic neurons and α-synuclein inclusions formation in rats; also, rotenone induces microtubule destabilization. This review presents information about the experimental model of PD induced by rotenone, emphasizing its molecular characteristics beyond the inhibition of mitochondrial complex I.

Premotor, nonmotor and motor symptoms of Parkinson's Disease: A new clinical state of the art.

Parkinson's Disease (PD) is a neurodegenerative disorder that affects dopaminergic neurons in the mesencephalic substantia nigra, causing a progressive clinical course characterized by pre-motor, non-motor and motor symptoms, which negatively impact the quality of life of patients and cause high health care costs. Therefore, the present study aims to discuss the clinical manifestations of PD and to make a correlation with the gut-brain (GB) axis, approaching epidemiology and therapeutic perspectives, to better understand its clinical progression and identify symptoms early. A literature review was performed regarding the association between clinical progression, the gut-brain axis, epidemiology, and therapeutic perspectives, in addition to detailing pre-motor, non-motor symptoms (neuropsychiatric, cognitive, autonomic, sleep disorders, sensory abnormalities) and cardinal motor symptoms. Therefore, this article addresses a topic of extreme relevance, since the previously mentioned clinical manifestations (pre-motor and non-motor) can often act as prodromal markers for the early diagnosis of PD and may precede it by up to 20 years.

Caracterización de los síntomas no motores en pacientes con enfermedad de Parkinson

Introducción: la enfermedad de Parkinson es una de las enfermedades degenerativas más frecuentes y se caracteriza por presentar manifestaciones clínicas no motoras. Objetivo: caracterizar las manifestaciones clínicas no motoras de los pacientes que padecen de la enfermedad de Parkinson. Métodos: se realizó un estudio observacional, descriptivo, de corte transversal. El universo estuvo constituido por los pacientes con enfermedad de Parkinson que acudieron a la consulta de trastornos de movimiento del Hospital Provincial General Carlos Manuel de Céspedes en el período comprendido desde el 1 de julio del 2020 hasta el 31 de diciembre del 2020, mientras que la muestra se conformó con los pacientes que completaron todos las pruebas clinimétricas y que dieron su consentimiento informado para participar en el estudio. Resultados: la edad promedio fue de 69,05 años, predominando el sexo masculino. Las puntuaciones promedios de la Evaluación Cognitiva de Montreal y la Escala Unificada de la Enfermedad de Parkinson modificada por la Sociedad de Trastornos del Movimiento (parte I) fueron de 17,95 y 9,85 respectivamente. Conclusiones: Los dominios más afectados resultaron ser: el urinario, gastrointestinal y sueño/fatiga. La puntuación promedio obtenida al aplicar la Evaluación Cognitiva de Montreal fue baja. El impacto no motor de la enfermedad de Parkinson sobre las experiencias de la vida diaria fue alto.

Introduction: Parkinson's disease is one of the most frequent degenerative diseases and is characterized by non-motor clinical manifestations. Objective: to characterize the non-motor clinical manifestations of patients suffering from Parkinson's disease. Methods: an observational, descriptive, cross-sectional study was conducted. The universe consisted of patients with Parkinson's disease who attended the movement disorders consultation of the Carlos Manuel de Céspedes General Provincial Hospital in the period from July 1, 2020 to December 31, 2020, while the sample was made up of patients who completed all clinimetric tests and who gave their informed consent to participate in the study. Results: the mean age was 69.05 years, predominantly male. The average scores of the Montreal Cognitive Assessment and the Unified Parkinson's Disease Scale modified by the Society for Movement Disorders (part I) were 17.95 and 9.85 respectively. Conclusions: The most affected domains were: urinary, gastrointestinal and sleep/fatigue. The average score obtained when applying the Montreal Cognitive Assessment was low. The non-motor impact of Parkinson's disease on daily life experiences was high.

Introdução: a doença de Parkinson é uma das doenças degenerativas mais frequentes e é caracterizada por manifestações clínicas não motoras. Objetivo: caracterizar as manifestações clínicas não motoras de pacientes que sofrem da doença de Parkinson. Métodos: foi realizado um estudo observacional, descritivo e transversal. O universo consistiu em pacientes com Mal de Parkinson que atenderam à consulta de distúrbios de movimento do Hospital Geral Provincial Carlos Manuel de Céspedes no período de 1º de julho de 2020 a 31 de dezembro de 2020, enquanto a amostra foi composta por pacientes que concluíram todos os exames clinimétricos e que deram seu consentimento informado para participar do estudo. Resultados: a média de idade foi de 69,05 anos, predominantemente do sexo masculino. Os escores médios da Avaliação Cognitiva de Montreal e da Escala Unificada da Doença de Parkinson modificada pela Sociedade para Transtornos do Movimento (parte I) foram de 17,95 e 9,85, respectivamente. Conclusões: Os domínios mais afetados foram: urinário, gastrointestinal e sono/fadiga. O escore médio obtido na aplicação da Avaliação Cognitiva de Montreal foi baixo. O impacto não motor da doença de Parkinson nas experiências diárias de vida foi alto.

Neuropsychiatric and sleep study in autosomal dominant dopa-responsive dystonia.

Introduction: Although the diurnal fluctuation of motor dysfunction, reversible with small doses of dopamine, is a cornerstone for the phenotype of the autosomal dominant Segawa syndrome, the non-motor symptoms of this neurotransmitter deficiency have still received limited attention. Objective: This study aims to evaluate non-motor symptoms of this dopa-responsive dystonia through an intrafamilial comparative cross-sectional study. Methods: Seventeen individuals with a c.IVS5 + 3insT (c.626 + 3insT) variation in the GTP cyclohydrolase-1 gene (GCH1, HGNC: 4193) and 34 intrafamilial controls were studied using the Beck Depression Inventory-II, the Wiener Matrizen Test 2, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the MINI/MINI PLUS Questionnaires, the World Health Organization Quality of Life - BREF Instrument and a drug use assessment questionnaire. Results: No significant difference was found between the groups in the prevalence of sleep disorders and in cognitive function. Nevertheless, generalized anxiety disorder (p = 0.050) and attention-deficit/hyperactivity disorder in childhood (p = 0.011) were observed only in individuals without the molecular variation. The group with the GCH1 variation presented a worse perception about how safe they feel in their daily lives (p = 0.034), less satisfaction with themselves (p = 0.049) and with their relationships (p = 0.029), and a higher prevalence of past major depressive episodes before use of L-Dopa (p = 0.046). Conclusion: Low dopamine could have been protective against generalized anxiety disorder and attention-deficit/hyperactivity disorder in childhood in Segawa group individuals. The prevalence of depression was higher in individuals with the molecular variant prior to the L-Dopa treatment. Considering it, the penetrance estimates for the variant carriers increased from 58.8% to up to 88% in this large studied family. Additionally, neuropsychiatric tests of all individuals with a molecular diagnosis in an affected family are a valuable instrument for its clinical management.

Naturalistic Study of Depression Associated with Parkinson's Disease in a National Public Neurological Referral Center in Mexico.

Major depressive disorder (MDD) is a major health problem in Parkinson's disease (PD) patients. We described the clinical and sociodemographic factors of MDD among patients with PD at a national neurological referral center in Mexico. One hundred patients with PD + MDD were included in the study. All the patients were evaluated during the "ON" treatment phase of PD. Clinical scales for cognition (MMSE and MoCA) and MDD (MADRS) were applied. The mean age was 58.49 ± 11.02 years, and 57% of the sample was male. The most frequent symptom of PD was tremor (67%), and onset was more frequent on the right side (57%). Additionally, 49% of the patients with PD had moderate to severe (M/S) MDD. Selective serotonin reuptake inhibitors were the most frequent antidepressant treatment (69%). The scores of the scales were MADRS 21.33 ± 5.49, MoCA 21.06 ± 4.65, and MMSE 26.67 ± 1.20. The females had lower MMSE scores compared to the males (p = 0.043). The patients with M/S MDD had more rigidity at the beginning of PD (p = 0.005), fewer march alterations (p = 0.023), and a greater prevalence of left-side initial disease (p = 0.037). Rigidity was associated with M/S MDD (OR 3.75 p = 0.013). MDD was slightly more frequent in the males than in the females. The MDD symptoms and cognitive impairment were worse in the female population.

Effects of binary dance rhythm compared with quaternary dance rhythm in fatigue, sleep, and daily sleepiness of individuals with Parkinson's disease: A randomized clinical trial

Abstract Aim: People with Parkinson's disease constantly demonstrate low levels of physical activity, which is why dance has become increasingly important for the treatment of the disease. This study aimed to analyze the influence of binary and quaternary rhythm on fatigue, sleep, and daytime sleepiness in individuals with Parkinson's disease. Methods: 31 individuals participated in this randomized clinical trial with a mean age of 66.6 ± 10.2 years, 71% were male and 29% were female, allocated into two groups, binary and quaternary, where they participated in different dance interventions lasting 12 weeks. A questionnaire was applied including personal and clinical information; Mental State Mini-Examination (MMSE), Hoehn and Yahr (H&Y), Fatigue Severity Scale (FSS), Sleep Scale for Parkinson's Disease (PDSS), and Daytime Sleepiness Epworth Scale (ESS). Results: The groups that participated in binary rhythm classes showed improvement in sleep quality and daytime sleepiness after 12 weeks of intervention. However, no significant differences were found in the group that participated in the quaternary rhythm classes. Moreover, it was noted that the binary group managed to raise the heart rate during the 12 weeks of intervention, given that these results were not obtained in the quaternary group. Conclusion: The results showed the effectiveness of binary rhythm on non-motor symptoms and heart rate increase in individuals with Parkinson's disease. Thus, it is concluded that the binary rhythm was more effective than the quaternary rhythm.

Improvement of Non-motor Symptoms and Quality of Life After Deep Brain Stimulation for Refractory Dystonia: A 1-Year Follow-Up.

Introduction: Deep brain stimulation (DBS) is a treatment option for refractory dystonia's motor symptoms, while its non-motor symptoms (NMS) have been less systematically assessed. We aimed to describe the effects of DBS on NMS in refractory generalized inherited/idiopathic dystonia prospectively. Methods: We evaluated patients before and 1 year after DBS surgery and applied the following scales: Burke-Fahn-Marsden Rating Scale (BFMRS), NMS Scale for Parkinson's Disease (NMSS-PD), Parkinson's Disease Questionnaire-8, short-form Brief Pain Inventory (BPI), Neuropathic Pain Symptom Inventory (NPSI), and short-form McGill Pain Questionnaire (MPQ). Results: Eleven patients (38.35 ± 11.30 years) underwent surgery, all with generalized dystonia. Motor BFMRS subscore was 64.36 ± 22.94 at baseline and 33.55 ± 17.44 1 year after DBS surgery (47.9% improvement, p = 0.003). NMSS-PD had a significant change 12 months after DBS, from 70.91 ± 59.07 to 37.18 ± 55.05 (47.5% improvement, p = 0.013). NMS changes were mainly driven by changes in the gastrointestinal (p = 0.041) and miscellaneous domains (p = 0.012). Seven patients reported chronic pain before DBS and four after it. BPI's severity and interference scores were 4.61 ± 2.84 and 4.12 ± 2.67, respectively, before surgery, and 2.79 ± 2.31 (0.00-6.25) and 1.12 ± 1.32 (0.00-3.00) after, reflecting a significant improvement (p = 0.043 and p = 0.028, respectively). NPSI score was 15.29 ± 13.94 before, while it was reduced to 2.29 ± 2.98 afterward (p = 0.028). MPQ's total score was 9.00 ± 3.32 before DBS, achieving 2.71 ± 2.93 after (p = 0.028). Conclusions: DBS improves NMS in generalized inherited/idiopathic dystonia, including chronic pain.

Multidimensional Factors Can Explain the Clinical Worsening in People With Parkinson's Disease During the COVID-19 Pandemic: A Multicenter Cross-Sectional Trial.

Background: Self-reported clinical worsening by people with Parkinson's disease (PD) during social distancing may be aggravated in Brazil, where the e/tele-health system is precarious. Objectives: This study aims to investigate self-reported changes in motor and non-motor aspects during social distancing in people with PD living in Brazil and to investigate the factors that might explain these changes. Methods: In this multicenter cross-sectional trial, 478 people with a diagnosis of idiopathic PD (mean age = 67, SD = 9.5; 167 female) were recruited from 14 centers distributed throughout the five geographical regions of Brazil. The evaluators from each center applied a questionnaire by telephone, which included questions (previous and current period of social distancing) about the motor and non-motor experiences of daily living, quality of life, daily routine, and physical activity volume. Results: Self-reported clinical worsening in non-motor and motor aspects of daily life experiences (Movement Disorder Society-Unified PD Rating Scale-parts IB and II-emotional and mental health, and fear of falling) and in the quality of life was observed. Only 31% of the participants reported a guided home-based physical activity with distance supervision. Perceived changes in the quality of life, freezing of gait, decreased physical activity volume, daily routine, and fear of falling explained the self-reported clinical worsening (P < 0.05). Conclusions: Self-reported clinical worsening in people with PD living in Brazil during social distancing can also be aggravated by the precarious e/tele-health system, as perception of decreased physical activity volume and impoverishment in daily routine were some of the explanatory factors. Considering the multifaceted worsening, the implementation of a remote multi-professional support for these people is urgent.

Smell tests to distinguish Parkinson's disease from other neurological disorders: a systematic review and meta-analysis.

Introduction: Olfactory impairment has been considered for differential diagnosis in Parkinson's disease (PD) patients. The authors aimed to identify the tests used to assess the olfactory function in PD patients and examine these tests' ability to distinguish them from other neurological disorders.Areas covered: Cross-sectional studies published until May 2020 comparing the olfactory function of PD patients to other neurological disorders were searched on PubMed, PsycInfo, Cinahl, and Web of Science databases using search terms related to PD, olfactory function, and assessment. Five thousand three hundred and four studies were screened, and 35 were included in the systematic review. Six smell tests that evaluated a total of 1,544 PD patients were identified. Data of 1,144 patients included in the meta-analyses revealed worse smell performance than individuals with other neurological disorders, such as progressive supranuclear palsy and essential tremor, but not with idiopathic rapid eye movement sleep behavior disorder.Expert opinion: The University of Pennsylvania Smell Identification Test was the most used test to assess the olfactory function of PD. Smell loss was worse in PD than in some neurological disorders. The smell tests' ability in differentiating PD from other neurological disorders still deserves more attention in future studies. Protocol register (PROSPERO/2018-CRD42018107009).

Beyond the Typical Syndrome: Understanding Non-motor Features in Niemann-Pick Type C Disease.

Niemann-Pick type C (NPC) is a rare autosomal recessive disorder characterized by storage of unesterified glycolipids and cholesterol in lysosome. NPC's clinical presentation is highly heterogeneous, depending on the time of onset. It encompasses visceral, neurological, and/or psychiatric manifestations. As the motor findings are so important and devastating in this disease, there is a lack of description about non-motor symptoms, even though they play important role in quality of life of NPC patients. We described the most common non-motor findings in NPC like cognitive dysfunction, neuroimaging, psychiatric symptoms, sleep disorders, seizures, hearing problems, respiratory and other systemic features, bladder and fecal dysfunction, hypersalivation, and malnutrition. In this review, we highlighted the importance of these undervalued symptoms and their management. Specific measures of all aforementioned clinical features may work as relevant biomarkers in order to evaluate successful therapies in future clinical trials.

The impact of brazilian samba on parkinson's disease: analysis by the disease subtypes / O impacto do samba brasileiro na doença de parkinson: análise através dos subtipos da doença / El impacto del samba brasileño en la enfermedad de parkinson: análisis a través de los subtipos de la enfermedad

ABSTRACT Introduction: People with Parkinson's disease constantly have low levels of physical activity. Dancing has become increasingly important for treating the disease and can help improve non-motor symptoms. Objective: To analyze the influence of Brazilian samba on the non-motor symptoms of PD according to TD and PGID subtypes. Methods: A 12-week, non-randomized clinical trial, through comparison with a control group. The 23 individuals who agreed to participate in the activities formed the experimental group (EG) and the 24 individuals who opted not to participate in the Brazilian samba classes comprised the control group (CG). A questionnaire was applied, composed of validated instruments. Mini Mental State Examination - MMSE; HY - Disability Scale; Unified Parkinson's Disease Rating Scale - UPDRS 1 and total values; Parkinson's Disease Questionnaire - PDQ-39, Parkinson's Disease Sleep Scale - PDSS; Beck Depression Inventory - BDI; Fatigue Severity Scale - FSS and Magnitude of Perceived Changes. Results: After the twelve weeks of intervention, it was observed that the EG showed improvement in the scores of all the tests. The comparison between groups, however, indicated a significant difference in the post-UPDRS1 period in which the EG presented improvement in cognitive impairment, while the CG presented a deficit in these values. The results of the division between disease subtypes show a greater change in the values between individuals of the TD group, when comparing the EG with the CG. For the EG, the greatest difference between pre- and post- intervention was fatigue. Conclusion: There was a positive trend in all the variables studied after the application of the protocol. This demonstrates that interventions such as dance may have greater effects on non-motor symptoms, depending on the expected progression of the disease. The scarcity of studies that use this approach in their analyses may explain the lack of evidence in this symptomatology related to dance. Level of evidence II; Therapeutic studies - Investigating the results of treatment.

RESUMO Introdução: As pessoas com doença de Parkinson constantemente apresentam baixos níveis de atividade física. A dança tem se tornado cada vez mais importante para o tratamento da doença e pode ajudar a melhorar os sintomas não motores. Objetivo: Analisar a influência do samba brasileiro nos sintomas não motores da DP, segundo os subtipos TD e PGID. Métodos: Ensaio clínico não randomizado com duração de 12 semanas por meio de comparação com grupo controle. Os 23 indivíduos que aceitaram participar das atividades formaram o grupo experimental (GE) e os 24 indivíduos que optaram por não participar das aulas de dança brasileira formaram o grupo controle (GC). Um questionário foi aplicado, composto por instrumentos validados: Mini Exame do Estado Mental - MEEM; HY - Escala de Grau de Incapacidade; Escala Unificada de Avaliação da Doença de Parkinson - UPDRS 1 e valores totais; Questionário sobre a Doença de Parkinson - PDQ-39; Escala de Sono para a Doença de Parkinson - PDSS; Inventário de Depressão de Beck - BDI; Escala de Severidade de Fadiga - FSS e Magnitude das Alterações Percebidas. Resultados: Após doze semanas de intervenção, observou-se que o GE apresentou melhora nos escores de todos os testes. A comparação entre os grupos, no entanto, indicou uma diferença significativa no período pós-UPDRS1 em que o GE apresentou melhora no comprometimento cognitivo, enquanto o GC apresentou déficit nesses valores. Os resultados da divisão entre os subtipos da doença apresentam uma maior mudança nos valores entre os indivíduos do grupo TD ao comparar o GE com o GC. Em relação ao GE, a maior diferença entre a pré e pós-intervenção foi relacionada à fadiga. Conclusão: Houve tendência positiva em todas as variáveis estudadas após a aplicação do protocolo. Isso demonstra que intervenções como a dança podem ter maiores efeitos sobre os sintomas não motores, dependendo da progressão esperada da doença. A escassez de estudos que utilizam essa abordagem em suas análises pode explicar a falta de evidências nessa sintomatologia relacionadas à dança. Nível de evidência II; Estudos terapêuticos-Investigação dos resultados do tratamento.

RESUMEN Introducción: Las personas con enfermedad de Parkinson constantemente presentan bajos niveles de actividad física. La danza se ha vuelto cada vez más importante para el tratamiento de la enfermedad y puede ayudar a mejorar los síntomas no motores. Objetivo: Analizar la influencia del samba brasileño en los síntomas no motores de la EP, según los subtipos TD y PGID. Métodos: Ensayo clínico no aleatorizado con duración de 12 semanas, por medio de comparación con grupo control. Los 23 individuos que aceptaron participar en las actividades formaron el grupo experimental (GE) y los 24 individuos que optaron por no participar en las clases de danza brasileña formaron el grupo control (GC). Fue aplicado un cuestionario, compuesto por instrumentos validados: Mini Examen del Estado Mental - MEEM; HY - Escala del Grado de Incapacidad; Escala unificada de evaluación de la Enfermedad de Parkinson - UPDRS 1 y valores totales; Cuestionario sobre la Enfermedad de Parkinson - PDQ-39; Escala de Sueño de la Enfermedad de Parkinson - PDSS; Inventario de Depresión de Beck - BDI; Escala de Severidad de la Fatiga - FSS y Magnitud de las Alteraciones Percibidas. Resultados: Después de doce semanas de intervención, se observó que el GE presentó una mejora en los puntajes de todos los tests. La comparación entre los grupos, sin embargo, indicó una diferencia significativa en el período post-UPDRS1 en que el GE presentó una mejora en el compromiso cognitivo, mientras que el GC presentó déficit en esos valores. Los resultados de la división entre los subtipos de la enfermedad presentan un mayor cambio en los valores entre los individuos del grupo TD al comparar el GE con el GC. Con relación al GE, la mayor diferencia encontrada entre la pre y post intervención fue relacionada a la fatiga. Conclusión: Hubo tendencia positiva en todas las variables estudiadas después de la aplicación del protocolo. Eso demuestra que intervenciones como la danza pueden tener mayores efectos sobre los síntomas no motores, dependiendo de la progresión esperada de la enfermedad. La escasez de estudios que utilizan ese abordaje en sus análisis, puede explicar la falta de evidencias en esa sintomatología cuando relacionadas a la danza. Nivel de evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamiento.

State-of-the-art pharmacotherapy for autonomic dysfunction in Parkinson's disease.

Introduction: Autonomic dysfunction is one of the most frequent and disabling non-motor symptoms of Parkinson's disease (PD). It includes, among others, orthostatic hypotension (OH), sialorrhea, constipation, erectile dysfunction (ED), urinary dysfunction, and diaphoresis. They are usually under-recognized and suboptimally managed.Areas covered: Recommended treatments for dysautonomias are summarized with a description of the mechanism of action and observed results. The pathophysiology of each disorder is reviewed to pinpoint possible therapeutic targets. Drugs approved for treating dysautonomia in the general population along with those under development for PD-related dysautonomia are also reviewed. Finally, the key elements of each symptom that should be addressed in clinical trials' design are considered.Expert opinion: Midodrine, droxidopa, fludrocortisone, and domperidone may be used for OH treatment. Sialorrhea can be managed with botulin toxin injections and oral glycopyrrolate. Erectile dysfunction can benefit from sildenafil treatment, as urinary dysfunction can from solifenacin. Macrogol, lubiprostone, and probiotics might be effective in treating constipation. Further research is needed to determine adequate treatment for diaphoresis in PD patients. Multidisciplinary management of motor and non-motor symptoms in PD is the best approach for dysautonomias in PD.

Diagnósticos fonoaudiológicos y síntomas no motores en pacientes con Enfermedad de Parkinson / Phonoaudiological diagnoses and non-motor symptoms in patients with Parkinson's disease

Objetivo: Este estudio descriptivo se orientó a conocer el perfil clínico-epidemiológico de la Enfermedad de Parkinson (EP) y la coexistencia entre síntomas no motores (SNM) y diagnósticos fonoaudiológicos (DF). Método: La muestra estuvo conformada por 34 personas con Parkinson idiopático (26 hombres y 8 mujeres), cuyas historias clínicas fueron analizadas para describir la coexistencia de DF, como la hipofonía, la disprosodia, la disartria y la disfagia, con síntomas no motores, tales como: trastornos gastrointestinales, depresión, trastornos del sueño y deterioro cognitivo. Resultados: Los resultados señalan que las personas con Parkinson tenían edades entre los 25 a los 86 años. En cuanto a la fase, se clasificaron en: estadio I el 11,7%, II el 17,6%, III el 47%, IV el 14,7% y V el 8,8%. El 47% de los pacientes llegó al servicio de Fonoaudiología en una etapa avanzada de la EP. Los SNM más frecuentes fueron trastornos del sueño (67,6%), depresión (58,8%), alteraciones gastrointestinales (29,4%) y deterioro cognitivo (15%). Los DF se distribuyeron así: disprosodia (38%), hipofonía (33%), disartria (18%) y disfagia (11%). Discusión: se observa una alta frecuencia tanto de SNM (como la depresión y los trastornos del sueño), como de SF (especialmente disprosodia e hipofonía). Esta sintomatología provoca, por una parte, la reducción del deseo de relacionarse socialmente y por otro, dificultades para hacerse entender al presentar un volumen de voz reducido o prosodia (además de trastornos de la melodía, inflexiones, marcadores paralingüísticos) de la expresión oral del lenguaje. Conclusión: los trastornos del sueño y la depresión podrían tener un impacto negativo significativo en las funciones fonoaudiológico de las personas con Parkinson.

Objective: This descriptive study was aimed at understanding the clinical-epidemiological profile of Parkinson's disease (PD) and the coexistence between non-motor symptoms (NMS) and phonoaudiological diagnoses (PD). Methods: The sample comprised 34 people with idiopathic Parkinson's (26 men and 8 women). Their clinical histories were analysed to describe the coexistence of PD, such as hypophonia, dysprosody, dysarthria and dysphagia, with non-motor symptoms, such as gastrointestinal disorders, depression, sleep disorders and cognitive impairment. Results: The results indicate that people with Parkinson's are between the ages of 25 and 86. In terms of phase, they were classified as: stage I 11.7%, II 17.6%, III 47%, IV 14.7% and V 8.8%. 47% of patients reached the Speech Therapy service at an advanced stage of PD. The most frequent NMS were sleep disorders (67.6%), depression (58.8%), gastrointestinal disorders (29.4%) and cognitive impairment (15%). The PD were distributed as follows: dysprosody (38%), hypophonia (33%), dysarthria (18%) and dysphagia (11%). Discussion: a high frequency of both NMS (such as depression and sleep disorders) and PD (especially dysprosody and hypophonia) is observed. This symptomatology causes a reduction in the desire to relate socially, and difficulties in making oneself understood by presenting a reduced voice volume or prosody (in addition to melody of speech disorders, inflections, paralinguistic markers) of the oral language expression. Conclusion: sleep disorders and depression could have a significant negative impact on the speech and hearing functions of people with Parkinson's.

Frequency and Dynamics of Non-motor Symptoms Presentation in Hispanic Patients With Parkinson Disease.

The clinical phenotype of Parkinson's disease (PD) encompasses a wide range of non-motor symptoms (NMS) compromising the quality of life of affected patients. Currently, information about NMS in PD is scarce among Hispanic populations. Furthermore, few studies have reported the temporal pattern of NMS presentation. We conducted a cross-sectional study aimed to describe the frequency and time of NMS occurrence in Hispanic patients with PD using the self-completed NMS questionnaire (NMSQuest). Participants were interrogated about the time of each NMS presentation respect to the onset of motor symptoms. The frequency of NMS was described according to gender, age at disease onset, disease duration and Hoehn and Yahr (H&Y) stage. We enrolled 120 patients, 73.33% males and 26.66% females, with a mean age of 63.33 ± 8.60 years. All the participants presented at least 1 NMS. The median number of NMS per patient was 12. The most frequent NMS domains were miscellaneous, urinary tract, sleep/fatigue, and gastrointestinal tract symptoms, with no significant gender differences. The most frequent individual NMS were nocturia, urinary urgency, feeling sadness, and constipation. Any patient reported NMS before the onset of motor manifestations. The pattern of occurrence of NMS domains in our population was as follows: attention/memory, cardiovascular, gastrointestinal tract, perceptual problems/hallucinations, mood/cognition, urinary, miscellaneous, sleep/fatigue, and sexual function. Nausea/vomiting was the earliest symptom observed in all patients, whereas sexual dysfunction and changes in interest for sex were the last symptoms to occur. We found no differences in the total number and frequency of NMS between participants grouped according to their age at disease onset. Conversely, patients with a duration of disease >10 years reported a higher frequency of NMS compared to participants with a duration of disease < 10 years. The total number of NMS per patient increased as the HY stage progressed. The proportion of patients presenting symptoms of the gastrointestinal tract, urinary tract, mood/cognition, cardiovascular, and sexual function domains was higher in the HY 4-5 group. Our study provides relevant data to improve our understanding of NMS in PD, which may contribute to anticipate and plan diagnostic and therapeutic strategies among Hispanic PD patients.

Factores asociados con deterioro cognitivo en una cohorte mexicana multicéntrica de Parkinson: estudio transversal comparativo.

INTRODUCTION: Cognitive impairment is common in Parkinson's disease and represents a risk for dementia. Identifying associated factors will help implement early interventions and study its progression. OBJECTIVE: To identify factors associated with cognitive impairment. METHOD: Cross-sectional study of 306 subjects with Parkinson's disease who were assessed for 12 months. Demographics and clinical variables were analyzed as explanatory variables, and cognitive impairment as outcome variable. Significant variables were used to construct a cognitive impairment predictive model. RESULTS: Cognitive impairment was reported in 43.8%. Female gender (p = 0.001, odds ratio [OR] = 1.77), age at diagnosis (p < 0.001, mean deviation [MD] = 5.7), level of education (p < 0.001, MD = -2.9), disease duration (p = 0.003, MD = 1.7), MDS-UPDRS part III score (p < 0.001, MD = 9.7), presence of anxiety (p = 0.007, OR = 2.11), hallucinations (p = 0.029, OR = 2.27) and freezing of gait (p = 0.048, OR = 1.91) were predictors for cognitive impairment. The use of type B monoamine oxidase inhibitors was associated with less cognitive impairment (p = 0.001). CONCLUSIONS: Predictive factors that were consistent with those previously reported were identified. Prospective studies are required in order to clarify the effect of type B monoamine oxidase inhibitors on cognition.

INTRODUCCIÓN: El deterioro cognitivo en Parkinson es común y representa un riesgo para demencia. Identificar los factores asociados ayudará a implementar intervenciones tempranas y estudiar la progresión del deterioro cognitivo. OBJETIVO: Identificar factores asociados con deterioro cognitivo. MÉTODO: Estudio transversal de 306 sujetos con Parkinson evaluados durante los últimos 12 meses. Se estudiaron variables demográficas y clínicas como explicativas y el deterioro cognitivo como desenlace. Las variables significativas se utilizaron para construir un modelo predictor de deterioro cognitivo. RESULTADOS: El 43.8 % reportó deterioro cognitivo. El sexo femenino (p = 0.001, RM = 1.77), edad al diagnóstico (p < 0.001, desviación media [DM] 5.7), escolaridad (p < 0.001, DM −2.9), duración de enfermedad (p = 0.003, DM 1.7), puntuación en MDS-UPDRS parte III (p < 0.001, DM 9.7), presencia de ansiedad (p = 0.007, RM = 2.11), de alucinaciones (p = 0.029, RM = 2.27) y congelamientos de la marcha (p = 0.048, RM = 1.91) fueron predictores para deterioro cognitivo. El uso de inhibidores ­monoamina-oxidasa tipo B se asoció con menor deterioro cognitivo (p = 0.001). CONCLUSIONES: Se identificaron factores predictores consistentes con lo reportado previamente. Se requieren estudios prospectivos para aclarar el efecto de los inhibidores monoamina-oxidasa tipo B en la cognición.