RESUMEN

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. OBJECTIVES: Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. METHODS: We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. RESULTS: We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. CONCLUSIONS: This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

RESUMEN

Herpes simplex virus type 1 (HSV-1) is a persistent human pathogen, and the emergence of strains resistant to Acyclovir (ACV, reference drug) shows the urgency to develop new treatments. We report the antiherpetic mechanism of the action of lasiodiplodan (LAS-N, (1 → 6)-ß-d-glucan) and its sulfonated derivative (LAS-S3) in vitro and in vivo. LAS-S3 showed anti-HSV-1 action with high selectivity indices for HSV-1 KOS (88.1) and AR (189.2), sensitive and resistant to ACV, respectively. LAS-S3 inhibited >80% of HSV-1 infection in different treatment protocols (virucidal, adsorption inhibition, and post-adsorption effects), even at low doses, and showed a preventive effect and DNA and protein synthesis inhibition. The antiherpetic effect was confirmed in vivo by the cosmetic LAS-S3-CRÈME decreasing cutaneous lesions of HSV-1, including the AR strain. LAS-S3 possessed a broad-spectrum mechanism of action acting in the early and post-adsorption stages of HSV-1 infection, and LAS-S3-CRÈME is a potential antiherpetic candidate for patients infected by HSV-1-resistant strains.

Asunto(s)

RESUMEN

BACKGROUND: Photodynamic therapy (PDT) activates a photosensitizer by visible light to generate cytotoxic oxygen species that lead to cell death. With proper illumination, PDT is often used in applications on superficial and sub-surface lesions. Sporotrichosis infection occurs by Sporothrix fungi which causes a skin wound, worsened by Candida albicans infections. This study investigated the photosensitizing efficiency of the Ru(phen)2(pPDIp)(PF6)2 complex, RupPDIp, against S. brasiliensis and C. albicans. MATERIAL AND METHODS: RupPDIp efficiency against these fungi was tested using 450 nm (blue light and 36 J/cm2) and 525 nm (green light, 25.2 J/cm2) at 0.05-20 µM concentrations. To ensure PDT effectiveness, control groups were tested in the absence and in the presence of RupPDIp under light irradiation and in the dark. RESULTS: RupPDIp eliminated both fungi at ≤5.0 µM. Green light showed the best results, eliminating S. brasiliensis and C. albicans colonies at RupPDIp 0.5 µM and 0.05 µM, respectively. CONCLUSION: RupPDIp is a promising photosensitizer in aPDT, eliminating 106 CFU/mL of both fungi at 450 nm and 525 nm, with lower light doses and concentrations when treated with the green light compared to the blue light.

Asunto(s)

RESUMEN

BACKGROUND: Noninvasive stimulation has been widely used in the past 30 years to study and treat a large number of neurological diseases, including movement disorders. OBJECTIVE: In this critical review, we illustrate the rationale for use of these techniques in movement disorders and summarize the best medical evidence based on the main clinical trials performed to date. METHODS: A nationally representative group of experts performed a comprehensive review of the literature in order to analyze the key clinical decision-making factors driving transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in movement disorders. Classes of evidence and recommendations were described for each disease. RESULTS: Despite unavoidable heterogeneities and low effect size, TMS is likely to be effective for treating motor symptoms and depression in Parkinson's disease (PD). The efficacy in other movement disorders is unclear. TMS is possibly effective for focal hand dystonia, essential tremor and cerebellar ataxia. Additionally, it is likely to be ineffective in reducing tics in Tourette syndrome. Lastly, tDCS is likely to be effective in improving gait in PD. CONCLUSIONS: There is encouraging evidence for the use of noninvasive stimulation on a subset of symptoms in selected movement disorders, although the means to optimize protocols for improving positive outcomes in routine clinical practice remain undetermined. Similarly, the best stimulation paradigms and responder profile need to be investigated in large clinical trials with established therapeutic and assessment paradigms that could also allow genuine long-term benefits to be determined.

Asunto(s)

RESUMEN

BACKGROUND: Increasing numbers of mutations causing monogenic forms of Parkinson's disease (PD) have been described, mostly among patients in Europe and North America. Since genetic architecture varies between different populations, studying the specific genetic profile of Brazilian patients is essential for improving genetic counseling and for selecting patients for clinical trials. OBJECTIVE: We conducted a systematic review to identify genetic studies on Brazilian patients and to set a background for future studies on monogenic forms of PD in Brazil. METHODS: We searched MEDLINE, EMBASE and Web of Science from inception to December 2019 using terms for "Parkinson's disease", "genetics" and "Brazil". Two independent reviewers extracted the data. For the genes LRRK2 and PRKN, the estimated prevalence was calculated for each study, and a meta-analysis was performed. RESULTS: A total of 32 studies were included, comprising 94 Brazilian patients with PD with a causative mutation, identified from among 2,872 screened patients (3.2%). PRKN mutations were causative of PD in 48 patients out of 576 (8.3%). LRRK2 mutations were identified in 40 out of 1,556 patients (2.5%), and p.G2019S was the most common mutation (2.2%). CONCLUSIONS: PRKN is the most common autosomal recessive cause of PD, and LRRK2 is the most common autosomal dominant form. We observed that there was a lack of robust epidemiological studies on PD genetics in Brazil and, especially, that the diversity of Brazil's population had not been considered.

Asunto(s)

RESUMEN

PURPOSE: To investigate the metal screw-in anchor failure mode and load to failure for 2 different eyelet alignments after anchor insertion in ovine humeri. METHODS: Sixteen ovine humeri were dissected, and a 5-mm metal anchor with 2 nonabsorbable polyblend polyethylene sutures was inserted into them in the proximal position of the greater tuberosity. The alignment of the anchors after insertion was adjusted to make 2 test groups, each with 8 specimens: In group 1, the anchor eyelets were malpositioned, whereas in group 2, the anchor eyelets were aligned according to the manufacturer's instructions. After insertion, cyclic tests from 10 N to 180 N were performed with a frequency of 1 Hz for 200 cycles; specimens were then loaded to failure to evaluate the maximum load of the system and observe the associated failure mode. RESULTS: The mean ultimate failure load in group 2 was not significantly different from that in group 1 (P = .472). CONCLUSIONS: For metallic screw-in suture anchors, the alignment of the eyelet does not change the failure mode and the load to failure after cyclic loading of the bone-anchor-suture system in ovine humeri. CLINICAL RELEVANCE: Our results indicate that on the basis of this anchor model, the position of the eyelet in the greater tuberosity does not interfere directly with the biomechanical performance of the system.

RESUMEN

AIMS: This study aims to investigate the efficacy of transcutaneous tibial nerve home stimulation for overactive bladder (OAB) in women with Parkinson's disease (PD). METHODS: The current study is a prospective, randomized, double-blind, sham-controlled trial. Home intervention was carried out and assessments were conducted at a tertiary hospital in South Brazil. Women with PD and OAB symptoms were included in the study. Patients were randomly divided into two groups: (1) stimulation and (2) sham. Both groups underwent intervention at home for 12 weeks. Patients were evaluated at baseline and at 12 weeks (end of intervention), 30- and 90-day follow-up. The primary outcome was the mean reduction in the number of urgency incontinence episodes, and secondary outcomes included daytime and nighttime urinary frequency, urinary urgency episodes, use of pad (reported in a 24-h bladder diary), OAB-V8 and King's Health Questionnaire scores, and maintenance of symptom relief after discontinuation of the intervention. RESULTS: In total, 30 consecutive patients completed the study (15/group). The stimulation group showed a reduction in nighttime urinary frequency (0.9 ± 0.6), urinary urgency (1.0 ± 1.2), urgency incontinence episodes (0.5 ± 0.6), use of pads (1.3 ± 1.2), and OAB-V8 (1.3 ± 1.2) and King's Health Questionnaire scores. In a 30-day and 90-day follow-up, 8 (53.3%) and 5 (33.3%) stimulation patients, respectively, reported full maintenance of symptom relief after discontinuation of the intervention. Stimulation patients presented a statistically significant improvement of symptoms as compared with sham patients (p = .001). CONCLUSIONS: Transcutaneous tibial nerve home stimulation can be used in clinical practice as an effective nonpharmacological resource for the reduction of OAB symptoms in women with PD, and the resulting relief seems to persist in the follow-up (30 and 90 days).

Asunto(s)

RESUMEN

Aneurysms of the sinus of Valsalva are rare. Unruptured sinus of Valsalva aneurysm is usually asymptomatic and rarely presents as right ventricular outflow obstruction, myocardial infarction as a result of coronary artery compression, conduction disturbances, or endocarditis. They have only been reported as the presumed source of embolism in six cases. We report a patient with right sinus of Valsalva rupture to the right atrium and embolization of aneurysm contents to the pulmonary vasculature.

RESUMEN

Three patients with eosinophilic meningitis (EoM) were investigated in two hospitals in Porto Alegre, Southern Brazil. These patients had a common exposure after the ingestion of raw mollusks in a religious ritual. Two of them had an uncommon presentation with intense lower distal extremities pain and small fiber neuropathy as defined by an electroneuromyography (ENMG) study. All three patients were positive for Angiostrongylus cantonensis serology and recovered after antihelminthic and anti-inflammatory treatment. Increased awareness of A. cantonensis infection is important to avoid new infections and to improved recognition and handling of cerebral angiostrongyliasis.

Asunto(s)

RESUMEN

BACKGROUND: There are currently no methods to predict the development of levodopa-induced dyskinesia (LID), a frequent complication of Parkinson's disease (PD) treatment. Clinical predictors and single nucleotide polymorphisms (SNP) have been associated to LID in PD. OBJECTIVE: To investigate the association of clinical and genetic variables with LID and to develop a diagnostic prediction model for LID in PD. METHODS: We studied 430 PD patients using levodopa. The presence of LID was defined as an MDS-UPDRS Part IV score ≥1 on item 4.1. We tested the association between specific clinical variables and seven SNPs and the development of LID, using logistic regression models. RESULTS: Regarding clinical variables, age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists were associated to LID. Only CC genotype of ADORA2A rs2298383 SNP was associated to LID after adjustment. We developed two diagnostic prediction models with reasonable accuracy, but we suggest that the clinical prediction model be used. This prediction model has an area under the curve of 0.817 (95% confidence interval [95%CI] 0.77‒0.85) and no significant lack of fit (Hosmer-Lemeshow goodness-of-fit test p=0.61). CONCLUSION: Predicted probability of LID can be estimated with reasonable accuracy using a diagnostic clinical prediction model which combines age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists.

Asunto(s)

RESUMEN

OBJECTIVE: Individuals with Parkinson's disease (PD) and freezing of gait (FOG) present peripheral and central sensitivity disturbances that impair motor performance. This study aimed to investigate long-term effects of plantar sensory stimulation on brain activity, brain connectivity, and gait velocity of individuals with PD and FOG. METHODS: Twenty-five participants were enrolled in this clinical trial (NCT02594540). Plantar sensory stimulation was delivered using the Automated Mechanical Peripheral Stimulation therapy (AMPS). Volunteers were randomly assigned to real or placebo AMPS groups and received eight sessions of treatment. The primary outcome was brain activity (task-based fMRI-active ankle dorsi-plantar flexion). Secondary outcomes were brain connectivity (resting state-RS fMRI) and gait velocity. fMRI was investigated on the left, right, and mid-sensory motor regions, left and right basal ganglia. RESULTS: No changes in brain activity were observed when task-based fMRI was analyzed. After real AMPS, RS functional connectivity between basal ganglia and sensory-related brain areas increased (insular and somatosensory cortices). Gait velocity also increased after real AMPS. A positive correlation was found between gait velocity and the increased connectivity between sensory, motor and supplementary motor cortices. CONCLUSION: Plantar sensory stimulation through AMPS was not able to modify brain activity. AMPS increased the RS brain connectivity mainly in areas related to sensory processing and sensorimotor integration. Plantar stimulation could be a way to improve plantar sensitivity and consequently ameliorate gait performance. However, the mechanisms behind the way AMPS influences brain pathways are still not completely known.

Asunto(s)

RESUMEN

Abstract Background: There are currently no methods to predict the development of levodopa-induced dyskinesia (LID), a frequent complication of Parkinson's disease (PD) treatment. Clinical predictors and single nucleotide polymorphisms (SNP) have been associated to LID in PD. Objective: To investigate the association of clinical and genetic variables with LID and to develop a diagnostic prediction model for LID in PD. Methods: We studied 430 PD patients using levodopa. The presence of LID was defined as an MDS-UPDRS Part IV score ≥1 on item 4.1. We tested the association between specific clinical variables and seven SNPs and the development of LID, using logistic regression models. Results: Regarding clinical variables, age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists were associated to LID. Only CC genotype of ADORA2A rs2298383 SNP was associated to LID after adjustment. We developed two diagnostic prediction models with reasonable accuracy, but we suggest that the clinical prediction model be used. This prediction model has an area under the curve of 0.817 (95% confidence interval [95%CI] 0.77‒0.85) and no significant lack of fit (Hosmer-Lemeshow goodness-of-fit test p=0.61). Conclusion: Predicted probability of LID can be estimated with reasonable accuracy using a diagnostic clinical prediction model which combines age of PD onset, disease duration, initial motor symptom and use of dopaminergic agonists.

Resumo Introdução: No momento, não há métodos para se predizer o desenvolvimento de discinesias induzidas por levodopa (DIL), uma frequente complicação do tratamento da doença de Parkinson (DP). Preditores clínicos e polimorfismos de nucleotídeo único (SNP) têm sido associados às DIL na DP. Objetivo: Investigar a associação entre variáveis clínicas e genéticas com as DIL e desenvolver um modelo de predição diagnóstica de DIL na DP. Métodos: Foram avaliados 430 pacientes com DP em uso de levodopa. A presença de DIL foi definida como escore ≥1 no item 4.1 da MDS-UPDRS Parte IV. Nós testamos a associação entre variáveis clínicas específicas e sete SNPs com o desenvolvimento de DIL, usando modelos de regressão logística. Resultados: Em relação às variáveis clínicas, idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos estiveram associados às DIL. Apenas o genótipo CC do SNP rs2298383 no gene ADORA2A esteve associado com DIL após o ajuste. Nós desenvolvemos dois modelos preditivos diagnósticos com acurácia razoável, mas sugerimos o uso do modelo preditivo clínico. Esse modelo de predição tem uma área sob a curva de 0,817 (intervalo de confiança de 95% [IC95%] 0,77‒0,85) e sem perda significativa de ajuste (teste de qualidade de ajuste de Hosmer-Lemeshow p=0,61). Conclusão: A probabilidade prevista de DIL pode ser estimada, com acurácia razoável, por meio do uso de um modelo preditivo diagnóstico clínico, que combina a idade de início da doença, duração da doença, sintomas motores iniciais e uso de agonistas dopaminérgicos.

Asunto(s)

RESUMEN

PURPOSE: Subthalamic nucleus deep brain stimulation (STN-DBS) parameters, for example the frequency of stimulation, seem to affect speech and voice aspects. However, this influence is not well understood. This study aimed to investigate the impact of low- and high-frequency STN-DBS on voice and speech for people with Parkinson's disease. METHODS: Nineteen individuals with Parkinson's disease who received bilateral STN-DBS were assessed for motor performance (Unified Parkinson's Disease Rating Scale-III), perceptual evaluation of voice (grade, roughness, breathiness, asthenia, strain, and instability [GRBASI]), dysarthria assessment, and computerized acoustic analysis of voice upon receiving low-frequency (60 Hz) and high-frequency (130 Hz) STN-DBS. RESULTS: In the GRBASI protocol, asthenia, and instability were significantly better at 130 Hz of stimulation. In the dysarthria evaluation, the phonation aspect, articulation, and grade of dysarthria showed deterioration at the same high-frequency condition. There was no significant difference for any vocal acoustic measures. CONCLUSION: The high-frequency of STN-DBS may affect speech and voice differently, leading to an amelioration of the vocal production, but with adverse effects in the speech control.

Asunto(s)

RESUMEN

BACKGROUND: Obesity, diabetes mellitus may be related to the health, the relationship and the physiological capacity of the production of thyroid hormones (TH), triiodothyronine (T3) and thyroxine (T4). OBJECTIVES: The main aims of this review are to describe the relationship between obesity, appetite, weight management, hormonal mechanisms of diabetes mellitus and hypothyroidism post-bariatric surgery. METHODOLOGY: An in-depth literature search was conducted to identify scientific studies, which analyzed the correlation between diabetes mellitus and hypothyroidism post-bariatric surgery. RESULTS: Bariatric surgery decreases hypothyroidism, reduces the need for pharmacological action (such as levothyroxine), controls the weight and body fat and increases the sensitivity to leptin and insulin. CONCLUSION: The reduction of the stomach and intestine by bariatric surgery is an evolutionary and beneficial action, because it may lead to a drastic decrease on numbers of conditions such as diabetes, obesity, hypothyroidism, and others. Thus, new studies should also focus on patients' post-operatory conditions, such as lifetime, regulation and functioning of organs after reduced nutrition, and consumption and delivery of nutrients to health maintenance.

Asunto(s)

RESUMEN

Nordic walking's (NW) degree of effectiveness regarding health-related parameters in people with Parkinson's Disease (PD) is a subject of debate. While NW seems to improve functionality, a clear non-motor benefit has not been demonstrated. The aim of this randomized controlled trial was to compare the effects of 9-week NW and free walking (FW) training programs on quality of life, cognitive function, and depressive symptoms in individuals with PD. Thirty-three people with PD, (Hoehn and Yahr 1-4) were randomized into two groups: NW (n = 16) and FW (n = 17). We analyzed quality of life, cognitive function, depressive symptoms, and motor symptoms. Significant improvements were found in the overall, physical, psychological, social participation, and intimacy domains of quality of life, as well as in cognitive function and depressive symptoms for both groups. Only the NW group showed improvement in the autonomy domain. Individuals with PD had a similar enhancement of non-motor symptoms after walking training, with or without poles. However, the NW group showed a more significant improvement in the autonomy domain, strengthening the applied and clinical potential of NW in people with PD. Future studies are needed to determine the efficacy of walking training without poles in subjects with PD.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

Parkinson's disease (PD) is a progressive and multifactorial neurodegenerative disease. It has been suggested that a dysregulation of the hypothalamic-pituitary-adrenal axis (HPA) occurs in PD. Furthermore, this dysregulation may be involved in triggering, exacerbation or progression of disease. The objective of this study was to systematically review the literature regarding cortisol levels and their relation with motor, cognitive and behavioral symptoms in patients with PD. A systematic search was performed in PubMed and Embase databases, according to PRISMA norms. Twenty-one studies were included, which evaluated baseline levels of cortisol and motor, cognitive, behavioral symptoms, drugs administration or deep brain stimulation to PD treatment. Sample size ranged from 7 to 249 individuals. In 14 studies that assessed cortisol levels in PD patients, seven showed elevation of cortisol levels. In relation to symptomatology, high levels of cortisol were associated with worst functional scores evaluated by UPDRS, depression and behavior in risk preference. Medication interactions showed an influence on the regulation of cortisol release, mainly, conventional drugs used in the PD's treatment, such as levodopa. The results found in this review point to a possible relationship between cortisol levels and symptoms in PD, indicating that an HPA axis dysfunction related to cortisol level occurs in PD.

Asunto(s)