RUBENS GISBERT CURY
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
18 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 18
- Non-motor effects of deep brain stimulation in Parkinson?s disease motor subtypes(2023) JOST, Stefanie T.; KONITSIOTI, Agni; LOEHRER, Philipp A.; ASHKAN, Keyoumars; RIZOS, Alexandra; SAUERBIER, Anna; GHILARDI, Maria Gabriela dos Santos; ROSENKRANZ, Franz; STROBEL, Lena; GRONOSTAY, Alexandra; BARBE, Michael T.; EVANS, Julian; VISSER-VANDEWALLE, Veerle; NIMSKY, Christopher; FINK, Gereon R.; SILVERDALE, Monty; CURY, Rubens G.; FONOFF, Erich T.; ANTONINI, Angelo; CHAUDHURI, K. Ray; TIMMERMANN, Lars; MARTINEZ-MARTIN, Pablo; DAFSARI, Haidar S.Introduction: Deep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with 'postural instability and gait difficulty' (PIGD) experience more beneficial non-motor effects than 'tremor-dominant' patients undergoing DBS for PD.Methods: In this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and-motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests.Results: In 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores.Conclusions: This study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS.
- Tic Status in Tourette Syndrome Due to Depletion of the Deep Brain Stimulation Battery(2023) PARMERA, Jacy Bezerra; YAMAMOTO, Joyce Yuri Silvestre; CURY, Rubens Gisbert
- Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region(2023) LISTIK, Clarice; LAPA, Jorge Dornellys; CASAGRANDE, Sara Carvalho Barbosa; BARBOSA, Egberto Reis; IGLESIO, Ricardo; GODINHO, Fabio; DUARTE, Kleber Paiva; TEIXEIRA, Manoel Jacobsen; CURY, Rubens GisbertBackground Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. Objective To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. Methods The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemisphereswas correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. Results Five patients were included. The baseline BFM motor and disability subscores were 78.30 +/- 13.55 (62.00-98.00) and 20.60 +/- 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). Conclusions These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients.
- Does TRODAT-1 SPECT Uptake Correlate with Cerebrospinal Fluid alpha-Synuclein Levels in Mid-Stage Parkinson's Disease?(2023) COUTINHO, Artur M.; GHILARDI, Maria Gabriela; CAMPOS, Ana Carolina P.; ETCHEBEHERE, Elba; FONOFF, Fernanda C.; CURY, Rubens G.; PAGANO, Rosana L.; MARTINEZ, Raquel C. R.; FONOFF, Erich T.Background: Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and alpha-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and alpha-synuclein levels in PD. Methods: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of alpha-synuclein. Results: We found that alpha-synuclein in the CSF was correlated with global cognition (positive correlation, r(2) = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r(2) = 0.4, p = 0.005), and striatum (positive correlation, r(2) = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF alpha-synuclein, and cognition, thus suggesting that they may be lost with disease progression. Conclusions: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition.
- Optimizing Noninvasive Stimulation to Treat Gait Problems in Parkinson Disease(2020) CURY, Rubens Gisbert; CARRA, Rafael; REIS, Janaina; BARBOSA, Egberto R.
- Application of machine learning and complex network measures to an EEG dataset from ayahuasca experiments(2022) ALVES, Caroline L.; CURY, Rubens Gisbert; ROSTER, Kirstin; PINEDA, Aruane M.; RODRIGUES, Francisco A.; THIELEMANN, Christiane; CIBA, ManuelAyahuasca is a blend of Amazonian plants that has been used for traditional medicine by the inhabitants of this region for hundreds of years. Furthermore, this plant has been demonstrated to be a viable therapy for a variety of neurological and mental diseases. EEG experiments have found specific brain regions that changed significantly due to ayahuasca. Here, we used an EEG dataset to investigate the ability to automatically detect changes in brain activity using machine learning and complex networks. Machine learning was applied at three different levels of data abstraction: (A) the raw EEG time series, (B) the correlation of the EEG time series, and (C) the complex network measures calculated from (B). Further, at the abstraction level of (C), we developed new measures of complex networks relating to community detection. As a result, the machine learning method was able to automatically detect changes in brain activity, with case (B) showing the highest accuracy (92%), followed by (A) (88%) and (C) (83%), indicating that connectivity changes between brain regions are more important for the detection of ayahuasca. The most activated areas were the frontal and temporal lobe, which is consistent with the literature. F3 and PO4 were the most important brain connections, a significant new discovery for psychedelic literature. This connection may point to a cognitive process akin to face recognition in individuals during ayahuasca-mediated visual hallucinations. Furthermore, closeness centrality and assortativity were the most important complex network measures. These two measures are also associated with diseases such as Alzheimer's disease, indicating a possible therapeutic mechanism. Moreover, the new measures were crucial to the predictive model and suggested larger brain communities associated with the use of ayahuasca. This suggests that the dissemination of information in functional brain networks is slower when this drug is present. Overall, our methodology was able to automatically detect changes in brain activity during ayahuasca consumption and interpret how these psychedelics alter brain networks, as well as provide insights into their mechanisms of action.
- Long-Term Outcome of Dentatotomy in a Dystonic Patient(2016) TEIXEIRA, Manoel Jacobsen; FRANCA, Carina C.; ANDRADE, Daniel Ciampi de; ROGANO, Luis Augusto Carvalho; LEPSKI, Guilherme; FONOFF, Erich Talamoni; CURY, Rubens GisbertDystonia is characterized by sustained or intermittent muscle contractions leading to abnormal movements and impairment in daily activities. Stereotactic dentatotomy has been a treatment option in cases of spasticity or dystonia, especially in patients with cerebral palsy, but the long-term effect of dentatotomy in dystonia is still unknown. Here we describe a dystonic patient who underwent dentatotomy for symptomatic treatment of refractory dystonia and whose 20-year follow-up showed improvement in symptoms.
- Recent Advances in the Treatment of Genetic Forms of Parkinson's Disease: Hype or Hope?(2023) CAVALLIERI, Francesco; CURY, Rubens G.; GUIMARAES, Thiago; FIORAVANTI, Valentina; GRISANTI, Sara; ROSSI, Jessica; MONFRINI, Edoardo; ZEDDE, Marialuisa; FONZO, Alessio Di; VALZANIA, Franco; MORO, ElenaParkinson's disease (PD) is a multifarious neurodegenerative disease. Its pathology is characterized by a prominent early death of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies with aggregated alpha-synuclein. Although the alpha-synuclein pathological aggregation and propagation, induced by several factors, is considered one of the most relevant hypotheses, PD pathogenesis is still a matter of debate. Indeed, environmental factors and genetic predisposition play an important role in PD. Mutations associated with a high risk for PD, usually called monogenic PD, underlie 5% to 10% of all PD cases. However, this percentage tends to increase over time because of the continuous identification of new genes associated with PD. The identification of genetic variants that can cause or increase the risk of PD has also given researchers the possibility to explore new personalized therapies. In this narrative review, we discuss the recent advances in the treatment of genetic forms of PD, focusing on different pathophysiologic aspects and ongoing clinical trials.
- Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial(2022) SCHILSKY, Michael L.; CZLONKOWSKA, Anna; ZUIN, Massimo; CASSIMAN, David; TWARDOWSCHY, Carlos; POUJOIS, Aurelia; GONDIM, Francisco De Assis A.; DENK, Gerald; CURY, Rubens G.; OTT, Peter; MOORE, Joanna; ALA, Aftab; D'INCA, Renata; COUCHONNAL-BEDOYA, Eduardo; D'HOLLANDER, Koenraad; DUBOIS, Nicolas; KAMLIN, C. Omar F.; WEISS, Karl HeinzBackground Wilson disease is an inherited disorder of copper transport. Whereas penicillamine is used therapeutically to re-establish copper balance, trientine is indicated for patients with penicillamine intolerance. We aimed to compare penicillamine with trientine tetrahydrochloride (TETA4) for maintenance therapy in patients with Wilson disease. Methods We conducted a randomised, open-label, non-inferiority, phase 3 trial at 15 health-care centres across nine countries (patients were recruited from 13 of these health-care centres across Brazil, Europe, and the USA). We enrolled patients aged 18-75 years with stable Wilson disease who were treated for at least 1 year with penicillamine. Patients entered a 12-week period to determine stability through clinical assessment by site investigators and predefined thresholds for serum non-caeruloplasmin-bound copper (NCC; by an exchangeable copper assay; 25-150 mu g/L), 24 h urinary copper excretion (100-900 mu g/24 h), and alanine aminotransferase (ALT; <2 x upper limit of normal). Stable patients were randomly assigned (1:1) to continue receiving the maintenance twice daily dose of oral penicillamine or switched mg-for-mg to oral TETA4 centrally with a web-based system using minimisation. The primary endpoint, assessed 24 weeks after randomisation, was NCC by speciation assay. The non-inferiority margin of mean difference in NCC by speciation assay was -50 mu g/L, as estimated by a general linear model for repeated visits, adjusted for baseline values. Further data on safety and efficacy were collected during a 24-week extension period. Data were analysed using an intention-to-treat approach. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03539952 (active, not recruiting). Findings Between June 4, 2018, and March 10, 2020, 77 patients were screened. 53 patients were randomly assigned (27 to the penicillamine group and 26 to the TETA4 group). After 24 weeks, the mean difference in serum NCC by speciation assay between the penicillamine group and TETA4 group was -9.1 mu g/L (95% CI -24.2 to 6.1), with the lower limit of the 95% CI within the defined non-inferiority margin. At 24 weeks, urinary copper excretion was lower with TETA4 than with penicillamine (mean difference 237.5 mu g/24 h (99% CI 115.6 to 359.4). At 48 weeks, TETA4 remained non-inferior to penicillamine in terms of NCC by speciation assay (mean difference NCC -15.5 mu g/L [95% CI -34.5 to 3.6]). Urinary copper excretion at 48 weeks remained in the expected range for well treated patients in both study groups, and the mean difference (124.8 mu g/24 h [99% CI -37.6 to 287.1]) was not significantly different. At 24 weeks and 48 weeks, masked clinical adjudication of stability assessed by three independent clinicians confirmed clinical stability (100%) of all participants, in agreement with the stability seen with the NCC by speciation assay. There were no notable changes in either the Clinical Global Impression of Change or Unified Wilson Disease Rating Scale (neurological assessment) from baseline (pre-randomisation) at weeks 24 and 48. The mean change in serum total copper from baseline to 24 weeks was 17.6 mu g/L (99% CI -9.5 to 44.7) with penicillamine and -6.3 mu g/L (-34.7 to 22.1) with TETA4, and the mean change in serum total caeruloplasmin from baseline to 24 weeks was 1.8 mg/L (-19.2 to 22.8) with penicillamine and -2.2 mg/L (-6.1 to 1.7) with TETA4. All liver enzymes were similar at 24 weeks and 48 weeks, with the exception of elevated ALT concentration at 48 weeks for patients in the TETA4 group. Penicillamine was associated with three post-randomisation serious adverse events (leukopenia, cholangiocarcinoma, and hepatocellular cancer); none were reported for TETA4. The most common treatment-emergent adverse events were headache for penicillamine (five [19%] of 27 patients vs two [8%] of 26) and abdominal pain for TETA4 (one [4%] vs four [15%]); all treatment-emergent adverse events resolved and were mild to moderate. One patient developed a rash with TETA4 that resolved on discontinuation of therapy. Interpretation The efficacy of TETA4 as oral maintenance therapy was non-inferior to penicillamine and well tolerated in adults with Wilson disease.
- The Therapeutic Potential of Non-Invasive and Invasive Cerebellar Stimulation Techniques in Hereditary Ataxias(2023) BENUSSI, Alberto; BATSIKADZE, Giorgi; FRANCA, Carina; CURY, Rubens G.; MAAS, Roderick P. P. W. M.The degenerative ataxias comprise a heterogeneous group of inherited and acquired disorders that are characterized by a progressive cerebellar syndrome, frequently in combination with one or more extracerebellar signs. Specific disease-modifying interventions are currently not available for many of these rare conditions, which underscores the necessity of finding effective symptomatic therapies. During the past five to ten years, an increasing number of randomized controlled trials have been conducted examining the potential of different non-invasive brain stimulation techniques to induce symptomatic improvement. In addition, a few smaller studies have explored deep brain stimulation (DBS) of the dentate nucleus as an invasive means to directly modulate cerebellar output, thereby aiming to alleviate ataxia severity. In this paper, we comprehensively review the clinical and neurophysiological effects of transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and dentate nucleus DBS in patients with hereditary ataxias, as well as the presumed underlying mechanisms at the cellular and network level and perspectives for future research.