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
16 resultados
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Agora exibindo 1 - 10 de 16
- Deep Brain Stimulation in Patients With Mutations in Parkinson's Disease-Related Genes: A Systematic Review(2019) OLIVEIRA, Lais Machado de; BARBOSA, Egberto Reis; AQUINO, Camila Catherine; MUNHOZ, Renato Puppi; FASANO, Alfonso; CURY, Rubens GisbertBackground Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), and careful selection of candidates is a key component of successful therapy. Although it is recognized that factors such as age, disease duration, and levodopa responsiveness can influence outcomes, it is unclear whether genetic background should also serve as a parameter. Objectives The aim of this systematic review is to explore studies that have evaluated DBS in patients with mutations in PD-related genes. Methods We performed a selective literature search for articles regarding the effects of DBS in autosomal dominant or recessive forms of PD or in PD patients with genetic risk factors. Data regarding changes in motor and nonmotor scores and the presence of adverse events after the stimulation were collected. Results A total of 25 studies were included in the systematic review, comprising 135 patients. In the shorter term, most patients showed marked or satisfactory response to subthalamic DBS, although leucine rich repeat kinase 2 carriers of R114G mutations had higher rates of unsatisfactory outcome. Longer term follow-up data were scarce but suggested that motor benefit is sustained. Patients with the glucosidase beta acid (GBA) mutation showed higher rates of cognitive decline after surgery. Motor outcome was scarce for pallidal DBS. Few adverse events were reported. Conclusions Subthalamic DBS results in positive outcomes in the short term in patients with Parkin, GBA, and leucine-rich repeat kinase 2 (non-R144G) mutations, although the small sample size limits the interpretation of our findings. Longer and larger cohorts of follow-up, with broader nonmotor symptom evaluations will be necessary to better customize DBS therapy in this population.
- Transcutaneous magnetic spinal cord stimulation for freezing of gait in Parkinson's disease(2020) MENEZES, Janaina Reis; CARRA, Rafael Bernhart; NUNES, Glaucia Aline; SIMOES, Juliana da Silva; TEIXEIRA, Manoel Jacobsen; DUARTE, Kleber Paiva; ANDRADE, Daniel Ciampi de; BARBOSA, Egberto Reis; MARCOLIN, Marco Antonio; CURY, Rubens GisbertDopaminergic drugs partially alleviate gait problems in Parkinson's disease, but the effects are not sustained in the long-term. Particularly, the freezing of gait directly impacts patients' quality of life. Experimental epidural spinal cord stimulation (SCS) studies have suggested positive effects on locomotion among PD patients, but the effects of non-invasive stimulation have never been explored. Here, we investigated in a prospective, open-label, pilot study the efficacy and safety of non-invasive magnetic stimulation of the spinal cord in five patients with PD who experienced gait problems, including freezing of gait. A trial of transcutaneous magnetic SCS was performed at the level of the fifth thoracic vertebra. The primary outcome was the change in freezing of gait 7 days after stimulation. Secondary outcome measures included changes in gait speed and UPDRS part III. After non-invasive spinal cord stimulation, patients experienced a 22% improvement in freezing of gait (p = 0.040) and 17.4% improvement in the UPDRS part III (p = 0.042). Timed up and go times improved by 48.2%, although this did not reach statistical significance (p = 0.06). Patients' global impression of change was 'much improved' for four patients. Improvement in gait after stimulation was reversible, since it returned to baseline scores 4 weeks after stimulation. No severe side effects were recorded. This pilot study suggests that transcutaneous magnetic spinal cord stimulation is feasible and can potentially improve gait problems in PD, without severe adverse effects. Large scale phase II trials are needed to test this hypothesis.
- Advances in DBS Technology and Novel Applications: Focus on Movement Disorders(2022) POTEL, Sina R.; MARCEGLIA, Sara; MEONI, Sara; KALIA, Suneil K.; CURY, Rubens G.; MORO, ElenaPurpose of Review Deep brain stimulation (DBS) is an established treatment in several movement disorders, including Parkinson's disease, dystonia, tremor, and Tourette syndrome. In this review, we will review and discuss the most recent findings including but not limited to clinical evidence. Recent Findings New DBS technologies include novel hardware design (electrodes, cables, implanted pulse generators) enabling new stimulation patterns and adaptive DBS which delivers potential stimulation tailored to moment-to-moment changes in the patient's condition. Better understanding of movement disorders pathophysiology and functional anatomy has been pivotal for studying the effects of DBS on the mesencephalic locomotor region, the nucleus basalis of Meynert, the substantia nigra, and the spinal cord. Eventually, neurosurgical practice has improved with more accurate target visualization or combined targeting. A rising research domain emphasizes bridging neuromodulation and neuroprotection. Recent advances in DBS therapy bring more possibilities to effectively treat people with movement disorders. Future research would focus on improving adaptive DBS, leading more clinical trials on novel targets, and exploring neuromodulation effects on neuroprotection.
- 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.
- Targeting the hot spot in a patient with essential tremor and Parkinson's disease: Tractography matters(2018) LISTIKA, Clarice; SANTIAGO, Natally; REIS, Paul Rodrigo; GODINHO, Fabio; DUARTE, Kleber; TEIXEIRA, Manoel Jacobsen; BARBOSA, Egberto Reis; CURY, Rubens GisbertIntroduction: Thalamic ventralis intermedius deep brain stimulation (VIM-DBS) is generally effective in treating refractory tremor in Parkinson's disease (PD) and in essential tremor (ET), but some patients do not respond well due to side effects or from loss of the effect of stimulation over time. The caudal zona incerta (ZI) has emerged as a promising target in ET, and the effects of ZI-DBS on PD tremor are less studied. Here, we describe a rare situation in which both ET and PD coexist in a 72-year-old male referred for ZI-DBS due to refractory tremor. The aim of this study was to evaluate whether there was a difference in the area stimulated to improve each type of tremor and whether tractography could improve and predict motor outcome. Methods: Two months after the surgery, in order to define which of the cathodes was the most effective towards improving the tremor and parkinsonian symptoms, a double-blinded, monopolar evaluation was conducted on both hemispheres separately. Once the best contact and parameters were defined, the volume of tissue activation (VTA) was represented spatially for each type of tremor and, finally, the image model was fused with the tractography. Results: For both types of tremor, the hot spot stimulated region achieved the dentato-rubro-thalamic tract (DRTT) at the higher fiber density region. The DRTT fibers were asymmetrical between the right and left hemispheres. Conclusion: Regardless of the type of tremor, DRTT can be the most effective region for stimulation. Tractography should be considered when planning the surgical target since the DRTT is not always symmetrical, and the reconstruction of the VTA together with the tractography can greatly improve the DBS programming, and, probably, the patient's outcome to the stimulation.
- Pain in Parkinson's Disease: Current Concepts and a New Diagnostic Algorithm(2015) MYLIUS, Veit; ANDRADE, Daniel Ciampi de; CURY, Rubens Gisbert; TEEPKER, Michael; EHRT, Uwe; EGGERT, Karla Maria; BEER, Serafin; KESSELRING, Juerg; STAMELOU, Maria; OERTEL, Wolfgang H.; MOELLER, Jens Carsten; LEFAUCHEUR, Jean-PascalBackground: Pain is a significant burden for patients with Parkinson's disease (PD) with a high impact on quality of life. The present article aims at summarizing epidemiological, pathophysiological, clinical, and neurophysiological data regarding pain in PD. Methods: In this domain, a procedure of systematic assessment is still lacking for the syndromic diagnosis and should take into account pain characteristics, effects of dopaminergic treatment, motor fluctuations, and non-PD-associated pain. Findings: We propose an original questionnaire addressing an algorithm suitable for daily clinical practice. The questionnaire is based on a three-step approach addressing first the relationship between pain and PD (including temporal relationship with the course of the disease, association with motor fluctuations, and impact of antiparkinsonian treatment), before classifying pain into one of three main syndromes (i.e., musculoskeletal pain, psychomotor restlessness pain, and neuropathic pain). Conclusions: The proposed questionnaire allows the characteristics of each pain type to be determined according to its relationship with the disease and its treatment. The validation of the clinical use of this questionnaire will be the goal of a forthcoming work.
- Little Brain, Big Expectations(2020) CURY, Rubens Gisbert; FRANCA, Carina; BARBOSA, Egberto Reis; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi deThe cerebellum has been implicated in the mechanisms of several movement disorders. With the recent reports of successful modulation of its functioning, this highly connected structure has emerged as a promising way to provide symptomatic relief not yet obtained by usual treatments. Here we review the most relevant papers published to date, the limitations and gaps in literature, discuss why several papers have failed in showing efficacy, and present a new way of stimulating the cerebellum. References for this critique review were identified by searches on PubMed for the terms ""Parkinson's disease"", ""ataxia"", ""dystonia"", ""tremor"", and ""dyskinesias"" in combination with the type of stimulation and the stimulation site. Studies conducted thus far have shed light on the potential of cerebellar neuromodulation for attenuating symptoms in patients with some forms of isolated and combined dystonia, dyskinesia in Parkinson's disease, and neurodegenerative ataxia. However, there is still a high heterogeneity of results and uncertainty about the possibility of maintaining long-term benefits. Because of the complicated architecture of the cerebellum, the modulation techniques employed may have to focus on targeting the activity of the cerebellar nuclei rather than the cerebellar cortex. Measures of cerebellar activity may reduce the variability in outcomes.
- 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.
- Medical management after subthalamic stimulation in Parkinson's disease: a phenotype perspective(2020) BERTHOLO, Ana Paula; FRANCA, Carina; FIORINI, Wilma Silva; BARBOSA, Egberto Reis; CURY, Rubens GisbertSubthalamic nucleus deep brain stimulation (STN DBS) is an established treatment that improves motor fluctuations, dyskinesia, and tremor in Parkinson's disease (PD). After the surgery, a careful electrode programming strategy and medical management are crucial, because an imbalance between them can compromise the quality of life overtime. Clinical management is not straightforward and depends on several perioperative motor and non-motor symptoms. In this study, we review the literature data on acute medical management after STN DBS in PD and propose a clinical algorithm on medical management focused on the patient's phenotypic profile at the perioperative period. Overall, across the trials, the levodopa equivalent daily dose is reduced by 30 to 50% one year after surgery. In patients taking high doses of dopaminergic drugs or with high risk of impulse control disorders, an initial reduction in dopamine agonists after STN DBS is recommended to avoid the hyperdopaminergic syndrome, particularly hypomania. On the other hand, a rapid reduction of dopaminergic agonists of more than 70% during the first months can lead to dopaminergic agonist withdrawal syndrome, characterized by apathy, pain, and autonomic features. In a subset of patients with severe dyskinesia before surgery, an initial reduction in levodopa seems to be a more reasonable approach. Finally, when the patient's phenotype before the surgery is the severe parkinsonism (wearing-off) with or without tremor, reduction of the medication after surgery can be more conservative. Individualized medical management following DBS contributes to the ultimate therapy success.
- New players in basal ganglia dysfunction in Parkinson's disease(2020) MEONI, Sara; CURY, Rubens Gisbert; MORO, ElenaThe classical model of the basal ganglia (BG) circuit has been recently revised with the identification of other structures that play an increasing relevant role especially in the pathophysiology of Parkinson's disease (PD). Numerous studies have supported the spreading of the alpha-synuclein pathology to several areas beyond the BG and likely even before their involvement. With the aim of better understanding PD pathophysiology and finding new targets for treatment, the spinal cord, the pedunculopontine nucleus, the substantia nigra pars reticulata, the retina, the superior colliculus, the cerebellum, the nucleus parabrachialis and the Meynert's nucleus have been investigated both in animal and human studies. In this chapter, we describe the main anatomical and functional connections between the above structures and the BG, the relationship between their pathology and PD features, and the rational of applying neuromodulation treatment to improve motor and non-motor symptoms in PD. Some of these new players in the BG circuits might also have a potential intriguing role as early biomarkers of PD.