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
Resultados de Busca
Agora exibindo 1 - 10 de 16
- Surgical treatment of dystonia(2018) CURY, Rubens Gisbert; KALIA, Suneil Kumar; SHAH, Binit Bipin; JIMENEZ-SHAHED, Joohi; PRASHANTH, Lingappa Kumar; MORO, ElenaIntroduction: Treatment of dystonia should be individualized and tailored to the specific needs of patients. Surgical treatment is an important option in medically refractory cases. Several issues regarding type of the surgical intervention, targets, and predict factors of benefit are still under debate.Areas covered: To date, several clinical trials have proven the benefit and safety of deep brain stimulation (DBS) for inherited and idiopathic isolated dystonia, whereas there is still insufficient evidence in combined and acquired dystonia. The globus pallidus internus (GPi) is the target with the best evidence, but data on the subthalamic nucleus seems also to be promising. Evidence suggests that younger patients with shorter disease duration experience greater benefit following DBS. Pallidotomy and thalamotomy are currently used in subset of carefully selected patients. The development of MRI-guided focused ultrasound might bring new options to ablation approach in dystonia.Expert commentary: GPi-DBS is effective and safe in isolated dystonia and should not be delayed when symptoms compromise quality of life and functionality. Identifying the best candidates to surgery on acquired and combined dystonias is still necessary. New insights about pathophysiology of dystonia and new technological advances will undoubtedly help to tailor surgery and optimize clinical effects.
- Use of non-invasive stimulation in movement disorders: a critical review(2021) GODEIRO, Clecio; FRANCA, Carina; CARRA, Rafael Bernhart; SABA, Felipe; SABA, Roberta; MAIA, Debora; BRANDAO, Pedro; ALLAM, Nasser; RIEDER, Carlos R. M.; FREITAS, Fernando Cini; CAPATO, Tamine; SPITZ, Mariana; FARIA, Danilo Donizete de; CORDELLINI, Marcela; VEIGA, Beatriz A. A. G.; ROCHA, Maria Sheila G.; MACIEL, Ricardo; MELO, Lucio B. De; MOLLER, Patricia D. S.; JUNIOR, Magno R. R.; FORNARI, Luis H. T.; MANTESE, Carlos E.; BARBOSA, Egberto Reis; MUNHOZ, Renato P.; COLETTA, Marcus Vinicius Della; CURY, Rubens GisbertBackground: 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.
- 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.
- Gaps and roadmap of novel neuromodulation targets for treatment of gait in Parkinson's disease(2022) CURY, Rubens Gisbert; PAVESE, Nicola; KRAUSS, Joachim K.; MORO, ElenaGait issues in Parkinson's disease (PD) are common and can be highly disabling. Although levodopa and deep brain stimulation (DBS) of the subthalamic nucleus and the globus pallidus internus have been established therapies for addressing the motor symptoms of PD, their effects on gait are less predictable and not well sustained with disease progression. Given the high prevalence of gait impairment in PD and the limitations in currently approved therapies, there has been considerable interest in alternative neuromodulation targets and techniques. These have included DBS of pedunculopontine nucleus and substantia nigra pars reticulata, spinal cord stimulation, non-invasive modulation of cortical regions and, more recently, vagus nerve stimulation. However, successes and failures have also emerged with these approaches. Current gaps and controversies are related to patient selection, optimal electrode placement within the target, placebo effects and the optimal programming parameters. Additionally, recent advances in pathophysiology of oscillation dynamics have driven new models of closed-loop DBS systems that may or may not be applicable to gait issues. Our aim is to describe approaches, especially neuromodulation procedures, and emerging challenges to address PD gait issues beyond subthalamic nucleus and the globus pallidus internus stimulation.
- 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.
- Deep brain stimulation in Tourette's syndrome: evidence to date(2019) CASAGRANDE, Sara C. B.; CURY, Rubens G.; ALHO, Eduardo J. L.; FONOFF, Erich TalamoniTourette's syndrome (TS) is a neurodevelopmental disorder that comprises vocal and motor tics associated with a high frequency of psychiatric comorbidities, which has an important impact on quality of life. The onset is mainly in childhood and the symptoms can either fade away or require pharmacological therapies associated with cognitive-behavior therapies. In rare cases, patients experience severe and disabling symptoms refractory to conventional treatments. In these cases, deep brain stimulation (DBS) can be considered as an interesting and effective option for symptomatic control. DBS has been studied in numerous trials as a therapy for movement disorders, and currently positive data supports that DBS is partially effective in reducing the motor and non-motor symptoms of TS. The average response, mostly from case series and prospective cohorts and only a few controlled studies, is around 40% improvement on tic severity scales. The ventromedial thalamus has been the preferred target, but more recently the globus pallidus internus has also gained some notoriety. The mechanism by which DBS is effective on tics and other symptoms in TS is not yet understood. As refractory TS is not common, even reference centers have difficulties in performing large controlled trials. However, studies that reproduce the current results in larger and multicenter randomized controlled trials to improve our knowledge so as to support the best target and stimulation settings are still lacking. This article will discuss the selection of the candidates, DBS targets and mechanisms on TS, and clinical evidence to date reviewing current literature about the use of DBS in the treatment of TS.
- Effects of cerebellar neuromodulation in movement disorders: A systematic review(2018) FRANCA, Carina; ANDRADE, Daniel Ciampi de; TEIXEIRA, Manoel Jacobsen; GALHARDONI, Ricardo; SILVA, Valquiria; BARBOSA, Egberto Reis; CURY, Rubens GisbertBackground: The cerebellum is involved in the pathophysiology of many movement disorders and its importance in the field of neuromodulation is growing. Objectives: To review the current evidence for cerebellar modulation in movement disorders and its safety profile. Methods: Eligible studies were identified after a systematic literature review of the effects of cerebellar modulation in cerebellar ataxia, Parkinson's disease (PD), essential tremor (ET), dystonia and progressive supranuclear palsy (PSP). Neuromodulation techniques included transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS). The changes in motor scores and the incidence of adverse events after the stimulation were reviewed. Results: Thirty-four studies were included in the systematic review, comprising 431 patients. The evaluation after stimulation ranged from immediately after to 12 months after. Neuromodulation techniques improved cerebellar ataxia due to vascular or degenerative etiologies (TMS, tDCS and DBS), dyskinesias in PD patients (TMS), gross upper limb movement in PD patients (tDCS), tremor in ET (TMS and tDCS), cervical dystonia (TMS and tDCS) and dysarthria in PSP patients (TMS). All the neuromodulation techniques were safe, since only three studies reported the existence of side effects (slight headache after TMS, local skin erythema after tDCS and infectious complication after DBS). Eleven studies did not mention if adverse events occurred. Conclusions: Cerebellar modulation can improve specific symptoms in some movement disorders and is a safe and well-tolerated procedure. Further studies are needed to lay the groundwork for new researches in this promising target.
- 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.
- 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.