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
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- Guidelines for Parkinson's disease treatment consensus from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology- motor symptoms(2022) SABA, Roberta Arb; MAIA, Debora Palma; CARDOSO, Francisco Eduardo Costa; BORGES, Vanderci; ANDRADE, Luiz Augusto F.; FERRAZ, Henrique Ballalai; BARBOSA, Egberto Reis; RIEDER, Carlos Roberto de Mello; SILVA, Delson Jose da; CHIEN, Hsin Fen; CAPATO, Tamine; ROSSO, Ana Lucia; LIMA, Carlos Frederico Souza; BEZERRA, Jose Marcelo Ferreia; NICARETTA, Denise; BARSOTTINI, Orlando Graziani Povoas; GODEIRO-JUNIOR, Clecio; BARCELOS, Lorena Broseghini; CURY, Rubens Gisbert; SPITZ, Mariana; SILVA, Sonia Maria Cesar Azevedo; COLLETTA, Marcus Vinicius DellaThe treatment of Parkinson's disease (PD) is challenging, especially since it is considered highly individualized. The Brazilian Academy of Neurology has recognized the need to disseminate knowledge about the management of PD treatment, adapting the best evidence to the Brazilian reality. Thus, the main published treatment guidelines were reviewed based on the recommendations of group from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology.
- Should the Globus Pallidus Targeting Be Refined in Dystonia?(2022) LAPA, Jorge Dornellys da Silva; GODINHO, Fabio Luiz Franceschi; TEIXEIRA, Manoel Jacobsen; LISTIK, Clarice; IGLESIO, Ricardo Ferrareto; DUARTE, Kleber Paiva; CURY, Rubens GisbertBackground and Study Aims Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective therapy for primary generalized and focal dystonias, but therapeutic success is compromised by a nonresponder rate of up to 20%. Variability in electrode placement and in tissue stimulated inside the GPi may explain in part different outcomes among patients. Refinement of the target within the pallidal area could be helpful for surgery planning and clinical outcomes. The objective of this study was to discuss current and potential methodological (somatotopy, neuroimaging, and neurophysiology) aspects that might assist neurosurgical targeting of the GPi, aiming to treat generalized or focal dystonia. Methods We selected published studies by searching electronic databases and scanning the reference lists for articles that examined the anatomical and electrophysiologic aspects of the GPi in patients with idiopathic/inherited dystonia who underwent functional neurosurgical procedures. Results The sensorimotor sector of the GPi was the best target to treat dystonic symptoms, and was localized at its lateral posteroventral portion. The effective volume of tissue activated (VTA) to treat dystonia had a mean volume of 153mm (3) in the posterior GPi area. Initial tractography studies evaluated the close relation between the electrode localization and pallidothalamic tract to control dystonic symptoms. Regarding the somatotopy, the more ventral, lateral, and posterior areas of the GPi are associated with orofacial and cervical representation. In contrast, the more dorsal, medial, and anterior areas are associated with the lower limbs; between those areas, there is the representation of the upper limb. Excessive pallidal synchronization has a peak at the theta band of 3 to 8Hz, which might be responsible for generating dystonic symptoms. Conclusions Somatotopy assessment of posteroventral GPi contributes to target-specific GPi sectors related to segmental body symptoms. Tractography delineates GPi output pathways that might guide electrode implants, and electrophysiology might assist in pointing out areas of excessive theta synchronization. Finally, the identification of oscillatory electrophysiologic features that correlate with symptoms might enable closed-loop approaches in the future.
- 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.
- Effects of cerebellar transcranial magnetic stimulation on ataxias: A randomized trial(2020) FRANCA, Carina; ANDRADE, Daniel C. de; SILVA, Valquiria; GALHARDONI, Ricardo; BARBOSA, Egberto R.; TEIXEIRA, Manoel J.; CURY, Rubens G.Introduction: Cerebellar ataxia remains a neurological symptom orphan of treatment interventions, despite being prevalent and incapacitating. We aimed to study, in a double-blind design, whether cerebellar modulation could improve ataxia. Methods: We included patients with diagnosis of spinocerebellar ataxia type 3, multiple systems atrophy cerebellar type, or post-lesion ataxia. Patients received five sessions each of sham and active cerebellar 1 Hz deep repetitive transcranial magnetic stimulation in randomized order. Our primary outcome was the decrease in the Scale for the Assessment and Rating of Ataxia when comparing phases (active x sham). Secondary outcomes measures included the International Cooperative Ataxia Rating Scale, and other motor, cognitive, and quality of life scales. This study was registered at clinicaltrials.gov (protocol NCT03213106). Results: Twenty-four patients aged 29-74 years were included in our trial. After active stimulation, the Scale for the Assessment and Rating of Ataxia score was significantly lower than the score after sham stimulation [median (interquartile range) of 10.2 (6.2, 16.2) versus 12.8 (9.6, 17.8); p = 0.002]. The International Cooperative Ataxia Rating Scale score also improved after active stimulation versus sham [median (interquartile range) of 29.0 (21.0, 43.5) versus 32.8 (22.0, 47.0); p = 0.005]. Other secondary outcomes were not significantly modified by stimulation. No patient presented severe side effects, and nine presented mild and self-limited symptoms. Conclusions: Our protocol was safe and well-tolerated. These findings suggest that cerebellar modulation may improve ataxic symptom and provide reassurance about safety for clinical practice.
- Pregabalin for the Prevention of Oxaliplatin-Induced Painful Neuropathy: A Randomized, Double-Blind Trial(2017) ANDRADE, Daniel Ciampi De; TEIXEIRA, Manoel Jacobsen; GALHARDONI, Ricardo; FERREIRA, Karine S. L.; MILENO, Paula Braz; SCISCI, Nathalia; ZANDONAI, Alexandra; TEIXEIRA, William G. J.; SARAGIOTTO, Daniel F.; SILVA, Valquiria; RAICHER, Irina; CURY, Rubens Gisbert; MACARENCO, Ricardo; HEISE, Carlos Otto; BROTTO, Mario Wilson Iervolino; MELLO, Alberto Andrade De; MEGALE, Marcelo Zini; DOURADO, Luiz Henrique Curti; BAHIA, Luciana Mendes; RODRIGUES, Antonia Lilian; PARRAVANO, Daniella; FUKUSHIMA, Julia Tizue; LEFAUCHEUR, Jean-Pascal; BOUHASSIRA, Didier; SOBROZA, Evandro; RIECHELMANN, Rachel P.; HOFF, Paulo M.; SILVA, Fernanda Valerio Da; CHILE, Thais; DALE, Camila S.; NEBULONI, Daniela; SENNA, Luiz; BRENTANI, Helena; PAGANO, Rosana L.; SOUZA, Angela M. DeBackground. Patients with colorectal cancer (CRC) receiving oxaliplatin (OXA) develop acute and chronic painful oxaliplatin-induced peripheral neuropathy (OXAIPN). Acute and chronic OXA-related neuropathies have different pathophysiological bases, but both lead to a common phenomenon: central sensitization (CS) of nociceptive neuronal networks, leading to increased sensitivity (hyperlgesia, allodynia) in the somatosensory system, the common ground of chronic neuropathic pain. Because CS is related to increased risk of painful OXAIPN, we hypothesized that preemptive use of the anti-hyperalgesic drug pregabaline (known to decrease CS) during OXA infusions would decrease the incidence of chronic OXAIPN. Methods. Pain-free, chemotherapy-naive CRC patients receiving at least one cycle of modified-FLOX [5-FU(500 mg/m(2)) 1 leucovorin(20 mg/m(2))/week for] 6 weeks+oxaliplatin(85 mg/m2) at weeks 1-3-5 every 8 weeks] were randomized (1:1) into the study. Patients received either pregabalin or placebo for 3 days before and 3 days after each OXA infusion and were followed for up to 6 months. Clinical assessments were performed at baseline, at the end of chemotherapy, and after the follow-up period. The main outcome was average pain at the last visit assessed by the visual analogic scale (0-10) item of the Brief Pain Inventory (BPI). Secondary endpoints were presence of neuropathic pain according to the Douleur Neuropathique-4 (DN-4), pain dimensions (short-form McGill Pain Questionnaire [MPQ]), Neuropathic Pain Symptom Inventory (NPSI), and changes in nerve conduction studies (NCS) and side effect profile. Results. One hundred ninety-nine patients (57.0 +/- 10.7 years old, 98 female, 101 male) were randomized. Data from 56 patients were not included in the analyses (as they did not receive at least one full cycle of modified FLOX). Data from 78 patients in the pregabalin group and 65 patients in the placebo group were retained for analyses. At the last visit, pain intensity in the pregabalin group was 1.03 (95% confidence interval [CI] 50.79-1.26), and 0.85 (95% CI50.64-1.06) in the placebo group, which did not reach significance. Scores from the BPI, MPQ, DN-4, NPSI, and NCS and side-effect profiles and incidence of death did not differ between groups. Quality of life (QoL) score did not differ between groups (placebo = 576.9 +/- 23.1, pregabalin group 79.4 +/- 20.6). Mood scores were not significantly different between groups (placebo 9.7 [8.1-11.2]; pregabalin 6.8 [5.6-8.0]). Conclusion. The preemptive use of pregabalin during OXA infusions was safe, but did not decrease the incidence of chronic pain related to OXAIPN.
- The Parkinson disease pain classification system: results from an international mechanism-based classification approach(2021) MYLIUS, Veit; LLORET, Santiago Perez; CURY, Rubens G.; TEIXEIRA, Manoel J.; BARBOSA, Victor R.; BARBOSA, Egberto R.; I, Larissa Moreira; LISTIK, Clarice; FERNANDES, Ana M.; VEIGA, Diogo de Lacerda; BARBOUR, Julio; HOLLENSTEIN, Nathalie; OECHSNER, Matthias; WALCH, Julia; BRUGGER, Florian; HAGELE-LINK, Stefan; BEER, Serafin; RIZOS, Alexandra; CHAUDHURI, Kallol Ray; BOUHASSIRA, Didier; LEFAUCHEUR, Jean-Pascal; TIMMERMANN, Lars; GONZENBACH, Roman; KAGI, Georg; MOELLER, Jens Carsten; ANDRADE, Daniel Ciampi dePain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory and McGill pain questionnaire [MPQ], PDQ-8 quality of life score, MDS-UPDRS scores, and nonmotor symptoms). 159 nondemented PD patients (disease duration 10.2 +/- 7.6 years) and 37 healthy controls were recruited in 4 centers. PD-related pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain's Brief Pain Inventory and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression, and anxiety measures. Moderate intrarater and interrater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.
- Effect of Levodopa plus Carbidopa on the Laryngeal Electromyographic Pattern in Parkinson Disease(2017) NOFFS, Gustavo; DUPRAT, Andre de Campos; ZARZUR, Ana Paula; CURY, Rubens Gisbert; CATALDO, Berenice Oliveira; FONOFF, ErichBackground. Vocal impairment is one of the main debilitating symptoms of Parkinson disease (PD). The effect of levodopa on vocal function remains unclear. Objective. This study aimed to determine the effect of levodopa on electromyographic patterns of the laryngeal muscle in patients with PD. Study design. This is a prospective interventional trial. Methods. Nineteen patients with PD-diagnosed by laryngeal electromyography-were enrolled. Cricothyroid and thyroarytenoid (TA) muscle activities were measured at rest and during muscle contraction (phonation), when participants were on and off medication (12 hours after the last levodopa dose). Results. Prevalence of resting hypertonia in the cricothyroid muscle was similar in the off and on states (7 of 19, P = 1.00). Eight patients off medication and four patients on medication had hypertonic TA muscle at rest (P = 0.289). No electromyographic alterations were observed during phonation for either medication states. Conclusion. Despite a tendency for increased rest tracings in the TA muscle when participants were on medication, no association was found between laryngeal electromyography findings and levodopa + carbidopa administration.
- 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.
- Holmes Tremor Secondary to a Stabbing Lesion in the Midbrain(2017) CURY, Rubens Gisbert; BARBOSA, Egberto Reis; FREITAS, Christian; GODOY, Luis Filipe de Souza; PAIVA, Wellingson SilvaBackground: The development of Holmes tremor (HT) after a direct lesion of the midbraia has rarely been reported in the literature, although several etiologies have been linked with HT, such as stroke, brainstem tumors, multiple sclerosis, head trauma, or infections. Phenomenology Shown: A 31-year-old male, having been stabbed in the right eye, presented with a rest and action tremor in the left upper limb associated with left hemiparesis with corresponding post-contrast volumetric magnetic resonance imaging T1 with sagittal oblique reformation showing the knife trajectory reaching the right midbrain. Educational Value: Despite the rarity of the etiology of HT in the present case, clinicians working with persons with brain injurieshot should be aware of this type of situation.
- 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.