RAQUEL CHACON RUIZ MARTINEZ
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Long-Term Follow-Up on Bilateral Posterior Hypothalamic Deep Brain Stimulation for Treating Refractory Aggressive Behavior in a Patient with Cri du Chat Syndrome: Analysis of Clinical Data, Intraoperative Microdialysis, and Imaging Connectomics(2023) RIOS, Adriana Lucia Lopez; GERMANN, Jurgen; HUTCHISON, William D.; POSADA, Luis Fernando Botero; VELASQUEZ, Luisa Fernanda Ahunca; JIMENEZ, Francisco Aureliano Garcia; ESCOBAR, Jose Miguel Gloria; MARTINEZ, Raquel Chacon Ruiz; HAMANI, Clement; LEBRUN, Ivo; AUADA, Aline V. V.; BRAVO, Carlos Anibal Restrepo; GOUVEIA, Flavia VenetucciPosterior hypothalamic-deep brain stimulation (pHyp-DBS) has been reported as a successful treatment for reducing refractory aggressive behaviors in patients with distinct primary diagnoses. Here, we report on a patient with cri du chat syndrome presenting severe self-injury and aggressive behaviors toward others, who was treated with pHyp-DBS. Positive results were observed at long-term follow-up in aggressive behavior and quality of life. Intraoperative microdialysis and imaging connectomics analysis were performed to investigate possible mechanisms of action. Our results suggest the involvement of limbic and motor areas and alterations in main neurotransmitter levels in the targeted area that are associated with positive results following treatment.
- 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.
- Habenula activation patterns in a preclinical model of neuropathic pain accompanied by depressive-like behaviour(2022) ANTUNES, Geiza Fernanda; CAMPOS, Ana Carolina Pinheiro; ASSIS, Danielle Varin de; GOUVEIA, Flavia Venetucci; SENO, Midia Dias de Jesus; PAGANO, Rosana Lima; MARTINEZ, Raquel Chacon RuizPain and depression are complex disorders that frequently co-occur, resulting in diminished quality of life. The habenula is an epithalamic structure considered to play a pivotal role in the neurocircuitry of both pain and depression. The habenula can be divided into two major areas, the lateral and medial habenula, that can be further subdivided, resulting in 6 main subregions. Here, we investigated habenula activation patterns in a rat model of neuropathic pain with accompanying depressive-like behaviour. Wistar rats received active surgery for the development of neuropathic pain (chronic constriction injury of the sciatic nerve; CCI), sham surgery (surgical control), or no surgery (behavioural control). All animals were evaluated for mechanical nociceptive threshold using the paw pressure test and depressive-like behaviour using the forced swimming test, followed by evaluation of the immunoreactivity to cFos-a marker of neuronal activity-in the habenula and subregions. The Open Field Test was used to evaluate locomotor activity. Animals with peripheral neuropathy (CCI) showed decreased mechanical nociceptive threshold and increased depressive-like behaviour compared to control groups. The CCI group presented decreased cFos immunoreactivity in the total habenula, total lateral habenula and lateral habenula subregions, compared to controls. No difference was found in cFos immunoreactivity in the total medial habenula, however when evaluating the subregions of the medial habenula, we observed distinct activation patterns, with increase cFos immunoreactivity in the superior subregion and decrease in the central subregion. Taken together, our data suggest an involvement of the habenula in neuropathic pain and accompanying depressive-like behaviour.
- One year follow-up on a randomized study investigating serratus anterior muscle and pectoral nerves type I block to reduced neuropathic pain descriptors after mastectomy(2023) FLORES, Eva M. M.; GOUVEIA, Flavia V. V.; MATSUMOTO, Marcio; BONACIF, Tomas H. F. S.; KUROKI, Mayra A. A.; ANTUNES, Geiza Fernanda; CAMPOS, Ana Carolina P.; KIMACHI, Pedro P. P.; CAMPOS, Diego O. O.; SIMOES, Claudia M. M.; SAMPAIO, Marcelo M. C.; ANDRADE, Felipe E. M.; VALVERDE, Joao; BARROS, Alfredo C. S. D.; PAGANO, Rosana L. L.; MARTINEZ, Raquel C. R.Breast cancer is the second most common diagnosed type of cancer in women. Chronic neuropathic pain after mastectomy occurs frequently and is a serious health problem. In our previous single-center, prospective, randomized controlled clinical study, we demonstrated that the combination of serratus anterior plane block (SAM) and pectoral nerve block type I (PECS I) with general anesthesia reduced acute postoperative pain. The present report describes a prospective follow-up study of this published study to investigate the development of chronic neuropathic pain 12 months after mastectomy by comparing the use of general anesthesia alone and general anesthesia with SAM + PECS I. Additionally, the use of analgesic medication, quality of life, depressive symptoms, and possible correlations between plasma levels of interleukin (IL)-1 beta, IL-6, and IL-10 collected before and 24 h after surgery as predictors of pain and depression were evaluated. The results showed that the use of SAM + PECS I with general anesthesia reduced numbness, hypoesthesia to touch, the incidence of patients with chronic pain in other body regions and depressive symptoms, however, did not significantly reduce the incidence of chronic neuropathic pain after mastectomy. Additionally, there was no difference in the consumption of analgesic medication and quality of life. Furthermore, no correlation was observed between IL-1 beta, IL-6, and IL-10 levels and pain and depression. The combination of general anesthesia with SAM + PECS I reduced the occurrence of specific neuropathic pain descriptors and depressive symptoms. These results could promote the use of SAM + PECS I blocks for the prevention of specific neuropathic pain symptoms after mastectomy.
- Multi-centre analysis of networks and genes modulated by hypothalamic stimulation in patients with aggressive behaviours(2023) GOUVEIA, Flavia Venetucci; GERMANN, Jurgen; ELIAS, Gavin J. B.; BOUTET, Alexandre; LOH, Aaron; RIOS, Adriana Lucia Lopez; DIAZ, Cristina Torres; LOPEZ, William Omar Contreras; MARTINEZ, Raquel Chacon Ruiz; FONOFF, Erich Talamoni; BENEDETTI-ISAAC, Juan Carlos; GIACOBBE, Peter; PAVA, Pablo M. Arango; YAN, Han; IBRAHIM, George M.; LIPSMAN, Nir; LOZANO, Andres; HAMANI, ClementDeep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fiber tracts and functionally connected with brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas - together with patient age - were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network.
- Reduction of aggressive behaviour following hypothalamic deep brain stimulation: Involvement of 5-HT1A and testosterone(2023) GOUVEIA, Flavia Venetucci; DIWAN, Mustansir; MARTINEZ, Raquel C. R.; GIACOBBE, Peter; LIPSMAN, Nir; HAMANI, ClementBackground: Aggressive behaviour (AB) may occur in patients with different neuropsychiatric disorders. Although most patients respond to conventional treatments, a small percentage continue to experience AB despite optimized pharmacological management and are considered to be treatment-refractory. For these pa-tients, hypothalamic deep brain stimulation (pHyp-DBS) has been investigated. The hypothalamus is a key structure in the neurocircuitry of AB. An imbalance between serotonin (5-HT) and steroid hormones seems to exacerbate AB.Objectives: To test whether pHyp-DBS reduces aggressive behaviour in mice through mechanisms involving testosterone and 5-HT.Methods: Male mice were housed with females for two weeks. These resident animals become territorial and aggressive towards intruder mice placed in their cages. Residents had electrodes implanted in the pHyp. DBS was administered for 5 h/day for 8 consecutive encounters prior to the interaction with the intruder. After testing, blood and brains were recovered for measuring testosterone and 5-HT receptor density, respectively. In a second experiment, residents received WAY-100635 (5-HT1A antagonist) or saline injections prior to pHyp-DBS. After the first 4 encounters, the injection allocation was crossed, and animals received the alternative treatment during the next 4 encounters.Results: DBS-treated mice showed reduced AB that was correlated with testosterone levels and an increase in 5-HT1A receptor density in the orbitofrontal cortex and amygdala. Pre-treatment with WAY-100635 blocked the anti-aggressive effect of pHyp-DBS.Conclusions: This study shows that pHyp-DBS reduces AB in mice via changes in testosterone and 5-HT1A mechanisms.
- Unilateral Campotomy of Forel for Acquired Hemidystonia: An Open-Label Clinical Trial(2022) AZEVEDO, Angelo Rafael Cunha de; LOPEZ, William Omar Contreras; NAVARRO, Paula Alejandra; GOUVEIA, Flavia Venetucci; GERMANN, Juergen; ELIAS, Gavin J. B.; MARTINEZ, Raquel Chacon Ruiz; ALHO, Eduardo Joaquim Lopes; FONOFF, Erich TalamoniBACKGROUND: Hemidystonia (HD) is characterized by unilateral involuntary torsion movements and fixed postures of the limbs and face. It often develops after deleterious neuroplastic changes secondary to injuries to the brain. This condition usually responds poorly to medical treatment, and deep brain stimulation often yields unsatisfactory results. We propose this study based on encouraging results from case reports of patients with HD treated by ablative procedures in the subthalamic region.OBJECTIVE: To compare the efficacy of stereotactic-guided radiofrequency lesioning of the subthalamic area vs available medical treatment in patients suffering from acquired HD.METHODS: This is an open-label study in patients with secondary HD allocated according to their treatment choice, either surgical or medical treatment; both groups were followed for one year. Patients assigned in the surgical group underwent unilateral campotomy of Forel. The efficacy was assessed using the Unified Dystonia Rating Scale, Fahn-Marsden Dystonia Scale, Arm Dystonia Disability Scale, and SF-36 questionnaire scores.RESULTS: Patients in the surgical group experienced significant improvement in the Unified Dystonia Rating Scale, Fahn-Marsden Dystonia Scale, and Arm Dystonia Disability Scale (39%, 35%, and 15%, respectively) 1 year after the surgery, with positive reflex in quality-of-life measures, such as bodily pain and role-emotional process. Patients kept on medical treatment did not experience significant changes during the follow-up. No infections were recorded, and no neurological adverse events were associated with either intervention.CONCLUSION: The unilateral stereotaxy-guided ablation of Forel H1 and H2 fields significantly improved in patients with HD compared with optimized clinical treatment.
- Unravelling the Role of Habenula Subnuclei on Avoidance Response: Focus on Activation and Neuroinflammation(2023) ANTUNES, Geiza Fernanda; CAMPOS, Ana Carolina Pinheiro; MARTINS, Daniel de Oliveira; GOUVEIA, Flavia Venetucci; RANGEL JUNIOR, Miguel Jose; PAGANO, Rosana Lima; MARTINEZ, Raquel Chacon RuizUnderstanding the mechanisms responsible for anxiety disorders is a major challenge. Avoidance behavior is an essential feature of anxiety disorders. The two-way avoidance test is a preclinical model with two distinct subpopulations-the good and poor performers-based on the number of avoidance responses presented during testing. It is believed that the habenula subnuclei could be important for the elaboration of avoidance response with a distinct pattern of activation and neuroinflammation. The present study aimed to shed light on the habenula subnuclei signature in avoidance behavior, evaluating the pattern of neuronal activation using FOS expression and astrocyte density using GFAP immunoreactivity, and comparing control, good and poor performers. Our results showed that good performers had a decrease in FOS immunoreactivity (IR) in the superior part of the medial division of habenula (MHbS) and an increase in the marginal part of the lateral subdivision of lateral habenula (LHbLMg). Poor performers showed an increase in FOS in the basal part of the lateral subdivision of lateral habenula (LHbLB). Considering the astroglial immunoreactivity, the poor performers showed an increase in GFAP-IR in the inferior portion of the medial complex (MHbl), while the good performers showed a decrease in the oval part of the lateral part of the lateral complex (LHbLO) in comparison with the other groups. Taken together, our data suggest that specific subdivisions of the MHb and LHb have different activation patterns and astroglial immunoreactivity in good and poor performers. This study could contribute to understanding the neurobiological mechanisms responsible for anxiety disorders.