RICARDO GALHARDONI
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- Changes in motor cortical excitability in schizophrenia following transcranial direct current stimulation(2019) GORDON, Pedro Caldana; VALIENGO, Leandro da Costa Lane; PAULA, Vanessa Jesus Rodrigues de; GALHARDONI, Ricardo; ZIEMANN, Ulf; ANDRADE, Daniel Ciampi de; BRUNONI, Andre RussowskySchizophrenia is a disorder associated with cortical inhibition deficits. Transcranial direct current stimulation (tDCS) induces changes in cortical excitability in healthy subjects and individuals with neuropsychiatric disorders depending on the stimulation parameters. Our aim was to investigate whether a previously published tDCS protocol associated with symptomatic improvement in schizophrenia would induce changes in motor cortical excitability, assessed by transcranial magnetic stimulation paradigms, i.e., short-interval intracortical inhibition (SICI) and intra-cortical facilitation (ICF). We assessed cortical excitability measurements in 48 subjects with schizophrenia before and after a single session of active tDCS (20 min, 2 mA, anode over left dorsolateral prefrontal cortex, cathode over left temporoparietal cortex) or sham. Those who received active tDCS had a significant increase of SICI in the left motor cortex compared to those who received sham stimulation (Cohen's d = 0.54, p = .019). No changes were observed for ICF. In addition, lower SICI was associated with higher age (beta = -0.448, p < .01). Increase in intracortical inhibition may indicate a mechanism of action of tDCS in this population. Future studies should investigate whether this finding is a biomarker of treatment response for schizophrenia.
- Characterization of pain syndromes in patients with neuromyelitis optica(2020) VALERIO, Fernanda; APOSTOLOS-PEREIRA, Samira L.; SATO, Douglas Kazutoshi; CALLEGARO, Dagoberto; LUCATO, Leandro Tavares; BARBOZA, Victor Rosseto; SILVA, Valquiria A.; GALHARDONI, Ricardo; RODRIGUES, Antonia L. de Lima; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi deBackground Pain is common and refractory in spinal cord injury (SCI). Currently, most studies evaluated pain in male-predominant traumatic-SCI. Also, concomitant secondary pain syndromes and its temporal evolution were seldom reported. Methods We aimed to prospectively describe the main and secondary pain and its associated factors in inflammatory-SCI evaluating neuromyelitis optica (NMO) patients. In-remission NMO patients underwent neurological, imaging and autoantibody evaluations. Questionnaires detailing main and secondary pains, functional state, mood, catastrophizing, quality of life (QoL) and ""non-motor symptoms"" were used at two time points. Results Pain was present in 53 (73.6%) of the 72 patients included. At-level neuropathic pain was the most common main pain syndrome, affecting 32 subjects (60.4% of those with pain). Over 70% (n = 38) of this cohort reported two pain syndromes. Those without pain were significantly younger (26.1 +/- 12.7 y.o. in those without pain and 40.1 +/- 12.5, 37.2 +/- 11.4 y.o. in those whose main pain was neuropathic and non-neuropathic, respectively,p = .001), and no differences in the inflammatory status were observed between groups. On follow-up, one-fifth (n = 11) had a different main pain syndrome from the first visit. Pain impacted QoL as much as disability and motor strength. Conclusion Pain is a prevalent and disabling non-motor symptom in NMO-SCI. Most patients experience more than one pain syndrome which can change in time even in the absence of clinical relapse. Age of the inflammatory-SCI was a major determinant of pain. Acknowledging temporal changes and multiplicity of pain syndromes in NMO-SCI may give insights into more precise designs of clinical trials and general management of pain in SCI. Significance In this longitudinal study with NMO-related SCI, pain affected almost three-quarters of patients with NMO. Over 70% have more than one pain syndrome and at-level neuropathic pain is the most common type of pain syndrome. Patients without pain were significantly younger but had the same burden of inflammatory lesions than those with pain. During follow-up, up to one fifth of patients presented with changes in the main pain syndromes, which can occur even in the absence of clinical activity of the inflammatory disease. In this cohort, Pain affected quality of life as much as disability or motor strength.
conferenceObject Subthalamic deep brain stimulation modulates small fiber-dependent sensory threshold in Parkinson's disease(2015) CURY, R. G.; GALHARDONI, R.; FONOFF, E. T.; GHILARDI, M. G. dos Santos; MYCZKOWSKI, M.; MARCOLIN, M. A.; BARBOSA, E. R.; TEIXEIRA, M. J.; ANDRADE, D. Ciampi de- 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.
- Repetitive TMS does not improve cognition in patients with TBI(2019) NEVILLE, Iuri Santana; ZANINOTTO, Ana Luiza; HAYASHI, Cintya Yukie; RODRIGUES, Priscila Aparecida; GALHARDONI, Ricardo; ANDRADE, Daniel Ciampi de; BRUNONI, Andre Russowsky; AMORIM, Robson L. Oliveira; TEIXEIRA, Manoel Jacobsen; PAIVA, Wellingson SilvaObjective To determine whether high-frequency repetitive transcranial magnetic stimulation (rTMS) improves cognition in patients with severe traumatic brain injury. Methods A single-center, randomized, double-blind, placebo-controlled study of rTMS was conducted in patients aged 18-60 years with chronic (> 12 months postinjury) diffuse axonal injury (DAI). Patients were randomized to either a sham or real group in a 1:1 ratio. A 10-session rTMS protocol was used with 10-Hz stimulation over the left dorsolateral prefrontal cortex (DLPFC). Neuropsychological assessments were performed at 3 time points: at baseline, after the 10th rTMS session, and 90 days after intervention. The primary outcome was change in executive function evaluated using the Trail Making Test Part B. Results Thirty patients with chronic DAI met the study criteria. Between-group comparisons of performance on TMT Part B at baseline and after the 10th rTMS session did not differ between groups (p = 0.680 and p = 0.341, respectively). No significant differences were observed on other neuropsychological tests. No differences in adverse events between treatment groups were observed. Conclusions Cognitive function in individuals with chronic DAI is not improved by high-frequency rTMS over the left DLPFC, though it appears safe and well-tolerated in this population.
- 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.
bookPart Fisiopatologia da Dor Neuropática(2019) ANDRADE, Daniel Ciampi de; TEIXEIRA, Manoel Jacobsen; GALHARDONI, Ricardo; SIQUEIRA, Silvia Regina Dowgan Tesseroli de; SIQUEIRA, José Tadeu Tesseroli deconferenceObject A phase III, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of pregabalin in the prevention and reduction of oxaliplatin-induced painful neuropathy (PreOx)(2015) ANDRADE, Daniel Ciampi de; TEIXEIRA, Manoel Jacobsen; GALHARDONI, Ricardo; FERREIRA, Karine A. S. L.; MALIENO, Paula Braz; SCISCI, Nathalia; RIECHELMANN, Rachel Pimenta; TEIXEIRA, William G. J.; SARAGIOTTO, Daniel Fernandes; SILVA, Valquiria Aparecida; RAICHER, Irina; CASTRO, Isac de; PARRAVANO, Daniella; FUKUSHIMA, Julia Tizue; LEFAUCHEUR, Jean-Pascal; BOUHASSIRA, Didier; MACARENCO, Ricardo Silvestre e Silva; MELLO, Evandro Sobroza de; HOFF, Paulo Marcelo- Evidence for increased motor cortical facilitation and decreased inhibition in atypical depression(2016) VERONEZI, B. P.; MOFFA, A. H.; CARVALHO, A. F.; GALHARDONI, R.; SIMIS, M.; BENSENOR, I. M.; LOTUFO, P. A.; MACHADO-VIEIRA, R.; DASKALAKIS, Z. J.; BRUNONI, A. R.Objective: Major depressive disorder (MDD) is a clinically heterogeneous condition. However, the role of cortical glutamate and gamma-aminobutyric acid (GABA) receptor-mediated activity, implicated in MDD pathophysiology, has not been explored in different MDD subtypes. Our aim was to assess the atypical and melancholic depression subtypes regarding potential differences in GABA and glutamate receptor-mediated activity through established transcranial magnetic stimulation (TMS) neurophysiological measures from the motor cortex. Method: We evaluated 81 subjects free of antidepressant medication, including 21 healthy controls and 20 patients with atypical, 20 with melancholic, and 20 with undifferentiated MDD. Single and paired-pulse TMS paradigms were used to evaluate intracortical facilitation (ICF), cortical silent period (CSP), and short intracortical inhibition (SICI), which index glutamate, GABA(B) receptor-, and GABA(A) receptor-mediated activity respectively. Results: Patients with MDD demonstrated significantly decreased mean CSP values than healthy controls (Cohen's d = 0.22-0.3, P < 0.01 for all comparisons). Atypical depression presented a distinct cortical excitability pattern of decreased cortical inhibition and increased cortical facilitation, that is, an increased mean ICF and SICI ratios than other depression subtypes (d = 0.22-0.33, P < 0.01 for all comparisons). Conclusion: Different MDD subtypes may demonstrate different neurophysiology in relation to GABA(A) and glutamatergic activity. TMS as an investigational tool might be useful to distinguish between different MDD subtypes.
- Sifting the wheat from the chaff? Evidence for the existence of an asymmetric fibromyalgia phenotype(2020) KAZIYAMA, Helena H.; BARBOUR, Julio; GALHARDONI, Ricardo; SILVA, Valquiria Aparecida da; SIQUEIRA, Silvia R. D. Tesseroli de; LISTIK, Clarice; SANTOS, Gabriel Jose dos; YENG, Lin T.; MARCOLIN, Marco Antonio; RAICHER, Irina; TEIXEIRA, Manoel J.; ANDRADE, Daniel Ciampi deBackground The different phenotypic presentations of fibromyalgia (FM) have been infrequently studied and may have diagnostic and therapeutic implications. The aim of this study was to explore differences between FM patients with classical symmetric (s-FM) presentation and FM patients with marked asymmetric (a-FM) pain. Methods We performed two consecutive cross-sectional studies on FM patients and matched healthy volunteers (HV). FM patients were divided into a-FM (and s-FM groups according to their score of pain intensity on each body side; patients with a difference of >= 40 mm in VAS between left and right sides were classified as a-FM, otherwise classified as s-FM. Participants (FM = 32; HV = 31) were assessed for clinical, cortical excitability (CE), quantitative sensory testing (QST; study 1), and intraepidermal nerve fibre density (IENFD) determinations (study 2). Results While pain intensity did not significantly differ between s-FM and a-FM patients, pain interference in daily activities was significantly higher in the a-FM as compared to the s-FM group (54.7 +/- 8.9 and 37.6 +/- 13.5;p < .0001). PPT was significantly lower in the more painful side of a-FM as compared to the HV (27.7 +/- 7.9 and 49.9 +/- 13.0;p < .0001), while PPT in the less painful side of a-FM was significantly higher than PPT values in the s-FM (35.8 +/- 8.3 and 27.7 +/- 5.5;p = .031). S-FM and a-FM had significantly abnormal intracortical inhibition values on CE measurements compared to HV. There were no significant differences in IENFD between groups. Conclusions Within the current FM criteria, there exist different phenotypes with clinical, psychophysics, and neurophysiological findings that are not related to peripheral IENFD abnormalities. Significance Current fibromyalgia criteria may contain different phenotypes of fibromyalgia based on the lateralization of pain.