MARIA CONCEPCION GARCIA OTADUY
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Radiologia, Hospital das Clínicas, Faculdade de Medicina
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina
LIM/44 - Laboratório de Ressonância Magnética em Neurorradiologia, Hospital das Clínicas, Faculdade de Medicina
13 resultados
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- Contralateral ictal electrographic involvement is associated with decreased memory performance in unilateral mesial temporal sclerosis(2015) PASSARELLI, Valmir; CASTRO-LIMA FILHO, Humberto; ADDA, Carla C.; PRETURLON-SANTOS, Ana P.; VALERIO, Rosa M.; JORGE, Carmen L.; PUGLIA- JR., Paulo; LYRA, Katarina; OTADUY, Maria G.; WEN, Hung-Tzu; CASTRO, Luiz H.Purpose: To evaluate the effect of contralateral electrographic involvement on memory performance (measured by neuropsychological and Wada memory testing) in patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS). Methods: We studied 51 patients with medically-refractory epilepsy associated with unilateral MTS (27 women, 30/51, left MTS) submitted to prolonged non-invasive video-EEG monitoring and bilateral Wada testing. According to ictal electrographic involvement, patients were classified as: Contralateral ictal involvement, when one or more seizures evolved with rhythmic activity in the temporal region contralateral to the MTS or exclusive ipsilateral ictal involvement if all seizures showed ictal EEG activity exclusively on the MTS side. Wada testing involved a twelve-item memory paradigm. Wada memory asymmetry score was calculated for each patient subtracting the number of recalled items after injection on the lesion side from the number of recalled items after contralateral injection. Expected asymmetry (EA) was considered if Wade memory asymmetry > 0, and Symmetrical or Reversed memory asymmetry (S-RA) when <= 0. Neuropsychological testing was applied in the 51 patients and in 40 healthy controls. Verbal Memory was evaluated with the Rey Auditory Verbal Learning Test (RAVLT), considering the number of recalled items on immediate recall after the initial five consecutive encoding trials (RAVLT 6), a post-interference delayed (30 min) recall (RAVLT 7), and recall after 7 days. Nonverbal memory was tested with Wechsler Memory Scale-III (WMS-III) Faces subtests 1 e 2. Results: Groups did not differ in demographic, clinical and video-EEG monitoring variables. S-RA was observed more frequently in the group with contralateral ictal involvement (57.2% vs. 27.0%; p: 0.03). Logistic regression analysis considering demographic, clinical, hippocampal volume and video-EEG monitoring variables showed contralateral ictal involvement as the only independent variable associated with S-RA (coefficient = 1.32, p = 0.029, odds ratio 3.77; 95% CI 1.1-12.47). Additionally, the patient group with contralateral ictal EEG involvement displayed worse verbal and nonverbal memory scores compared to healthy controls. Conclusion: In this cohort of unilateral MTS patients, contralateral ictal involvement was associated with decreased memory performance on Wada and on neuropsychological testing.
- Analysis of the posterior cingulate cortex with [ 18 F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods(2015) COUTINHO, Artur M.N.; PORTO, Fábio H.G.; ZAMPIERI, Poliana F.; OTADUY, Maria C.; PERROCO, Tíbor R.; OLIVEIRA, Maira O.; NUNES, Rafael F.; PINHEIRO, Toulouse Leusin; BOTTINO, Cassio M.C.; LEITE, Claudia C.; BUCHPIGUEL, Carlos A.ABSTRACT Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. OBJECTIVE To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. METHODS Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. RESULTS The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. CONCLUSION rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls.
- Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study(2015) ZANETTI, Marcus V.; OTADUY, Maria C.; SOUSA, Rafael T. de; GATTAZ, Wagner F.; BUSATTO, Geraldo F.; LEITE, Claudia C.; MACHADO-VIEIRA, RodrigoBackground: The hippocampus has been highly implicated in the pathophysiology of bipolar disorder (BD). Nevertheless, no study has longitudinally evaluated hippocampal metabolite levels in bipolar depression under treatment with lithium. Methods: Nineteen medication-free BD patients (78.9% treatment-naive and 73.7% with BD type II) presenting an acute depressive episode and 17 healthy controls were studied. Patients were treated for 6 weeks with lithium in an open-label trial. N-acetyl aspartate (NAA), creatine, choline, myo-Inositol, and glutamate levels were assessed in the left hippocampus before (week 0) and after (week 6) lithium treatment using 3T proton magnetic resonance spectroscopy (1H-MRS). The metabolite concentrations were estimated using internal water as reference and voxel segmentation for partial volume correction. Results: At baseline, acutely depressed BD patients and healthy controls exhibited similar hippocampal metabolites concentrations, with no changes after 6 weeks of lithium monotherapy. A significant correlation between antidepressant efficacy and increases in NAA concentration over time was observed. Also, there was a significant positive correlation between the changes in glutamate concentrations over follow-up and plasma lithium levels at endpoint. Mixed effects model analysis revealed a bimodal effect of lithium plasma levels in hippocampal glutamate concentrations: levels of 0.2 to 0.49 mmol/L (n=9) were associated with a decrease in glutamate concentrations, whereas the subgroup of BD subjects with ""standard"" lithium levels (>= 0.50 mmol/L; n = 10) showed an overall increase in glutamate concentrations over time. Conclusions: These preliminary results suggest that lithium has a bimodal action in hippocampal glutamate concentration depending on the plasma levels.
conferenceObject Myo-Inositol Reduction in Medial Prefrontal Cortex of Obsessive Compulsive Disorder: A Proton Magnetic Resonance Spectroscopy Study(2015) BATISTUZZO, Marcelo; HOEXTER, Marcelo; COSTA, Fabiana; SHAVITT, Roseli; LOPES, Antonio; CAPPI, Carolina; MATHIS, Alice De; NATASHA, Senc O.; HENNING, Anke; PASTORELLO, Bruno; LEITE, Claudia; MIGUEL, Euripedes; OTADUY, Maria- Gray matter volumes in patients with bipolar disorder and their first-degree relatives(2015) NERY, Fabiano G.; GIGANTE, Alexandre Duarte; AMARAL, Jose A.; FERNANDES, Francy B. F.; BERUTTI, Mariangeles; ALMEIDA, Karla M.; CARNEIROC, Camila de Godoi; DURAN, Fabio Luis Souza; OTADUY, Maria G.; LEITE, Claudia Costa; BUSATTO, Geraldo; LAFER, BenyBipolar disorder (BD) is highly heritable. First-degree relatives of BD patient have an increased risk to develop the disease. We investigated abnormalities in gray matter (GM) volumes in healthy first-degree relatives of BD patients to identify possible brain structural endophenotypes for the disorder. 3D T1-weighted magnetic resonance images were obtained from 25 DSM-IV BD type I patients, 23 unaffected relatives, and 27 healthy controls (HC). A voxel-based morphometry protocol was used to compare differences in GM volumes between groups. BD patients presented reduced GM volumes bilaterally in the thalamus compared with HC. Relatives presented no global or regional GM differences compared with HC. Our negative results do not support the role of GM volume abnormalities as endophenotypes for BD. Thalamic volume abnormalities may be associated the pathophysiology of the disease.
- Does MRS Lactate Peak Correlate with Lactate in the CSF and Blood?(2015) SHIBAO, Simone; OTADUY, Maria C. G.; KOK, Fernando; LEITE, Claudia C.Purpose Cerebrospinal fluid (CSF) or brain parenchyma lactate detection is important for the diagnosis of some diseases with aerobic cellular metabolism compromise. Our purpose is to correlate intraventricular magnetic resonance spectroscopy (MRS) lactate detection and quantification to CSF and blood lactate concentration. Methods Twenty-one patients (13 females; mean age 5 years) suspected of having mitochondrial disorders underwent proton MRS with point-resolved spectroscopy (TE = 144 ms). The volume of interest was positioned in the lateral ventricles, and LCModel was used for the MRS lactate peak detection and quantification. CSF and venous blood samples were obtained for lactate quantification immediately after MRS. Comparisons between MRS, CSF, and blood lactate detection and quantification were performed. p < 0.05 was considered significant. Results In our series, CSF lactate levels were high in 11 patients (52%) and blood serum lactate levels were high in 3 patients (14%). MRS was able to detect a lactate peak in all patients. A positive correlation between MRS lactate quantification and CSF lactate was observed (Pearson correlation coefficient = 0.750; p < 0.0001). Blood lactate did not correlate with lactate levels in the lateral ventricle measured by MRS or direct determinations of CSF lactate concentration. When noting the lactate quantification obtained by MRS, only 8 patients (as opposed to 14) presented higher values than the established normality threshold of 1.7 mmol/L. Considering CSF puncture concentration as the gold standard, we obtained 64% of sensitivity and 90% of specificity for MRS quantification. Conclusion If MRS shows increased lactate levels in the ventricles, CSF puncture is not needed for lactate increase confirmation.
- A Longitudinal (6-week) 3T H-1-MRS Study on the Effects of Lithium Treatment on Anterior Cingulate Cortex Metabolites in Bipolar Depression(2015) MACHADO-VIEIRA, Rodrigo; GATTAZ, Wagner F.; ZANETTI, Marcus V.; SOUSA, Rafael T. De; CARVALHO, Andre F.; SOEIRO-DE-SOUZA, Marcio G.; LEITE, Claudia C.; OTADUY, Maria C.The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no Longitudinal study has specifically evaluated lithium's effects on ACC metabolites using H-1-MRS, as well as its association with clinical improvement in bipolar depression. This H-1-MRS (TE=35 ms) study evaluated 24 drug-free BD patients during depressive episodes and after lithium treatment at therapeutic levels. Brain metabolite levels (N-acetyl aspartate (NM), creatine (tCr), choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline (week 0) and after lithium monotherapy (week 6). The present investigation showed that ACC glutamate (Glu/tCr) and glutamate +glutamine (Glx/tCr) significantly increased after six weeks of lithium therapy. Regarding the association with clinical improvement, remitters showed an increase in myoinositol levels (ml/tCr) after lithium treatment compared to non-remitters. The present findings reinforce a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets for lithium's therapeutic effects in BD.
- Anterior cingulate Glutamate-Glutamine cycle metabolites are altered in euthymic bipolar I disorder(2015) SOEIRO-DE-SOUZA, Marcio Gerhardt; HENNING, Anke; MACHADO-VIEIRA, Rodrigo; MORENO, Ricardo A.; PASTORELLO, Bruno F.; LEITE, Claudia da Costa; VALLADA, Homero; OTADUY, Maria Concepcion GarciaBipolar disorder (BD) has been consistently associated with abnormalities in the Glutamate/GABA-Glutamine cycle. Magnetic resonance spectroscopy (MRS) studies have reported increased brain Glutamate (Glu) and Glx (Glu+Glutamine) in subjects with BD. However, data on separate measures of GABA and Glutamine (Gln) in BD are sparse due to overlapping resonant signals. The development of new sequence methods in the quantification of these metabolites has allowed a better understanding of the Glu/GABA-Gln cycle but data on this field of research remains sparse in BD. Eighty-eight subjects (50 euthymic BD and 38 HC) underwent 3T proton magnetic resonance spectroscopy (1H MRS) in the anterior cingulate cortex (ACC; 2 x 2 x4.5 cm(3)) using a two-dimensional JPRESS sequence. GABA, Glutamine (Gln) and Glutamate (Glu) were quantified with the Pro Fit program. Using image segmentation and known creatine (Cre) concentrations for white and grey matter, metabolite concentrations were calculated for the excited MRS voxel. GABA levels did not differ between groups. Gin level was higher in euthymic BD patients than in healthy controls. The Glu level and Glu/Gln ratio were lower in BD patients than in controls. The use of anticonvulsants was associated with Gln increase but did not affect Glu or Glu/Gln. Neither lithium nor antipsychotic use influenced metabolite levels. The ACC MRS findings indicate that the glutamatergic function in euthymic medicated BD patients is altered relative to controls. Whether this feature is a metabolic signature of euthymic BD subjects should be the focus of future studies.
- DTI-based tractography of the arcuate fasciculus in patients with polymicrogyria and language disorders(2015) ANDRADE, Celi S.; FIGUEIREDO, Kenya G.; VALERIANO, Cassia; MENDOZA, Melanie; VALENTE, Kette D. R.; OTADUY, Maria C. G.; LEITE, Claudia C.Objectives: To assess the integrity of the arcuate fasciculus (AF) with diffusion tensor imaging (DTI) and tractography in patients with congenital polymicrogyria (PMG) and language disorders. Methods: Twelve patients with PMG and 12 matched controls were prospectively evaluated with DTI (32 gradient encoding directions, b-value = 1000 s/mm(2)) at 3.0 T. The AF was virtually dissected with a deterministic streamline approach. DTI metrics included FA (fractional anisotropy), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). A subset of patients (n = 4) was evaluated to assess cognitive performance and language skills. Results: Qualitative evaluation revealed several abnormalities in tracts size and architecture in nearly all PMG patients. Remarkably, in 3 patients with bilateral PMG, the AF was not delineated on both hemispheres. In comparison to controls, patients exhibited significant decrease of FA (p = 0.003) in addition to increase of RD (p = 0.03) in the right AF, whereas there was significant increase of MD in the left AF (p = 0.04). All 4 patients with language evaluation had suboptimal performance on lexical fluency and prosodic linguistic. Conclusions: DTI and tractography suggest that the AF is severely disrupted in patients with PMG, providing an anatomical in vivo substrate for the language disorders commonly associated with these cortical malformations.
conferenceObject GAD1 Polymorphisms are Associated with Glutamatergic Activity in the Anterior Cingulate in Bipolar I Disorder(2015) SOEIRO-DE-SOUZA, Marcio G.; OTADUY, Maria; VALLADA, Homero