ANA LUIZA COSTA ZANINOTTO
Projetos de Pesquisa
Unidades Organizacionais
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
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- Longitudinal assessment of magnetization transfer ratio, brain volume, and cognitive functions in diffuse axonal injury(2022) MACRUZ, Fabiola Bezerra de Carvalho; FELTRIN, Fabricio Stewan; ZANINOTTO, Ana; GUIRADO, Vinicius Monteiro de Paula; OTADUY, Maria Concepcion Garcia; TSUNEMI, Miriam Harumi; NUCCI, Mariana Penteado; RIMKUS, Carolina; ANDRADE, Celi Santos; LEITE, Claudia da CostaBackground Diffuse axonal injury (DAI) is a frequent mechanism of traumatic brain injury (TBI) that triggers a sequence of parenchymal changes that progresses from focal axonal shear injuries up to inflammatory response and delayed axonal disconnection. Objective The main purpose of this study is to evaluate changes in the axonal/myelinic content and the brain volume up to 12 months after TBI and to correlate these changes with neuropsychological results. Methods Patients with DAI (n = 25) were scanned at three time points after trauma (2, 6, and 12 months), and the total brain volume (TBV), gray matter volume, and white matter volume (WMV) were calculated in each time point. The magnetization transfer ratio (MTR) for the total brain (TB MTR), gray matter (GM MTR), and white matter (WM MTR) was also quantified. In addition, Hopkins verbal learning test (HVLT), Trail Making Test (TMT), and Rey-Osterrieth Complex Figure test were performed at 6 and 12 months after the trauma. Results There was a significant reduction in the mean TBV, WMV, TB MTR, GM MTR, and WM MTR between time points 1 and 3 (p < .05). There was also a significant difference in HVLT-immediate, TMT-A, and TMT-B scores between time points 2 and 3. The MTR decline correlated more with the cognitive dysfunction than the volume reduction. Conclusion A progressive axonal/myelinic rarefaction and volume loss were characterized, especially in the white matter (WM) up to 1 year after the trauma. Despite that, specific neuropsychological tests revealed that patients' episodic verbal memory, attention, and executive function improved during the study. The current findings may be valuable in developing long-term TBI rehabilitation management programs.
- Transcranial Direct Current Stimulation for Post-Concussion Syndrome: Study Protocol for a Randomized Crossover Trial(2017) AMORIM, Robson Luis Oliveira de; BRUNONI, Andre Russowsky; OLIVEIRA, Mirian Akiko Furutani de; ZANINOTTO, Ana Luiza Costa; NAGUMO, Marcia Mitie; GUIRADO, Vinicius Monteiro de Paula; NEVILLE, Iuri Santana; BENUTE, Glaucia Rosana Guerra; LUCIA, Mara Cristina Souza de; PAIVA, Wellingson Silva; ANDRADE, Almir Ferreira de; TEIXEIRA, Manoel JacobsenBackground: Mild traumatic brain injury (MTBI) represents 70-80% of all treated brain injuries. A considerable proportion of MTBI patients experience post-concussion symptoms for a prolonged period after MTBI, and these symptoms are diagnosed as persistent post-concussion syndrome (PPCS). PPCS is defined as a range of physical, cognitive, and emotional symptoms. However, memory and executive dysfunction seems to be one of the most debilitating symptoms. Recently, non-invasive brain stimulation has been studied as a potential treatment method for traumatic brain injury (TBI) patients. Therefore, our primary goal is to verify the effects of transcranial direct current stimulation (tDCS) in patients with PPCS who demonstrate cognitive deficits in long-term episodic memory, working memory, and executive function following MTBI. Methods/design: This is a randomized crossover trial of patients with a history of MTBI with cognitive deficits in memory and executive function. Thirty adult patients will be randomized in a crossover manner to receive three weekly sessions of anodal tDCS (2mA) at left dorsolateral prefrontal cortex, left temporal cortex, and sham stimulation that will be performed at 7-day intervals (washout period). The clinical diagnosis of PPCS will be determined using the Rivermead Post-Concussion Symptoms Questionnaire. Patients who meet the inclusion criteria will be assessed with a neuropsychological evaluation. A new battery of computerized neuropsychological tests will be performed before and immediately after each stimulation. Statistical analysis will be performed to determine trends of cognitive improvement. Discussion: There is paucity of studies regarding the use of tDCS in TBI patients, and although recent results showed controversial data regarding the effects of tDCS in such patients, we will address specifically patients with PPCS and MTBI and no brain abnormalities on CT scan other than subarachnoid hemorrhage. Moreover, due to the missing information on literature regarding the best brain region to be studied, we will evaluate two different regions to find immediate effects of tDCS on memory and executive dysfunction.
- Effects of transcranial LED therapy on the cognitive rehabilitation for diffuse axonal injury due to severe acute traumatic brain injury: study protocol for a randomized controlled trial(2018) SANTOS, Joao Gustavo Rocha Peixoto dos; ZANINOTTO, Ana Luiza Costa; ZANGARO, Renato Amaro; CARNEIRO, Ana Maria Costa; NEVILLE, Iuri Santana; ANDRADE, Almir Ferreira de; TEIXEIRA, Manoel Jacobsen; PAIVA, Wellingson SilvaBackground: Photobiomodulation describes the use of red or near-infrared light to stimulate or regenerate tissue. It was discovered that near-infrared wavelengths (800-900 nm) and red (600 nm) light-emitting diodes (LED) are able to penetrate through the scalp and skull and have the potential to improve the subnormal cellular activity of compromised brain tissue. Different experimental and clinical studies were performed to test LED therapy for traumatic brain injury (TBI) with promising results. One of the proposals of this present study is to develop different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients. Methods/design: This is a double-blinded, randomized, controlled trial of patients with diffuse axonal injury (DAI) due to a severe TBI in an acute stage (less than 8 h). Thirty two patients will be randomized to active coil helmet and inactive coil (sham) groups in a 1:1 ratio. The protocol includes 18 sessions of transcranial LED stimulation (627 nm, 70 mW/cm(2), 10 J/cm(2)) at four points of the frontal and parietal regions for 30 s each, totaling 120 s, three times per week for 6 weeks, lasting 30 min. Patients will be evaluated with the Glasgow Outcome Scale Extended (GOSE) before stimulation and 1, 3, and 6 months after the first stimulation. The study hypotheses are as follows: (1) transcranial LED therapy (TCLT) will improve the cognitive function of DAI patients and (2) TCLT will promote beneficial hemodynamic changes in cerebral circulation. Discussion: This study evaluates early and delayed effects of TCLT on the cognitive rehabilitation for DAI following severe acute TBI. There is a paucity of studies regarding the use of this therapy for cognitive improvement in TBI. There are some experimental studies and case series presenting interesting results for TBI cognitive improvement but no clinical trials.
- Cognitive Assessment in Patients with Traumatic Brain Injury(2020) ZANINOTTO, Ana Luiza; GUIRADO, Vinicius Monteiro de Paula; LUCIA, Mara Cristina Souza De; ANDRADE, Almir Ferreira de; TEIXEIRA, Manoel Jacobsen; PAIVA, Wellingson SilvaTraumatic brain injury (TBI) is a major public health problem in Western countries. ATBI brings many negative consequences, including behavioral and cognitive changes, which affect social adjustment and the performance of functional activities. Cognitive evaluation after TBI is a complex issue in what pertains to definition of the most appropriate questionnaires for clinical use in a comprehensive analysis of the condition of the patient. In this paper, we described a critical review of the main cognitive assessment tests currently used in clinical and research settings in patients with TBI.
- Repetitive Transcranial Magnetic Stimulation (rTMS) for the cognitive rehabilitation of traumatic brain injury (TBI) victims: study protocol for a randomized controlled trial(2015) NEVILLE, Iuri Santana; HAYASHI, Cintya Yukie; HAJJ, Simone Alves El; ZANINOTTO, Ana Luiza Costa; SABINO, Juliana Perez; SOUSA JR., Leonardo Moura; NAGUMO, Marcia Mitie; BRUNONI, Andre Russowsky; SHIEH, Barbara Dal Forno Silva; AMORIM, Robson Luis Oliveira; TEIXEIRA, Manoel Jacobsen; PAIVA, Wellingson SilvaBackground: Repetitive Transcranial Magnetic Stimulation (rTMS) has been proposed as a new tool in neurological rehabilitation of victims of traumatic brain injury (TBI). However, its usefulness to treat this condition has never been tested rigorously. The primary goal is to conduct a study protocol to determine whether rTMS used to cognitive rehabilitation of victims of TBI with diffuse axonal injury (DAI) is a safe instrument and if it enhances cognitive function recovery. Methods: Double-blind randomized controlled trial of patients with diffuse axonal injury. Thirty-six patients will be randomized to either an active coil group or sham group in a 1: 1 ratio. rTMS protocol: 10 sessions of high-frequency rTMS (10 Hz) over the left dorsolateral prefrontal cortex (DLPFC). Cortical Excitability measures will be obtained. Neuropsychological evaluations will be performed 1 week before, 1 week and 3 months after rTMS. There are 2 study hypotheses: (1) rTMS over the left DLPFC in patients with DAI will improve cognitive function and (2) whether rTMS is safe in TBI patients. Discussion: This study evaluates the immediate and delayed effects of rTMS over the DLPFC on the cognitive domain of patients with DAI following TBI. rTMS has shown good results in treating major depression and may be promising for patients with TBI. As such, the results of this study can greatly modify the cognitive rehabilitation strategies.
- DTI-derived parameters differ between moderate and severe traumatic brain injury and its association with psychiatric scores(2022) ZANINOTTO, Ana Luiza; GRASSI, Daphine Centola; DUARTE, Dante; RODRIGUES, Priscila Aparecida; CARDOSO, Ellison; FELTRIN, Fabricio Stewan; GUIRADO, Vinicius Monteiro de Paula; MACRUZ, Fabiola Bezerra de Carvalho; OTADUY, Maria Concepcion Garcia; LEITE, Claudia da Costa; PAIVA, Wellingson Silva; ANDRADE, Celi SantosBackground and aim Diffusion tensor imaging (DTI) parameters in the corpus callosum have been suggested to be a biomarker for prognostic outcomes in individuals with diffuse axonal injury (DAI). However, differences between the DTI parameters on moderate and severe trauma in DAI over time are still unclear. A secondary goal was to study the association between the changes in the DTI parameters, anxiety, and depressive scores in DAI over time. Methods Twenty subjects were recruited from a neurological outpatient clinic and evaluated at 2, 6, and 12 months after the brain injury and compared to matched age and sex healthy controls regarding the DTI parameters in the corpus callosum. State-Trace Anxiety Inventory and Beck Depression Inventory were used to assess psychiatric outcomes in the TBI group over time. Results Differences were observed in the fractional anisotropy and mean diffusivity of the genu, body, and splenium of the corpus callosum between DAI and controls (p < 0.02). Differences in both parameters in the genu of the corpus callosum were also detected between patients with moderate and severe DAI (p < 0.05). There was an increase in the mean diffusivity values and the fractional anisotropy decrease in the DAI group over time (p < 0.02). There was no significant correlation between changes in the fractional anisotropy and mean diffusivity across the study and psychiatric outcomes in DAI. Conclusion DTI parameters, specifically the mean diffusivity in the corpus callosum, may provide reliable characterization and quantification of differences determined by the brain injury severity. No correlation was observed with DAI parameters and the psychiatric outcome scores.
- The Effects of Repetitive Transcranial Magnetic Stimulation on Anxiety in Patients With Moderate to Severe Traumatic Brain Injury: A Post-hoc Analysis of a Randomized Clinical Trial(2020) RODRIGUES, Priscila Aparecida; ZANINOTTO, Ana Luiza; VENTRESCA, Hayden M.; NEVILLE, Iuri Santana; HAYASHI, Cintya Yukie; BRUNONI, Andre R.; GUIRADO, Vinicius Monteiro de Paula; TEIXEIRA, Manoel Jacobsen; PAIVA, Wellingson SilvaBackground: Traumatic brain injury (TBI) is one of the leading causes of neuropsychiatric disorders in young adults. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to improve psychiatric symptoms in other neurologic disorders, such as focal epilepsy, Parkinson's disease, and fibromyalgia. However, the efficacy of rTMS as a treatment for anxiety in persons with TBI has never been investigated. This exploratory post-hoc analyzes the effects of rTMS on anxiety, depression and executive function in participants with moderate to severe chronic TBI. Methods: Thirty-six participants with moderate to severe TBI and anxiety symptoms were randomly assigned to an active or sham rTMS condition in a 1:1 ratio. A 10-session protocol was used with 10-Hz rTMS stimulation over the left dorsolateral prefrontal cortex (DLPFC) for 20 min each session, a total of 2,000 pulses were applied at each daily session (40 stimuli/train, 50 trains). Anxiety symptoms; depression and executive function were analyzed at baseline, after the last rTMS session, and 90 days post intervention. Results: Twenty-seven participants completed the entire protocol and were included in the post-hoc analysis. Statistical analysis showed no interaction of group and time (p > 0.05) on anxiety scores. Both groups improved depressive and executive functions over time, without time and group interaction (p(s) < 0.05). No adverse effects were reported in either intervention group. Conclusion: rTMS did not improve anxiety symptoms following high frequency rTMS in persons with moderate to severe TBI.
article How can transcranial magnetic stimulation change the way we treat traumatic brain injury?(2018) NEVILLE, Iuri S.; GOMES-OSMAN, Joyce; AMORIM, Robson L. O.; HAYASHI, Cintya Y.; GALHARDONI, Ricardo; ZANINOTTO, Ana Luiza; TEIXEIRA, Manoel J.; PAIVA, Wellingson S.Background: Traumatic brain injury (TBI) is a major health and socioeconomic problem worldwide. Despite improvements in the acute management of TBI over the past decades, which has led to better outcomes, there remains a need for novel treatment protocols that facilitate or enhance neuroplasticity and brain repair. There have been an increasing number of scientific publications describing the use of transcranial magnetic stimulation (TMS) for assessment and treatment in many research settings and clinical conditions, including TBI. Method: This study aimed to identify the role of TMS, a noninvasive brain stimulation technique, in the assessment and treatment of TBI by reviewing articles published to date from the PubMed database. Results: Most published articles on TMS in TBI are case reports. The use of TMS was reported as both a diagnostic tool and therapeutic instrument. There are few controlled trials of TMS in patients with TBI. Conclusion: TMS has the potential to modify the care of patients with TBI. TMS is an important instrument for evaluating brain injury from a functional perspective and also providing insights into neuromodulation approaches that may enhance recovery.- Longitudinal whole-brain analysis of multi-subject diffusion data in diffuse axonal injury(2022) GRASSI, Daphine Centola; ZANINOTTO, Ana Luiza; FELTRIN, Fabricio Stewan; MACRUZ, Fabiola Bezerra de Carvalho; OTADUY, Maria Concepcion Garcia; LEITE, Claudia da Costa; GUIRADO, Vinicius Monteiro de Paula; PAIVA, Wellingson Silva; ANDRADE, Celi SantosBackground: Diffuse axonal injury occurs with high acceleration and deceleration forces in traumatic brain injury (TBI). This lesion leads to disarrangement of the neuronal network, which can result in some degree of deficiency. The Extended Glasgow Outcome Scale (GOS-E) is the primary outcome instrument for the evaluation of TBI victims. Diffusion tensor imaging (DTI) assesses white matter (WM) microstructure based on the displacement distribution of water molecules. Objective: To investigate WM microstructure within the first year after TBI using DTI, the patient's clinical outcomes, and associations. Methods: We scanned 20 moderate and severe TBI victims at 2 months and 1 year after the event. Imaging processing was done with the FMRIB software library; we used the tract-based spatial statistics software yielding fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for statistical analyses. We computed the average difference between the two measures across subjects and performed a one-sample t-test and threshold-free cluster enhancement, using a corrected p-value < 0.05. Clinical outcomes were evaluated with the GOS-E. We tested for associations between outcome measures and significant mean FA clusters. Results: Significant clusters of altered FA were identified anatomically using the JHU WM atlas. We found increasing spotted areas of FA with time in the right brain hemisphere and left cerebellum. Extensive regions of increased MD, RD, and AD were observed. Patients presented an excellent overall recovery. Conclusions: There were no associations between FA and outcome scores, but we cannot exclude the existence of a small to moderate association.
- Longitudinal changes in brain volumetry and cognitive functions after moderate and severe diffuse axonal injury(2018) FELTRIN, Fabricio Stewan; ZANINOTTO, Ana Luiza; GUIRADO, Vinicius M. P.; MACRUZ, Fabiola; SAKUNO, Daniel; DALAQUA, Mariana; MAGALHAES, Luiz Gustavo Antunes; PAIVA, Wellingson Silva; ANDRADE, Almir Ferreira de; OTADUY, Maria C. G.; LEITE, Claudia C.Background and objective: Diffuse axonal injury (DAI) induces a long-term process of brain atrophy and cognitive deficits. The goal of this study was to determine whether there are correlations between brain volume loss, microhaemorrhage load (MHL) and neuropsychological performance during the first year after DAI. Methods: Twenty-four patients with moderate or severe DAI were evaluated at 2, 6 and 12 months post-injury. MHL was evaluated at 3months, and brain volumetry was evaluated at 3, 6 and 12 months. The trail making test (TMT) was used to evaluate executive function (EF), and the Hopkins verbal learning test (HVLT) was used to evaluate episodic verbal memory (EVM) at 6 and 12 months. Results: There were significant white matter volume (WMV), subcortical grey matter volume and total brain volume (TBV) reductions during the study period (p < 0.05). MHL was correlated only with WMV reduction. EF and EVM were not correlated with MHL but were, in part, correlated with WMV and TBV reductions. Conclusions: Our findings suggest that MHL may be a predictor of WMV reduction but cannot predict EF or EVM in DAI. Brain atrophy progresses over time, but patients showed better EF and EVM in some of the tests, which could be due to neuroplasticity.