LUIZ HENRIQUE MARTINS CASTRO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Neurologia, Faculdade de Medicina - Docente
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
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- Analysis of fractional anisotropy and mean diffusivity in refractory and non-refractory idiopathic generalized epilepsies(2018) LOBATO, Mauricio; GARCIA, Lucas; AMARO JR., Edson; OTADUY, Maria; JORGE, Carmen; CASTRO, Luiz H.Purpose: To compare white matter bundles and fiber tract changes in seizure-free and non-seizure-free idiopathic generalized epilepsy (IGE) patients. Method: Forty adult patients with IGE underwent a 3 T brain MRI with DTI sequences. According to seizure control status, eighteen patients were classified as refractory (R) if they had presented at least one incapacitating seizure in the previous six months, while on appropriate antiepileptic drug treatment. Twenty two seizure-free patients with adequate seizure control were considered non-refractory (NR). We compared fractional anisotropy (FA) and mean diffusivity (MD) values in sixteen white matter tracts in the R and NR groups, and in twenty healthy subjects. Results: R and NR groups did not differ in gender, age and education. We found decreased FA in two tracts in the R group (forceps major and right uncinate fasciculus) and approaching statistical significance in two tracts in the NR group (right cingulate gyrus and right uncinate fasciculus) group, as well as increased MD in six tracts in the R group (forceps minor, left thalamic anterior radiation, right inferior longitudinal fasciculus, right longitudinal superior parietal and temporal fasciculi, and right cingulate gyrus) and in five tracts in the NR group (forceps minor, left thalamic anterior radiation, right inferior longitudinal fasciculus, right longitudinal superior parietal and temporal fasciculi), compared to controls. No differences were noted comparing FA and MD values between R and NR groups. Conclusions: In our patient population, refractory IGE patients on adequate antiepileptic drug treatment did not present more severe white matter tract involvement compared to non-refractory patients.
- 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.
- Contralateral Interictal and Ictal EEG Epileptiform Activity Accentuate Memory Impairment in Unilateral Mesial Temporal Sclerosis Patients(2017) PINTO, Lecio F.; ADDA, Carla C.; SILVA, Liliane C. A.; BANASKIWITZ, Natalie H. C.; PASSARELLI, Valmir; JORGE, Carmen L.; VALERIO, Rosa M.; CASTRO, Luiz H.Objective: Memory impairment is a recognized complication of mesial temporal sclerosis (MTS). Epileptiform activity may negatively impact on cognition. We evaluated the impact of contralateral EEG involvement on memory in unilateral MTS (uMTS) patients. Method: Retrospective review of 121 right-handed uMTS patients (69 left) evaluated with prolonged video-EEG and verbal and nonverbal memory tests (Rey Auditory Verbal Learning Test and Rey-Osterrieth Complex figure), with additional very delayed trials. Patients were classified according to ictal/interictal EEG findings and MTS side as left or right concordant or discordant. Thirty-nine normal individuals who underwent the same neuropsychological battery served as controls. Results: Demographic, disease, and treatment features did not differ among groups. On the 7-day verbal memory free recall, left discordant performed significantly worse than controls and right concordant, recognized fewer words, and had more recognition errors than all other groups, including left concordant. For nonverbal memory, right discordant performed significantly worse than controls on delayed recall, and attained lower scores than other groups on immediate and 7-day recall, but this difference did not reach statistical significance. Left discordant had higher scores of memory complaints than controls and disclosed a trend toward accentuated memory impairment compared with the other groups over time. Conclusions: Our results suggest that contralateral electrographic involvement in uMTS was associated with more pronounced memory impairment for verbal material in left discordant patients, and to a lesser extent, for nonverbal material in right discordant patients. Left discordant group also had increased memory complaints.
- Leukoencephalopathy resolution after atypical mycobacterial treatment: a case report(2015) OLIVEIRA, Marcos C. B.; SATO, Douglas Kazutoshi; SOARES-NETO, Herval R.; LUCATO, Leandro T.; CALLEGARO, Dagoberto; NITRINI, Ricardo; MEDEIROS, Raphael S. S.; MISU, Tatsuro; FUJIHARA, Kazuo; CASTRO, Luiz H.Background: Association of leukoencephalopathy and atypical mycobacteriosis has been rarely reported. We present a case that is relevant for its unusual presentation and because it may shed further light on the pathogenic mechanisms underlying reversible encephalopathies. Case report: We report the case of a Hispanic 64-year-old woman with cognitive decline and extensive leukoencephalopathy. Magnetic resonance imaging revealed white-matter lesions with increased water diffusivity, without blood-brain-barrier disruption. Brain biopsy showed tissue rarefaction with vacuolation, mild inflammation, few reactive astrocytes and decreased aquaporin water-channel expression in the lesions. Six months later, she was diagnosed with atypical mycobacterial pulmonary infection. Brain lesions resolved after antimycobacterial treatment. Conclusion: We hypothesize leukoencephalopathic changes and vasogenic edema were associated with decreased aquaporin expression. Further studies should clarify if reversible leukoencephalopathy has a causal relationship with decreased aquaporin expression and atypical mycobacterial infection, and mechanisms underlying leukoencephalopathy resolution after antimycobacterial treatment. This article may contribute to the understanding of pathogenic mechanisms underlying magnetic resonance imaging subcortical lesions and edema, which remain incompletely understood.
- Acute Disseminated Encephalomyelitis in COVID-19: presentation of two cases and review of the literature(2020) LOPES, Cesar Castello Branco; BRUCKI, Sonia Maria Dozzi; PASSOS NETO, Carlos Eduardo Borges; CORAZZA, Luiza Alves; BAIMA, Jose Pedro Soares; FIORENTINO, Matheus Dalben; TATSCH, Joao Fellipe Santos; MARTIN, Maria da Graca Morais; LUCATO, Leandro Tavares; GOMES, Helio Rodrigues; ROCHA, Maria Sheila Guimaraes; FORTINI, Ida; NITRINI, Ricardo; CASTRO, Luiz H.Background: Neurological manifestations of COVID-19 are still incompletely understood. Neurological manifestations may be due to direct viral effect on neurons and glial cells, to an immune-mediated response to the virus, or to a hypercoagulable state and associated endothelial damage, as well as to severe systemic disease with prolonged intensive care unit stay. Objective: To describe two patients with severe SARS-CoV-2 infection and delayed recovery of consciousness after sedation withdrawal, in whom MRI disclosed multifocal white matter brain lesions, compatible with the diagnosis of acute disseminated encephalomyelitis. Methods: Observational report of two cases of severe COVID-19 infection in patients from two tertiary hospitals in Sao Paulo, Brazil. Results: These patients underwent neurologic and systemic evaluation for delayed awakening after sedation withdrawal. MRI displayed multifocal centrum semiovale lesions, suggestive of demyelinating inflammation. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for SARS-CoV-2 was negative in both cases. Conclusion: A recurrent pattern of multifocal white matter lesions can occur in COVID-19 patients, possibly associated with delayed awakening. Additional studies are necessary to elucidate the role of the viral infection and of inflammatory and immune-mediated associated changes in neurological manifestations of COVID-19.
- Clinical, cerebrospinal fluid, and neuroimaging findings in COVID-19 encephalopathy: a case series(2021) TUMA, Raphael L.; GUEDES, Bruno F.; CARRA, Rafael; IEPSEN, Bruno; RODRIGUES, Julia; CAMELO-FILHO, Antonio Edvan; KUBOTA, Gabriel; FERRARI, Maira; STUDART-NETO, Adalberto; OKU, Mariana Hiromi; TERRIM, Sara; LOPES, Cesar C. B.; PASSOS NETO, Carlos E. B.; FIORENTINO, Matheus D.; SOUZA, Julia C. C.; BAIMA, Jose Pedro S.; SILVA, Tomas; PERISSINOTTI, Iago; MARTIN, Maria da Graca M.; GONCALVES, Marcia; FORTINI, Ida; SMID, Jerusa; ADONI, Tarso; LUCATO, Leandro; NITRINI, Ricardo; GOMES, Helio; CASTRO, Luiz H.Objective To describe the clinical, neurological, neuroimaging, and cerebrospinal fluid (CSF) findings associated with encephalopathy in patients admitted to a COVID-19 tertiary reference center. Methods We retrospectively reviewed records of consecutive patients with COVID-19 evaluated by a consulting neurology team from March 30, 2020 through May 15, 2020. Results Fifty-five patients with confirmed SARS-CoV-2 were included, 43 of whom showed encephalopathy, and were further divided into mild, moderate, and severe encephalopathy groups. Nineteen patients (44%) had undergone mechanical ventilation and received intravenous sedatives. Eleven (26%) patients were on dialysis. Laboratory markers of COVID-19 severity were very common in encephalopathy patients, but did not correlate with the severity of encephalopathy. Thirty-nine patients underwent neuroimaging studies, which showed mostly non-specific changes. One patient showed lesions possibly related to CNS demyelination. Four had suffered an acute stroke. SARS-CoV-2 was detected by RT-PCR in only one of 21 CSF samples. Two CSF samples showed elevated white blood cell count and all were negative for oligoclonal bands. In our case series, the severity of encephalopathy correlated with higher probability of death during hospitalization (OR = 5.5 for each increment in the degree of encephalopathy, from absent (0) to mild (1), moderate (2), or severe (3), p < 0.001). Conclusion In our consecutive series with 43 encephalopathy cases, neuroimaging and CSF analysis did not support the role of direct viral CNS invasion or CNS inflammation as the cause of encephalopathy.
- Comorbid epilepsy and psychogenic non-epileptic seizures: How well do patients and caregivers distinguish between the two(2014) GORDON, Pedro C.; VALIENGO, Leandro da Costa Lane; PROENCA, Inah C. G. F.; KURCGANT, Daniela; JORGE, Carmen Lisa; CASTRO, Luiz H.; MARCHETTI, Renato L.Purpose: To determine whether patients with comorbid epilepsy and psychogenic nonepileptic seizure (PNES) and their caregivers can distinguish between these two events at least one year after initial diagnosis, and to investigate factors associated with correct identification. Methods: Adult patients with at least a one year diagnosis of both epilepsy and PNES, confirmed through video-electroencephalography (VEEG), were selected. Patients and a caregiver of their choice were interviewed and shown videos containing the patients' epileptic and PNES events. Variables associated with correct identification of events by patients and their caregivers were evaluated. Results: Twenty-four patients participated in the study. Mean time between VEEG diagnosis and enrollment in the study was 26.8 months (+/- 12.4). Six of patients correctly distinguished between the events shown. Factors associated with correct identification were the absence of intellectual disability, unremitted PNES, and a degree of preserved awareness during the PNES event. Twelve caregivers correctly distinguished between the events shown. Factors associated with correct identification among caregivers were the presentation of only one epileptic seizure type in the patient, and the participation of the caregiver during VEEG monitoring and communication of PNES diagnosis to the patient. Conclusion: A significant proportion of patients with epilepsy and PNES and their caregivers seem to be unable to discriminate between these events a year after diagnosis. These findings have implications for both clinical follow-up and research involving this population. Future research should further investigate methods that would allow patients and their caregivers to better distinguish between these two events.
- The intracarotid etomidate Wada test: A 54-patient series(2014) PASSARELLI, Valmir; PINTO, Lecio F.; JORGE, Carmen L.; PUGLIA, Paulo; ADDA, Carla C.; WEN, Hung-Tzu; CASTRO, Luiz H.Hemispheric language dominance and isolated hemispheric memory function evaluation can be undertaken with the intracarotid injection of a general anesthetic agent (Wada test). Amobarbital has been traditionally used as the anesthetic agent, but legal and commercial constraints limit its use. We evaluated the use of etomidate as an alternative agent for the Wada test in a series of 54 consecutive adult patients with mesial temporal sclerosis undergoing presurgical evaluation for epilepsy surgery. Language lateralization and hemispheric memory function evaluation were successfully achieved in all cases. Side effects (somnolence, tremor, and dystonia) were infrequent, minor, and transient and did not require interruption of the procedure. Etomidate appears to be a safe and effective alternative agent to amobarbital in the Wada test. Similarly to the amobarbital Wada test, the ability of the etomidate Wada test to predict postoperative memory decline remains unclear.
- Low prevalence but high specificity of material-specific memory impairment in epilepsy associated with hippocampal sclerosis(2013) CASTRO, Luiz H.; SILVA, Liliane C. A. M.; ADDA, Carla C.; BANASKIWITZ, Natalie H. C.; XAVIER, Alana B.; JORGE, Carmen L.; VALERIO, Rosa M.; NITRINI, RicardoPurposeMaterial-specific memory impairment is used as a lateralizing tool in the evaluation of temporal lobe epilepsy. Lateralizing ability of material-specific memory deficits in temporal lobe epilepsy remains controversial. MethodsWe studied memory impairment profiles of verbal and nonverbal memory deficits with eight memory subtests of four neuropsychological instruments (two verbal and two nonverbal) in 87 right-handed patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS; 44 right - R, 43 left - L) and 42 controls, with an IQ>70, at least 8years of education, and without comorbidities. Key FindingsSelective verbal memory impairment was noted in 11 of 43 or 25.6% of left MTS cases, with 82.2% specificity, whereas selective nonverbal memory impairment was noted in 11 of 42 or 26.2% of right MTS cases, with 92% specificity. Nonlateralizing profiles of memory performance were seen in the remaining 65 of 87 patients. Approximately half (46/87 or 52.9%) of the patients had intact memory function in both modalities, equally distributed between patients with right MTS (23/44) and left MTS (23/43). Global impairment of both memory types was seen in 12 of 87 or 13.8% of patients, equally distributed between the two groups (7/43 left and 5/44 right). SignificanceLateralizing profiles of selective verbal and nonverbal memory deficits are highly specific for left and right MTS, although infrequently encountered in our patients. Nonlateralizing profiles predominated in this population. These findings suggest hemispheric asymmetry memory function, with complex functional interaction of the hippocampi, and possible compensatory mechanisms in the setting of a unilateral lesion.
- Left-sided epileptiform activity influences language lateralization in right mesial temporal sclerosis(2024) ALMEIDA, Juliana Passos de; CASTRO, Bettina Martins; PASSARELLI, Valmir; CHAIM, Khallil Taverna; CASTRO-LIMA, Humberto; LISTIK, Clarice; JORGE, Carmen Lisa; VALERIO, Rosa; ARANTES, Paula Ricci; JR, Edson Amaro; PIPEK, Leonardo Zumerkorn; CASTRO, Luiz H.Objective: To investigate the association between left epileptiform activity and language laterality indices (LI) in patients with right mesial temporal sclerosis (MTS).Methods: Twenty-two patients with right MTS and 22 healthy subjects underwent fMRI scanning while performing a language task. LI was calculated in multiple regions of interest (ROI). Data on the presence of left epileptiform abnormalities were obtained during prolonged video-EEG monitoring.Results: After correction for multiple comparisons, LI was reduced in the middle temporal gyrus in the left interictal epileptiform discharges (IED+) group, compared with the left IED- group (p < 0.05).Significance: Using a responsive reading naming fMRI paradigm, right MTS patients who presented left temporal interictal epileptiform abnormalities on video-EEG showed decreased LI in the middle temporal gyrus, indicating decreased left middle temporal gyrus activation, increased right middle temporal gyrus activation or a combination of both, demonstrative of language network reorganization, specially in the MTG, in this patient population.Plain Language Summary: This research studied 22 patients with right mesial temporal sclerosis (a specific type of epilepsy) comparing them to 22 healthy individuals. Participants were asked to perform a language task while undergoing a special brain imaging technique (fMRI). The findings showed that patients with epilepsy displayed a change in the area of the brain typically responsible for language processing. This suggests that their brains may have adapted due to their condition, altering the way language is processed.