A prediction algorithm for drug response in patients with mesial temporal lobe epilepsy based on clinical and genetic information

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOMesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide121FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2013/07559-

Effectiveness of a web-based self-help tool to reduce problem gambling: A randomized controlled trial.

Problem gambling constitutes a public health concern associated with psychopathological comorbidity, substance use, and financial difficulties. Most individuals with gambling problems avoid counseling services due to perceived stigma and their preference for self-reliance. Treatment accessibility could be improved through web-based interventions. We recruited 360 individuals with gambling problems and randomized them to a web-based intervention (n = 185) or an active control group consisting of a self-help manual for problem gambling (n = 175). The primary outcome was the number of days of gambling in the last 30 days. Secondary outcomes included money spent in the last 30 days, time gambling in the last 7 days, gambling-related problems, consumption of alcohol and cigarettes, and psychopathological comorbidity measured at posttreatment and 6-month follow-up. The primary outcome decreased significantly for both groups, with no significant difference between the groups. There were significant group × time interactions according to the Gambling Symptom Assessment Scale (F = 8.83, p <0 .001), the Problem Gambling Severity Index (F = 3.54, p = 0.030), for cigarettes smoked in the last 7 days (F = 26.68, p < 0.001), the Patient Health Questionnaire-9 (F = 19.41, p <0 .001), and the Generalized Anxiety Disorder-7 (F = 41.09, p <0 .001) favoring the intervention group. We experienced an overall high dropout rate (76%). Win Back Control seems to be an effective low-threshold treatment option for individuals with gambling problems that might otherwise be unapproachable for outpatient treatment services. Nevertheless, the high dropout rate should be considered when interpreting the study results, as they may have introduced a degree of variability

EEG spike source localization before and after surgery for temporal lobe epilepsy: a BOLD EEG-fMRI and independent component analysis study

Simultaneous measurements of EEG-functional magnetic resonance imaging (fMRI) combine the high temporal resolution of EEG with the distinctive spatial resolution of fMRI. The purpose of this EEG-fMRI study was to search for hemodynamic responses (blood oxygen level-dependent - BOLD responses) associated with interictal activity in a case of right mesial temporal lobe epilepsy before and after a successful selective amygdalohippocampectomy. Therefore, the study found the epileptogenic source by this noninvasive imaging technique and compared the results after removing the atrophied hippocampus. Additionally, the present study investigated the effectiveness of two different ways of localizing epileptiform spike sources, i.e., BOLD contrast and independent component analysis dipole model, by comparing their respective outcomes to the resected epileptogenic region. Our findings suggested a right hippocampus induction of the large interictal activity in the left hemisphere. Although almost a quarter of the dipoles were found near the right hippocampus region, dipole modeling resulted in a widespread distribution, making EEG analysis too weak to precisely determine by itself the source localization even by a sophisticated method of analysis such as independent component analysis. On the other hand, the combined EEG-fMRI technique made it possible to highlight the epileptogenic foci quite efficiently.58258

Surgical planning with 18F-FDG SPECT in refractory neocortical temporal lobe epilepsy: case report

INTRODUCTION: Several patients with partial epilepsies do not present an easily identified epileptogenic focus on scalp EEG or visible lesion on MRI. There are some useful functional neuroimaging techniques that could be considered in these cases, such as interictal positron emission tomography (PET) scan and ictal single-photon emission computed tomography (SPECT). These techniques can guide the placement of deep electrodes or even prevent their use in some situations. Unfortunately, PET scanners are not easily available in a great number of epilepsy centers because of its cost. OBJECTIVE: To demonstrate that 18F-FDG SPECT could be a good alternative replacing PET scan on localization of epileptic focus and surgical planning in places where this technology is not available. MATERIALS AND METHODS: Case report of a patient with refractory neocortical temporal lobe epilepsy, with normal MRI and nuclear EEG localization. RESULTS: The patient was submitted to interictal 18F-FDG SPECT scan, that showed hypometabolism in the anterior, mesial and lateral parts of the right temporal lobe. These areas were surgically resected and the patient outcome after 24 moths has been very good (Engel IB). CONCLUSION: We suggest that in some situations an interictal 18F-FDG SPECT scan could replace 18F-FDG PET scan where this technique is not available.INTRODUÇÃO: Muitos portadores de epilepsias parciais não apresentam foco epileptogênico facilmente identificado na investigação com EEG de superfície e ressonância magnética (RM). Nestes casos o uso de técnicas de neuroimagem funcional como a tomografia por emissão de pósitrons (PET) interictal e a tomografia por emissão de fóton único (SPECT) ictal devem ser considerados, visando evitar a colocação de eletrodos profundos em alguns casos ou guiar o posicionamento destes em outros. O exame de PET, no entanto, não é disponível em grande parte dos centros de epilepsia, principalmente por seu alto custo. OBJETIVO: O nosso objetivo é demonstrar que a utilização de FDG-18F SPECT interictal pode ser uma boa alternativa ao uso do PET na localização do foco e planejamento cirúrgico. MATERIAIS E MÉTODOS: Relato de uma paciente com epilepsia parcial de lobo temporal neocortical, refratária a tratamento clínico, com RM normal e EEG ictal sem localização definida do foco epileptogênico. RESULTADOS: Após a extensa investigação pré cirúrgica sem resultados satisfatórios optou-se pela realização de exame de medicina nuclear FDG-18F SPECT interictal. O exame demonstrou hipometabolismo na região anterior das porções mesial e lateral do lobo temporal direito. A paciente foi, então, submetida à ressecção destas áreas e permanece com excelente controle de crises (Engel IB) 24 meses após a cirurgia. CONCLUSÃO: O FDG-18F SPECT pode tornar-se um substituto do PET nos locais onde esta tecnologia não é disponível.16917

Genetic and environmental aetiologies of associations between dispositional mindfulness and ADHD traits: a population-based twin study

© The Author(s) 2019. To get additional insight into the phenotype of attentional problems, we examined to what extent genetic and environmental factors explain covariation between lack of dispositional mindfulness and attention-deficit/hyperactivity disorder (ADHD) traits in youth, and explored the incremental validity of these constructs in predicting life satisfaction. We used data from a UK population-representative sample of adolescent twins (N = 1092 pairs) on lack of dispositional mindfulness [Mindful Attention Awareness Scale (MAAS)], ADHD traits [Conners’ Parent Rating Scale-Revised (CPRS-R): inattentive (INATT) and hyperactivity/impulsivity (HYP/IMP) symptom dimensions] and life satisfaction (Students’ Life Satisfaction Scale). Twin model fitting analyses were conducted. Phenotypic correlations (rp) between MAAS and CPRS-R (INATT: rp = 0.18, HYP/IMP: rp = 0.13) were small, but significant and largely explained by shared genes for INATT (% rp INATT–MAAS due to genes: 93%, genetic correlation rA = 0.37) and HYP/IMP (% rp HYP/IMP–MAAS due to genes: 81%; genetic correlation rA = 0.21) with no significant contribution of environmental factors. MAAS, INATT and HYP/IMP significantly and independently predicted life satisfaction. Lack of dispositional mindfulness, assessed as self-reported perceived lapses of attention (MAAS), taps into an aspect of attentional functioning that is phenotypically and genetically distinct from parent-rated ADHD traits. The clinically relevant incremental validity of both scales implicates that MAAS could be used to explore the underlying mechanisms of an aspect of attentional functioning that uniquely affects life satisfaction and is not captured by DSM-based ADHD scales. Further future research could identify if lack of dispositional mindfulness and high ADHD traits can be targeted by different therapeutic approaches resulting in different effects on life satisfactio

Proton MRS may predict AED response in patients with TLE

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)P>Purpose: To compare relative N-acetylaspartate (NAA) measurements in temporal lobe epilepsy (TLE) patients with good response to the first trial of antiepileptic drugs (AEDs) (an important prognostic factor) to TLE patients who failed the first AED monotherapy and required further AED trials with monotherapy or polytherapy. Methods: We studied 25 consecutive TLE patients who responded to first AED (responders) and 21 who did not (failure-group), as well as 27 controls. Patients were seen regularly in our Epilepsy Service and underwent electroencephalography (EEG) investigation, high-resolution magnetic resonance imaging (MRI), and single-voxel proton MR spectroscopy. Voxels were tailored to the medial temporal region on each side and involved the anterior hippocampus. Results: Analysis of variance (ANOVA) demonstrated significant variation of NAA/creatine (NAA/Cr) values in both hippocampi, ipsilateral and contralateral to the EEG focus (p < 0.001 and p = 0.021) across the groups. Pairwise post hoc comparisons showed reduced NAA/Cr in both hippocampi of failure-group compared to controls (p < 0.001) and compared to responders (p < 0.05), but not between the controls and responders. Individual analyses showed NAA/Cr ratios lower than 2 SDs (standard deviations) below the mean of controls in 9 of 21 patients (42.8%) in the failure-group (6 with unilateral and 3 with bilateral reduction) but in none of the responders. Discussion: These results indicate that patients with TLE who respond well to the first AED have significantly less evidence of neuronal and axonal damage/dysfunction compared to those who are refractory to the first AED trial.515783788Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Surgical Planning With18f-fdg Spect In Refractory Neocortical Temporal Lobe Epilepsy: Case Report [avaliação Pré-cirúrgica De Epilepsia Neocortical De Lobo Temporal Com Utilização De Fdg-18f Spect: Relato De Caso]

Introduction: Several patients with partial epilepsies do not present an easily identified epileptogenic focus on scalp EEG or visible lesion on MRI. There are some useful functional neuroimaging techniques that could be considered in these cases, such as interictal positron emission tomography (PET) scan and ictal single-photon emission computed tomography (SPECT). These techniques can guide the placement of deep electrodes or even prevent their use in some situations. Unfortunately, PET scanners are not easily available in a great number of epilepsy centers because of its cost. Objective: To demonstrate that 18F-FDG SPECT could be a good alternative replacing PET scan on localization of epileptic focus and surgical planning in places where this technology is not available. Materials and Methods: Case report of a patient with refractory neocortical temporal lobe epilepsy, with normal MRI and nuclear EEG localization. Results: The patient was submitted to interictal 18F-FDG SPECT scan, that showed hypometabolism in the anterior, mesial and lateral parts of the right temporal lobe. These areas were surgically resected and the patient outcome after 24 moths has been very good (Engel IB). Conclusion: We suggest that in some situations an interictal 18F-FDG SPECT scan could replace 18F-FDG PET scan where this technique is not available.123169173Cendes, F., Partial epilepsies: An Overview (2003) Arq. Neuropsiquiatr, 61 (SUPPL. 1), pp. 1-7Elchebehere, E.C.S.C., Yacubian, E.M.T., Camargo, E.E., SPECT Cerebral em epilepsia (2000) Epilepsia, pp. 155-165. , Guerreiro CAM, editor, 3rd ed. Lemos;Palmini, A., Calcagnotto, M.E., Cendes, F., Epilepsias refratárias: Diagnóstico sindrômico, topográfico e etiológico (2000) Epilepsia, pp. 369-378. , Guerreiro CAM, editor, 3rd ed. Lemos;Henry, T.R., Van Heertum, R.L., Positron emission tomography in epilepsy care (2003) Semin Ncl Med, 33 (2), pp. 88-104Palmini, A., Najm, I., Avanzini, G., Babb, T., Guerrini, R., Foldvary-Schaefer, N., Jackson, G., Vinters, H.V., Terminology and classification of the cortical dysplasias (2004) Neurology, 62 (6 SUPPL. 3), pp. S2-S8Lee, S.K., Yun, C.H., Oh, J.B., Intracranial ictal onset zone in nonlesional lateral temporal lobe epilepsy on scalp ictal EEG (2003) Neurology, 61, pp. 757-764Salanova, V., Andermann, F., Rasmussen, T., Parietal lobe epilepsy: Clinical manifestations and outcome in 82 patients treated surgically between 1929 and 1988 (1995) Brain, 118, pp. 607-627Duncan, J.S., Imaging and epilepsy (1997) Brain, 102, pp. 339-377Bronen, R.A., Epilepsy: The role of MR imaging (1992) Am J Radiol, 159, pp. 1165-1174Semah, F., Picot, M.-C., Adam, C., Is the underlying cause of epilepsy a major prognostic factor for recurrence? (1998) Neurology, 51, pp. 1256-1262Santos, S.L.M., Ghizoni, E., Li, L.M., Dynamic assessment of high-resolution MRI with multi-planar reconstruction increases the yield of lesion detection in patients with partial epilepsy (2005) J Epilepsy Clin Neurophysiol, 11 (3), pp. 111-116Barkovich, A.J., Rowley, H.A., Andermann, F., MR in partial epilepsy: Value of high-resolution techniques (1995) AJNR, 16, pp. 339-343Knowlton, R.C., The role of FDG-PET, ictal SPECT and MEG in the epilepsy surgery evaluation (2006) Epilepsy and Behavior, 8, pp. 91-101Spencer, S.S., The relative contributions of MRI, SPECT and PET imaging in epilepsy (1994) Epilepsia, 35 (SUPPL. 6), pp. S72-S89Duarte, P.S., Zhuang, H., King, D., Hipometabolismo cerebral em pacientes com esclerose mesial temporal demons trado pelo FDG-PET (2000) Arq. Neuropsiquiatr, 58 (3 -B), pp. 869-876Diehl, B., LaPresto, E., Najm, I., Neocortical temporal FDG-PET hypometabolism correlates with temporal lobe atrophy in hippocampal sclerosis associated with microscopic cortical dysplasia (2003) Epilepsia, 44 (4), pp. 559-564Schwartz, W.J., Smith, C.B., Davidsen, L., Metabolic mapping of functional activity in the hypotalomo - neurohypophysial system of the rat (1979) Science, 205, pp. 723-72

Antiepileptic drug response in temporal lobe epilepsy A clinical and MRI morphometry study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Objective: To investigate the relationship between brain MRI and clinical characteristics and patterns of antiepileptic drug (AED) response in patients with mesial temporal lobe epilepsy (MTLE). Methods: A total of 165 MTLE patients were divided into seizure-free with AED (AED responders, n = 50), pharmacoresistant (n = 87), and remitting-relapsing seizure control group (n = 28). All groups were evaluated regarding age, frequency of seizures, and age at epilepsy onset, duration of epilepsy, febrile seizures, presence and side of hippocampal atrophy (HA), and initial precipitating injuries. For gray matter (GM) MRI voxel-based morphometry (VBM) we selected only patients with unilateral HA on visual MRI analysis (n = 100). Comparisons were made between all groups and 75 healthy controls. Results: Age at epilepsy onset was lower (p = 0.005) and initial frequency of seizures was higher in the pharmacoresistant compared with the other 2 groups (p = 0.018). All groups showed GM atrophy compared to controls in ipsilateral hippocampus, bilateral parahippocampal gyri, frontal, occipital, parietal, and cerebellar areas. In the AED responders group, such findings were more restricted to areas ipsilateral to the epileptic focus and more widespread in the pharmacoresistant and remitting-relapsing groups. VBM pairwise comparisons showed areas with GM volume reduction in the pharmacoresistant and remitting-relapsing groups compared with AED responders in bilateral periorbital frontal (p < 0.01), cingulum (p < 0.05), and temporal lobe contralateral to the epileptic focus (p < 0.05). Conclusions: Pharmacoresistant and remitting-relapsing groups presented a similar pattern of GM atrophy, which was more widespread compared with AED responders. Conversely, age at epilepsy onset was lower and initial seizure frequency was higher in pharmacoresistant patients. Neurology(R) 2010;75:1695-1701o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.751916951701Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)NovartisJanssenConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [05/56578-4, 06/50626-0

Multiple Organ Failure In Septic Patients.

Multiple organ failure (MOF) is the main cause of death in ICUs, especially affecting septic patients. It is strongly related to number of systems with failure, type of system involved, risk factors such as age, previous chronic diseases, delayed or inadequate resuscitation, persistent infection, immune suppression, and others. The prognoses is worse for patients rather than in elective or emergency surgical patients. The objective of this article is to provide data from our university teaching hospital ICU related to the incidence of septic patients, the distribution of MOF, and distribution of failure among each of the organs. The mortality rate, relationship between mortality and age, and mortality and types of organs affected were evaluated. The main bacterial causes of sepsis were also identified. A retrospective evaluation was done of 249 patients admitted to the ICU in a 4 month period during 1999. Fifty four patients had sepsis diagnosed by ACCS/SCCM criteria. There were 37 men and 17 women; 24 medical and 30 post-surgical patients (9 after elective surgery and 21 emergency patients). APACHE II score was calculated on admission and MOF, measured for the first five days, was diagnosed using Marshall and Meakins criteria. The statistical method used was non-parametric Mann-Whitney test, p61 years 13/19 (68%), died. There were 23 patients with positive bacterial culture. The most frequent bacteria found were: Pseudomonas aeruginosa (5), multiresistant Acinetobacter baumanii (3), Staphylococcus epidermidis (3), Enterobacter aerogenes (3), Klebsiella pneumoniae (2) and multiresistant Staphylococcus aureus (2). The mean value +/- SD of APACHE II (mortality risk) for survivors was 21 +/- 18 and for non-survivors 42 +/- 26 (p<0.001). We conclude that MOF due to sepsis in an ICU is frequent, with high mortality related to the number of failing organs, age and high APACHE II.5310311