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.10311

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

Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI

<p>Abstract</p> <p>Background</p> <p>Mesial temporal lobe epilepsy (MTLE), the most common type of focal epilepsy in adults, is often caused by hippocampal sclerosis (HS). Patients with HS usually present memory dysfunction, which is material-specific according to the hemisphere involved and has been correlated to the degree of HS as measured by postoperative histopathology as well as by the degree of hippocampal atrophy on magnetic resonance imaging (MRI). Verbal memory is mostly affected by left-sided HS, whereas visuo-spatial memory is more affected by right HS. Some of these impairments may be related to abnormalities of the network in which individual hippocampus takes part. Functional connectivity can play an important role to understand how the hippocampi interact with other brain areas. It can be estimated via functional Magnetic Resonance Imaging (fMRI) resting state experiments by evaluating patterns of functional networks. In this study, we investigated the functional connectivity patterns of 9 control subjects, 9 patients with right MTLE and 9 patients with left MTLE.</p> <p>Results</p> <p>We detected differences in functional connectivity within and between hippocampi in patients with unilateral MTLE associated with ipsilateral HS by resting state fMRI. Functional connectivity resulted to be more impaired ipsilateral to the seizure focus in both patient groups when compared to control subjects. This effect was even more pronounced for the left MTLE group.</p> <p>Conclusions</p> <p>The findings presented here suggest that left HS causes more reduction of functional connectivity than right HS in subjects with left hemisphere dominance for language.</p

Analysis of factors related to anti-epileptic drug resistance in mesial temporal lobe epilepsy

Orientadores: Fernando Cendes, Íscia Lopes-CendesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: O objetivo foi realizar uma análise multifatorial dos aspectos clínicos e de ressonância magnética (quantitativos e qualitativos) relacionados à resistência ao tratamento com drogas anti-epilépticas (DAES) em pacientes com epilepsia de lobo temporal mesial e melhor caracterizar o grupo de resposta intermediário a DAES, aqui denominado remitente-recorrente. Foram incluídos 165 pacientes e divididos em 3 grupos de acordo com a resposta medicamentosa: 50 respondedores (31 mulheres) , 87 não respondedores ao uso de DAES (53 mulheres) e 28 remitentes-recorrentes (17 mulheres) . Estes foram avaliados quanto à idade, freqüência de crises e idade no início destas, presença de crises febris, presença e lateralidade da atrofia hipocampal à análise visual, fatores precipitantes e DAES utilizadas. A quantificação dos volumes hipocampais foi realizada através de volumetria manual pelo software DISPLAY e as comparações dos volumes médios de ambos os hipocampos foi realizada entre os 3 grupos e 30 controles sadios por ANOVA. As imagens de ressonância magnética também foram avaliadas através da técnica de Morfometria Baseada em Voxel (VBM) com o software SPM 5 (Statistical Parametric Mapping)/MATLAB 7.7.0, comparando os três grupos com 75 indivíduos normais e entre si através de Teste -T. Observamos que idade de início das crises foi menor (p=0,005) e a freqüência das crises ao início foi maior (p=0,018) em farmacorresistentes quando comparado aos outros 2 grupos. As DAES mais utilizadas foram a carbamazepina e o clobazam (em associação) em todos os grupos. As doses de carbamazepina utilizadas foram maiores em farmacorresistentes (p<0,001) e remitentes-recorrentes (p=0,02) em comparação aos responsivos. Em relação ao clobazam, observamos dose significativamente maior somente nos farmacorresistentes em comparação aos outros dois grupos (p=0,017). A comparação da média dos volumes hipocampais entre os 3 grupos e controle evidenciou diferenças somente entre farmacorresistentes e controles bilateralmente (esquerda ,p = 0,004; direita, p=0,02). A análise por VBM evidenciou atrofia de substância cinzenta em todos os grupos. No grupo farmacorresponsivo tal atrofia foi mais restrita a áreas ipsilaterais ao foco epileptigênico, ao passo que nos grupos farmacorresistente e remitente-recorrente esta atrofia apresentou-se mais difusa. A comparação entre os grupos evidenciou as seguintes áreas com maior redução de substância cinzenta nos grupos farmacorresistente e remitenterecorrente quando comparados aos farmacorresponsivos: frontal periorbital bilateral (p<0,01), cíngulo (p<0,05) e temporal contralateral ao foco epileptogênico (p<0,05). Desta forma, observamos que embora as características clínicas demonstrassem mais similaridades entre os grupos respondedor e remitente-recorrente, a análise de VBM mostrou redução de substância cinzenta mais difusa em farmacorresistentes e remitentesrecorrentes. Assim pudemos observar que as variáveis clínicas relacionadas ao pior prognóstico foram idade e freqüência de início de crises. Em relação às variáveis estruturais, embora a atrofia de substância cinzenta (SC) se apresentasse mais difusamente em pacientes de pior resposta medicamentosa, também ocorre em áreas extra-hipocampais e mesmo extratemporais em pacientes considerados farmacorresponsivos mesmo que ipsilateralmente ao foco epileptogênico. Por último, conseguimos caracterizar clínica e estruturalmente o grupo remitente-recorrente, observado na prática clínica, porém até então muito pouco reconhecido na literaturaAbstract: The objective of the present work was 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).In order to do that,one hundred sixty five MTLE patients were divided into seizure-free with AED (50 AEDresponders, 31 women), 87 pharmacoresistants (53 women), and 28 remitting-relapsing seizure control group (17 women). All groups were evaluated regarding age, frequency of seizures and age at epilepsy onset, duration of epilepsy, febrile seizures (FS), presence and side of hippocampal atrophy on visual inspection (HA), initial precipitating injuries (IPIs), type and quantity of AEDS used. The right and left hipoccampi from 99 patients belonging to all three groups (43 pharmacoresistants, 31 pharmacoresponsive and 25 remitting-relapsing subjects). were submitted to manual morphometry by DISPLAY software (Brain Imaging Centre, Montreal, Canada) as well as hipoccampi selected from 30 healthy controls. The calculated mean from those hipoccampi were compared within subjects and with controls. 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. Age at epilepsy onset was lower (p=0,005) and initial frequency of seizures was higher in pharmacoresistants compared with the other two groups (p=0,018). The most used AEDS were carbamazepine and clobazam (always in association). The highest carbamazepine dose was observed in pharmacorresistants (p<0,001) and remitting-relapsing group (p=0,02). The highest dose of clobazam occurred only in pharmacoresistant group (p=0,017). The comparison between the mean hippocampi volumes from three groups and controls showed differences only on the pharmacoresistants left (p=0,004) and right(p=0,02) hippocampus comparing to controls. 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 pharmacoresistants and remitting-relapsing groups. VBM pairwise comparisons showed areas with GM volume reduction in pharmacoresistants and remitting-relapsing 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). We may conclude that, pharmacoresistants and remittingrelapsing patients presented a similar pattern of GM atrophy which was more widespread compared with AED-responders on VBM. We could also observe that age at epilepsy onset was lower (p=0,005) and initial seizure frequency was higher in pharmacoresistantsDoutoradoNeurocienciasDoutor em Ciência

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

A Prediction Algorithm for Drug Response in Patients with Mesial Temporal Lobe Epilepsy Based on Clinical and Genetic Information

<div><p>Mesial 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 nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy. For this, we divided 237 patients into two groups: 75 responsive and 162 refractory to antiepileptic drug therapy. We genotyped 119 SNPs in <i>ABCB1</i>, <i>ABCC2</i>, <i>CYP1A1</i>, <i>CYP1A2</i>, <i>CYP1B1</i>, <i>CYP2C9</i>, <i>CYP2C19</i>, <i>CYP2D6</i>, <i>CYP2E1</i>, <i>CYP3A4</i>, and <i>CYP3A5</i> genes. We used 98 additional SNPs to evaluate population stratification. We assessed a first scenario using only clinical variables and a second one including SNP information. The random forests algorithm combined with leave-one-out cross-validation was used to identify the best predictive model in each scenario and compared their accuracies using the area under the curve statistic. Additionally, we built a variable importance plot to present the set of most relevant predictors on the best model. The selected best model included the presence of hippocampal sclerosis and 56 SNPs. Furthermore, including SNPs in the model improved accuracy from 0.4568 to 0.8177. Our findings suggest that adding genetic information provided by SNPs, located on drug transport and metabolism genes, can improve the accuracy for predicting which patients with mesial temporal lobe epilepsy are likely to be refractory to drug treatment, making it possible to identify patients who may benefit from epilepsy surgery sooner.</p></div

Variable importance plot.

<p>Each point represents the mean decreased accuracy estimate (y-axis), for each clinical variable and SNP genotype selected by the model (x-axis). Letter codes (AB and BB), after SNP name, indicate heterozygote and the alternative homozygote allele for each SNP, respectively.</p

Percentage that each AED appears in monotherapy or polytherapy in the responsive and refractory patients.

<p>Percentage that each AED appears in monotherapy or polytherapy in the responsive and refractory patients.</p

<i>ABCC2</i> mRNA relative quantification.

<p>The boxplots include dots for each sample, showing the relative quantification of ABCC2 mRNA, in terms of 2^-ΔΔCT (y-axis), between hippocampal tissue from refractory MTLE patients and control autopsies.</p