Ictal fear is associated with anxiety symptoms and interictal dysphoric disorder in drug-resistant mesial temporal lobe epilepsy.

Interictal dysphoric disorder (IDD) is a poorly understood psychiatric disorder of epilepsy patients. Interictal dysphoric disorder is characterized by depressive, somatoform, and affective symptoms observed in up to 5.9% of drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This study aimed to evaluate the association between ictal fear (IF) and the psychiatric symptoms and diagnosis in MTLE-HS patients. We included 116 (54.3% male) consecutive adult patients (36 ±â€¯11 years) with MTLE-HS. Anxiety and depression symptoms were evaluated by the Hospital Anxiety and Depression Scale (HADS) and the psychiatric diagnosis were according to Fourth Edition of the Diagnosis and Statistical Manual of Mental Disorders (DSM-IV). The independent association between the occurrence of IF aura and the psychiatric diagnosis was determined by binary regression. When compared to those with other auras or without aura, patients reporting IF have higher HADS anxiety, but not HADS depression, scores. Ictal fear was independently associated with the diagnosis of interictal dysphoric disorder (OR, IC 95% = 7.6, 1.3-43.2, p = 0.02), but not with the diagnosis of anxiety (OR, CI 95% = 0.72, 0.08-6.0, p = 0.73), depression (OR, CI 95% = 0.94, 0.19-4.8, p = 0.94) or psychotic disorders (p = 0.99). Only patients with drug-resistant MTLE-HS were included and the small number of cases with DD diagnosis in the sample. In MTLE-HS patients, the occurrence of IF is associated with higher levels of anxiety symptoms and IDD. The results provide insights about fear-related neural network connections with anxiety symptoms and the IDD in MTLE-HS.

Amygdala levels of the GluA1 subunit of glutamate receptors and its phosphorylation state at serine 845 in the anterior hippocampus are biomarkers of ictal fear but not anxiety.

Fear is a conscious state caused by exposure to real or imagined threats that trigger stress responses that affect the body and brain, particularly limbic structures. A sub-group of patients with mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) have seizures with fear, which is called ictal fear (IF), due to epileptic activity within the brain defensive survival circuit structures. Synaptic transmission efficacy can be bi-directionally modified through potentiation (long-term potentiation (LTP)) or depression (long-term depression (LTD)) as well as the phosphorylation state of Ser831 and Ser845 sites at the GluA1 subunit of the glutamate AMPA receptors, which has been characterized as a critical event for this synaptic plasticity. In this study, GluA1 levels and the phosphorylation at Ser845 and Ser831 in the amygdala (AMY), anterior hippocampus (aHIP) and middle gyrus of temporal neocortex (CX) were determined with western blots and compared between MTLE-HS patients who were showing (n = 06) or not showing (n = 25) IF. Patients with IF had an 11% decrease of AMY levels of the GluA1 subunit (p = 0.05) and a 21.5% decrease of aHIP levels of P-GluA1-Ser845 (p = 0.009) compared to patients not showing IF. The observed associations were not related to imbalances in the distribution of other concomitant types of aura, demographic, clinical or neurosurgical variables. The lower levels of P-GluA1-Ser845 in the aHIP of patients with IF were not related to changes in the levels of the serine/threonine-protein phosphatase PP1-alpha catalytic subunit or protein kinase A activation. Taken together, the GluA1 subunit levels in AMY and P-GluA1-Ser845 levels in the aHIP show an overall accuracy of 89.3% (specificity 95.5% and sensitivity 66.7%) to predict the presence of IF. AMY levels of the GluA1 subunit and aHIP levels of P-GluA1-Ser845 were not associated with the psychiatric diagnosis and symptoms of patients. Taken together with previous findings in MTLE-HS patients with IF who were evaluated by stereotactic implanted depth electrodes, we speculate our findings are consistent with the hypothesis that AMY is not a centre of fear but together with other sub-cortical and cortical structures integrates the defensive circuit that detect and respond to threats. This is the first report to address neuroplasticity features in human limbic structures connected to the defensive survival circuits, which has implications for the comprehension of highly prevalent psychiatric disorders and symptoms.

Predictors of Hospital Mortality and the Related Burden of Disease in Severe Traumatic Brain Injury: A Prospective Multicentric Study in Brazil.

Traumatic brain injury (TBI) is a worldwide social, economic, and health problem related to premature death and long-term disabilities. There were no prospective and multicentric studies analyzing the predictors of TBI related mortality and estimating the burden of TBI in Brazil. To address this gap, we investigated prospectively: (1) the hospital mortality and its determinants in patients admitted with severe TBI we analyzed in three reference centers; (2) the burden of TBI estimated by the years of life lost (YLLs) due to premature death based on the hospital mortality considering the hospital mortality. Between April 2014 and January 2016 (22 months), all the 266 patients admitted with Glasgow coma scale (GCS), ≤ 8 admitted in three TBI reference centers were included in the study. These centers cover a population of 1,527,378 population of the Santa Catarina state, Southern Brazil. Most patients were male (n = 230, 86.5%), with a mean (SD) age of 38 (17) years. Hospital mortality was 31.1% (n = 83) and independently associated with older age, worse cranial CT injury by the Marshall classification, the presence of subarachnoid hemorrhage in the CT, lower GCS scores and abnormal pupils at admission. The final multiple logistic regression model including these variables showed an overall accuracy for hospital mortality of 77.9% (specificity 88.6%, sensitivity 53.8%, PPV 67.7%, and NPV 81.1%). The estimated annual incidence of hospitalizations and mortality due to severe TBI were 9.5 cases and 5.43 per 100,000 inhabitants, respectively. The estimated YLLs in 22 months, in the 2 metropolitan areas were 2,841, corresponding to 1,550 YLLs per year and 101.5 YLLs per 100,000 people every year. The hospital mortality did not change significantly since the end of the 1990s and was similar to other centers in Brazil and Latin America. Significant predictors of hospital mortality were the same as those of studies worldwide, but their strength of association seemed to differ according to countries income. Present study results question the extrapolation of TBI hospital mortality models for high income to lower- and middle-income countries and therefore have implications for TBI multicentric trials including countries with different income levels.

Mortality in severe traumatic brain injury: a multivariated analysis of 748 Brazilian patients from Florianópolis City.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of incapacity and mortality worldwide, with most of the burden occurring in low-income and middle-income countries. A number of clinical, demographic, and neurosurgical variables of patients with TBI were associated with their outcome. METHODS: We investigated the mortality of Brazilian patients with severe TBI at the time of discharge, using a multiple logistic regression analysis. Clinical, demographic, radiologic, and neurosurgical variables, and mortality at time of discharge of all consecutive patients (n = 748) with severe TBI (admission Glasgow scale < or = 8) treated in our intensive care unit were analyzed. The variables were collected in a prospective manner between January 1994 and December 2003. RESULTS: Eighty-four percent (n = 631) of the patients were men. The mean age was 34.8 (+/-16.3) years and the mortality was 33.3%. After the multiple logistic regression, the adjusted odds ratio (OR) for death was higher in older (> 60 years) than younger (up to 30 years) patients (OR = 2.51, 95% confidence interval [CI] 1.31-4.79, p = 0.006). The mortality was also associated with sub-arachnoid hemorrhage (OR = 1.86, 95% CI = 1.23-2.81, p = 0.003) on computed tomography (CT) scan; admission Glasgow Scale of 3 or 4 in comparison to 7 or 8 (OR = 3.97, 95% CI = 2.49- 6.31, p < 0.001); bilateral midryasis (OR = 11.52, 95% CI = 5.56-23.87, p < 0.0001), or anisocoria (OR = 2.65, 95% CI = 1.69-4.17, p < 0.0001) in comparison to isocoric pupils. There was a trend for higher mortality in patients with type III injury on the Marshall classification of CT (OR = 3.63, 95% CI = 0.84-15.76, p = 0.08) than in patients with normal CT. Patients without thoracic trauma disclose higher mortality than patients with associated thoracic trauma do (OR = 2.02, 95% CI = 1.19-3.41, p = 0.009). The final model presented disclosed 76.9% of overall correct prediction with the survival and death predicted at 87.6% and 55.6%, respectively. CONCLUSION: Age, CT findings, Glasgow coma scale, pupil examination, and the presence of thoracic trauma at admission were independently associated with mortality at the time of discharge in Brazilian patients with severe TBI.