Peripheral levels of sST2 are increased in patients with temporal lobe epilepsy: Additional evidence of low-grade inflammation.

Inflammation plays a pivotal role in temporal lobe epilepsy (TLE) pathophysiology. IL-33 can act as a transcription factor or as a cytokine, the latter through the transmembrane ST2 receptor or its soluble isoform (sST2), presenting a dual role in neurological diseases. The aim of this study was to determine the plasma levels of IL-33 and sST2 in parallel with clinical features in patients with TLE. Peripheral blood from patients and controls was sampled for the measurement of plasma levels of IL-33 and sST2 by enzyme-linked immunoassay (ELISA). While there were similar levels of IL-33 between controls and patients, sST2 were increased in patients. IL33 and sST2 plasma levels were not associated with TLE-related clinical features. In a subgroup analysis, IL-33 levels correlated with memory performance. In conclusion, our results reinforce the concept of chronic low-grade inflammation in patients with TLE.

Circulating levels of adipokines are altered in patients with temporal lobe epilepsy.

OBJECTIVE: A persistent low-grade inflammatory state has been described in patients with temporal lobe epilepsy (TLE) in the interictal period. Adipokines are cytokines produced by the adipose tissue that can influence inflammatory response. The purpose of this study was to evaluate the plasma levels of adipokines in patients with TLE in comparison with controls. In addition, we sought to investigate whether the levels of adipokines were associated with clinical parameters in TLE. METHODS: Forty patients with TLE and 40 controls were enrolled in this study. All participants were subjected to clinical assessment that included the Mini International Neuropsychiatric Interview (MINI) and the Hamilton Depression Rating Scale (HAM-D). Peripheral blood was drawn, and plasma levels of adipokines (adiponectin, leptin, and resistin) were measured by enzyme-linked immunoassay (ELISA). RESULTS: People with TLE presented higher leptin and lower adiponectin and resistin levels in comparison with controls. The levels of these adipokines correlated negatively with illness length but not with other clinical parameters. In a binary logistic regression model, higher leptin and lower adiponectin levels remained as significant predictors of TLE diagnosis. CONCLUSIONS: These results corroborate the view that TLE is a multisystemic condition associated with low-grade inflammation.

A critique of phrenology in Moby-Dick.

Phrenology has a fascinating, although controversial, place in the history of localizationism of brain and mental functions. The 2 main proponents of phrenology were 2 German-speaking doctors, Joseph Gall (1758-1828) and Johann Spurzheim (1776-1832). According to their theory, a careful examination of skull morphology could disclose personality characters. Phrenology was initially restricted to medical circles and then diffused outside scientific societies, reaching nonscientific audiences in Europe and North America. Phrenology deeply penetrated popular culture in the 19th century and its tenets can be observed in British and American literature. Here we analyze the presence of phrenologic concepts in Moby-Dick; or, The Whale, by Herman Melville (1819-1891), one of the most prominent American writers. In his masterpiece, he demonstrates that he was familiarized with Gall and Spurzheim's writings, but referred to their theory as "semi-science" and "a passing fable." Of note, Melville's fine irony against phrenology is present in his attempt to perform a phrenologic and physiognomic examination of The Whale. Thus, Moby-Dick illustrates the diffusion of phrenology in Western culture, but may also reflect Melville's skepticism and criticism toward its main precepts.

Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state.

INTRODUCTION: Markers of low-grade peripheral inflammation have been reported amongst people with epilepsy. The mechanisms underlying this phenomenon are unknown. We attempted to characterize peripheral immune cells and their activation status in people with temporal lobe epilepsy (TLE) and healthy controls. METHODS AND RESULTS: Twenty people with TLE and 19 controls were recruited, and peripheral blood lymphocyte and monocyte subsets evaluated ex vivo by multi-color flow cytometry. People with TLE had higher expression of HLA-DR, CD69, CTLA-4, CD25, IL-23R, IFN-γ, TNF and IL-17 in CD4(+) lymphocytes than controls. Granzyme A, CTLA-4, IL-23R and IL-17 expression was also elevated in CD8(+) T cells from people with TLE. Frequency of HLA-DR in CD19(+) B cells and regulatory T cells CD4(+)CD25(+)Foxp3(+) producing IL-10 was higher in TLE when compared with controls. A negative correlation between CD4(+) expressing co-stimulatory molecules (CD69, CD25 and CTLA-4) with age at onset of seizures was found. The frequency of CD4(+)CD25(+)Foxp3(+) cells was also positively correlated with age at onset of seizures. CONCLUSION: Immune cells of people with TLE show an activation profile, mainly in effector T cells, in line with the low-grade peripheral inflammation.

Screening for depression in people with epilepsy: comparative study among neurological disorders depression inventory for epilepsy (NDDI-E), hospital anxiety and depression scale depression subscale (HADS-D), and Beck depression inventory (BDI).

PURPOSE: We aimed to assess and compare the psychometric properties of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Hospital Anxiety and Depression Scale Depression Subscale (HADS-D), and Beck Depression Inventory (BDI) as screening instruments for depression and suicidality in people with epilepsy. METHODS: One hundred twenty-six people (54% women) diagnosed with epilepsy were recruited and evaluated on their sociodemographic and clinical features. Depression and suicide risk were assessed with a structured psychiatric interview, the Mini International Neuropsychiatric Interview (MINI-Plus), and the performance of NDDI-E, HADS-D, and BDI was evaluated. RESULTS: The sensitivity and specificity of BDI for the diagnosis of depression was around 90%; HADS-D and NDDI-E have sensitivity higher than 80%, and specificity was greater than 75%. For identifying suicide risk, the NDDI-E sensitivity was 92.9%, and HADS-D sensitivity was 85.7%, and a reasonable specificity (68%) was observed for both instruments. All instruments showed a negative predictive value of over 90%. Comparisons of the areas under the ROC curve for these instruments were not significantly different regarding depression or moderate/severe risk of suicide. CONCLUSION: All three instruments evaluated have clinical utility in the screening of depression in people with epilepsy. Both NDDI-E and HADS-D are brief efficient screening instruments to identify depression in people with epilepsy. The BDI is a more robust instrument, but it takes longer to apply, which hampers its use by busy clinicians and by people with cognitive impairment.

A critical and descriptive approach to interictal behavior with the Neurobehavior Inventory (NBI).

PURPOSE: The purpose of this study was to test the psychometric properties of the Neurobehavior Inventory (NBI) in a group of temporal lobe epilepsy (TLE) patients from a tertiary care center, correlating its scores with the presence of psychiatric symptoms. METHODS: Clinical and sociodemographic data from ninety-six TLE outpatients were collected, and a neuropsychiatric evaluation was performed with the following instruments: Mini-Mental State Examination (MMSE), structured psychiatric interview (MINI-PLUS), Neurobehavior Inventory (NBI), and Hamilton Depression Rating Scale (HAM-D). RESULTS: Some traits evaluated by the NBI showed adequate internal consistency (mean inter-item correlation between 0.2 and 0.4) and were frequent, such as religiosity (74%) and repetitiveness (60.4%). Principal component analysis showed three factors, named here as emotions (Factor 1), hyposexuality (Factor 2), and unusual ideas (Factor 3). Depressive symptoms on HAM-D showed a strong association with emotions and hyposexuality factors. When patients with left TLE and right TLE were compared, the former exhibited more sadness (p=0.017), and the latter, a greater tendency toward sense of personal destiny (p=0.028). CONCLUSION: Depression influences NBI scoring, mainly emotionality and hyposexuality traits. Neurobehavior Inventory subscales can be better interpreted with an appropriate evaluation of comorbid mood and anxiety disorders. Compromise in left temporal mesial structures is associated with increased tendency toward sad affect, whereas right temporal pathology is associated with increased beliefs in personal destiny.

Suicidality in temporal lobe epilepsy: measuring the weight of impulsivity and depression.

OBJECTIVE: The aim of the work described here was to measure the role of psychopathological features, specifically impulsivity and depression, in suicidality in patients with temporal lobe epilepsy (TLE). METHODS: Neuropsychiatric evaluation of 66 outpatients with TLE was performed with the following instruments: a structured clinical interview (Mini International Neuropsychiatric Interview Plus), the Barratt Impulsiveness Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Brief Psychiatric Rating Scale. RESULTS: A current Axis I psychiatric diagnosis, mainly mood and anxiety disorders, was assigned to 37 subjects (56.1%) Presence of suicide risk was identified in 19 patients (28.8%), and 14 (21.2%) had attempted suicide. Frequency of seizures (P=0.012), current major depression (P=0.001), and motor impulsivity (P=0.005) were associated with suicide risk on univariate analysis. Logistic regression stressed the main relevance of major depression (OR=12.82, 95% CI=2.58-63.76, P=0.002) and motor impulsivity (OR=1.21, 95% CI=1.06-1.38, P=0.005) to suicide risk. CONCLUSION: Depression has a major influence on suicidality in epilepsy. Motor impulsivity is also relevant and may be an important component of depression in TLE associated with suicide risk.

Brazilian version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E).

OBJECTIVE: The purpose of this research was to evaluate the Brazilian-Portuguese version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and to assess its psychometric properties. METHODS: This study involved 98 outpatients who underwent psychopathological evaluation with the Mini International Neuropsychiatric Interview-Plus Version, Hamilton Depression Scale (HAM-D), and a Portuguese version of the NDDI-E. RESULTS: The NDDI-E was easily understood and quickly administered to most of the patients. At a cutoff score >15, NDDI-E had a sensitivity of 81.5%, a specificity of 83.1%, and a negative predictive value of 92.2% for diagnosis of major depression. Internal consistency reliability of the NDDI-E was 0.79, and there was also a positive correlation between the NDDI-E and the HAM-D (P<0.001). CONCLUSION: The Brazilian-Portuguese version of NDDI-E can be used as a practical screening tool to improve recognition of depression in Brazilian people with epilepsy.

Psychiatric disorders in temporal lobe epilepsy: an overview from a tertiary service in Brazil.

PURPOSE: To evaluate the frequency and intensity of psychiatric disorders in a group of temporal lobe epilepsy (TLE) patients from a tertiary-care center. METHODS: Clinical and sociodemographic data of 73 patients were collected and a neuropsychiatric evaluation was performed with the following instruments: Mini-Mental State Examination (MMSE), structured clinical interview (MINI-PLUS), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), Brief Psychiatric Rating Scale (BPRS). RESULTS: Patients with TLE showed a high frequency of lifetime psychiatric disorders (70%), the most frequent being mood disorders (49.3%). At assessment, 27.4% of the patients were depressed and 9.6% met criteria for bipolar disorder. Nevertheless, depression had not been properly diagnosed nor treated. Anxiety disorders were also frequent (42.5%), mainly generalized anxiety disorder (GAD) (21.9%). Obsessive compulsive disorder (OCD) was present in 11.0% and psychotic disorders in 5.5% of the sample. Patients with left mesial temporal sclerosis (LMTS) exhibited more psychopathologic features, mainly anxiety disorders (p=0.006), and scored higher on HAM-A and HAM-D (p<0.05 in both). CONCLUSION: TLE is related to a high frequency of psychiatric disorders, such as anxiety and depression, which are usually underdiagnosed and undertreated. Damage to the left mesial temporal lobe, seen in LMTS, seems to be an important pathogenic lesion linked to a broad range of psychopathological features in TLE, mainly anxiety disorders. The present study prompts discussion on the recognition of the common psychiatric disorders in TLE, especially on the Brazilian setting.