Coagulation biomarkers and coronavirus disease 2019 phenotyping: a prospective cohort study.

BACKGROUND: Because severe acute respiratory syndrome coronarivus 2 (SARS-CoV-2) leads to severe conditions and thrombus formation, evaluation of the coagulation markers is important in determining the prognosis and phenotyping of patients with COVID-19. METHODS: In a prospective study that included 213 COVID-19 patients admitted to the intensive care unit (ICU) the levels of antithrombin, C-reactive protein (CRP); factors XI, XII, XIII; prothrombin and D-dimer were measured. Spearman's correlation coefficient was used to assess the pairwise correlations between the biomarkers. Hierarchical and non-hierarchical cluster analysis was performed using the levels of biomarkers to identify patients´ phenotypes. Multivariate binary regression was used to determine the association of the patient´s outcome with clinical variables and biomarker levels. RESULTS: The levels of factors XI and XIII were significantly higher in patients with less severe COVID-19, while factor XIII and antithrombin levels were significantly associated with mortality. These coagulation biomarkers were associated with the in-hospital survival of COVID-19 patients over and above the core clinical factors on admission. Hierarchical cluster analysis showed a cluster between factor XIII and antithrombin, and this hierarchical cluster was extended to CRP in the next step. Furthermore, a non-hierarchical K-means cluster analysis was performed, and two phenotypes were identified based on the CRP and antithrombin levels independently of clinical variables and were associated with mortality. CONCLUSION: Coagulation biomarkers were associated with in-hospital survival of COVID-19 patients. Lower levels of factors XI, XII and XIII and prothrombin were associated with disease severity, while higher levels of both CRP and antithrombin clustered with worse prognosis. These results suggest the role of coagulation abnormalities in the development of COVID-19 and open the perspective of identifying subgroups of patients who would benefit more from interventions focused on regulating coagulation.

Dual assessment of abnormal cardiac electrical dispersion and diastolic dysfunction for early detection of the epileptic heart condition.

BACKGROUND: People with epilepsy (PWE) are at increased risk for premature death due to many factors. Sudden unexpected death in epilepsy (SUDEP) is among the most important causes of death in these individuals and possibly, sudden cardiac death (SCD) in epilepsy is also as important. The possibility of concurrent derangement in electrical and mechanical cardiac function, which could be a marker of early cardiac involvement in PWE, has not been investigated in that population. METHODS: Electrical dispersion indices (T-wave peak to T-wave end, TpTe; QT dispersion, QTd; QT interval corrected for heart rate, QTc) were analyzed in patients with pharmacoresistant temporal lobe epilepsy and compared to a control group. The electromechanical relationship between those indices and echocardiographic parameters were further assessed in PWE. RESULTS: In 19 PWE and 21 controls, we found greater TpTe and QTd in PWE (TpTe: 91.6 ± 16.4 ms vs. 65.2 ± 12.1 ms, p < 0.0001; and QTd: 45.3 ± 13.1 ms vs. 19 ± 6.2 ms, p < 0.0001, respectively). QTc was similar between PWE and controls (419.2 ± 31.4 ms vs. 435.1 ± 31.4 ms, p = 0.12). In multivariate linear regression, TpTe, QTc, and epilepsy duration were related to left ventricular mass; QTc was associated with left atrial volume; QTc, the number of seizures per month, epilepsy duration and antiseizure medication explained 81% of E/A mitral wave Doppler ratio. CONCLUSIONS: This is the first report to demonstrate concurrent electrical dispersion and diastolic dysfunction in PWE. These noninvasive biomarkers could prove useful in early detection of the "Epileptic Heart" condition.

The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats.

We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala correlates negatively with innate anxiety-related behavior on the elevated plus maze (n = 20) but positively with expression of defensive-learned behavior (i.e., freezing) on Pavlovian aversive (fear) conditioning (n = 29). The microinfusion of ERK1/2 inhibitor (FR180204, n = 8-13/group) or MEK inhibitor (U0126, n = 8-9/group) into the basolateral amygdala did not affect anxiety-related behavior but impaired the evocation (anticipation) of conditioned-defensive behavior (n = 9-11/group). In conclusion, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala predicts anxiety in humans and the innate anxiety- and conditioned freezing behaviors in rats. However, the ERK1/2 in the basolateral AMY is only required for the expression of defensive-learned behavior. These results support a dissociate ERK-dependent mechanism in the amygdala between innate anxiety-like responses and the anticipation of learned-defensive behavior. These findings have implications for understanding highly prevalent psychiatric disorders related to the defensive circuit manifested by anxiety and fear. HIGHLIGHTS: The P-ERK1,2/Total-ERK1,2 ratio in the amygdala (AMY) correlates negatively with anxiety symptoms in patients with mesial temporal lobe epilepsy. The P-ERK1,2/Total-ERK1,2 in the amygdala correlates negatively with the anxiety-like behavior and positively with freezing-learned behavior in naive rats. ERK1,2 in the basolateral amygdala is required for learned-defensive but not for the anxiety-like behavior expression in rats.

How predictable is heart rate variability in Brazilian patients with drug-resistant mesial temporal lobe epilepsy?

This study aimed to compare heart rate variability (HRV) in patients with drug-resistant mesial temporal lobe epilepsy (MTLE) with healthy controls and to analyze their clinical and sociodemographic variables predictive for HRV. Thirty-nine consecutive patients with drug-resistant MTLE were included in the study. The control group included twenty-seven healthy participants matched by age and gender. Seven HRV indices (HR, RR, rMSSD, SDNN, LF, HF, and LF/HF) were compared between patients and controls. The clinical and sociodemographic variables independently associated with the HRV indices were identified by multiple linear regression. In comparison with controls, the patients with MTLE showed a significant reduction in RR, rMSSD, SDNN, LF, HF, and LF/HF indices (t value 1.97-5.97, p < 0.05). Multiple regression models showed that disease duration predicted 11-22% of the analyzed HRV indices. Time domain indices showed higher association with disease duration than coefficients in frequency domain. Patients with drug-resistant MTLE present cardiac autonomic tone dysfunction, showing a significant reduction in their HRV indices (RR, SDNN, rMSSD, LF, HF, and LF/HF). Disease duration has a negative association with all HRV indices. This study contributes to understanding the relationship between MTLE and the cardiac autonomic tone, with possible implications for sudden unexpected death in epilepsy.

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.

Left ventricle end-systolic elastance, arterial-effective elastance, and ventricle-arterial coupling in Epilepsy.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a tragic event. Cardiac models of sudden death state that, paradoxically, healthy individuals compose most of the victims of this event. Exploration of cardiac physiological variables related to outcome could help unveil risk markers for sudden death in epilepsy. We investigated left ventricle end-systolic elastance, arterial-effective elastance and ventricle-arterial coupling (VAC) in PWE compared with controls. MATERIAL & METHODS: Adult patients with temporal lobe epilepsy without known cardiovascular diseases were submitted to treadmill test and transthoracic echocardiogram. Individuals without epilepsy matched by sex, age, and body mass index composed the control group. Cardiac risk factors, exercise performance, autonomic data from treadmill test, systolic and diastolic function, morphological cardiac data, and left ventricle pressure-volume loop were recorded. RESULTS: Sixty subjects were consecutively enrolled (30 PWE and 30 controls). Epilepsy duration was 22.5 ± 10.7 years (age of onset 15.2 ± 10.1 years). Treadmill variables were significantly worse in TLE patients compared with controls. End-systolic elastance, arterial-effective elastance, and ventricle-arterial coupling were similar between groups. Female sex, percentage of maximal predicted heart rate achieved in exercise, exercise time, and epilepsy duration explained 28,4% of VAC in PWE in multiple stepwise linear regression (P = .018). CONCLUSIONS: Some aspects of the cardiac pressure-volume curves, mainly linked to left ventricle systolic performance, contractile function and their interaction with afterload appears normal in young PWE and cannot explain their increase risk to adverse outcomes or lower physical fitness.

Quality of life long after temporal lobe epilepsy surgery.

OBJECTIVES: To identify variables independently associated with a meaningful improvement in QOL long after surgical treatment of drug-resistant MTLE-HS patients. MATERIAL & METHODS: We prospectively evaluated 72 consecutive MTLE-HS surgically treated patients and analyzed pre and post-surgical variables independently associated with a meaningful improvement in QOL evaluated by the Quality of Life in Epilepsy-31 (QOLIE-31) overall score, and its domain scores determined at follow-up after 36 to 131 months (mean 93 months) after surgery. RESULTS: The mean overall QOLIE-31 score and its subdomain scores improved significantly after surgery (p < 0.01), and 55 patients (76.4%) had a meaningful QOL improvement. Being seizure-free (Engel IA) after surgery showed a non-significant association (OR 2.63, CI 95% 0.53 to 13.05, p = 0.23) and lower depressive symptoms a significant association (OR 4.15, CI 95% 1.19 to 14.53, p = 0.03) with meaningful improvement of QOL. CONCLUSIONS: Patients with MTLE-HS who underwent epilepsy surgery show a sustained, meaningful improvement in their QOL. Pre-surgical variables do not predict long-term QOL improvement after surgery. Lower levels of depressive symptoms at postoperative evaluation are associated with meaningful QOL improvement.

Employment status as a major determinant for lower physical activity of patients with epilepsy: A case-control study.

BACKGROUND: People with epilepsy (PWE) may have a sedentary lifestyle and less physical activity (PA) as they are often advised against engaging in sports, despite a plethora of evidence suggesting seizure control, major health and psychosocial benefits associated with PA. We aimed to investigate PWE's beliefs on PA and their level of PA compared to controls. METHODS: The Baecke questionnaire for measuring habitual PA in adults, comprising three domains (occupational PA, leisure, and locomotion), was applied in 97 consecutive PWE (96.9% with focal epilepsy, 39.2% well controlled with pharmacological treatment) and 45 healthy controls matched for gender, age, and socioeconomic characteristics. RESULTS: The total Baecke score was significantly lower in PWE than controls (7.6 ±â€¯1.5 versus 8.2 ±â€¯1.2; p < 0.01). PWE showed a significantly lower employment rate than controls (34.0% versus 73.3%; p < 0.01), and consequently lower occupational PA (p < 0.01). Physical exercise during sports time (p = 0.23) and leisure activities (p = 0.55) scores were similar between patients and controls. When PWE and controls' sociodemographic characteristics were analyzed together by multiple linear regression, 21% of the Baecke total score variation was explained by diagnosis of epilepsy (B = -0.26; p = 0.05), years of education (B = -0.35; p = 0.03), and occupational status (B = -0.41; p < 0.01). However, diagnosis of epilepsy alone explained only 4% (B = -0.64; p = 0.01) of Baecke total score variation. CONCLUSION: The level of PA in PWE is only slightly lower than in controls (8% lower score) and it may be explained by lower occupational PA, probably related to lower employment rate among PWE.

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.

Anxiety and depressive symptoms long after mesial temporal epilepsy surgery: A prospective study.

BACKGROUND: Anxiety and depressive symptoms are prevalent in patients with refractory mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) before and after anterior temporal lobectomy (ATL). AIMS: (1) To follow the levels of anxiety and depressive symptoms long-term after ATL among patients with refractory MTLE-HS; (2) To identify pre- and postsurgical variables associated with the levels of anxiety and depressive symptoms after surgery. METHODS: We compared the levels of anxiety and depressive symptoms determined by the Hospital Anxiety and Depression Scale (HADS) before and long after ATL (mean 104 months, range 70-130) in 41 consecutive patients refractory MTLE-HS. The last follow-up was between September 2018 and March 2020. We also determined pre- and postsurgical variables independently associated with the HADS scores after surgery. RESULTS: The scores of HADS and its subdomains related to anxiety and depression decreased significantly (p < 0.01) after ATL. After multiple linear regressions, the HADS-Anxiety scores before surgery (B = 0.47, CI 95% 0.20 to 0.75, p = 0.001) and at follow-up after surgery (B = 0.07, CI 0.00 to 0.14, p = 0.05) remain independently and positively associated with HADS-Anxiety scores after surgery. The HADS-Depression scores after surgery were independently positively associated with HADS-Depression scores before surgery (B = 0.39, CI 95% 0.10 to 0.76, p = 0.01) and worse seizure control after surgery (B = 1.55, CI 95% 0.23 to 2.87, p = 0.02). CONCLUSION: Anxiety and depressive symptoms in patients with MTLE-HS significantly improved after ATL. Presurgical levels of anxiety and depressive symptoms, respectively, were positively associated with the postsurgical levels of those symptoms. Length of follow-up is associated with anxiety, and worse seizure control is associated with depressive symptoms after ATL. The results have implications for the surgical management of MTLE-HS patients.

Neuronal activity regulated pentraxin (narp) and GluA4 subunit of AMPA receptor may be targets for fluoxetine modulation.

Fluoxetine is the foremost prescribed antidepressant. Drugs acting on monoaminergic system may also regulate glutamatergic system. Indeed, the investigation of proteins associated with this system, such as Narp (neuronal activity-dependent pentraxin) and GluA4 subunit of AMPA receptor may reveal poorly explored modulations triggered by conventional antidepressants. This study aimed to uncover neurochemical mechanisms underlying the chronic fluoxetine treatment, mainly by evaluating these protein targets in the prefrontal cortex and in the hippocampus. Mice received a daily administration of fluoxetine (0.1, 1 or 10 mg/kg, p.o.) or potable water (vehicle group) for 21 days. These animals were submitted to the forced swim test (FST) to verify antidepressant-like responses and the open-field test (OFT) to assess locomotor activity. Modulation of signaling proteins was analyzed by western blot. Chronic treatment with fluoxetine (1 and 10 mg/kg) was effective, since it reduced the immobility time in the FST, without altering locomotor activity. Fluoxetine 10 mg/kg increased CREB phosphorylation and BDNF expression in the prefrontal cortex and hippocampus. Noteworthy, in the hippocampus fluoxetine also promoted Akt activation and augmented Narp expression. In the prefrontal cortex, a significant decrease in the expression of the GluA4 subunit and Narp were observed following fluoxetine administration (10 mg/kg). The results provide evidence of novel molecular targets potentially involved in the antidepressant effects of fluoxetine, since in mature rodents Narp and GluA4 are mainly expressed in the GABAergic parvalbumin-positive (PV+) interneurons. This may bring new insights into the molecular elements involved in the mechanisms underlying the antidepressant effects of fluoxetine.

Faux Pas Recognition Test: transcultural adaptation and evaluation of its psychometric properties in Brazil.

Introduction: Many neuropsychiatric and neurodegenerative disorders produce Theory of Mind impairment. We aimed to implement a Brazilian Portuguese version of the Faux Pas Recognition Test (FPRT) and evaluate its psychometric properties.Methods: We first completed an English-Brazilian Portuguese translation and adaptation to obtain an FPRT Brazilian Portuguese version. We performed a multicentric study with 153 healthy participants (68.6% women), mean age of 38.8 years (SD = 14.6) and 12.9 years of schooling (SD = 4.5). Linear regression analysis was performed to evaluate the association of social class, age, schooling, and FPRT scores. The psychometric analyses comprised item analysis, exploratory factor analysis, reliability, and validity analysis.Results: Normative data in a Brazilian population is presented. A positive correlation of scores with years of schooling, social class, and an inverse relation with age was found. The exploratory factorial analysis found a two-component structure, one component, consisting of questions 1 through 6 (Eigenvalue 5.325) and another component, consisting of questions 7 and 8 (Eigenvalue 1.09). Cronbach's alpha of the 20 stories was .72. All control stories had a poor discriminative index.Conclusion: The FPRT Brazilian Portuguese version demonstrated good internal consistency and, psychometric properties and is adequate for use even in lower educational contexts in Brazil.

Early Alpha Reactivity is Associated with Long-Term Mental Fatigue Behavioral Impairments.

The quantitative analysis of electroencephalogram (qEEG) is a suitable tool for mental fatigue (MF) assessment. Here, we evaluated the effects of MF on behavioral performance and alpha power spectral density (PSD) and the association between early alpha PSD reactivity and long-term behavioral MF impairments. Nineteen right-handed adults (21.21 ± 1.77 years old) had their EEG measured during five blocks of the visual oddball paradigm (~ 60 min). A paired t-test was used to compare first and last block values of cognitive performance and alpha PSD. The sample was divided into high (HAG) and low alpha group (LAG) by early alpha PSD median values. The behavioral performance of the HAG and LAG was compared across the blocks by a two-way ANOVA with repeated measures (groups and blocks). MF impairs general behavioral performance and increases alpha PSD. The HAG presents more behavioral impairment when compared to LAG across the task. Simple linear regression between early alpha PSD and behavioral performance across the task can predict 19 to 39% of variation in general behavior impairment by MF. In conclusion, MF induction impairs general behavioral and increases alpha PSD. The other finding was that higher alpha PSD reactivity is associated to higher long-term behavioral impairments of MF. This work contributes to existing knowledge of MF by providing evidence that the possibility of investigating early electrophysiological biomarkers to predict long-term MF impairments.

How predictable is cognitive performance in Brazilian patients with pharmacoresistant mesial temporal lobe epilepsy?

OBJECTIVE: The objective of the study was to investigate the independent association between clinical, demographic, psychiatric, radiologic, electrophysiological, and pharmacologic variables and cognitive performance of Brazilian patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE). METHODS: Ninety-three patients with pharmacoresistant MTLE related to hippocampal sclerosis (HS) were included in the study. Multiple linear regressions were done to identify predictor variables for 24 cognitive tests. Independent variables analyzed were sex, hand dominance, age, years of education, marital status, work activity, history for an initial precipitant injury (IPI), family history of epilepsy, lesion side, antiseizure medication (ASM) treatment type, ASM serum levels, benzodiazepine (BDZ) treatment, age at epilepsy onset, disease duration, monthly frequency of seizures, and Hospital Anxiety and Depression Scale (HADS) scores. RESULTS: Years of education was an independent and positive predictor in 22 of the 24 cognitive tests evaluated. Male sex was also a positive predictor of one cognitive test. Variables negatively associated with cognitive performance were left side lesion (10 tests), disease duration (5 tests), polytherapy (3 tests), ASM serum levels (3 tests), and BDZ treatment or not working (1 test each). The regression model explained between 6% and 44% of the cognitive test scores variation. SIGNIFICANCE: In Brazilian patients with pharmacoresistant MTLE-HS, up to 44% of cognitive test scores variation is predictable by clinical, demographic, psychiatric, radiologic, electrophysiology, and pharmacological variables. The identification of predictors of cognitive performance may be helpful for better planning of patient care.

Self-reported adherence among people with epilepsy in Brazil.

BACKGROUND: Nonadherence rates among people with epilepsy (PWE) are widely variable, ranging from 26% to 95.4%. We aimed to identify nonadherence in Brazil, its determinant factors, its impact on patients' management, and to compare it with other chronic nonparoxysmal diseases. METHODS: A multicenter observational case-control study was conducted between March 2015 and October 2016, and 153 subjects were included. Subjects' clinical-epidemiological data were surveyed with the Morisky-Green test (MGT), Brief Medication Questionnaire (BMQ), and the Liverpool adverse events profile (LAEP). RESULTS: One hundred three PWE and 50 controls with other, nonparoxysmal chronic conditions were interviewed; both groups were matched according to age and socioeducational level. People with epilepsy were aged 36.4 ±â€¯13.9 (range 18-67), 55% were women, mean age at epilepsy onset was 18.1 ±â€¯15.5 years, 51.5% had pharmacoresistant epilepsy, and 48.5% were on monotherapy. 74.8% of patients and 70.0% controls were nonadherent to treatment according to MGT (p = 0.58); and barrier of recall (BMQ) was associated with nonadherence in 78% of PWE and 76% of controls (p = 0.84). Binary logistic regression analysis revealed LAEP (OR 1.05; 95%CI = 1.01-1.09; p = 0.03) and self-reported frequency of forgetfulness on the last three months (OR 19.13; 95%CI = 2.40-152.28; p < 0.01) as the main factors associated with nonadherence. Nonadherent subjects did not have more seizures and did not need emergency treatment more often than adherent ones. CONCLUSION: Three of four PWE were not fully adherent to their treatment. Adherence assessment should be routine in all outpatient visits as well as interventions aimed to improving it. Adverse events are important predictors of adherence, and they should be considered when choosing the initial treatment of epilepsy.

Resting Cardiac Vagal Tone is Associated with Long-Term Frustration Level of Mental Workload: Ultra-short Term Recording Reliability.

Excessive mental workload represent a critical risk factor for workplace accidents. Heart rate variability (HRV) is a non-invasive low cost electrophysiological autonomic biomarker related to emotional and cognitive regulation. Several studies report that mental overload impairs parasympathetic-mediated HRV indices (e.g. rMSSD). However, the influence of resting state HRV as a predictor of long-term mental workload impairments remains unknown. Thirty participants (22 males; 8 females) had their HRV measured (5-min period) before performing the number search task. After the task, the mental load was accessed by the NASA-TLX questionnaire. A simple linear regression model between HRV and NASA-TLX dimensions showed that resting state rMSSD is associated to physical demand (ND-2, R2 = 0.143, p = 0.03) and frustration level (ND-6, R2 = 0.175, p = 0.02) dimensions of mental workload. The comparison between 1 and 5-min epochs suggests that regression models remain reliable even using the ultra-short term HRV (< 1 min) recording values (R2 values from 0.11 to 0.15 for ND-2 and R2 values from 0.16 to 0.19 for ND-6). These results suggest that resting state HRV is associated to long-term effects of mental workload on physical and emotional demands. In addition, the ultra-short term HRV indices remains reliable to assess ND-2 and ND-6 dimensions of mental workload when compared to gold-standard time interval (> 5 min). The resting state cardiac autonomic tone assessment optimizes the physiological approach with a quick, non-invasive and low-cost assessment that can provide insights about mental load adjustments to prevent work-related accidents.

Single antiepileptic drug levels do not predict adherence and nonadherence.

OBJECTIVES: To investigate the significance of "subtherapeutic" vs "therapeutic" antiepileptic drug (AED) plasma levels with respect to treatment adherence. MATERIAL AND METHODS: One hundred and seventy patients with refractory temporal lobe epilepsy who underwent video-EEG monitoring in view of a surgical indication had their AEDs (carbamazepine, phenobarbital, phenytoin, and valproate) rapidly withdrawn following a standardized schedule. Plasma levels were measured at admission, and during the 2 days of drug withdrawal. Adherence and nonadherence were identified by the development of plasma levels from day 1 through day 3. Frequencies of an initial level below the reference range in both groups were compared. RESULTS: Adherence was found in 73.2% of cases, and nonadherence in 26.8%. Low levels were seen equally often (about 1/4 of cases) in adherent and nonadherent cases. The vast majority (73.7%) of low levels had another explanation than nonadherence (eg low-dose treatment or enzyme induction). Of 42 nonadherent cases, the vast majority of 76.2% had unsuspicious plasma levels at admission. CONCLUSIONS: "Subtherapeutic" AED plasma levels only rarely are caused by nonadherence whereas levels in the "therapeutic range" by no means prove that the patient is adherent to treatment. For meaningful interpretation, any level needs to be compared with other levels of the same patient. Our findings strongly emphasize the principle of individualized therapeutic AED monitoring as promoted by the Therapeutic Strategies Commission of the ILAE.

Determinants for Meaningful Clinical Improvement of Pain and Health-Related Quality of Life After Spinal Cord Stimulation for Chronic Intractable Pain.

OBJECTIVES: Previous studies demonstrated significant improvement in mean pain scores and quality of life (QOL) scales in patients with chronic pain who underwent spinal cord stimulation (SCS). However, the number of individuals who experience relevant improvements in QOL, termed the meaningful clinical improvement (MCI), is not known. The present study investigated changes in pain measurements based on MCI after SCS. MATERIALS AND METHODS: Thirty-four patients with chronic intractable pain completed scales of pain (visual analogue scale [VAS]), QOL (SF-36), and psychological dimensions during a 22-month follow-up period (mean). Patient-centered MCI of the VAS and SF-36 domain scores were determined based on the MacNab criteria of surgical global effectiveness. Independent presurgical predictors for MCI in the VAS and SF-36 domains were analyzed using multiple binary logistic regression. RESULTS: There was significant improvement of pain and QOL after the SCS (p < 0.00001). Twenty-three patients (67.6%) reached an MCI of pain, and 16 (47.7%)-23 (67.7%) reported an MCI of QOL. Predictors of MCI included ≥80% paresthesia coverage of the painful area, lower levels of anxiety and catastrophizing symptoms, shorter pain duration, female gender and no use of opioids before surgery. MCI of pain and QOL was observed in 50%-70% of patients with chronic pain after SCS. CONCLUSIONS: The identification of determinants for MCI is a challenge to improve the accuracy of prognostic models in SCS for patients with chronic pain. Our results, if confirmed in other populations with a larger sample size, have implications for patients with chronic pain who are candidates for SCS treatment.

Increased cardiac stiffness is associated with autonomic dysfunction in patients with temporal lobe epilepsy.

Autonomic dysfunction is linked to sudden death regardless of the presence of structural heart disease. The pathway from autonomic dysfunction to sudden death is not fully understood, but myocardial sympathetic stimulation leading to arrhythmia and/or cardiac fibrosis might play a role. Our goal was to evaluate cardiac stiffness by echocardiography and its association with clinical, structural, and autonomic variables in people with epilepsy (PWE) compared to healthy controls. A 12-lead electrocardiogram, treadmill testing, and transthoracic echocardiography from 30 patients with temporal lobe epilepsy (TLE) without any known cardiovascular disorders were compared to 30 individuals without epilepsy matched by sex, age, and body mass index. Distribution of cardiovascular risk factors was similar in both groups. PWE had a higher left ventricle stiffness, left ventricle filling pressure, and greater left atrial volume as well as markers of autonomic dysfunction such as impaired chronotropic index and percentage achieved of predicted peak heart rate at effort. In multiple regressions, autonomic dysfunction explained 52% of stiffness and carbamazepine treatment and polytherapy with antiepileptic drugs (AEDs) explained, additionally, 6% each. Stiffness is increased in young patients with TLE and is related to autonomic dysfunction and to a lesser extent, carbamazepine use and polytherapy with AEDs.

Mesial temporal lobe epilepsy with hippocampal sclerosis is infrequently associated with neuronal autoantibodies.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is characterized by its well-defined clinical profile. Limbic encephalitis is increasingly recognized as a possible etiology of adult-onset MTLE-HS, and neuronal autoantibodies have been detected in patients even without previous signs of encephalitis. The aim of this study is to analyze the frequency of specific autoantibodies in patients with MTLE-HS. A case-control study was carried out with 100 patients with MTLE-HS and 50 healthy controls. Sera samples from subjects were tested by indirect immunofluorescence assay for detection of anti-N-methyl-d-aspartate receptor (NMDA-R), anti-contactin-associated protein-like 2 (CASPR2), anti-leucine-rich glioma inactivated 1 (LGI1), anti-gamma aminobutyric acid B receptor (GABA-B-R), anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1 and 2 receptors (AMPA-1-R and AMPA-2-R), and enzyme-linked immunosorbent assay for detection of anti-glutamic acid decarboxylase 65 (GAD65). Mean age of patients and controls was 41.2 vs 42 years, and 55% vs 56% were female. Mean duration of epilepsy was 27.2 years. No neuronal autoantibodies were found in either group, except for anti-GAD65 in 3 patients and 2 controls. This study adds to the mounting evidence that, in Brazilian patients, MTLE-HS without signs and symptoms of autoimmune encephalitis may be infrequently associated with these autoantibodies. Differences regarding accuracy of used methodologies for autoantibody detection and genetic and environmental characteristics are discussed. Further works with different methodologies tested simultaneously in different populations may help clarify the incongruent study results about autoantibodies in MTLE-HS.