Theory of mind in epilepsy.

Epilepsy is characterized by recurrent, chronic, and unprovoked seizures. Epilepsy has a significant negative impact on a patient's quality of life even if seizures are well controlled. In addition to the distress caused by seizures, patients with epilepsy (PwE) may suffer from cognitive impairment with serious social consequences such as poor interpersonal relationships, loss of employment, and reduced social networks. Pathological changes and functional connectivity abnormalities observed in PwE can disrupt the neural network responsible for the theory of mind. Theory of mind is the ability to attribute mental states to other people (intentions, beliefs, and emotions). It is a complex aspect of social cognition and includes cognitive and affective constructs. In recent years, numerous studies have assessed the relationship between social cognition, including the theory of mind, in PwE, and suggested impairment in this domain. Interventions targeting the theory of mind can be potentially helpful in improving the quality of life of PwE.

Female sex is strongly associated with cognitive impairment in HIV infection.

BACKGROUND: Neurocognitive disorders remain frequent despite highly active antiretroviral treatment (HAART). The CNS is known as the sanctuary of HIV infection, where persistent neuroinflammation occurs regardless of viral suppression. Moreover, opportunistic infections, neurovascular damage and HAART neurotoxicity contribute to neurocognitive impairment. Therefore, detailed epidemiological studies might help to elucidate those complex mechanisms. OBJECTIVE: To investigate the prevalence of cognitive impairment and the associated sociodemographic, clinical and neuropsychological variables among HIV-infected patients admitted to a tertiary centre, in southern Brazil. METHODS: An observational, cross-sectional and analytic study was conducted between February 2019 and March 2020, in Hospital Nereu Ramos (HNR), with148 HIV-infected patients. They were interviewed, submitted to the International HIV Dementia Scale (IHDS) and had their medical data analysed. RESULTS: The prevalence of cognitive impairment was 69.6%. It was higher among women (OR = 3.5; 95% CI 1.5-8; p < 0.01), independently of depression, educational status and age. Full years of schooling were strongly associated with IHDS scores (p < 0.01). Patient Health Questionnaire-9 (PHQ-9) scores for depression (p = 0.8), time since HIV diagnosis (p = 0.2), CD4+ cell counts (p = 0.8) and viral load (p = 0.8) were not associated with IHDS scale. CONCLUSION: A high prevalence of cognitive impairment in HIV-infected patients was identified, independently associated with the female sex and fewer years of schooling. Further studies are needed to clarify the differences in the pathophysiology between sexes and the role of cognitive reserve in prevention of cognitive impairment in HIV infection.

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.

Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study.

OBJECTIVES: To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients. METHODS: Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1 year after ATL in 77 consecutive patients with unilateral MTLE-HS. RESULTS: The overall QOLIE-31 score and all its subscale scores increased significantly (p < 0.0001) 1 year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1-16.1, p = 0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2-14.5, p = 0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity. SIGNIFICANCE: These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients.

Decline in word-finding: The objective cognitive finding most relevant to patients after mesial temporal lobe epilepsy surgery.

PURPOSE: The purpose of this study was to investigate the following: i) the objective impairment in neuropsychological tests that were associated with the subjective perception of cognitive function decline in Brazilian patients who underwent mesial temporal lobe epilepsy (MTLE) surgery and ii) the predictive variables for those impaired objective neuropsychological tests. METHODS: Forty-eight adults with MTLE (27 right HS and 23 male) were divided according to their perception of changes (Decline or No-decline) of cognitive function domain of the QOLIE-31 questionnaire applied before and 1year after the ATL. The mean (SD) of changes in the raw score difference of the neuropsychological tests before and after the ATL was compared between Decline and No-decline groups. Receiver Operating Characteristic curves, sensitivity, specificity, and predictive values were used to assess the optimum cutoff points of neuropsychological test score changes to predict patient-reported subjective cognitive decline. KEY FINDINGS: Six (12.5%) patients reported a perception of cognitive function decline after ATL. Among the 25 cognitive tests analyzed, only changes in the Boston Naming Test (BNT) were associated with subjective cognitive decline reported by patients. A reduction of ≥8 points in the raw score of BNT after surgery had 91% of sensitivity and 45% specificity for predicting subjective perception of cognitive function decline by the patient. Left side surgery and age older than 40years were more associated with an important BNT reduction with overall accuracy of 91.7%, 95% predictive ability for no impairment, and 75% for impairment of cognitive function. SIGNIFICANCE: Impairment in word-finding seems to be the objective cognitive finding most relevant to Brazilian patients after mesial temporal lobe epilepsy surgery. Similar to American patients, the side of surgery and age are good predictors for no decline in the BNT, but shows a lower accuracy to predict its decline. If replicated in other populations, the results may have wider implications for the surgical management of patients with drug-resistant MTLE.

Variables associated with physical health-related quality of life in Parkinson's disease patients presenting for deep brain stimulation.

Deep brain stimulation (DBS) benefits Parkinson's disease (PD) patient's quality of life specially in domains as mobility, activities of daily living (ADL) and bodily discomfort (BD), but little is known about the variables associated with these HRQOL domains in patients presenting for DBS. The objective is to evaluate variables associated with of HRQOL in a Brazilian sample of PD patients presenting for DBS treatment, specifically in the domains related with motor symptoms. In a cross-sectional study of 59 PD patients evaluated at outpatient Unit for Movement Disorders, multiple linear regression analysis was performed to identify independent variables associated with mobility, ADL and BD domains of the 39-item Parkinson's disease questionnaire (PDQ-39). UPDRS III "on" scores, duration of the disease, age, presence of comorbidities and anxiety and depressive symptoms quantified by hospital anxiety and depression scale (HADS), were the independent variables. In our results, HADS scores were independently associated to mobility domain: ß coefficient 1.36 (95 % CI 0.55-2.15) and BD domain: ß coefficient 1.57 (95 % CI 0.67-2.48). UPDRS III "on" scores were independently associated to mobility domain: 0.42 (95 % CI 0.03-0.81). The model of each multiple linear regression analysis explains 25 % of the mobility domain variability (p < 0.01) and 24 % of the BD domain variability (p < 0.01). Psychiatric symptoms were at least as relevant to quality of life as motor symptoms in PD patients presenting for DBS treatment. The effect of treating these psychiatric symptoms on patients' HRQOL deserves further investigation.

Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury.

INTRODUCTION: Changes in hormone blood levels during the acute phase of traumatic brain injury (TBI) have been described in the literature. The objective was to investigate the association among several hormones plasma levels in the acute phase of severe TBI and the hospital mortality rate of male patients. METHODS: The independent association among plasma levels of TSH, LH, FSH, GH, free T4, cortisol, IGF-1 and total testosterone was measured 10 hours and 30 hours after severe TBI and the hospital mortality of 60 consecutive male patients was evaluated. RESULTS: At least one hormonal level abnormality was demonstrated in 3.6-73.1% of patients. The multiple logistic regressions showed a trend for an independent association among hospital mortality and normal or elevated LH levels measured at 10 hours (OR = 3.7, 95% CI = 0.8-16.3, p = 0.08) and 30 hours (OR = 3.9, 95% CI = 0.9-16.7, p = 0.06). Admission with abnormal pupils and a lower Glasgow Coma Score also were independently associated with hospital mortality. CONCLUSION: The hormonal changes are frequent in the acute phase of severe TBI. The hormones plasma levels, excepting the LH, are not highly consistent with the hospital mortality of male patients.

Cognitive Performance of Brazilian Patients With Favorable Outcomes After Severe Traumatic Brain Injury: A Prospective Study.

OBJECTIVE: The aim of this study was to investigate the cognitive performance of patients with favorable outcomes, determined by the Glasgow Outcome Scale, 1 yr after hospital discharge due to severe traumatic brain injury. DESIGN: This was a prospective case-control study. From 163 consecutive adult patients with severe traumatic brain injury included in the study, 73 patients had a favorable outcome (Glasgow Outcome Scale score of 4 or 5) 1 yr after hospital discharge and were eligible for the cognitive evaluation, of which 28 completed the evaluations. The latter were compared with 44 healthy controls. RESULTS: The average loss of cognitive performance among participants with traumatic brain injury varied between 13.35% and 43.49% compared with the control group. Between 21.4% and 32% of the patients performed below the 10th percentile on three language tests and two verbal memory tests, whereas 39% to 50% performed below this threshold on one language test and three memory tests. Longer hospital stay, older age, and lower education were the most important predictors of worse cognitive performance. CONCLUSION: One year after a severe traumatic brain injury, a significant proportion of Brazilian patients with the favorable outcome determined by Glasgow Outcome Scale still showed significant cognitive impairment in verbal memory and language domains.

Predictors of quality of life in patients with refractory mesial temporal lobe epilepsy.

PURPOSE: The identification of variables associated with health-related quality of life (HRQoL) in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) would improve surgical decision-making and post-operatory follow-up in this group of patients. METHODS: We analyzed the independent association between the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) of 81 consecutive patients with refractory MTLE-HS. The clinical, demographic, radiological and electrophysiological variables were analyzed by multiple linear regression analysis. KEY FINDINGS: Approximately 36% (adjusted R(2)=0.36; R coefficient=0.66) of the QOLIE-31 overall score variance was explained by the history of initial precipitant injury, family history of epilepsy, disease duration, age of epilepsy onset, seizure frequency and presence of psychiatric axis-II diagnosis. The variance of QOLIE-31 sub-scales was: seizure worry=7%; overall QOL=11%; emotional well-being=32%; energy/fatigue=38%; cognitive function=13%; medication effects=7%; social function=13% (R coefficient between 0.30 and 0.65). SIGNIFICANCE: The pre-surgical variables studied had relatively low prediction capacity for the overall QOLIE-31 score and its sub-scales in this set of Brazilian patients with refractory MTLE-HS.

Is self-report sleepiness associated with cognitive performance in temporal lobe epilepsy?

OBJECTIVES: Sleepiness and cognitive impairment are common symptoms observed in patients with epilepsy. We investigate whether self-reported sleepiness is associated with cognitive performance in patients with refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Seventy-one consecutive patients with MTLE-HS were evaluated with the Stanford Sleepiness Scale (SSS) before neuropsychological evaluation. Their mean SSS scores were compared with controls. Each cognitive test was compared between patients with (SSS ≥ 3) or without sleepiness (SSS < 3). Imbalances were controlled by regression analysis. Patients reported a significantly higher degree of sleepiness than controls (p < 0.0001). After multiple linear regression analysis, only one test (RAVLT total) remained associated with self-reported sleepiness. CONCLUSION: Self-reported sleepiness was significantly higher in MTLE-HS patients than controls, but did not affect their cognitive performance. If confirmed in other populations, our results may have implications for decision making about sleepiness screening in neuropsychological settings.

Neuropsychological functioning and brain energetics of drug resistant mesial temporal lobe epilepsy patients.

Interictal hypometabolism is commonly measured by 18-fluoro-deoxyglucose Positron Emission Tomography (FDG-PET) in the temporal lobe of patients with mesial temporal lobe epilepsy (MTLE-HS). Left temporal lobe interictal FDG-PET hypometabolism has been associated with verbal memory impairment, while right temporal lobe FDG-PET hypometabolism is associated with nonverbal memory impairment. The biochemical mechanisms involved in these findings remain unknown. In comparison to healthy controls (n=21), surgically treated patients with MTLE-HS (n=32, left side=17) had significant lower scores in the Rey Auditory Verbal Learning Test (RAVLT retention and delayed), Logical Memory II (LMII), Boston Naming test (BNT), Letter Fluency and Category Fluency. We investigated whether enzymatic activities of the mitochondrial enzymes Complex I (C I), Complex II (C II), Complex IV (C IV) and Succinate Dehydrogenase (SDH) from the resected samples of the middle temporal neocortex (mTCx), amygdala (AMY) and hippocampus (HIP) were associated with performance in the RAVLT, LMII, BNT and fluency tests of our patients. After controlling for the side of hippocampus sclerosis, years of education, disease duration, antiepileptic treatment and seizure outcome after surgery, no independent associations were observed between the cognitive test scores and the analyzed mitochondrial enzymatic activities (p>0.37). Results indicate that memory and language impairment observed in MTLE-HS patients are not strongly associated with the levels of mitochondrial CI, CII, SDH and C IV enzymatic activities in the temporal lobe structures ipsilateral to the HS lesion.

Synaptosomal glutamate release and uptake in mice lacking the cellular prion protein.

Glutamate plays a central role in the fast excitatory synaptic transmission and is a key neurotransmitter involved in several neurophysiological processes. Glutamate levels on the synaptic cleft are related to neural excitability, neuroplasticity, and neuronal damage associated with excitotoxicity. Mice lacking the cellular prion protein (PrP(c)) gene (Prnp) present a decreased astrocytic glutamate uptake in cultures, higher neuronal excitability in vitro and sensitivity to pro-convulsant drugs in vivo, and age-dependent memory impairment. Here, we investigate if PrP(c) might be involved in neuronal uptake and release of glutamate. For this purpose, we compared synaptosomal preparations from the cerebral cortex, entorhinal cortex, hippocampus, cerebellum, and olfactory bulb of 3- or 9-month-old PrP(c) null mice and with respective wild-type controls. Although we observed differences in synaptosomal glutamate release and uptake regarding the age of mice and the brain structure studied, these differences were similar for PrP(c) null mice and their respective wild-type controls. Therefore, despite a possible correlation between neuronal glutamate transporters, excitability, and neuronal damage, our results suggest that PrP(c) expression is not critical for neuronal glutamate transport.

Limited predictive power of hospitalization variables for long-term cognitive prognosis in adult patients with severe traumatic brain injury.

OBJECTIVES: Traumatic brain injury (TBI) is a main cause of mortality and morbidity. Association studies between hospitalization variables and cognitive impairment after TBI are frequently retrospective, including non-consecutive patients showing variable degrees of TBI severity, and poor management of missing (drop out) cases. METHODS: We assessed prospectively the demographic and hospitalization variables of 234 consecutive patients with severe TBI (admission Glasgow Coma Scale [GCS] ≤8) and determined their independent association with cognitive performance in a representative sample (n = 46) of surviving patients (n = 172) evaluated 3 (±1.8) years after hospitalization. RESULTS: In all, 85% of patients were male and the mean age was 34 (SD ±13) years. The education level was 9 (±4.7) years. As expected, education and age showed a moderately to strong linear relationship with the cognitive performance in 14 of 15 neuropsychological tests (R coefficient = 0.6-0.8). The cognitive test scores were not independently associated with gender, admission GCS, associated trauma, and Marshal CT classification. Admission-elevated blood glucose levels and the presence of sub-arachnoid haemorrhage were independently associated with lower scores on Rey Auditory Verbal Learning retention and Logical Memory-I tests, respectively. CONCLUSIONS: After correction for education and age distribution, the variables that are commonly associated with mortality or Glasgow Outcome Scale including admission pupils' examination, Marshal CT Classification, GCS, and serum glucose showed a limited predictive power for long-term cognitive prognosis. Identification of clinical, radiological, and laboratory variables as well as new biomarkers independently associated with cognitive outcome remains an important challenge for further work involving severe TBI patients.

Is self-report sleepiness associated with cognitive performance in temporal lobe epilepsy? / A sonolência auto-relatada está associada ao desempenho cognitivo na epilepsia do lobo temporal?

ABSTRACT Sleepiness and cognitive impairment are common symptoms observed in patients with epilepsy. We investigate whether self-reported sleepiness is associated with cognitive performance in patients with refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Seventy-one consecutive patients with MTLE-HS were evaluated with the Stanford Sleepiness Scale (SSS) before neuropsychological evaluation. Their mean SSS scores were compared with controls. Each cognitive test was compared between patients with (SSS ≥ 3) or without sleepiness (SSS < 3). Imbalances were controlled by regression analysis. Patients reported a significantly higher degree of sleepiness than controls (p < 0.0001). After multiple linear regression analysis, only one test (RAVLT total) remained associated with self-reported sleepiness. Conclusion: Self-reported sleepiness was significantly higher in MTLE-HS patients than controls, but did not affect their cognitive performance. If confirmed in other populations, our results may have implications for decision making about sleepiness screening in neuropsychological settings.

RESUMO A sonolência e o comprometimento cognitivo são queixas comuns na epilepsia. Investigamos se a sonolência relatada pelo paciente está associada ao desempenho cognitivo na epilepsia do lobo temporal mesial refratária com esclerose do hipocampo (ELTM-EH). 71 pacientes com ELTM-EH foram avaliados pela Escala de Sonolência de Stanford (ESS) antes da avaliação neuropsicológica. A média na ESS foi comparada com a de controles. Cada teste foi comparado entre os pacientes com sonolência (ESS ≥ 3) ou sem sonolência (ESS <3). Diferenças foram controladas por regressão logística múltipla. Os pacientes relataram uma sonolência maior do que os controles (p <0,0001). Após a regressão, a sonolência relatada pelos pacientes mostrou-se associada a apenas um teste (RAVLT total). Os pacientes com ELTM-EH referem mais sonolência do que os controles, mas esta não foi associada com a cognição. Se confirmado em outras populações, nossos resultados implicarão na tomada de decisão sobre o impacto da sonolência no contexto neuropsicológico.

Psychiatric disorders and health-related quality of life after severe traumatic brain injury: a prospective study.

Traumatic brain injury (TBI) is a major cause of death and disability and impairs health-related quality of life (HRQOL). Psychiatric disorders have been recognized as major components of TBI morbidity, yet few studies have addressed the relationship between these outcomes. Sample size, selection bias, and retrospective design, are methodological limitations for TBI-related psychiatric studies. For this study, 33 patients with severe TBI were evaluated prospectively regarding demographic, clinical, radiological, neurosurgical, laboratory, and psychosocial characteristics, as well as psychiatric manifestations and HRQOL, 18 months after hospitalization. Psychiatric manifestations were assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Hospital Anxiety and Depression Scale (HADS), the Brief Psychiatric Rating Scale (BPRS), and the Apathy Evaluation Scale (AES). HRQOL was determined using the Medical Outcomes Study's 36-item Short-Form Health Survey (SF-36). Following TBI, a significant increase in the prevalence of major depressive disorder (MDD) and generalized anxiety disorder (p=0.02), and a significant decrease in the prevalence of alcohol and cannabinoid abuse (p=0.001) were observed. The most frequent psychiatric disorders following severe TBI were found to be MDD (30.3%), and personality changes (33.3%). In comparison to patients without personality changes, patients with personality changes experienced a decline in general health and impairments in physical and social functioning. Patients with MDD showed impairment in all SF-36 domains compared to non-depressed patients. This prospective TBI-related psychiatric study is the first to demonstrate a significant association between MDD, personality changes, and HRQOL, following severe TBI in a well-defined sample of patients.

Psychiatric disorders and traumatic brain injury.

Psychiatric disorders after traumatic brain injury (TBI) are frequent. Researches in this area are important for the patients' care and they may provide hints for the comprehension of primary psychiatric disorders. Here we approach epidemiology, diagnosis, associated factors and treatment of the main psychiatric disorders after TBI. Finally, the present situation of the knowledge in this field is discussed.