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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., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The central autonomic network, which is connected to the limbic system structures including the amygdala (AMY) and anterior hippocampus (aHIP), regulates the sympathetic and parasympathetic modulation of visceromotor, neuroendocrine, pain, and behavior manifestations during stress responses. Heart rate variability (HRV) is useful to estimate the cardiac autonomic tone. The levels of phosphorylation on the Ser831 and Ser845 sites of the GluA1 subunit of the AMPAr (P-GluA1-Ser845 and P-GluA1-Ser831) are useful markers of synaptic plasticity. The relation between synaptic plasticity in the human limbic system structures and autonomic regulation in humans is unknown. This study investigated the association between HRV and neurochemistry biomarkers of synaptic plasticity in AMY and aHIP. HRV indices were obtained from the resting state electrocardiogram of patients with drug-resistant mesial temporal lobe epilepsy (MTLE, n = 18) and the levels of P-GluA1-Ser845 and P-GluA1-Ser831 in the AMY and aHIP resected during the epilepsy surgery. A backward stepwise multiple linear regression models were used to analyze the association between HRV and synaptic plasticity biomarkers controlling for imbalances in the distribution of sociodemographic, clinical, neuroimaging, and neurosurgical variables. P-GluA1-Ser845 levels in AMY show a negative association (p < 0.05) with the 3 investigated parasympathetic autonomic HRV indices (SDNN, rMSSD, and HF) predicting 24 to 40% of their variation. The final multiple linear regression models include disease duration and levels of P-GluA1-Ser845 and predict 24 to 56% of cardiac autonomic tone variation (p < 0.01). P-GluA1-Ser845 levels in AMY and aHIP are negatively associated with the resting HRV in MTLE-HS indicating that increased synaptic efficiency in amygdala is associated with a parasympathetic cardiac autonomic tone impairment. The results suggest that specific changes in synaptic plasticity may be involved in the brain-heart axis regulation by the limbic system.

Objective: Parkinson's disease (PD) is often accompanied by stigma, which could contribute to a worse prognosis. The objective of this study is to identify the variables associated with stigma in PD patients who are candidates for deep brain stimulation (DBS)., Methods: We investigated sociodemographic and clinical variables associated with stigma in a sample of 54 PD patients indicated for DBS. The independent variables were motor symptoms assessed by the Movement Disorder Society-sponsored revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS III), depressive symptoms measured by the Hospital Anxiety and Depression Scale, age, disease duration and the presence of a general medical condition. The Mobility, Activities of daily living and Emotional well-being domains of the 39-item Parkinson's Disease Questionnaire (PDQ-39) were also investigated as independent variables, and the Stigma domain of the PDQ-39 scale was considered the outcome variable., Results: After multiple linear regression analysis, activities of daily living remained associated with the Stigma domain (B = 0.42 [95%CI 0.003-0.83], p = 0.048). The full model accounted for 15% of the variance in the Stigma domain (p = 0.03)., Conclusions: Although causal assumptions are not appropriate for cross-sectional studies, the results suggest that ADL difficulties could contribute to greater stigma in PD patients with refractory motor symptoms who are candidates for DBS.

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.

Introduction: Facet joint injections (FJIs) of anesthetic and corticosteroids are useful for the diagnosis and treatment of low back pain (LBP). In the current study, we evaluated the efficacy of FJI on LBP treatment and the predictive variables of pain recurrence after FJI., Methods: We included and followed prospectively forty-three consecutive patients with chronic LBP treated with FJI. Clinical assessments were carried out at a baseline 1 week before FJIs and after a 6-month follow-up visit using the visual analog scale (VAS) for pain, Oswestry Disability Index (ODI) for disability-specific measure and MacNab criteria for global effectiveness, and compared through analysis using paired-samples " t " tests. Multiple cox-regression analysis was used to identify the presurgical variables independently associated with pain recurrence anytime during the follow-up. In addition to the demographic, clinical, and surgical data, we also analyzed psychometric scales: Pain Catastrophizing Scale (PCS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI)., Results: After a 6-month follow-up, thirty-two patients (74.4%) showed a clinically significant reduction of pain and twenty-seven (62.8%) reported a clinically significant improvement of disability. Presurgical catastrophizing (PCS score ≥ 5, adjusted HR 4.4, CI 95% 1.7-11.3, p = 0.002) and smoking (Adjusted HR 12.5, CI 95% 1.1-138.9, p = 0.04) remains associated with pain recurrence., Conclusion: FJI reduces LBP and disability of patients with unresponsive LBP. Pain-related cognitive and behavioral factors determined by pain catastrophizing and smoking were independently associated with pain recurrence after lumbar FJI. The results support the need of a multidisciplinary approach for presurgical evaluation of patients with chronic pain., (Copyright © 2019 Campos, Linhares, Sarda, Santos, Lin, Latini and Walz.)

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., (© 2018 International Neuromodulation Society.)

Aim: Evaluating the recurrence patterns of high-grade astrocytomas in patients who were treated with radiotherapy (RT) plus temozolomide (TMZ)., Background: The current literature suggests that reducing the margins added to the CTV does not significantly change the risk of recurrence and overall survival; thus, we decided to analyze our data and to examine the possibility of changing the adopted margins., Materials and Methods: From February 2008 till September 2013, 55 patients were treated for high-grade astrocytomas, 20 patients who had been confirmed to have recurrence were selected for the present study. Post-operative MRI was superimposed on the planning CT images in order to correlate the anatomical structures with the treatment targets. Recurrences were defined according to the Response Assessment Criteria for Glioblastoma. The mean margins of the PTV initial and PTV boost were 1.2 cm and 1.4 cm, respectively. The analysis of the percentage of the recurrence volume (Vol rec ) within the 100% isodose surface was based on the following criteria: (I) Central: >95% of the Vol rec ; (II) In-field: 81-95% of the Vol rec ; (III) Marginal: 20-80% of the Vol rec ; and (IV) Outside: <20% of the Vol rec ., Results: Of the 20 patients, 13 presented with central recurrences, 3 with in-field recurrences, 2 with marginal recurrences and 2 with outside recurrences. Therefore, the lower Vol rec within 100% of the prescribed dose was considered in the classification., Conclusions: Of the selected patients, 80% had ≥81-95% of the Vol rec within 100% of the prescribed dose and predominantly had central or in-field recurrences. These results are comparable with those from the literature.

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Glucocorticoids (GC) released during stress response exert feedforward effects in the whole brain, but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC are the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events. Through a quasi-randomized controlled study, we show that a single high dexamethasone dose significantly reduces in a dose-dependent manner the levels of GluA1-Ser831 phosphorylation in the amygdala resected during surgery for temporal lobe epilepsy. This is the first report demonstrating GC effects on key markers of synaptic neuroplasticity in the human limbic system. The results contribute to understanding how GC affects the human brain under physiologic and pharmacologic conditions.

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: β coefficient 1.36 (95 % CI 0.55-2.15) and BD domain: β 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.

Background: The aim of this systematic review was to answer the focused question, "What are the prevalence and the epidemiological characteristics of trigeminal neuralgia in the general population?", Types of Studies Reviewed: This systematic review included observational population-based studies reporting the prevalence of trigeminal neuralgia (TN). The authors developed specific search strategies for LILACS, PubMed, ScienceDirect, Scopus, Web of Science, and Google Scholar. The authors evaluated the methodological quality of the included studies using criteria from the Agency for Healthcare Research and Quality., Results: Among 728 studies, the authors selected only 3 for inclusion. Two studies were classified as having low risk of bias and 1 as having moderate risk. The sample size ranged from 1,838 to 13,541 adults. This review identified a higher prevalence of TN in women, ranging from 0.03% (95% confidence interval [CI], 0.01-0.08) to 0.3% (95% CI, 0.16-0.55). The maxillary and mandibular branches of the trigeminal nerve were the most affected. The proportion between women and men who had TN was 3 to 1, and those in the age bracket between 37 and 67 years were the most affected., Conclusions and Practical Implications: The authors of this review identified a higher prevalence of TN in women older than 40 years that usually affected the maxillary and mandibular branches. Further research is required to validate the prevalence of TN in a well-structured, population-based study without a convenience sample., (Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Mitochondrial respiratory chain complexes enzymatic (MRCCE) activities were successfully evaluated in frozen brain samples. Epilepsy surgery offers an ethical opportunity to study human brain tissue surgically removed to treat drug resistant epilepsies. Epilepsy surgeries are done with hemodynamic and laboratory parameters to maintain physiology, but there are no studies analyzing the association among these parameters and MRCCE activities in the human brain tissue. We determined the intra-operative parameters independently associated with MRCCE activities in middle temporal neocortex (Cx), amygdala (AMY) and head of hippocampus (HIP) samples of patients (n = 23) who underwent temporal lobectomy using multiple linear regressions. MRCCE activities in Cx, AMY and HIP are differentially associated to trans-operative mean arterial blood pressure, O2 saturation, hemoglobin, and anesthesia duration to time of tissue sampling. The time-course between the last seizure occurrence and tissue sampling as well as the sample storage to biochemical assessments were also associated with enzyme activities. Linear regression models including these variables explain 13-17 % of MRCCE activities and show a moderate to strong effect (r = 0.37-0.82). Intraoperative hemodynamic and laboratory parameters as well as the time from last seizure to tissue sampling and storage time are associated with MRCCE activities in human samples from the Cx, AMYG and HIP. Careful control of these parameters is required to minimize confounding biases in studies using human brain samples collected from elective neurosurgery.

Objective: To evaluate predictors of non-return to work (nRTW) among social, demographic, clinical, and psychiatric variables after severe traumatic brain injury (TBI) in a cohort of Brazilian patients., Methods: Prospective study. Forty-three community-dwelling individuals treated at a Level I trauma center at the time of TBI were evaluated 18 months after trauma. Measures included DSM-IV-TR criteria for personality changes after TBI and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) to assess psychiatric diagnosis. Hospitalization variables included Glasgow Coma Scale scores, pupil examination findings, associated limb trauma, Marshall computed tomography classification, and blood glucose levels., Results: After multiple logistic regression analysis, only the diagnosis of personality changes was found to be independently associated with nRTW, with an adjusted odds ratio of 10.92 (p = 0.02, 95% confidence interval 1.41-84.28)., Conclusions: In this study, personality changes were an independent predictor of nRTW after severe TBI. Ways to predict risk factors associated with personality changes after severe brain injury could aid in identification of early and effective interventions that might ease the burden associated with this condition.

Objective: To evaluate the validity and utility of the Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory (BDI), and Hospital Anxiety and Depression Scale (HADS) as screening tools for depression after severe traumatic brain injury (TBI)., Methods: Forty-six consecutive survivors of severe TBI were evaluated at a median of 15 months after injury. Receiver operating characteristic (ROC) analysis was performed using HAM-D, BDI, and HADS as predictors, and the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) as gold standard., Results: The area under the curve (AUC) for HAM-D was 0.89, and the optimal cutoff point was 7 (sensitivity 92.9%, specificity 78.1%); for the BDI, the AUC was 0.946 and the optimal cutoff point was 14 (sensitivity 92.3%, specificity 96.7%); for the HADS, the AUC was 0.947 and the optimal cutoff point was 9 (sensitivity 100%, specificity 80.7%); and for the HADS depression subscale, the AUC was 0.937 and the optimal cutoff point was 6 (sensitivity 92.9%, specificity 83.9%). There were no statistically significant differences among the AUCs., Conclusion: Our findings support a high validity and utility for the HAM-D, BDI, and HADS as screening tools for depression in patients with severe TBI, without major changes in standard cutoff points.

We compared the lifetime prevalence and the prevalence of headache during the previous year in patients with Parkinson's disease (PD) and control subjects. We also investigated the association between the side of PD symptom onset and the side of the headache. We interviewed 98 consecutive patients with an established diagnosis of PD between December 2010 and January 2012. The control group consisted of the 98 oldest sex-matched individuals from the nationwide Brazilian headache database. PD patients showed a significantly lower prevalence (40.8%) of headache in the previous year than controls (69.4%) (adjusted OR 0.5, CI 95% 0.2-0.9, p = 0.03). PD patients also showed a lower prevalence of headache throughout life (74.5%) than controls (93.9%) (adjusted OR 0.2, CI 95% 0.1-0.6, p = 0.01). Considering only patients who presented headache during the previous year, PD patients showed a higher association with occurrence of migraine than tension-type headache compared with controls (adjusted OR 3.3, CI 95% 1.2-8.9, p = 0.02). The headache side was ipsilateral to the side of PD onset in 21 patients (84%), with a concordance of 85.7% on the left side and 81.8% on the right side (p < 0.01). The prevalence of primary headache was significantly lower in patients with PD than controls. The predominant side of headache was ipsilateral to the side of initial motor signs of PD.

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., (© 2012 The British Psychological Society.)

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.

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: The association between biomarkers of oxidative stress and the prognosis of patients with traumatic brain injury (TBI) remains inconclusive., Objective: The objective was to investigate the association between plasma levels of lipid peroxidation (thiobarbituric acid reactive species [TBARS]) and protein oxidation (carbonyl) biomarkers and the hospital mortality of patients with severe TBI., Methods: Plasma levels of TBARS and carbonyl were determined in 79 consecutive patients with severe TBI (Glasgow Coma Scale [GCS] ≤8) at a median of 12 hours (interquartile range [IQ] 25-75, 6.5-19.0), 30 hours (IQ 25-75, 24.7-37.0), and 70 (IQ 25-75, 55.0-78.5) hours after TBI and were compared with age- and sex-matched controls. The association between the TBARS and carbonyl levels and the hospital mortality was analyzed by multiple logistic regression analysis., Results: The mean age of patients was 34.8 years. Eighty-six percent were male. The TBARS and carbonyl levels were significantly higher in patients than in controls. There was a trend (P = .09) for higher plasma levels of TBARS and carbonyl proteins at 12 hours, but not at 30 or 70 hours, after trauma in nonsurvivors than in survivors. These findings were not confirmed after the adjustments by multiple logistic regression analysis. The final model showed a higher adjusted odds ratio for death for patients with admission GCS lower than 5 (odds ratio [OR] = 4.04; 95% confidence interval [CI], 1.33-12.13; P = .01) than those with higher GCS scores. Abnormal pupils were also associated with higher mortality (OR = 3.97; 95% CI, 1.22-12.13; P = .02). There was a nonsignificant trend for association between glucose greater than or equal to 150 mm/dL in the first 12 hours and death than levels between 70 and 149 mg/dL (OR = 2.92; 95% CI, 0.96-9.02; P = .06)., Conclusions: Plasma levels of TBARS and carbonyl increase significantly in the first 70 hours after severe TBI but are not independently associated with the hospital mortality., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: We investigate the demographic, clinical and surgical variables associated with wound and ventriculoperitoneal (VP) shunt infections in a well-defined group of patients submitted to neurosurgical myelomeningocele repair., Methods: We analyzed the data of sixty consecutive patients with a myelomeningocele diagnosis submitted to neurosurgical repair between January 2002 and December 2005. Multiple logistic regression analysis identified clinical, demographic and neurosurgical variables that were independently associated with the occurrence of wound and VP shunt infections., Results: Seven patients (11.7%) developed wound infections after myelomeningocele repair and two (3.3%) presented with sepsis unrelated to the neurosurgical procedures. Forty-six patients (76.7%) received a VP shunt and nine of them (19.6%) had VP shunt infection. There was a non-significant trend (p=0.09) for a higher association between thoracic than lumbar or sacral topography and the occurrence of any type of infection. Among patients who underwent VP shunt placement, there was a non-significant trend for a higher association between VP shunt infection and thoracic topography compared to lumbar or sacral regions (adjusted OR 4.3; CI 95% 0.7-24.7; p=0.10). Evans' index scores higher than 70 were ten times more associated with VP shunt infection (adjusted OR 10.5; CI 95% 1.6-67.4; p=0.01) than lower scores., Conclusion: The thoracic topography of myelomeningocele has a trend for a higher association with infection in general and VP shunt infection. Evans' index scores higher than 70 were independently associated with VP shunt infection., (Copyright © 2012 Elsevier B.V. All rights reserved.)

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.

Background: Traumatic brain injury (TBI) is a worldwide cause of morbidity and mortality. Pentraxin 3 (PTX3) is a humoral component of the innate immune system which has been studied as a marker of inflammatory, infections or cardiovascular pathologies. To investigate the association between serum levels of PTX3 and the hospital mortality of patients with severe TBI., Methods: The independent association between serum PTX3 levels after severe TBI (Glasgow Coma Scale, GCS ≤ 8) and hospital mortality was analyzed in a prospective study of 83 consecutive patients by a multiple logistic regression analysis. The leukocyte count in the same sample was analyzed as another marker of inflammatory response., Results: The mean age of patients was 35 years and 85% were male. Serum PTX3 levels were determined 18.0 (SD ± 17.0) h after TBI. Patients who died showed a mean serum PTX3 level of 9.95 μg/ml (SD ± 6.42) in comparison to 5.46 μg/ml (SD ± 4.87) of the survivor group (P = 0.007). Elevated serum PTX3 levels remain significantly associated with mortality (P = 0.04) in the subset of patients with isolated TBI (n = 34). There were no differences in the leukocytes count measured in the same blood sample used for PTX3 determination in survivors and non-survivors (P = 0.56). The final multiple logistic regression model including age, pupillary examination, GCS, associated trauma, and PTX3 levels shows that serum levels of PTX3 which were higher than 10 μg/ml were independently associated with the patients mortality (adjusted OR 3.06, CI 95% 1.03-9.15, P = 0.04)., Conclusions: Serum PTX3 levels after severe TBI are independently associated with higher hospital mortality and may be a useful marker of TBI and its prognosis.

Objective: Trigeminal neuralgia is the most common facial pain. It may be treated with percutaneous balloon compression (PBC), which is considered to be a safe and efficient procedure. The purpose of this study was to review our results with PBC and to assess the factors influencing the outcome., Method: A multivariate analysis was used to study 39 patients during a 50-month postoperative period., Results: There was predominance of the female gender (54%), the right side of the face (84%) and V2V3 roots of trigeminal nerve (33%). The mean age was 62.3 years. No major complications or deaths occurred. Among all variables, postoperative hypoesthesia was the single prognostic factor capable of positively influencing the results (p=0.02). Most patients (80%) were pain-free after 50 months with a 90% satisfaction rate., Conclusion: PBC was a safe procedure with low morbidity, no mortality, high approval ratings, and was an important improving on patients' quality of life.

Background: Hemangioblastomas (HB) are rare lesions accounting for 2% of all spinal cord tumors. They are highly vascular, benign tumors that occur either sporadically or in the presence of von Hippel-Lindau disease. Spinal cord HB are usually diagnosed in adult patients and their incidence in early infancy is an extreme rarity., Methods: We present a case of a 1-month-old male with a back deformity and left leg hypomotility. MRI of the spine revealed an intramedullary tumor extending from level T6 to T12., Results: The tumor was excised completely, using standard microsurgical techniques via a posterior approach. The histological diagnosis was spinal cord HB., Conclusion: A review of the literature revealed that this neoplasm is composed of 3 major cell types: endothelial cells, pericytes and stromal cells. Complete microsurgical removal is the treatment of choice for spinal cord HB because the tumor is benign. To the best of our knowledge, sporadic spinal cord HB at this age has not been reported so far., (Copyright © 2011 S. Karger AG, Basel.)

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.

Cellular prion protein (PrP(c)) gene (Prnp) null mice (Prnp0/0) show higher sensitivity to seizures, enhanced brain oxidative stress, and their neurons exhibit higher excitability "in vitro". Mitochondrial respiration is a useful parameter for the determination of cellular metabolic rate and it is a major source of reactive oxygen species (ROS). In the present study, we investigated the mitochondrial function of different brain areas of Prnp0/0 adult mice and then compared this to normal control animals. Baseline mitochondrial respiration (stages 3 and 4), respiratory control ratio (RCR) and membrane potential were evaluated in the neocortex, entorhinal cortex, hippocampus, and cerebellum. No differences in these parameters were detected between Prnp0/0 and wild-type mice. Thus, we concluded that baseline mitochondrial respiration might not be directly related with the higher oxidative stress previously observed in brains from Prnp0/0 mice.

Objective: To describe the outcomes in our first 40 microelectrode-guided thalamotomies for parkinsonian tremor., Methods: Twenty-four left-sided and 16 right-sided thalamotomies were performed between October 1984 and January 1996; the mean follow-up period was 35.8 months (range, 1-152 mo). The results were evaluated retrospectively and semiquantitatively by a disinterested observer (MNL) and correlated with the quality of the microelectrode recording and the number and size of radiofrequency lesions made. The first 20 and second 20 procedures were evaluated separately., Results: At the last follow-up, the Unified Parkinson's Disease Rating Scale showed no or virtually no tremor in the upper limb in 75% of patients or in the lower limb in 73% of patients. No significant persistent complications were found. These results were achieved at the expense of having to repeat the procedure on 11 sides (in 5 because of technical problems and in 6 for no obvious reason). Total or nearly total abolition of tremor occurred after the first procedure in 40% of the first 20 operations and in 65% of the second 20. Eight of the first 20 procedures and 2 of the second 20 failed for technical reasons. Lesions were made larger in the second 20 procedures than in the first 20. With the use of an electrode with a 1.1 x 3-mm bare tip for 60 seconds, it seems that lesions had to be created at 60 degrees C or more to produce a successful result., Conclusion: Thalamotomy with microelectrode recording is an effective procedure with which to treat tremor in patients with Parkinson's disease and may involve fewer complications than conventional techniques. The procedure appears to involve a learning curve.

Background: Focal intracranial infections caused by Salmonella species are uncommon. The authors report a case of multiple brain abscesses caused by Salmonella typhi., Case Description: A 2-month-old girl was admitted to the hospital because of diarrhea, vomiting, fever, and poor feeding. Neurological examination revealed cervical hyperextension and absence of sucking and Moro reflexes. During the next 20 hours she developed complex partial seizures with secondary generalization and alternated irritability with drowsiness. Investigation showed hemoglobin 6.3 g/dl; white blood cell count of 19500/mm3 with a marked shift to the left. The analysis of the cerebrospinal fluid revealed white cell count of 1695/mm3, lymphocytes 61%, protein 300 mg/dl and glucose 6 mg/dl. The patient was treated for acute gastroenterocolitis, sepsis, and meningitis. Blood culture taken on the day of admission showed gram-negative bacilli, later identified as S. typhi. Computed tomography scan demonstrated a lesion in the right parietal lobe compatible with a brain abscess. Follow-up computed tomography after 7 days showed several other lesions with the same features. Surgical drainage of the right parietal lesion was performed on the 13th day, through a burr hole. The patient was discharged 5 weeks after admission without neurological deficit., Conclusion: Bacteremia, sepsis, and meningitis are relatively common in children with Salmonella infection but intracranial abscesses are very rare. Surgical drainage combined with prolonged antibiotic therapy (drug of choice: chloramphenicol) is the best treatment for Salmonella brain abscesses. The possibility of intracranial infection should be considered in patients with Salmonellosis and neurological dysfunction.