Search

The molecular mechanisms mediating manganese (Mn)-induced neurotoxicity, particularly in the immature central nervous system, have yet to be completely understood. In this study, we investigated whether mitogen-activated protein kinases (MAPKs) and tyrosine hydroxylase (TH) could represent potential targets of Mn in striatal and hippocampal slices obtained from immature rats (14 days old). The aim of this study was to evaluate if the MAPK pathways are modulated after subtoxic Mn exposure, which do not significantly affect cell viability. The concentrations of manganese chloride (MnCl2; 10-1,000 M) caused no change in cell viability in slices exposed for 3 or 6 hours. However, Mn exposure significantly increased extracellular signal-regulated kinase (ERK) 1/2, as well as c-Jun N-terminal kinase (JNK) 1/2/3 phosphorylation at both 3 and 6 hours incubations, in both brain structures. Furthermore, Mn exposure did not change the total content or phosphorylation of TH at the serine 40 site in striatal slices. Thus, Mn at concentrations that do not disrupt cell viability causes activation of MAPKs (ERK1/2 and JNK1/2/3) in immature hippocampal and striatal slices. These findings suggest that altered intracellular MAPKs signaling pathways may represent an early event concerning the effects of Mn in the immature brain. 1. Intro [ABSTRACT FROM AUTHOR]

The epileptogenesis may involve a variety of signaling events that culminate with synaptic reorganization. Mitogen-activated protein kinases (MAPKs) and AKT may be activated by diverse stimulus including neurotransmitter, oxidative stress, growth factors and cytokines and are involved in synaptic plasticity in the hippocampus and cerebral cortex. The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. We analyze the phosphorylation profile of MAPKs (ERK1/2, p38, JNK1/2/3) and AKT by western blotting in the hippocampus (Hip) and cortex (Ctx) of male adult wistar rats in different periods, after pilocarpine induced status epilepticus (Pilo-SE) and compared with control animals. Biochemical analysis were done in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period) and 50 days (chronic period) after Pilo-SE onset. Hence, the main findings include increased phosphorylation of ERK1 and p38 in the Hip and Ctx 1 and 12 h after the Pilo-SE onset. The JNK2/3 isoform (54 kDa) phosphorylation was decreased at 3 h after the Pilo-SE onset and in the chronic period in the Hip and Ctx. The AKT phosphorylation increased only in the Hip during the latent period. Our study demonstrates, in a systematic manner, the profile of MAPKs and AKT modulation in the hippocampus and cerebral cortex in response to pilocarpine. Based in the role of each signaling enzyme is possible that these changes may be related, at least partially, to modifications in the intrinsic neuronal physiology and epileptogenic synaptic network that appears in the MTLE-HS. [ABSTRACT FROM AUTHOR]

The causes of Parkinson's disease (PD) are unknown, but there is evidence that exposure to environmental agents, including a number of viruses, toxins, agricultural chemicals, dietary nutrients, and metals, is associated with its development in some cases. The presence of smell loss and the pathological involvement of the olfactory pathways in the early stages of PD are in accord with the tenants of the olfactory vector hypothesis. This hypothesis postulates that some forms of PD may be caused or catalyzed by environmental agents that enter the brain via the olfactory mucosa. In this article, we provide an overview of evidence implicating xenobiotics agents in the etiology of PD and review animal, mostly rodent, studies in which toxicants have been introduced into the nose in an attempt to induce behavioral or neurochemical changes similar to those seen in PD. The available data suggest that this route of exposure results in highly variable outcomes, depending upon the involved xenobiotic, exposure history, and the age and species of the animals tested. Some compounds, such as rotenone, paraquat, and 6-hydroxydopamine, have limited capacity to reach and damage the nigrostriatal dopaminergic system via the intranasal route. Others, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), readily enter the brain via this route in some species and influence the function of the nigrostriatal pathway. Intranasal infusion of MPTP in some rodents elicits a developmental sequence of behavioral and neurochemical changes that closely mimics that seen in PD. For this reason, such an MPTP rodent model appears to be an ecologically valid means for assessing novel palliative treatments for both the motor and non-motor symptoms of PD. More research is needed, however, on this and other ecologically valid models. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To investigate the frequency and patterns of headache in a well-defined and homogeneous group of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) patients. Methods: One hundred consecutive MTLE-HS patients under comprehensive presurgical evaluation were evaluated from May 2009 to April 2010. A standardized questionnaire was applied according to the criteria of the International Headache Society (IHS). Headache diagnosis was based on the second edition of the International Classification of Headache Disorders (ICHD-II). Results: Ninety-two patients (92%) had at least one headache episode during the previous 12 months. Migraine occurred in 51.9% of patients and tension-type headache (TTH) in 39.1%. Patients with migraine presented higher frequency (p =0.002) and severity of episodes (p <0.001), as well as lateralized pain (p =0.001) than individuals with TTH. MTLE-HS patients with unilateral HS and predominantly unilateral headache (irrespective of the type), presented pain ipsilateral to the HS (OR 8.5; CI 95%=2.1–35.1; p =0.003). Conclusions: Headache is a frequent clinical symptom of lateralizing value, which may share common pathophysiology with epileptogenesis among MTLE-HS patients. [Copyright &y& Elsevier]

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

Abstract: Clinical and demographic presurgical variables may be associated with unfavorable postsurgical neurological outcome in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). However, few reports include preoperative psychiatric disorders as a factor predictive of long-term postsurgical MTLE-HS neurological outcome. We used Engel’s criteria to follow 186 postsurgical patients with MTLE-HS for an average of 6 years. DSM-IV criteria and psychiatric comorbidity criteria specific to epilepsy (interictal dysphoric disorder, postictal and interictal psychosis) were used to assess presurgical psychiatric disorders. Kaplan–Meier event-free survival and adjusted hazard ratios were estimated with unconditional logistic regression. Seventy-seven (41.4%) patients had a preoperative Axis I psychiatric diagnosis. Thirty-six patients had depression, 11 interictal dysphoric disorder, 14 interictal psychosis, 6 postictal psychosis, and 10 anxiety disorders. Twenty-three (12.4%) patients had Axis II personality disorders. Regarding seizure outcome, preoperative anxiety disorders (P =0.009) and personality disorders (P =0.003) were positively correlated with Engel class 1B (remaining auras) or higher. These findings emphasize the importance of presurgical psychiatric evaluation, counseling, and postsurgical follow-up of patients with epilepsy and psychiatric disorders. [Copyright &y& Elsevier]

Abstract: The cellular prion protein (PrP C ) is a neuronal anchored glycoprotein that has been associated with distinct functions in the CNS, such as cellular adhesion and differentiation, synaptic plasticity and cognition. Here we investigated the putative involvement of the PrP C in the innate fear-induced behavioural reactions in wild-type (WT), PrP C knockout (Prnp 0/0 ) and the PrP C overexpressing Tg-20 mice evoked in a prey versus predator paradigm. The behavioural performance of these mouse strains in olfactory discrimination tasks was also investigated. When confronted with coral snakes, mice from both Prnp 0/0 and Tg-20 strains presented a significant decrease in frequency and duration of defensive attention and risk assessment, compared to WT mice. Tg-20 mice presented decreased frequency of escape responses, increased exploratory behaviour, and enhancement of interaction with the snake, suggesting a robust fearlessness caused by PrP C overexpression. Interestingly, there was also a discrete decrease in the attentional defensive response (decreased frequency of defensive alertness) in Prnp 0/0 mice in the presence of coral snakes. Moreover, Tg-20 mice presented an increased exploration of novel environment and odors. The present findings indicate that the PrP C overexpression causes hyperactivity, fearlessness, and increased preference for visual, tactile and olfactory stimuli-associated novelty, and that the PrP c deficiency might lead to attention deficits. These results suggest that PrP c exerts an important role in the modulation of innate fear and novelty-induced exploration. [Copyright &y& Elsevier]

Abstract: The cellular prion protein (PrP C ) is a sialoglycoprotein involved in neuroplasticity processes and synaptic transmission. This study investigated behavioural responses (balance in the rota-rod test at 24rpm, motility in the open-field test, anxiety in the elevated plus-maze test) in Zurich developed wild-type adult mice (WT, controls of normal PrP C expression), in knockout (KO) mice (Prnp 0/0, with no PrP C expression), and in PrP C overexpressing Tg-20 mice. After 8min in the rota-rod test, Tg-20 animals presented significantly fewer falls (1.08±1.56 falls) than both WT (7.27±4.36) and KO (7.6±6.15) mice (p <0.01). In the open field test, Tg-20 animals showed significantly increased motility [rearing=23.4±7.85, crossing=97.30±32.11) when compared with KO mice (rearing=5.45±3.69 and crossing=59.73±15.43) or WT mice (rearing=6.5±20.23 and crossing=45.18±20.33) (p <0.01). In the elevated plus-maze test, Tg-20 mice showed less anxiety (head projections=7.3±1.62) when compared with WT animals (3.38±0.67) (p <0.05). Moreover, KO mice spent more time in the centre of the plus maze (37.80±5.57s) than did WT mice (22.57±3.82) (p <0.05). PrP C overexpressing mice evoked increased motility, less anxiety, and increased equilibrium when compared with WT control animals in the behavioural protocols used. KO animals also tended to evoke fewer anxiety-related responses in the elevated plus-maze test. These findings indicate that the levels of PrP C in adult life are associated with possible changes in motility, anxiety, and equilibrium. [Copyright &y& Elsevier]

Cellular prion protein (PrPc) has a pivotal role in prion diseases. PrPc is a specific receptor for laminin (LN) γ1 peptide and several lines of evidence indicate that it is also involved in neural plasticity. Here we investigated whether the interaction between PrPc and LN plays a role in rat memory formation. We found that post-training intrahippocampal infusion of PrPc-derived peptides that contain the LN binding site ( and ) or of anti-PrPc or anti-LN antibodies that inhibit PrPc–LN interaction impaired inhibitory avoidance memory retention. The amnesic effect of anti-PrPc antibodies and peptide was reversed by co-infusion of a LN γ1 chain-derived peptide containing the PrPc-binding site, suggesting that PrPc–LN interaction is indeed crucial for memory consolidation. In addition, peptide and anti-PrPc or anti-LN antibodies also inhibited the activation of hippocampal cAMP-dependent protein kinase A (PKA) and extracellular regulated kinase (ERK1/2), two kinases that mediate the up-regulation of signaling pathways needed for consolidation of inhibitory avoidance memory. Our findings show that, through its interaction with LN, hippocampal PrPc plays a critical role in memory processing and suggest that this role is mediated by activation of both PKA and ERK1/2 signaling pathways. [ABSTRACT FROM AUTHOR]

Summary: Neocortical development is a highly complex process encompassing cellular proliferation, neuronal migration and cortical organization. At any time this process can be interrupted or modified by genetic or acquired factors causing malformations of cortical development (MCD). Epileptic seizures are the most common type of clinical manifestation, besides developmental delay and focal neurological deficits. Seizures due to MCD are frequently pharmacoresistant, especially those associated to focal cortical dysplasia (FCD). Surgical therapy results have been reported since 1971, however, currently available data from surgical series are still limited, mainly due to small number of patients, distinct selection of candidates and surgical strategies, variable pathological diagnosis and inadequate follow-up. This study addresses the possibilities of seizure relief following resection of focal cortical dysplasia, and the impact of presurgical evaluation, extent of resection and pathological findings on surgical outcome. We included 41 patients, 22 adults and 19 children and adolescents, with medically intractable seizures operated on from 1996 to 2002. All were submitted to standardized presurgical evaluation including high-resolution MRI, Video-EEG monitoring and ictal SPECT. Post-surgical seizure outcome was classified according to Engel''s schema. Univariate and multivariate analysis were performed. Fifteen patients had temporal and 26 extratemporal epilepsies. Of the total 26 patients (63.4%) reached seizure-free status post-operatively. There was no correlation between outcome and age at surgery, duration of epilepsy, frequency of seizures, and pathological findings. There was, however, a clear correlation with topography of FCD (temporal versus extratemporal) and regional ictal EEG onset, on univariate as well as multivariate analysis. [Copyright &y& Elsevier]

Purpose: We analyze a series of patients with mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) submitted to presurgical investigation with scalp sphenoidal, followed by foramen ovale electrodes (FO), and, when necessary, with depth temporal electrodes. We sought to evaluate the clinical utility of FO in patients with MTLE-HS. Methods: We included patients who had phase I investigation with bitemporal independent seizures, nonlateralized ictal onsets, or ictal onset initiating in the side contralateral to the side of hippocampal sclerosis. Patients whose implanted FO failed to demonstrate an unambiguous unilateral ictal onset were later evaluated with depth hippocampal electrodes. Results: Between May 1994 and December 2004, 64 patients met our inclusion criteria: 33 female (51.5%) and 31 male subjects (48.5%). The mean age at enrollment was 37.66 ± 10.6 years (range, 12–56 years). The groups with nonlateralized surface ictal EEG onsets and contralateral EEG onsets had a greater chance of lateralization with FO when compared with the group with bilateral independent seizures on surface EEG (p < 0.01). Foramen ovale electrodes lateralized the seizures in 60% of patients. Seventy percent of patients became seizure free after temporal lobectomy. Five patients were implanted with depth temporal electrodes after FO video-EEG monitoring. The depth-electrode EEG onsets confirmed the results of FO video-EEG monitoring in all patients, and the surgery was refused. Conclusions: In MTLE-HS, FO is a reliable method for lateralization of seizures that are not clearly recorded by surface EEGs. [ABSTRACT FROM AUTHOR]

Purpose: We sought to analyze the contralateral volumes of the temporal pole, posterior segment of the temporal lobe, amygdala, hippocampus, and parahippocampal gyrus in patients with temporal lobe epilepsy (TLE) due to histologically proven mesial temporal lobe sclerosis (MTLS), seizure free for ≥4 years of postsurgical follow-up. Methods: Forty-six (23 male) TLE patients, operated on between 1996 and 2001, with histopathologic diagnosis of MTLS, and a postsurgical follow-up of ≥4 years, had their temporal lobe structures manually segmented, measured, and compared with those of 23 normal volunteers, paired as groups for sex, age, and handedness. Results: The mean volumes of the contralateral temporal pole, hippocampus, and parahippocampal gyrus in TLE patients were significantly lower than those in controls. Conclusions: MRI volumetric data show that the damage in TLE due to MTS may be more widespread and bilateral, even in patients with unilateral TLE by clinical and neurophysiological criteria. Our results are relevant to the discussion of epileptogenic mechanisms in TLE. [ABSTRACT FROM AUTHOR]

Purpose: Posterior cortex epilepsies (PCEs) encompass a group of epilepsies originating from the occipital, parietal, or occipital border of the temporal lobe, or from any combination of these regions. When their seizures are refractory to pharmacologic treatment, these patients are usually referred for surgery. The aim of our study was to analyze clinical characteristics of all PCE patients referred for surgery from 1994 to 2003, and to search for predictors of surgical outcome. Methods: We performed a retrospective analysis of clinical and laboratory data from 81 consecutive refractory PCE patients referred for surgery. Surgical and nonsurgical groups of patients were compared, and detailed analyses of all variables of the surgical cases were performed in the search for predictors of seizure outcome. Results: Risk factors for PCEs included gliosis (34.56%), malformations of cortical development (33.33%), tumors (8.64%), brain trauma (3.70%), Sturge–Weber disease (4.93%), vascular malformations (3.70%), family history of epilepsy (3.70%), history of CNS infections (2.46%), and low IQ (2.46%). Of the 81 patients, 44 were submitted to surgery at the time of the completion of this study. Surgical treatment was highly effective in improving seizures (p < 0.001) when compared with previous pharmacologic treatment alone. Twenty-eight (65.11%) patients became seizure free after surgery versus none in the nonsurgical group. Regarding outcome predictors, patients with shorter duration of epilepsy and those without neurologic abnormalities on clinical examination had higher chances of favorable evolution. Conclusions: Surgical treatment is effective for the treatment of PCEs and superior to pharmacologic therapy alone. In our series, shorter duration of epilepsy and normal neurologic examination were the only independent variables that predicted better surgical outcome. [ABSTRACT FROM AUTHOR]

1. Cellular prion (PrPc) is a plasma membrane protein involved with copper uptake, protection against oxidative stress, cell adhesion, differentiation, signaling, and survival in the central nervous system 2. Deletion of PrPc gene ( Prnp) in mice enhances sensitivity to seizures in vivo and neuronal excitability in vitro which can be related to: (i) disrupted Ca+2-activated K+ currents, with loss of IHAP conductance in hippocampus; (ii) abnormal GABA-A inhibition in the hippocampus; (iii) mossy fiber reorganization in the hippocampus; (iv) changes in ectonucleotidases in both hippocampus and neocortex; and (v) higher levels of neocortical and subcortical oxidative stress. Moreover, postnatal Prnp knockout mice showed a significant reduction of after hyperpolarization potentials in hippocampal CA1 cells. 3. Taken together, these findings suggest that loss of PrPc function contributes to the hyperexcitable and synchronized activities underlying epileptic seizures generated in neocortex and hippocampus. Hence, the role of PrPc on human symptomatic, cryptogenic or idiopathic epileptic syndromes deserves further investigation. [ABSTRACT FROM AUTHOR]

Cellular prion (PrPc) is a plasma membrane glycosyphosphatidylinositol-anchored protein present in neurons but also in other cell types. Protein conservation among species suggests that PrPc may have important physiological roles. Cellular and molecular approaches have established several novel features of the regulation of PrPc expression, cellular trafficking as well as its participation in copper uptake, protection against oxidative stress, cell adhesion, differentiation, signaling and cell survival. It is therefore likely that PrPc plays pleiotropic roles in neuronal and non-neuronal cells, and as such the loss of function of PrPc may be an important component of various diseases. [Copyright &y& Elsevier]

The ectonucleotidase pathway is an important metabolic source of extracellular adenosine. Adenosine has potent anticonvulsant effects on various models of epilepsy. One of these models is pentylenetetrazol (PTZ) kindling, in which repeated administration of subconvulsive doses of this drug induces progressive intensification of seizure activity. In this study, we examine the effect of a single convulsive injection (60 mg/kg, i.p.) or 10 successive (35 mg/kg, i.p.) injections of PTZ on synaptosomal ectonucleotidases. Our results have shown that no changes in ectonucleotidase activities were seen at 0, 1, and 24 h or at 5 days after a single convulsive PTZ injection. However, after PTZ-kindling, rats which were more resistant to seizure development presented an increase in ATP hydrolysis in synaptosomes from hippocampus and cerebral cortex (44% and 28%, respectively). These results suggest that changes in nucleotide hydrolysis may represent an important mechanism in the modulation of chronic epileptic activity in this model. [ABSTRACT FROM AUTHOR]

Background Neurocysticercosis (NCC) is the most common parasitic disease of the human central nervous system and a major health problem for most developing countries. The most common clinical manifestations of NCC are epileptic seizures. Whenever epilepsy and NCC coexist in the same patient, an uncertainty may rise about a causal relationship between them. Observation We described a female patient with disseminated calcified NCC lesions and intractable epilepsy. Her medical history included cysticercotic meningoencephalitis and status epilepticus caused by active NCC. Fundoscopy showed the ocular presence of parasite; computed tomography of the brain showed evidence of cystic lesions with the scolex and calcified lesions; enzyme-linked immunosorbent assay of the cerebrospinal fluid was positive for cysticercosis. Epileptic seizures started after an 8-year silent period. Magnetic resonance imaging showed left hippocampal sclerosis. Plain x-ray film showed calcifications in muscles and subcutaneous tissue. Video-electroencephalography and ictal and interictal single-photon emission computed tomography disclosed left mesial temporal lobe epilepsy. The patient underwent left temporal lobectomy and has been seizure free since surgery, for a follow-up of 4 years. Conclusion This case report highlights and supports surgical therapy in patients with epileptic seizures and calcified NCC, even when there are several calcifications, provided that clear localization of epilepsy has been determined by means of a presurgical workup. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about the dilated Cardiomyopathy and Creutzfeldt-Jakob disease.

Objective: To investigate the relationship between the levels of adipokines and other endocrine biomarkers and patient outcomes in hospitalized patients with COVID-19. Methods: In a prospective study that included 213 subjects with COVID-19 admitted to the intensive care unit, we measured the levels of cortisol, C-peptide, glucagonlike peptide-1, insulin, peptide YY, ghrelin, leptin, and resistin.; their contributions to patient clustering, disease severity, and predicting in-hospital mortality were analyzed. Results: Cortisol, resistin, leptin, insulin, and ghrelin levels significantly differed between severity groups, as defined by the World Health Organization severity scale. Additionally, lower ghrelin and higher cortisol levels were associated with mortality. Adding biomarkers to the clinical predictors of mortality significantly improved accuracy in determining prognosis. Phenotyping of subjects based on plasma biomarker levels yielded two different phenotypes that were associated with disease severity, but not mortality. Conclusion: As a single biomarker, only cortisol was independently associated with mortality; however, metabolic biomarkers could improve mortality prediction when added to clinical parameters. Metabolic biomarker phenotypes were differentially distributed according to COVID-19 severity but were not associated with mortality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Autonomic dysfunction may account for sudden unexpected death in patients with epilepsy (PWE). On the other hand, low cardiovascular fitness, which may affect autonomic function, is a risk factor for sudden death and all-cause mortality in the general population. Little is known about autonomic variables and cardiovascular response to exercise in PWE. We submitted thirty consecutive PWE with no known cardiovascular diseases to maximal treadmill test, comparing them with matched controls. All individuals were submitted to clinical assessment, 12-lead electrocardiogram (ECG) and echocardiogram to exclude cardiovascular disease. Maximal/exhaustive treadmill test using the Bruce protocol was then performed. Clinical-epidemiological features were similar in both groups, regarding age, sex, body mass index and traditional cardiovascular risk factors. PWE achieved a lower peak heart rate (163.8 ± 21.28 bpm × 180.9 ± 12.52 bpm; p = 0.002), lower duration of exercise (673.6 ± 148.27 s × 784.4 ± 155.72 s; p = 0.004), lower Duke Score (11.8 ± 2.48 × 13.4 ± 2.28; p = 0.02) and lower achieved metabolic equivalent of task (MET) (12.8 ± 2.49 × 14.5 ± 2.46; p = 0.006). Chronotropic incompetence was more frequent in PWE. Female gender, age of epilepsy onset, number of secondarily generalized seizures and polytherapy were associated to lower cardiovascular fitness in multiple linear regression. Increased risk for SUDEP in PWE may be associated with autonomic disturbances of the cardiovascular system secondary to low cardiovascular fitness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

Mutations in the human prion protein gene (PRNP) are responsible for hereditary diseases called transmissible spongiform encephalopathies (TSE) and a polymorphic site at codon 129 determines sensitivity to infectious forms of these maladies. More recently, codon 129 has been related to cognition performance in the elderly, in Alzheimer disease (AD) and in Down syndrome. Furthermore, a rare polymorphism at codon 171 was described in 23% of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS), the most common form of surgically remediable epileptic syndrome. Thus, a method that permits fast and efficient screening of PRNP mutations and polymorphisms in patients, in high risk populations, and in family members is desirable. In the present study, we established the conditions for analysis of the PRNP open reading frame using denaturing high-performance liquid chromatography (DHPLC), whereby unpurified PCR products were subjected to denaturing and reannealing steps leading to heteroduplex formation. We described specific profiles for the PRNP polymorphisms at codons 129 (M/V), 117 (A/A silent), 219 (E/K), 171 (N/S), and the octarepeat deletion using amplified DNA from 562 samples. The chromatograms for TSE-associated mutations at codons 102 (P/L), 183 (T/A), and 210 (V/I) were also determined. Specificity of the DHPLC profile for each PRNP variant allele was confirmed in 100% of the samples by direct and cloned DNA sequencing in addition to endonuclease digestion when applicable. Therefore, the present study shows that DHPLC is a rapid, highly accurate and efficient technique for the detection of PRNP genetic variants. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Intranasal NaDMDC administration in mice induces motor impairments that lasts until 35 days. • Melatonin treatment protects against motor deficits induced by NaDMDC in early and late phases. • Melatonin reduces the oxidative/nitrosative damages induced by NaDMDC in brain structures of mice. • The dopaminergic nigrostriatal pathway was protect by melatonin treatment. Exposure to fungicide ziram (zinc dimethyldithiocarbamate) has been associated with increased incidence of Parkinson's disease (PD). We recently demonstrated that the intranasal (i.n.) administration of sodium dimethyldithiocarbamate (NaDMDC, a more soluble salt than ziram) induces PD-like behavioral and neurochemical alterations in mice. We now investigated the putative neuroprotective effects of melatonin on behavioral dificits and neurochemical alterations induced by i.n. NaDMDC. Melatonin treatment (3, 10 or 30 mg/kg, i.p.) was given 1 h before NaDMDC administration (1 mg/nostril) during 4 consecutive days and we evaluated early (up to 7 days) and late (up to 35 days) NaDMDC-induced behavioral and neurochemical alterations. Melatonin treatment protected against early motor and general neurological impairments observed in the open field and neurological score of severity, respectively, and late deficits in rotarod test. Melatonin prevented the NaDMDC-induced alterations in the striatal tyrosine hydroxylase immunocontent. Melatonin also protected against increased levels of oxidative stress markers (4-hydroxynonenal and 3-nitrotyrosine) in the striatum, as well as the NaDMDC-induced increase of 4-hydroxynonenal and TNF, markers of oxidative stress and inflammation, respectively, in the olfactory bulb. These results further detail the mechanisms underlying NaDMDC toxicity and demonstrate the neuroprotective effects of melatonin against the neuronal damage induced by NaDMDC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]